Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

PubMed

Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

2015-01-25

Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

ERIC Educational Resources Information Center

Bodner, George M.

1986-01-01

Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

The Use of an Imagery Mnemonic to Teach the Krebs Cycle

ERIC Educational Resources Information Center

Morisaki, Ryoma; Bon, Charles; Levitt, Jacob O.

2016-01-01

The Krebs Cycle is a highly taught biochemical pathway that is traditionally difficult to learn. Twenty-seven undergraduate students were randomized to a rote memorization arm or to a mnemonic arm. They were given a pre-test, then shown a lecture corresponding to their assigned method, and then given an immediate Week 0 post-test and a Week 4…

Late Quaternary Glaciation of the Naches River Drainage Basin, Washington Cascades

NASA Astrophysics Data System (ADS)

Sheffer, H. B.; Goss, L.; Shimer, G.; Carson, R. J.

2014-12-01

The Naches River drainage basin east of Mount Rainer includes tributary valleys of the Little Naches, American, Bumping, and Tieton rivers. An investigation of surface boulder frequency, weathering rind thicknesses, and soil development on moraines in these valleys identified two stages of Pleistocene glaciations in the American, Bumping, and Tieton drainages, followed by Neoglaciation. These stages include a more extensive early glaciation (Hayden Creek?), and the later Evans Creek Glaciation (25-15 ka). Thick forest cover, limited road cuts, and widespread post-glacial mass wasting hamper efforts to determine the maximum extent of glaciation. However, glacial striations at Chinook Pass, moraine complexes in the vicinity of Goose Egg Mountain, ice-transported boulders and striations on Pinegrass Ridge, and a boulder field possibly derived from an Evans Creek jökulhaup in the Tieton River valley, all point to extensive Pleistocene ice in the central tributaries of the Naches River. Lowest observed ice elevations in the Tieton (780 m), Bumping (850 m), and American (920 m) drainages increase towards the north, while glacial lengths decrease from 40 to 28 km. The Little Naches is the northernmost drainage in the study, but despite a maximum elevation (1810 m) that exceeds the floor of ice caps to the south, glacially-derived sediments are not evident and the surrounding peaks lack cirques. The absence of ice in the Little Naches drainage, along with the systematic northward change in glacial length and lowest observed ice elevations in the other drainages, are likely due to a precipitation shadow northeast of Mount Rainier. In contrast, the source of glacial ice in the Tieton drainage to the southeast was the Goat Rocks peaks. Ground-based study of neoglacial moraines and analysis of 112 years of topographic maps and satellite imagery point to rapid retreat of the remaining Goat Rocks glaciers following the Little Ice Age.

Validity of the AusTOM scales: A comparison of the AusTOMs and EuroQol-5D

PubMed Central

Unsworth, Carolyn A; Duckett, Stephen J; Duncombe, Dianne; Perry, Alison; Skeat, Jemma; Taylor, Nicholas

2004-01-01

Background Clinicians require brief outcome measures in their busy daily practice to document global client outcomes. Based on the UK Therapy Outcome Measure, the Australian Therapy Outcome Measures were designed to capture global therapy outcomes of occupational therapy, physiotherapy and speech pathology in the Australian clinical context. The aim of this study was to investigate the construct (convergent) validity of the Australian Therapy Outcome Measures (AusTOMs) by comparing it with the EuroQuol-5D (EQ-5D). Methods The research was a prospective, longitudinal cohort study, with data collected over a seven month time period. The study was conducted at a total of 13 metropolitan and rural health-care sites including acute, sub-acute and community facilities. Two-hundred and five clients were asked to score themselves on the EQ-5D, and the same clients were scored by approximately 115 therapists (physiotherapists, speech pathologists and occupational therapists) using the AusTOMs at admission and discharge. Clients were consecutive admissions who agreed to participate in the study. Clients of all diagnoses, aged 18 years and over (a criteria of the EQ-5D), and able to give informed consent were scored on the measures. Spearman rank order correlation coefficients were used to analyze the relationships between scores from the two tools. The clients were scored on the AusTOMs and EQ-5D. Results There were many health care areas where correlations were expected and found between scores on the AusTOMs and the EQ-5D. Conclusion In the quest to measure the effectiveness of therapy services, managers, health care founders and clinicians are urgently seeking to undertake the first step by identifying tools that can measure therapy outcome. AusTOMs is one tool that can measure global client outcomes following therapy. In this study, it was found that on the whole, the AusTOMs and the EQ-5D measure similar constructs. Hence, although the validity of a tool is never

The evolution of the Krebs cycle: A promising subject for meaningful learning of biochemistry.

PubMed

da Costa, Caetano; Galembeck, Eduardo

2016-05-06

Evolution has been recognized as a key concept for biologists. To enhance comprehension and motivate biology undergraduates for the contents of central energetic metabolism, we addressed the Krebs cycle structure and functions in an evolutionary view. To this end, we created a study guide that contextualizes the emergence of the cyclic pathway, in light of the prokaryotic influence since the early anaerobic condition of the Earth to increase oxygen in the atmosphere. The study guide is composed of three interrelated sections: (1) a problem, designed to arouse curiosity, inform and motivate students, (2) a text about life evolution, including early microorganisms and the emergence of the Krebs cycle, and (3) questions for debate. The activity consisted on individual reading and peer discussion based on this written material, under the guidance of the instructors. The questions were designed to foster debate in an ever-increasing level of complexity and to strengthen the main contextual aspects leading to emergence, evolving, and permanency of a complex metabolic pathway. Based on classroom observation, analysis of student's written responses, and individual interviews, we noticed they were engaged and motivated by the task, especially during group discussion. The whole experience suggests that the study guide was a stimulus to broaden the comprehension of the Krebs cycle, reinforcing the evolutionary approach as an important subject for learning purposes. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:288-296, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.

PubMed

Remacha, Laura; Comino-Méndez, Iñaki; Richter, Susan; Contreras, Laura; Currás-Freixes, María; Pita, Guillermo; Letón, Rocío; Galarreta, Antonio; Torres-Pérez, Rafael; Honrado, Emiliano; Jiménez, Scherezade; Maestre, Lorena; Moran, Sebastian; Esteller, Manel; Satrústegui, Jorgina; Eisenhofer, Graeme; Robledo, Mercedes; Cascón, Alberto

2017-10-15

Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases. Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2 , c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio. Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR . ©2017 American Association for Cancer Research.

The krebs cycle enzyme α-ketoglutarate decarboxylase is an essential glycosomal protein in bloodstream African trypanosomes.

PubMed

Sykes, Steven; Szempruch, Anthony; Hajduk, Stephen

2015-03-01

α-Ketoglutarate decarboxylase (α-KDE1) is a Krebs cycle enzyme found in the mitochondrion of the procyclic form (PF) of Trypanosoma brucei. The bloodstream form (BF) of T. brucei lacks a functional Krebs cycle and relies exclusively on glycolysis for ATP production. Despite the lack of a functional Krebs cycle, α-KDE1 was expressed in BF T. brucei and RNA interference knockdown of α-KDE1 mRNA resulted in rapid growth arrest and killing. Cell death was preceded by progressive swelling of the flagellar pocket as a consequence of recruitment of both flagellar and plasma membranes into the pocket. BF T. brucei expressing an epitope-tagged copy of α-KDE1 showed localization to glycosomes and not the mitochondrion. We used a cell line transfected with a reporter construct containing the N-terminal sequence of α-KDE1 fused to green fluorescent protein to examine the requirements for glycosome targeting. We found that the N-terminal 18 amino acids of α-KDE1 contain overlapping mitochondrion- and peroxisome-targeting sequences and are sufficient to direct localization to the glycosome in BF T. brucei. These results suggest that α-KDE1 has a novel moonlighting function outside the mitochondrion in BF T. brucei. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A reverse KREBS cycle in photosynthesis: consensus at last

NASA Technical Reports Server (NTRS)

Buchanan, B. B.; Arnon, D. I.

1990-01-01

The Krebs cycle (citric acid or tricarboxylic acid cycle), the final common pathway in aerobic metabolism for the oxidation of carbohydrates, fatty acids and amino acids, is known to be irreversible. It liberates CO2 and generates NADH whose aerobic oxidation yields ATP but it does not operate in reverse as a biosynthetic pathway for CO2 assimilation. In 1966, our laboratory described a cyclic pathway for CO2 assimilation (Evans, Buchanan and Arnon 1966) that was unusual in two respects: (i) it provided the first instance of an obligate photoautotroph that assimilated CO2 by a pathway different from Calvin's reductive pentose phosphate cycle (Calvin 1962) and (ii) in its overall effect the new cycle was a reversal of the Krebs cycle. Named the 'reductive carboxylic acid cycle' (sometimes also called the reductive tricarboxylic acid cycle) the new cycle appeared to be the sole CO2 assimilation pathway in Chlorobium thiosulfatophilum (Evans et al. 1966) (now known as Chlorobium limicola forma thiosulfatophilum). Chlorobium is a photosynthetic green sulfur bacterium that grows anaerobically in an inorganic medium with sulfide and thiosulfate as electron donors and CO2 as an obligatory carbon source. In the ensuing years, the new cycle was viewed with skepticism. Not only was it in conflict with the prevailing doctrine that the 'one important property ... shared by all (our emphasis) autotrophic species is the assimilation of CO2 via the Calvin cycle' (McFadden 1973) but also some of its experimental underpinnings were challenged. It is only now that in the words of one of its early skeptics (Tabita 1988) 'a long and tortuous controversy' has ended with general acceptance of the reductive carboxylic acid cycle as a photosynthetic CO2 assimilation pathway distinct from the pentose cycle. (Henceforth, to minimize repetitiveness, the reductive pentose phosphate cycle will often be referred to as the pentose cycle and the reductive carboxylic acid cycle as the carboxylic

A reverse KREBS cycle in photosynthesis: consensus at last.

PubMed

Buchanan, B B; Arnon, D I

1990-01-01

The Krebs cycle (citric acid or tricarboxylic acid cycle), the final common pathway in aerobic metabolism for the oxidation of carbohydrates, fatty acids and amino acids, is known to be irreversible. It liberates CO2 and generates NADH whose aerobic oxidation yields ATP but it does not operate in reverse as a biosynthetic pathway for CO2 assimilation. In 1966, our laboratory described a cyclic pathway for CO2 assimilation (Evans, Buchanan and Arnon 1966) that was unusual in two respects: (i) it provided the first instance of an obligate photoautotroph that assimilated CO2 by a pathway different from Calvin's reductive pentose phosphate cycle (Calvin 1962) and (ii) in its overall effect the new cycle was a reversal of the Krebs cycle. Named the 'reductive carboxylic acid cycle' (sometimes also called the reductive tricarboxylic acid cycle) the new cycle appeared to be the sole CO2 assimilation pathway in Chlorobium thiosulfatophilum (Evans et al. 1966) (now known as Chlorobium limicola forma thiosulfatophilum). Chlorobium is a photosynthetic green sulfur bacterium that grows anaerobically in an inorganic medium with sulfide and thiosulfate as electron donors and CO2 as an obligatory carbon source. In the ensuing years, the new cycle was viewed with skepticism. Not only was it in conflict with the prevailing doctrine that the 'one important property ... shared by all (our emphasis) autotrophic species is the assimilation of CO2 via the Calvin cycle' (McFadden 1973) but also some of its experimental underpinnings were challenged. It is only now that in the words of one of its early skeptics (Tabita 1988) 'a long and tortuous controversy' has ended with general acceptance of the reductive carboxylic acid cycle as a photosynthetic CO2 assimilation pathway distinct from the pentose cycle. (Henceforth, to minimize repetitiveness, the reductive pentose phosphate cycle will often be referred to as the pentose cycle and the reductive carboxylic acid cycle as the carboxylic

Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase.

PubMed

Elkalaf, Moustafa; Tůma, Petr; Weiszenstein, Martin; Polák, Jan; Trnka, Jan

2016-01-01

Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling. In permeabilized cells the inhibition was limited to NADH-linked respiration. We found a mixed inhibition of the Krebs cycle enzyme 2-oxoglutarate dehydrogenase complex (OGDHC) with an estimated IC50 3.93 [3.70-4.17] mM, which is pharmacologically plausible since it corresponds to micromolar extracellular concentrations. Increasing the lipophilic character of the used TPP+ compound further potentiates the inhibition of OGDHC activity. This effect of TPMP on the Krebs cycle ought to be taken into account when interpreting observations on cells and mitochondria in the presence of TPP+ derivatives. Compounds based on or similar to TPP+ derivatives may also be used to alter OGDHC activity for experimental or therapeutic purposes.

Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase

PubMed Central

Elkalaf, Moustafa; Tůma, Petr; Weiszenstein, Martin; Polák, Jan

2016-01-01

Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling. In permeabilized cells the inhibition was limited to NADH-linked respiration. We found a mixed inhibition of the Krebs cycle enzyme 2-oxoglutarate dehydrogenase complex (OGDHC) with an estimated IC50 3.93 [3.70–4.17] mM, which is pharmacologically plausible since it corresponds to micromolar extracellular concentrations. Increasing the lipophilic character of the used TPP+ compound further potentiates the inhibition of OGDHC activity. This effect of TPMP on the Krebs cycle ought to be taken into account when interpreting observations on cells and mitochondria in the presence of TPP+ derivatives. Compounds based on or similar to TPP+ derivatives may also be used to alter OGDHC activity for experimental or therapeutic purposes. PMID:27537184

Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.

PubMed

Zhang, Jimmy; Wang, Yves T; Miller, James H; Day, Mary M; Munger, Joshua C; Brookes, Paul S

2018-05-29

Succinate accumulates during ischemia, and its oxidation at reperfusion drives injury. The mechanism of ischemic succinate accumulation is controversial and is proposed to involve reversal of mitochondrial complex II. Herein, using stable-isotope-resolved metabolomics, we demonstrate that complex II reversal is possible in hypoxic mitochondria but is not the primary succinate source in hypoxic cardiomyocytes or ischemic hearts. Rather, in these intact systems succinate primarily originates from canonical Krebs cycle activity, partly supported by aminotransferase anaplerosis and glycolysis from glycogen. Augmentation of canonical Krebs cycle activity with dimethyl-α-ketoglutarate both increases ischemic succinate accumulation and drives substrate-level phosphorylation by succinyl-CoA synthetase, improving ischemic energetics. Although two-thirds of ischemic succinate accumulation is extracellular, the remaining one-third is metabolized during early reperfusion, wherein acute complex II inhibition is protective. These results highlight a bifunctional role for succinate: its complex-II-independent accumulation being beneficial in ischemia and its complex-II-dependent oxidation being detrimental at reperfusion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Evolution of the Krebs Cycle: A Promising Subject for Meaningful Learning of Biochemistry

ERIC Educational Resources Information Center

da Costa, Caetano; Galembeck, Eduardo

2016-01-01

Evolution has been recognized as a key concept for biologists. To enhance comprehension and motivate biology undergraduates for the contents of central energetic metabolism, we addressed the Krebs cycle structure and functions in an evolutionary view. To this end, we created a study guide that contextualizes the emergence of the cyclic pathway, in…

The Yeast Plasma Membrane ATP Binding Cassette (ABC) Transporter Aus1

PubMed Central

Marek, Magdalena; Milles, Sigrid; Schreiber, Gabriele; Daleke, David L.; Dittmar, Gunnar; Herrmann, Andreas; Müller, Peter; Pomorski, Thomas Günther

2011-01-01

The ATP binding cassette (ABC) transporter Aus1 is expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and is required for sterol uptake. These observations suggest that Aus1 promotes the translocation of sterols across membranes, but the precise transport mechanism has yet to be identified. In this study, an extraction and purification procedure was developed to characterize the Aus1 transporter. The detergent-solubilized protein was able to bind and hydrolyze ATP. Mutagenesis of the conserved lysine to methionine in the Walker A motif abolished ATP hydrolysis. Likewise, ATP hydrolysis was inhibited by classical inhibitors of ABC transporters. Upon reconstitution into proteoliposomes, the ATPase activity of Aus1 was specifically stimulated by phosphatidylserine (PS) in a stereoselective manner. We also found that Aus1-dependent sterol uptake, but not Aus1 expression and trafficking to the plasma membrane, was affected by changes in cellular PS levels. These results suggest a direct interaction between Aus1 and PS that is critical for the activity of the transporter. PMID:21521689

Validation of the Australian Propensity for Angry Driving Scale (Aus-PADS).

PubMed

Leal, Nerida L; Pachana, Nancy A

2009-09-01

The present study used a university sample to assess the test-retest reliability and validity of the Australian Propensity for Angry Driving Scale (Aus-PADS). The scale has stability over time, and convergent validity was established, as Aus-PADS scores correlated significantly with established anger and impulsivity measures. Discriminant validity was also established, as Aus-PADS scores did not correlate with Venturesomeness scores. The Aus-PADS has demonstrated criterion validity, as scores were correlated with behavioural measures, such as yelling at other drivers, gesturing at other drivers, and feeling angry but not doing anything. Aus-PADS scores reliably predicted the frequency of these behaviours over and above other study variables. No significant relationship between aggressive driving and crash involvement was observed. It was concluded that the Aus-PADS is a reliable and valid tool appropriate for use in Australian research, and that the potential relationship between aggressive driving and crash involvement warrants further investigation with a more representative (and diverse) driver sample.

Impaired in vivo mitochondrial Krebs cycle activity after myocardial infarction assessed using hyperpolarized magnetic resonance spectroscopy.

PubMed

Dodd, Michael S; Atherton, Helen J; Carr, Carolyn A; Stuckey, Daniel J; West, James A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Heather, Lisa C; Tyler, Damian J

2014-11-01

Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. © 2014 American Heart Association, Inc.

Impaired In Vivo Mitochondrial Krebs Cycle Activity After Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy

PubMed Central

Carr, Carolyn A.; Stuckey, Daniel J.; West, James A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Heather, Lisa C.; Tyler, Damian J.

2015-01-01

Background Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to, therefore, follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities. Methods and Results Using hyperpolarized carbon-13 (13C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks after surgically induced MI with reperfusion in female Wister rats. One week after MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28% to 84%). At 6 weeks after MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased 13C-label flux into citrate, glutamate, and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase flux. By 22 weeks, alterations were also seen in pyruvate dehydrogenase flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates. Conclusions The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations after MI in which reductions in Krebs cycle activity precede a reduction in pyruvate dehydrogenase flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment. PMID:25201905

Das Lektin aus der Erbse Pisum sativum : Bindungsstudien, Monomer-Dimer-Gleichgewicht und Rückfaltung aus Fragmenten

NASA Astrophysics Data System (ADS)

Küster, Frank

2002-11-01

Das Lektin aus Pisum sativum, der Gartenerbse, ist Teil der Familie der Leguminosenlektine. Diese Proteine haben untereinander eine hohe Sequenzhomologie, und die Struktur ihrer Monomere, ein all-ß-Motiv, ist hoch konserviert. Dagegen gibt es innerhalb der Familie eine große Vielfalt an unterschiedlichen Quartärstrukturen, die Gegenstand kristallographischer und theoretischer Arbeiten waren. Das Erbsenlektin ist ein dimeres Leguminosenlektin mit einer Besonderheit in seiner Struktur: Nach der Faltung in der Zelle wird aus einem Loop eine kurze Aminosäuresequenz herausgeschnitten, so dass sich in jeder Untereinheit zwei unabhängige Polypeptidketten befinden. Beide Ketten sind aber stark miteinander verschränkt und bilden eine gemeinsame strukturelle Domäne. Wie alle Lektine bindet Erbsenlektin komplexe Oligosaccharide, doch sind seine physiologische Rolle und der natürliche Ligand unbekannt. In dieser Arbeit wurden Versuche zur Entwicklung eines Funktionstests für Erbsenlektin durchgeführt und seine Faltung, Stabilität und Monomer-Dimer-Gleichgewicht charakterisiert. Um die spezifische Rolle der Prozessierung für Stabilität und Faltung zu untersuchen, wurde ein unprozessiertes Konstrukt in E. coli exprimiert und mit der prozessierten Form verglichen. Beide Proteine zeigen die gleiche kinetische Stabilität gegenüber chemischer Denaturierung. Sie denaturieren extrem langsam, weil nur die isolierten Untereinheiten entfalten können und das Monomer-Dimer-Gleichgewicht bei mittleren Konzentrationen an Denaturierungsmittel auf der Seite der Dimere liegt. Durch die extrem langsame Entfaltung zeigen beide Proteine eine apparente Hysterese im Gleichgewichtsübergang, und es ist nicht möglich, die thermodynamische Stabilität zu bestimmen. Die Stabilität und die Geschwindigkeit der Assoziation und Dissoziation in die prozessierten bzw. nichtprozessierten Untereinheiten sind für beide Proteine gleich. Darüber hinaus konnte gezeigt werden, dass auch unter

Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.

PubMed

Ivnitsky, Jury Ju; Schäfer, Timur V; Malakhovsky, Vladimir N; Rejniuk, Vladimir L

2004-10-01

Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.

Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III (AUS/FLUS)

PubMed Central

Ho, Allen S.; Sarti, Evan E.; Jain, Kunal S.; Wang, Hangjun; Nixon, Iain J.; Shaha, Ashok R.; Shah, Jatin P.; Kraus, Dennis H.; Ghossein, Ronald; Fish, Stephanie A.; Wong, Richard J.; Lin, Oscar

2014-01-01

Background: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5–15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. Methods: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan–Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. Results: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4–31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1–42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032). Conclusions: In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26

The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution.

PubMed

Meléndez-Hevia, E; Waddell, T G; Cascante, M

1996-09-01

The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into a single-solution problem, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.

Mitochondrial specialization revealed by single muscle fiber proteomics: focus on the Krebs cycle.

PubMed

Schiaffino, S; Reggiani, C; Kostrominova, T Y; Mann, M; Murgia, M

2015-12-01

We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mitochondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Avoiding Thiol Compound Interference: A Nanoplatform Based on High-Fidelity Au-Se Bonds for Biological Applications.

PubMed

Hu, Bo; Kong, Fanpeng; Gao, Xiaonan; Jiang, Lulu; Li, Xiaofeng; Gao, Wen; Xu, Kehua; Tang, Bo

2018-05-04

Gold nanoparticles (Au NPs) assembled through Au-S covalent bonds have been widely used in biomolecule-sensing technologies. However, during the process, detection distortions caused by high levels of thiol compounds can still significantly influence the result and this problem has not really been solved. Based on the higher stability of Au-Se bonds compared to Au-S bonds, we prepared selenol-modified Au NPs as an Au-Se nanoplatform (NPF). Compared with the Au-S NPF, the Au-Se NPF exhibits excellent anti-interference properties in the presence of millimolar levels of glutathione (GSH). Such an Au-Se NPF that can effectively avoid detection distortions caused by high levels of thiols thus offers a new perspective in future nanomaterial design, as well as a novel platform with higher stability and selectivity for the in vivo application of chemical sensing and clinical therapies. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance.

PubMed

Mishkovsky, Mor; Comment, Arnaud; Gruetter, Rolf

2012-12-01

The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undetectable. In particular, it provides direct evidence that transport across the inner mitochondria membrane is rate limiting in the brain. The hyperpolarized magnetic resonance protocol designed for this study opens the way to direct and real-time studies of TCA cycle kinetics.

In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance

PubMed Central

Mishkovsky, Mor; Comment, Arnaud; Gruetter, Rolf

2012-01-01

The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undetectable. In particular, it provides direct evidence that transport across the inner mitochondria membrane is rate limiting in the brain. The hyperpolarized magnetic resonance protocol designed for this study opens the way to direct and real-time studies of TCA cycle kinetics. PMID:22990416

A mitochondrial-like aconitase in the bacterium Bacteroides fragilis: implications for the evolution of the mitochondrial Krebs cycle.

PubMed

Baughn, Anthony D; Malamy, Michael H

2002-04-02

Aconitase and isocitrate dehydrogenase (IDH) enzyme activities were detected in anaerobically prepared cell extracts of the obligate anaerobe Bacteroides fragilis. The aconitase gene was located upstream of the genes encoding the other two components of the oxidative branch of the Krebs cycle, IDH and citrate synthase. Mutational analysis indicates that these genes are cotranscribed. A nonpolar in-frame deletion of the acnA gene that encodes the aconitase prevented growth in glucose minimal medium unless heme or succinate was added to the medium. These results imply that B. fragilis has two pathways for alpha-ketoglutarate biosynthesis-one from isocitrate and the other from succinate. Homology searches indicated that the B. fragilis aconitase is most closely related to aconitases of two other Cytophaga-Flavobacterium-Bacteroides (CFB) group bacteria, Cytophaga hutchinsonii and Fibrobacter succinogenes. Phylogenetic analysis indicates that the CFB group aconitases are most closely related to mitochondrial aconitases. In addition, the IDH of C. hutchinsonii was found to be most closely related to the mitochondrial/cytosolic IDH-2 group of eukaryotic organisms. These data suggest a common origin for these Krebs cycle enzymes in mitochondria and CFB group bacteria.

Dual Functions of α-Ketoglutarate Dehydrogenase E2 in the Krebs Cycle and Mitochondrial DNA Inheritance in Trypanosoma brucei

PubMed Central

Sykes, Steven E.

2013-01-01

The dihydrolipoyl succinyltransferase (E2) of the multisubunit α-ketoglutarate dehydrogenase complex (α-KD) is an essential Krebs cycle enzyme commonly found in the matrices of mitochondria. African trypanosomes developmentally regulate mitochondrial carbohydrate metabolism and lack a functional Krebs cycle in the bloodstream of mammals. We found that despite the absence of a functional α-KD, bloodstream form (BF) trypanosomes express α-KDE2, which localized to the mitochondrial matrix and inner membrane. Furthermore, α-KDE2 fractionated with the mitochondrial genome, the kinetoplast DNA (kDNA), in a complex with the flagellum. A role for α-KDE2 in kDNA maintenance was revealed in α-KDE2 RNA interference (RNAi) knockdowns. Following RNAi induction, bloodstream trypanosomes showed pronounced growth reduction and often failed to equally distribute kDNA to daughter cells, resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial membrane potential and contained mitochondria of substantially reduced volume. These results indicate that α-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis. PMID:23125353

Dual functions of α-ketoglutarate dehydrogenase E2 in the Krebs cycle and mitochondrial DNA inheritance in Trypanosoma brucei.

PubMed

Sykes, Steven E; Hajduk, Stephen L

2013-01-01

The dihydrolipoyl succinyltransferase (E2) of the multisubunit α-ketoglutarate dehydrogenase complex (α-KD) is an essential Krebs cycle enzyme commonly found in the matrices of mitochondria. African trypanosomes developmentally regulate mitochondrial carbohydrate metabolism and lack a functional Krebs cycle in the bloodstream of mammals. We found that despite the absence of a functional α-KD, bloodstream form (BF) trypanosomes express α-KDE2, which localized to the mitochondrial matrix and inner membrane. Furthermore, α-KDE2 fractionated with the mitochondrial genome, the kinetoplast DNA (kDNA), in a complex with the flagellum. A role for α-KDE2 in kDNA maintenance was revealed in α-KDE2 RNA interference (RNAi) knockdowns. Following RNAi induction, bloodstream trypanosomes showed pronounced growth reduction and often failed to equally distribute kDNA to daughter cells, resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial membrane potential and contained mitochondria of substantially reduced volume. These results indicate that α-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis.

Clinicopathological factors increased the risk of malignancy in thyroid nodules with atypical or follicular lesions of undetermined significance (AUS/FLUS) risk factor of malignancy in thyroid nodule with AUS/FLUS

PubMed Central

Hong, In Ki; Kim, Jun Ho; Cho, Young Up; Park, Shin-Young

2016-01-01

Purpose Ultrasound-guided fine needle aspiration (US-FNA) in thyroid nodules is presently most commonly used to identify whether these nodules are benign or malignant. However, atypical or follicular lesions of undetermined significance (AUS/FLUS), as categorized in the Bethesda System for reporting the results of FNA, cannot be classified as benign or malignant. Therefore, several clinical factors should be considered to assess the risk of malignancy in patients with AUS/FLUS. The purpose of the present study was to determine which clinical factor increased the risk of malignancy in patients with AUS/FLUS. Methods A retrospective study was done on 129 patients with fine needle aspiration categorized as AUS/FLUS from January 2011 through April 2015. Univariate and multivariate analyses were performed to assess the independent effect of risk factors such as age, sex, size of nodule, atypical descriptors, and ultrasonography criteria for malignancy. Results We identified that the presence of spiculated margin (odds ratio [OR], 5.655; 95% confidence interval [CI], 2.114-15.131; P = 0.001), nuclear grooving (OR, 3.697; 95% CI, 1.409-9.701; P = 0.008), irregular nuclei (OR, 3.903; 95% CI, 1.442-10.560; P = 0.001) were shown to be significantly related to malignancy on univariate and multivariate analyses. Conclusion We recommend that surgical resection of thyroid nodules be considered in patients with AUS/FLUS showing the histologic findings such as nuclear grooving, irregular nuclei along with spiculated margin of ultrasonographic finding. PMID:27073790

Comparative glycolysis and Krebs cycle metabolism of the bovine and murine mammary gland determined with [13C6] glucose and mass spectrometry

USDA-ARS?s Scientific Manuscript database

The compositions of bovine and murine milk differ significantly with respect to the proportions of lactose, protein, and fat. To better understand the metabolic origins of this difference, we interrogated the crossroads of glycolysis and the Krebs cycle in the mammary gland of cows and mice using a ...

Upregulation of Krebs cycle and anaerobic glycolysis activity early after onset of liver ischemia.

PubMed

Chan, Tom S; Cassim, Shamir; Raymond, Valérie-Ann; Gottschalk, Sven; Merlen, Grégory; Zwingmann, Claudia; Lapierre, Pascal; Darby, Peter; Mazer, Cyril David; Bilodeau, Marc

2018-01-01

The liver is a highly vascularized organ receiving a dual input of oxygenated blood from the hepatic artery and portal vein. The impact of decreased blood flow on glucose metabolism and how hepatocytes could adapt to this restrictive environment are still unclear. Using the left portal vein ligation (LPVL) rat model, we found that cellular injury was delayed after the onset of liver ischemia. We hypothesized that a metabolic adaptation by hepatocytes to maintain energy homeostasis could account for this lag phase. Liver glucose metabolism was characterized by 13C- and 1H-NMR spectroscopy and analysis of high-energy metabolites. ALT levels and caspase 3 activity in LPVL animals remained normal during the first 12 h following surgery (P<0.05). Ischemia rapidly led to decreased intrahepatic tissue oxygen tension and blood flow (P<0.05) and increased expression of Hypoxia-inducible factor 1-alpha. Intrahepatic glucose uptake, ATP/ADP ratio and energy charge level remained stable for up to 12 h after ligation. Entry of glucose in the Krebs cycle was impaired with lowered incorporation of 13C from [U-13C]glucose into glutamate and succinate from 0.25 to 12 h after LPVL. However, total hepatic succinate and glutamate increased 6 and 12 h after ischemia (P<0.05). Glycolysis was initially reduced (P<0.05) but reached maximum 13C-lactate (P<0.001) and 13C-alanine (P<0.01) enrichments 12 h after LPVL. In conclusion, early liver homeostasis stems from an inherent ability of ischemic hepatocytes to metabolically adapt through increased Krebs cycle and glycolysis activity to preserve bioenergetics and cell viability. This metabolic plasticity of hepatocytes could be harnessed to develop novel metabolic strategies to prevent ischemic liver damage.

[The modification of nitric oxide production by exogenous substrates of Krebs cycle during acute hypoxia].

PubMed

Kurhaliuk, N M; Kotsiuruba, A V; Sahach, V F

2005-01-01

Hypoxia causes the disruption of mitochondria electron respiratory chain, production of active oxygen forms and the unoxidative protection. In experiments on Wistar rats the influence of sodium succinate (50 mg/kg) and 6-ketoglutarate (200 mg/kg) on NO2-, NO3-, urea and polyamines contents in blood and liver under acute hypoxia (7% O2 in N2, 30 min) was investigated. Nitrite and nitrate content decreased in erythrocytes and liver but not in plasma under acute hypoxia. The exogenous succinate (SK) stimulated production of nitric oxide in erythrocytes and liver while 6-ketoglutarate (KG) only in liver. The switch from more intensive SK oxidation that reveals adrenomimetic influence and causes the synthesis and release of NO from erythrocyte, to less intensive KG correlates with well-known decrease of tissue respiration under the activation of the cholinergic system due to urea cycle activation particularly in liver. The activation of the SK oxidation takes place mainly under the different stress conditions and causes NO production in the blood cells. These conditions of the intensive and fast action under acute hypoxia are accompanied on the one hand by the increase of oxygen input ratio and on the other hand by activation of the free radical oxidation. The protective effect of the natural Krebs cycle intermediates--SK and KG in particular, is related to the regulation of NO synthesis and its metabolism in the main organs. These results proved the existence not only metabolite control of NO system by Krebs cycle intermediates, but the existence of the systemic mechanism for the support of the functional state of mitochondria under hypoxia.

Exploring traditional aus-type rice for metabolites conferring drought tolerance.

PubMed

Casartelli, Alberto; Riewe, David; Hubberten, Hans Michael; Altmann, Thomas; Hoefgen, Rainer; Heuer, Sigrid

2018-01-25

Traditional varieties and landraces belonging to the aus-type group of rice (Oryza sativa L.) are known to be highly tolerant to environmental stresses, such as drought and heat, and are therefore recognized as a valuable genetic resource for crop improvement. Using two aus-type (Dular, N22) and two drought intolerant irrigated varieties (IR64, IR74) an untargeted metabolomics analysis was conducted to identify drought-responsive metabolites associated with tolerance. The superior drought tolerance of Dular and N22 compared with the irrigated varieties was confirmed by phenotyping plants grown to maturity after imposing severe drought stress in a dry-down treatment. Dular and N22 did not show a significant reduction in grain yield compared to well-watered control plants, whereas the intolerant varieties showed a significant reduction in both, total spikelet number and grain yield. The metabolomics analysis was conducted with shoot and root samples of plants at the tillering stage at the end of the dry-down treatment. The data revealed an overall higher accumulation of N-rich metabolites (amino acids and nucleotide-related metabolites allantoin and uridine) in shoots of the tolerant varieties. In roots, the aus-type varieties were characterised by a higher reduction of metabolites representative of glycolysis and the TCA cycle, such as malate, glyceric acid and glyceric acid-3-phosphate. On the other hand, the oligosaccharide raffinose showed a higher fold increase in both, shoots and roots of the sensitive genotypes. The data further showed that, for certain drought-responsive metabolites, differences between the contrasting rice varieties were already evident under well-watered control conditions. The drought tolerance-related metabolites identified in the aus-type varieties provide a valuable set of protective compounds and an entry point for assessing genetic diversity in the underlying pathways for developing drought tolerant rice and other crops.

The yeast plasma membrane ATP binding cassette (ABC) transporter Aus1: purification, characterization, and the effect of lipids on its activity.

PubMed

Marek, Magdalena; Milles, Sigrid; Schreiber, Gabriele; Daleke, David L; Dittmar, Gunnar; Herrmann, Andreas; Müller, Peter; Pomorski, Thomas Günther

2011-06-17

The ATP binding cassette (ABC) transporter Aus1 is expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and is required for sterol uptake. These observations suggest that Aus1 promotes the translocation of sterols across membranes, but the precise transport mechanism has yet to be identified. In this study, an extraction and purification procedure was developed to characterize the Aus1 transporter. The detergent-solubilized protein was able to bind and hydrolyze ATP. Mutagenesis of the conserved lysine to methionine in the Walker A motif abolished ATP hydrolysis. Likewise, ATP hydrolysis was inhibited by classical inhibitors of ABC transporters. Upon reconstitution into proteoliposomes, the ATPase activity of Aus1 was specifically stimulated by phosphatidylserine (PS) in a stereoselective manner. We also found that Aus1-dependent sterol uptake, but not Aus1 expression and trafficking to the plasma membrane, was affected by changes in cellular PS levels. These results suggest a direct interaction between Aus1 and PS that is critical for the activity of the transporter.

Forschungspolitik USA weisen zunehmend ausländische Physikstudenten ab

NASA Astrophysics Data System (ADS)

Bührke, Thomas

2003-11-01

In keinem anderen Land der Erde ist der Anteil ausländischer Studenten im Fach Physik größer als in den USA. Nach den Terroranschlägen vom 11. September werden jedoch zunehmend ausländische Studenten, insbesondere aus China und dem mittleren Osten, abgewiesen - zum Leidwesen der Studenten und der Universitäten.http://www.aip.org/statistics

[Adaptation and validation of the neurological soft sign's scale of Krebs et al. to children].

PubMed

Halayem, S; Hammami, M; Fakhfakh, R; Gaddour, N; Tabbane, K; Amado, I; Krebs, M-O; Bouden, A

2017-04-01

Neurological soft signs (NSS) include anomalies in motor integration, coordination, sensory integration and lateralization and could be endophenotypic markers in autism spectrum disorders (ASD). Their characterization provides a more precise phenotype of ASD and more homogeneous subtypes to facilitate clinical and genetic research. Few scales for NSS have been adapted and validated in children including children with ASD. Our objective was to perform an adaptation to the child of a scale assessing neurological soft signs and a validation study in both general and clinical populations. We have selected the NSS scale of Krebs et al. (2000) already validated in adults. It encompasses 5 dimensions: motor coordination, motor integration, sensory integration, involuntary movement, laterality. After a preliminary study that examined 42 children, several changes have been made to the original version to adapt it to the child and to increase its feasibility, particularly in children with ASD. Then we conducted a validation study by assessing the psychometric properties of this scale in a population of 86 children including 26 children with ASD (DSM 5 Criteria) and 60 typically developing children. Children's ages ranged between 6 and 12 years, and patients and controls were matched for gender, age and intelligence. Patients were assessed using the Autism diagnostic Interview-revised and the Childhood Autism Rating Scale to confirm diagnosis. Typically developing children were assessed using the semi-structured Mini International Neuropsychiatric Interview for Children and Adolescents to eliminate any psychiatric disorder. All children with neurological pathologies (history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma) and obvious physical deformities or sensory deficits that could interfere with neurological assessment were excluded from the study. Both patients

Differentiated effect of ageing on the enzymes of Krebs' cycle, electron transfer complexes and glutamate metabolism of non-synaptic and intra-synaptic mitochondria from cerebral cortex.

PubMed

Villa, R F; Gorini, A; Hoyer, S

2006-11-01

The effect of ageing on the activity of enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism was studied in three different types of mitochondria of cerebral cortex of 1-year old and 2-year old male Wistar rats. We assessed the maximum rate (V(max)) of the mitochondrial enzyme activities in non-synaptic perikaryal mitochondria, and in two populations of intra-synaptic mitochondria. The results indicated that: (i) in normal, steady-state cerebral cortex the values of the catalytic activities of the enzymes markedly differed in the various populations of mitochondria; (ii) in intra-synaptic mitochondria, ageing affected the catalytic properties of the enzymes linked to Krebs' cycle, electron transfer chain and glutamate metabolism; (iii) these changes were more evident in intra-synaptic "heavy" than "light" mitochondria. These results indicate a different age-related vulnerability of subpopulations of mitochondria in vivo located into synapses than non-synaptic ones.

Structural Insights and the Surprisingly Low Mechanical Stability of the Au-S Bond in the Gold-Specific Protein GolB.

PubMed

Wei, Wei; Sun, Yang; Zhu, Mingli; Liu, Xiangzhi; Sun, Peiqing; Wang, Feng; Gui, Qiu; Meng, Wuyi; Cao, Yi; Zhao, Jing

2015-12-16

The coordination bond between gold and sulfur (Au-S) has been widely studied and utilized in many fields. However, detailed investigations on the basic nature of this bond are still lacking. A gold-specific binding protein, GolB, was recently identified, providing a unique opportunity for the study of the Au-S bond at the molecular level. We probed the mechanical strength of the gold-sulfur bond in GolB using single-molecule force spectroscopy. We measured the rupture force of the Au-S bond to be 165 pN, much lower than Au-S bonds measured on different gold surfaces (∼1000 pN). We further solved the structures of apo-GolB and Au(I)-GolB complex using X-ray crystallography. These structures showed that the average Au-S bond length in GolB is much longer than the reported average value of Au-S bonds. Our results highlight the dramatic influence of the unique biological environment on the stability and strength of metal coordination bonds in proteins.

Watershed scale response to climate change--Naches River Basin, Washington

USGS Publications Warehouse

Mastin, Mark C.; Hay, Lauren E.; Markstrom, Steven L.

2012-01-01

Fourteen basins for which the Precipitation Runoff Modeling System has been calibrated and evaluated were selected as study sites. Precipitation Runoff Modeling System is a deterministic, distributed parameter watershed model developed to evaluate the effects of various combinations of precipitation, temperature, and land use on streamflow and general basin hydrology. Output from five General Circulation Model simulations and four emission scenarios were used to develop an ensemble of climate-change scenarios for each basin. These ensembles were simulated with the corresponding Precipitation Runoff Modeling System model. This fact sheet summarizes the hydrologic effect and sensitivity of the Precipitation Runoff Modeling System simulations to climate change for the Naches River Basin below Tieton River in Washington.

Use of vegetation health data for estimation of aus rice yield in bangladesh.

PubMed

Rahman, Atiqur; Roytman, Leonid; Krakauer, Nir Y; Nizamuddin, Mohammad; Goldberg, Mitch

2009-01-01

Rice is a vital staple crop for Bangladesh and surrounding countries, with interannual variation in yields depending on climatic conditions. We compared Bangladesh yield of aus rice, one of the main varieties grown, from official agricultural statistics with Vegetation Health (VH) Indices [Vegetation Condition Index (VCI), Temperature Condition Index (TCI) and Vegetation Health Index (VHI)] computed from Advanced Very High Resolution Radiometer (AVHRR) data covering a period of 15 years (1991-2005). A strong correlation was found between aus rice yield and VCI and VHI during the critical period of aus rice development that occurs during March-April (weeks 8-13 of the year), several months in advance of the rice harvest. Stepwise principal component regression (PCR) was used to construct a model to predict yield as a function of critical-period VHI. The model reduced the yield prediction error variance by 62% compared with a prediction of average yield for each year. Remote sensing is a valuable tool for estimating rice yields well in advance of harvest and at a low cost.

Use of Vegetation Health Data for Estimation of Aus Rice Yield in Bangladesh

PubMed Central

Rahman, Atiqur; Roytman, Leonid; Krakauer, Nir Y.; Nizamuddin, Mohammad; Goldberg, Mitch

2009-01-01

Rice is a vital staple crop for Bangladesh and surrounding countries, with interannual variation in yields depending on climatic conditions. We compared Bangladesh yield of aus rice, one of the main varieties grown, from official agricultural statistics with Vegetation Health (VH) Indices [Vegetation Condition Index (VCI), Temperature Condition Index (TCI) and Vegetation Health Index (VHI)] computed from Advanced Very High Resolution Radiometer (AVHRR) data covering a period of 15 years (1991–2005). A strong correlation was found between aus rice yield and VCI and VHI during the critical period of aus rice development that occurs during March–April (weeks 8–13 of the year), several months in advance of the rice harvest. Stepwise principal component regression (PCR) was used to construct a model to predict yield as a function of critical-period VHI. The model reduced the yield prediction error variance by 62% compared with a prediction of average yield for each year. Remote sensing is a valuable tool for estimating rice yields well in advance of harvest and at a low cost. PMID:22574057

Wirkstoffe, Medikamente und Mathematische Bildverarbeitung

NASA Astrophysics Data System (ADS)

Bauer, Günter J.; Lorenz, Dirk A.; Maaß, Peter; Preckel, Hartwig; Trede, Dennis

Die Entwicklung neuer Medikamente ist langwierig und teuer. Der erste Schritt ist hierbei die Suche nach neuen Wirkstoffkandidaten, die für die Behandlung bislang schwer therapierbarer Krankheiten geeignet sind. Hierfür stehen der Pharma- und Biotechnologieindustrie riesige Substanzbibliotheken zur Verfügung. In diesen Bibliotheken werden die unterschiedlichsten Substanzen gesammelt, die entweder synthetisch hergestellt oder aus Pilzen, Bakterienkulturen und anderen Lebewesen gewonnen werden können.

Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats.

PubMed

Sudheesh, N P; Ajith, T A; Janardhanan, K K; Krishnan, C V

2009-08-01

Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (p<0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.

Lipid oxidation in minced beef meat with added Krebs cycle substrates to stabilise colour.

PubMed

Yi, G; Grabež, V; Bjelanovic, M; Slinde, E; Olsen, K; Langsrud, O; Phung, V T; Haug, A; Oostindjer, M; Egelandsdal, B

2015-11-15

Krebs cycle substrates (KCS) can stabilise the colour of packaged meat by oxygen reduction. This study tested whether this reduction releases reactive oxygen species that may lead to lipid oxidation in minced meat under two different storage conditions. KCS combinations of succinate and glutamate increased peroxide forming potential (PFP, 1.18-1.32 mmol peroxides/kg mince) and thiobarbituric acid reactive substances (TBARS, 0.30-0.38 mg malondialdehyde (MDA) equivalents/kg mince) under low oxygen storage conditions. Both succinate and glutamate were metabolised. Moreover, under high oxygen (75%) storage conditions, KCS combinations of glutamate, citrate and malate increased PFP (from 1.22 to 1.29 mmol peroxides/kg) and TBARS (from 0.37 to 0.40 mg MDA equivalents/kg mince). Only glutamate was metabolised. The KCS combinations that were added to stabilise colour were metabolised during storage, and acted as pro-oxidants that promoted lipid oxidation in both high and low oxygen conditions. Copyright © 2015. Published by Elsevier Ltd.

Influence of femtosecond laser radiation on cells of the transplantable tumour Krebs-2

NASA Astrophysics Data System (ADS)

Meshalkin, Yu P.; Popova, N. A.; Nikolin, V. P.; Kaledin, V. I.; Kirpichnikov, A. V.; Pestryakov, Efim V.

2012-06-01

The influence of femtosecond radiation of a titaniumsapphire laser on cells of the transplantable ascitic tumour Krebs-2 was studied. After in vitro irradiation by the pulsed fundamentalharmonic radiation with the wavelength 800 nm, pulse duration 30 fs, repetition rate 1 kHz, mean power 100 and 300 mW and exposure time 3 min, as well as by the second-harmonic radiation (40 nm, 50 fs, 120 mW), all cells were diffusely stained by the vital stain trypan blue, which may be an evidence of their death or abnormalities of membrane permeability. However, implantation of such cells to experimental animals led to formation of tumours at the transplantation site with the kinetics slightly different from the control one. In the group of mice to which the cells were inoculated after irradiation with second harmonic pulses of titanium-sapphire laser the inhibition of tumour growth was observed due to partial death of cells under the action of UV spectral components. To explain the mechanism of the observed phenomenon the possibility of pore formation (photoporation) in the cell membrane, described earlier in the papers on foreign DNA transfection into cells, is considered.

A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation

PubMed Central

Williams, Niamh C.; O’Neill, Luke A. J.

2018-01-01

Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP) production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs) and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria via the mitochondrial citrate- carrier. Cytosolic metabolism of citrate to acetyl-coenzyme A (acetyl-CoA) is important for both fatty-acid synthesis and protein acetylation, both of which have been linked to macrophage and DC activation. Citrate-derived itaconate has a direct antibacterial effect and also has been shown to act as an anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify citrate as an important metabolite for macrophage and DC effector function. PMID:29459863

A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation.

PubMed

Williams, Niamh C; O'Neill, Luke A J

2018-01-01

Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP) production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs) and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria via the mitochondrial citrate- carrier. Cytosolic metabolism of citrate to acetyl-coenzyme A (acetyl-CoA) is important for both fatty-acid synthesis and protein acetylation, both of which have been linked to macrophage and DC activation. Citrate-derived itaconate has a direct antibacterial effect and also has been shown to act as an anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify citrate as an important metabolite for macrophage and DC effector function.

The Density Matrix for Single-mode Light after k-Photon Absorption

NASA Astrophysics Data System (ADS)

Voigt, H.; Bandilla, A.

In order to continue and generalize the studies of the density matrix of a light field undergoing k-photon absorption, in this paper we put the emphasis on the off-diagonal elements. The solution obtained earlier for the diagonal elements describing the photon statistics can be found as a special case but will not be discussed again. The general solution calculated by recursion shows an asymptotic behaviour if the initial photon number is sufficiently high. Only the initial phase information survives. Illustrating the solution we start with coherent light and a generalized coherent state.Translated AbstractDie Dichtematrix eines Lichtstrahls nach k-Photonen-Absorption aus einer ModeWir führen die Betrachtungen über das Verhalten der Dichtematrix eines Lichtfeldes nach k-Photonen-Absorption aus einer Mode verallgemeinernd weiter und konzentrieren uns auf die Nichtdiagonalelemente. Die im folgenden angegebene allgemeine Lösung, die durch Rekursion gefunden wurde, enthält die schon früher erhaltene, jedoch hier nicht weiter diskutierte Lösung für die Diagonalelemente als Spezialfall. Sie zeigt ferner, daß es einen asymptotischen Zustand gibt, der eine von der Ausgangsintensität unabhängige Information über die Ausgangsphase enthält. Zur Diskussion der Lösung werden verschiedene Anfangsbedingungen betrachtet, so z. B. kohärentes Licht und kohärentes Licht, das ein Medium mit nichtlinearem Brechungsindex durchlaufen hat (Kerr-Effekt).

Bathymetry and Near-River Topography of the Naches and Yakima Rivers at Union Gap and Selah Gap, Yakima County, Washington, August 2008

USGS Publications Warehouse

Mastin, M.C.; Fosness, R.L.

2009-01-01

Yakima County is collaborating with the Bureau of Reclamation on a study of the hydraulics and sediment-transport in the lower Naches River and in the Yakima River between Union Gap and Selah Gap in Washington. River bathymetry and topographic data of the river channels are needed for the study to construct hydraulic models. River survey data were available for most of the study area, but river bathymetry and near-river topography were not available for Selah Gap, near the confluence of the Naches and Yakima Rivers, and for Union Gap. In August 2008, the U.S. Geological Survey surveyed the areas where data were not available. If possible, the surveys were made with a boat-mounted, single-beam echo sounder attached to a survey-grade Real-Time Kinematic (RTK) global positioning system (GPS). An RTK GPS rover was used on a walking survey of the river banks, shallow river areas, and river bed areas that were impenetrable to the echo sounder because of high densities of macrophytes. After the data were edited, 95,654 bathymetric points from the boat survey with the echo sounder and 1,069 points from the walking survey with the GPS rover were used in the study. The points covered 4.6 kilometers on the Yakima River and 0.6 kilometers on the Naches River. GPS-surveyed points checked within 0.014 to 0.047 meters in the horizontal direction and -0.036 to 0.078 meters in the vertical direction compared to previously established survey control points

Measurement of $W$ -Boson Helicity-Fractions in Top-Quark Decays with the CDF II Experiment and Prospects for an Early $$t\\overline{t}$$ Cross-Section Measurement with the CMS Experiment (in German)

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

Chwalek, Thorsten

2010-12-02

Aus was besteht die Welt? Die Frage nach den fundamentalen Bausteinen der Materie beschaftigte Wissenschaftler und Gelehrte zu allen Zeiten. Ausgehend von abstrakten philosophischen Uberlegungen wurde das Konzept von kleinsten, nicht weiter zerteilbaren Grundbausteinen der Materie bereits einige Jahrhunderte vor Christus von indischen und griechischen Philosophieschulen entwickelt. Etwa 450 v. Chr. pragte Demokrit den Begriff ´atomos, das “Unzerschneidbare”, fur die diskreten Grundbausteine der Materie. Doch erst in der jungeren Vergangenheit konnte dieses philosophische Konzept auch experimentell uberpruft werden.

Energie aus der Tiefe: Geothermische Stromerzeugung

NASA Astrophysics Data System (ADS)

Huenges, Ernst

2004-11-01

Die Erde birgt überall genug Wärme für die geothermische Erzeugung elektrischen Stroms, die allerdings Wassertemperaturen von über 150 °C braucht. So warme Gesteinsschichten liegen in Mitteleuropa in mindestens 4 km Tiefe. Ein Kraftwerk muss also beim Betrieb über tiefe Bohrungen Wasser durch das Tiefengestein zirkulieren und dort erhitzen. Von Natur aus ist das Gestein jedoch dafür meist zu wenig porös. Deshalb soll das Einpressen von Fluiden unter hohem Druck die natürlichen Risse im Reservoirgestein künstlich vergrößern. Diese Stimulationstechnik erprobte das GeoForschungsZentrum Potsdam erfolgreich an einer 4309 m tiefen Bohrung im Geothermielabor Groß Schönebeck. Eine zweite Bohrung soll nun eine langfristige Wasserzirkulation im Untergrund erforschen. Funktioniert sie stabil, dann soll eine Demonstrationsanlage Strom erzeugen.

Nichtkontinuierliche (zeitdiskrete) Signale

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

Zeitdiskrete Signale werden häufig aus zeitkontinuierlichen Signalen durch Abtastung erzeugt. Dass beide Signale gleichwertig sind, zeigt das Abtasttheorem (Kap. 116) von Shannon, sofern die Bedingung nach (116.2), f_{ab}≈(2{,}2 {\\ldots} 4)\\cdot fg) eingehalten wird. Digitale Signale haben Vorteile: Einfache Speicherung, Weiterverarbeitung in Rechnern, wenig störanfällige Übertragung. Für die Bearbeitung dieser Signale dienen die im Kapitel dargestellten Hilfsmittel: Diskrete Fouriertransformation; Schnelle Fouriertransformation; z-Transformation: Darstellung, Sätze zur z-Transformation, Korrespondenzen zu Zeitfunktionen, Beispiele.

Diagnostic Thyroidectomy May Be Preferable in Patients With Suspicious Ultrasonography Features After Cytopathology Diagnosis of AUS/FLUS in the Bethesda System

PubMed Central

Lee, Yong Sang; Kim, Hyeung Kyoo; Chang, Hojin; Kim, Seok Mo; Kim, Bup-Woo; Chang, Hang-Seok; Park, Cheong Soo

2015-01-01

Abstract Atypia/follicular lesion of undetermined significance (AUS/FLUS) is a new category in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) for which repeat fine-needle aspiration cytology (FNAC) is recommended. The aim of this study was to identify specific ultrasonography and clinical predictors of malignancy in a subset of thyroid nodules associated with cytology diagnoses of AUS/FLUS. Between January 2011 and December 2102, 5440 patients underwent thyroid surgery at our institution. Of these, 213 patients were diagnosed AUS/FLUS at the preoperative cytopathology diagnosis. The frequency of FNAC and ultrasonography images was compared between patients with cancerous and benign tumors based on their final pathology. Of the 213 patients, 158 (74.2%) were diagnosed with thyroid carcinoma in their final pathology reports. In univariate and multivariate analyses, the frequency of FNAC was not significantly correlated with the cancer diagnosis. Hypoechogenicity (odds ratio 2.521, P = 0.007) and microcalcification (odds ratio 3.247, P = 0.005) were statistically correlated with cancer risk. Although AUS/FLUS in cytopathology is recommended for repeating FNAC in BSRTC, we proposed that thyroid nodules with ultrasonography findings that suggest the possibility of cancer should undergo thyroidectomy with diagnostic intent. PMID:26705204

Einsteins Spuren in den Archiven der Wissenschaft: Physikgeschichte

NASA Astrophysics Data System (ADS)

Marx, Werner

2005-07-01

Die Erwähnungen und Zitierungen von Einsteins Arbeiten dokumentieren lediglich den quantifizierbaren Anteil von Einsteins Beitrag zur Physik. Gleichwohl belegen sie die außergewöhnliche Resonanz und Langzeitwirkung seiner Arbeiten. Die Häufigkeit der Zitierungen entspricht nicht der allgemeinen Einschätzung ihrer Bedeutung. Insbesondere die Pionierarbeiten werden inzwischen als bekannt vorausgesetzt und nicht mehr explizit zitiert. Interessanterweise ist seine nach 1945 meist zitierte Arbeit nicht eine der Pionierarbeiten zur Quantenphysik oder Relativitätstheorie, sondern jene aus dem Jahr 1935 zum berühmten Einstein-Podolsky-Rosen-Paradoxon.

Using NOAA/AVHRR based remote sensing data and PCR method for estimation of Aus rice yield in Bangladesh

NASA Astrophysics Data System (ADS)

Nizamuddin, Mohammad; Akhand, Kawsar; Roytman, Leonid; Kogan, Felix; Goldberg, Mitch

2015-06-01

Rice is a dominant food crop of Bangladesh accounting about 75 percent of agricultural land use for rice cultivation and currently Bangladesh is the world's fourth largest rice producing country. Rice provides about two-third of total calorie supply and about one-half of the agricultural GDP and one-sixth of the national income in Bangladesh. Aus is one of the main rice varieties in Bangladesh. Crop production, especially rice, the main food staple, is the most susceptible to climate change and variability. Any change in climate will, thus, increase uncertainty regarding rice production as climate is major cause year-to-year variability in rice productivity. This paper shows the application of remote sensing data for estimating Aus rice yield in Bangladesh using official statistics of rice yield with real time acquired satellite data from Advanced Very High Resolution Radiometer (AVHRR) sensor and Principal Component Regression (PCR) method was used to construct a model. The simulated result was compared with official agricultural statistics showing that the error of estimation of Aus rice yield was less than 10%. Remote sensing, therefore, is a valuable tool for estimating crop yields well in advance of harvest, and at a low cost.

The α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system.

PubMed

Baranowska, Urszula; Wiśniewska, Róża Julia

2017-07-30

α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein), are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

A new leaf rust resistance gene Lr79 mapped in chromosome 3BL from the durum wheat landrace Aus26582.

PubMed

Qureshi, Naeela; Bariana, Harbans; Kumran, Vikas Venu; Muruga, Sivasamy; Forrest, Kerrie L; Hayden, Mathew J; Bansal, Urmil

2018-05-01

A new leaf rust resistance gene Lr79 has been mapped in the long arm of chromosome 3B and a linked marker was identified for marker-assisted selection. Aus26582, a durum wheat landrace from the A. E. Watkins Collection, showed seedling resistance against durum-specific and common wheat-specific Puccinia triticina (Pt) pathotypes. Genetic analysis using a recombinant inbred line (RIL) population developed from a cross between Aus26582 and the susceptible parent Bansi with Australian Pt pathotype showed digenic inheritance and the underlying loci were temporarily named LrAW2 and LrAW3. LrAW2 was located in chromosome 6BS and this study focused on characterisation of LrAW3 using RILs lacking LrAW2. LrAW3 was incorporated into the DArTseq map of Aus26582/Bansi and was located in chromosome 3BL. Markers linked with LrAW3 were developed from the chromosome survey sequence contig 3B_10474240 in which closely-linked DArTseq markers 1128708 and 3948563 were located. Although bulk segregant analysis (BSA) with the 90 K Infinium array identified 51 SNPs associated with LrAW3, only one SNP-derived KASP marker mapped close to the locus. Deletion bin mapping of LrAW3-linked markers located LrAW3 between bins 3BL11-0.85-0.90 and 3BL7-0.63. Since no other all stage leaf rust resistance gene is located in chromosome 3BL, LrAW3 represented a new locus and was designated Lr79. Marker sun786 mapped 1.8 cM distal to Lr79 and Aus26582 was null for this locus. However, the marker can be reliably scored as it also amplifies a monomorphic fragment that serves as an internal control to differentiate the null status of Aus26582 from reaction failure. This marker was validated among a set of durum and common wheat cultivars and was shown to be useful for marker-assisted selection of Lr79 at both ploidy levels.

Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells.

PubMed

Sawa, Kenta; Uematsu, Takumi; Korenaga, Yusuke; Hirasawa, Ryuya; Kikuchi, Masatoshi; Murata, Kyohei; Zhang, Jian; Gai, Xiaoqing; Sakamoto, Kazuichi; Koyama, Tomoyuki; Satoh, Takumi

2017-03-16

Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2',7'-dichlorofluorescein diacetate fluorescence. In contrast, none of the KCIs-used at 1 mM-protected against cell death induced by high concentrations of glutamate-another type of oxidative stress-induced neuronal cell death. Because these protective KCIs did not have any toxic effects (at least up to 10 mM), they have potential use for therapeutic intervention against chronic neurodegenerative diseases.

Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

PubMed

Sookoian, Silvia; Castaño, Gustavo O; Scian, Romina; Fernández Gianotti, Tomas; Dopazo, Hernán; Rohr, Cristian; Gaj, Graciela; San Martino, Julio; Sevic, Ina; Flichman, Diego; Pirola, Carlos J

2016-02-01

Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and

The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates.

PubMed

Knauf, Felix; Mohebbi, Nilufar; Teichert, Carsten; Herold, Diana; Rogina, Blanka; Helfand, Stephen; Gollasch, Maik; Luft, Friedrich C; Aronson, Peter S

2006-07-01

A longevity gene called Indy (for 'I'm not dead yet'), with similarity to mammalian genes encoding sodium-dicarboxylate cotransporters, was identified in Drosophila melanogaster. Functional studies in Xenopus oocytes showed that INDY mediates the flux of dicarboxylates and citrate across the plasma membrane, but the specific transport mechanism mediated by INDY was not identified. To test whether INDY functions as an anion exchanger, we examined whether substrate efflux is stimulated by transportable substrates added to the external medium. Efflux of [14C]citrate from INDY-expressing oocytes was greatly accelerated by the addition of succinate to the external medium, indicating citrate-succinate exchange. The succinate-stimulated [14C]citrate efflux was sensitive to inhibition by DIDS (4,4'-di-isothiocyano-2,2'-disulphonic stilbene), as demonstrated previously for INDY-mediated succinate uptake. INDY-mediated efflux of [14C]citrate was also stimulated by external citrate and oxaloacetate, indicating citrate-citrate and citrate-oxaloacetate exchange. Similarly, efflux of [14C]succinate from INDY-expressing oocytes was stimulated by external citrate, alpha-oxoglutarate and fumarate, indicating succinate-citrate, succinate-alpha-oxoglutarate and succinate-fumarate exchange respectively. Conversely, when INDY-expressing Xenopus oocytes were loaded with succinate and citrate, [14C]succinate uptake was markedly stimulated, confirming succinate-succinate and succinate-citrate exchange. Exchange of internal anion for external citrate was markedly pH(o)-dependent, consistent with the concept that citrate is co-transported with a proton. Anion exchange was sodium-independent. We conclude that INDY functions as an exchanger of dicarboxylate and tricarboxylate Krebs-cycle intermediates. The effect of decreasing INDY activity, as in the long-lived Indy mutants, may be to alter energy metabolism in a manner that favours lifespan extension.

Inhibition of AMPK and Krebs cycle gene expression drives metabolic remodeling of Pten-deficient preneoplastic thyroid cells.

PubMed

Antico Arciuch, Valeria G; Russo, Marika A; Kang, Kristy S; Di Cristofano, Antonio

2013-09-01

Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators. ©2013 AACR.

Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice

PubMed Central

Sahni, Prateek V.; Zhang, Jimmy; Sosunov, Sergey; Galkin, Alexander; Niatsetskaya, Zoya; Starkov, Anatoly; Brookes, Paul S.; Ten, Vadim S.

2017-01-01

Background Reverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate. Methods Neonatal mice were subjected to Rice-Vannucci model of hypoxicischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H2O2 generation rate in the ischemic brain. Results While brain mitochondria from control mice exhibited a rotenonesensitive complex-I-dependent respiration, HI-brain mitochondria, at the initiation of reperfusion, demonstrated complex-II-dependent respiration, as rotenone minimally affected, but inhibition of complex-II ceased respiration. This was associated with a 30-fold increase of cerebral succinate concentration and significantly elevated H2O2 emission rate in HI-mice compared to controls. At sixty minutes of reperfusion, cerebral succinate content and the mitochondrial response to rotenone did not differ from that in controls. Conclusion These data are the first ex-vivo evidence, that at the initiation of reperfusion, brain mitochondria transiently shift their metabolism from complex-I-dependent oxidation of NADH toward complex II-linked oxidation of succinate. Our study provides a critical piece of support for existence of the RET-dependent mechanism of elevated ROS production in reperfusion. PMID:29211056

Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice.

PubMed

Sahni, Prateek V; Zhang, Jimmy; Sosunov, Sergey; Galkin, Alexander; Niatsetskaya, Zoya; Starkov, Anatoly; Brookes, Paul S; Ten, Vadim S

2018-02-01

BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H 2 O 2 generation rate in the ischemic brain.ResultsWhile brain mitochondria from control mice exhibited a rotenone-sensitive complex-I-dependent respiration, HI-brain mitochondria, at the initiation of reperfusion, demonstrated complex-II-dependent respiration, as rotenone minimally affected, but inhibition of complex-II ceased respiration. This was associated with a 30-fold increase of cerebral succinate concentration and significantly elevated H 2 O 2 emission rate in HI-mice compared to controls. At 60 min of reperfusion, cerebral succinate content and the mitochondrial response to rotenone did not differ from that in controls.ConclusionThese data are the first ex vivo evidence, that at the initiation of reperfusion, brain mitochondria transiently shift their metabolism from complex-I-dependent oxidation of NADH toward complex II-linked oxidation of succinate. Our study provides a critical piece of support for existence of the RET-dependent mechanism of elevated ROS production in reperfusion.

Zweitore, Vierpole

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

Zweitore (nach DIN 4899; alte Bezeichnung "Vierpole") sind Funktionseinheiten mit zwei Toren, wobei zu jedem Tor ein Klemmenpaar gehört. An eines der Tore wird das Eingangssignal angeschlossen, die zugehörigen Anschlüsse werden mit Eingangsklemmen bezeichnet. Entsprechend wird an den zwei Ausgangsklemmen das Ausgangssignal abgegriffen. Eventuell erforderliche Anschlüsse für eine Stromversorgung werden nicht mitgezählt. Der interne Aufbau besteht aus einer beliebigen Zusammenschaltung von Widerständen, Kondensatoren, Spulen, Transformatoren, Dioden, Transistoren usw. Es wird vorausgesetzt, dass die Zweitore zeitinvariant sind, d. h. die Eigenschaften hängen nicht von der Zeit ab.

Description of the ambulance services participating in the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest Epistry.

PubMed

Beck, Ben; Bray, Janet E; Smith, Karen; Walker, Tony; Grantham, Hugh; Hein, Cindy; Thorrowgood, Melanie; Smith, Anthony; Inoue, Madoka; Smith, Tony; Dicker, Bridget; Swain, Andy; Bosley, Emma; Pemberton, Katherine; McKay, Michael; Johnston-Leek, Malcolm; Cameron, Peter; Perkins, Gavin D; Finn, Judith

2016-12-01

The present study aimed to describe and examine similarities and differences in the current service provision and resuscitation protocols of the ambulance services participating in the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest (OHCA) Epistry. Understanding these similarities and differences is important in identifying ambulance service factors that might explain regional variation in survival of OHCA in the Aus-ROC Epistry. A structured questionnaire was completed by each of the ambulance services participating in the Aus-ROC Epistry. These ambulance services were SA Ambulance Service, Ambulance Victoria, St John Ambulance Western Australia, Queensland Ambulance Service, St John Ambulance NT, St John New Zealand and Wellington Free Ambulance. The survey aimed to describe ambulance service and dispatch characteristics, resuscitation protocols and details of cardiac arrest registries. We observed similarities between services with respect to the treatment of OHCA and dispatch systems. Differences between services were observed in the serviced population; the proportion of paramedics with basic life support, advanced life support or intensive care training skills; the number of OHCA cases attended; guidelines related to withholding or terminating resuscitation attempts; and the variables that might be used to define 'attempted resuscitation'. All seven participating ambulance services were noted to have existing OHCA registries. There is marked variation between ambulance services currently participating in the Aus-ROC Australian and New Zealand OHCA Epistry with respect to workforce characteristics and key variable definitions. This variation between ambulance services might account for a proportion of the regional variation in survival of OHCA. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Die Deutsche Statistische Gesellschaft in der Weimarer Republik und während der Nazidiktatur

NASA Astrophysics Data System (ADS)

Wilke, Jürgen

Nach anfänglichen Schwierigkeiten durch den 1. Weltkrieg erlangte die Deutsche Statistische Gesellschaft (DStatG) unter dem renommierten Statistiker und Vorsitzenden der DStatG, Friedrich Zahn, durch eine Vielzahl von Aktivitäten hohes Ansehen. Es gab Bestrebungen, Statistiker aus allen Arbeitsfeldern der Statistik in die DStatG zu integrieren, wobei die "Mathematische Statistik" nur zögerlich akzeptiert wurde (Konjunkturforschung, Zeitreihenanalyse). Nach der Machtübernahme 1933 durch Adolf Hitler geriet die DStatG in das Fahrwasser nationalsozialistischer Ideologie und Politik (Führerprinzip, Gleichschaltung des Vereinswesens). Damit war eine personelle Umstrukturierung in der DStatG verbunden. Politisch Missliebige und rassisch Verfolgte mussten die DStatG verlassen (Bernstein, Freudenberg, Gumbel u.a.). Unter den Statistikern gab es alle Abstufungen im Verhalten zum Regime von Ablehnung und zwangsweiser Anpassung über bereitwilliges Mitläufertum bis zu bewusster Täterschaft. Besonders die Bevölkerungsstatistik wurde durch die NS- Rassenpolitik auf lange Sicht diskreditiert. Im Rahmen von Wirtschaftsplanung und Aufrüstung wurden neue zukunftsträchtige statistische Modelle (Grünig, Bramstedt, Leisse) entwickelt.

Characterisation and mapping of adult plant stripe rust resistance in wheat accession Aus27284.

PubMed

Nsabiyera, Vallence; Bariana, Harbans S; Qureshi, Naeela; Wong, Debbie; Hayden, Matthew J; Bansal, Urmil K

2018-07-01

A new adult plant stripe rust resistance gene, Yr80, was identified in a common wheat landrace Aus27284. Linked markers were developed and validated for their utility in marker-assisted selection. Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is among the most important constraints to global wheat production. The identification and characterisation of new sources of host plant resistance enrich the gene pool and underpin deployment of resistance gene pyramids in new cultivars. Aus27284 exhibited resistance at the adult plant stage against predominant Pst pathotypes and was crossed with a susceptible genotype Avocet S. A recombinant inbred line (RIL) population comprising 121 lines was developed and tested in the field at three locations in 2016 and two in 2017 crop seasons. Monogenic segregation for adult plant stripe rust response was observed among the Aus27284/Avocet S RIL population and the underlying locus was temporarily designated YrAW11. Bulked-segregant analysis using the Infinium iSelect 90K SNP wheat array placed YrAW11 in chromosome 3B. Kompetitive allele specific PCR (KASP) primers were designed for the linked SNPs and YrAW11 was flanked by KASP_65624 and KASP_53292 (3 cM) proximally and KASP_53113 (4.9 cM) distally. A partial linkage map of the genomic region carrying YrAW11 comprised nine KASP and two SSR markers. The physical position of KASP markers in the pseudomolecule of chromosome 3B placed YrAW11 in the long arm and the location of markers gwm108 and gwm376 in the deletion bin 3BL2-0.22 supported this conclusion. As no other stripe rust resistance locus has been reported in chromosome 3BL, YrAW11 was formally designated Yr80. Marker KASP_ 53113 was polymorphic among 94% of 81 Australian wheat cultivars used for validation.

AusLAMP long period magnetotellurics: progress update and new insights into Victorian geology and mineral prospectivity

NASA Astrophysics Data System (ADS)

Chopping, R. G.; Duan, J.; Czarnota, K.; Kemp, T.

2016-12-01

It is becoming generally accepted that world-class mineral deposits have a footprint on a scale of the lithosphere. For this reason, Australia has embarked on the Australian Lithospheric Architecture Magnetotelluric Project (AusLAMP) to map the conductivity of the mid to lower crust and the lithospheric mantle. AusLAMP is a collaborative project between Geoscience Australia, State and Territory Geological Surveys and Universities. The project aims to collect long-period magnetotelluric data across the Australian continent on a nominal 0.5x0.5° ( 55x55 km) grid. To date, more than 450 sites have been acquired including all sites for the state of Victoria, two-thirds of sites in South Australia and Tasmania, and approximately 25 stations in Western Australia. Progress is ramping up with acquisition to turn to the state of New South Wales, the remainder of South Australia and also acquisition in northern Australia. To support this increasing acquisition activity, additional instruments have been purchased to add to those already in Australia. 3D inversion results are now available for AusLAMP Victoria. In collaboration with the National Computational Infrastructure (NCI), the 3D ModEM codes were optimised for use on the NCI's supercomputer, speeding up large-scale inversions by an order of magnitude. The results of these inversions indicate anomalously conductive lithospheric mantle associated with the central region of Victoria which contains significant mineral deposits and prospectivity, and also anomalous resistive lithosphere associated with the southern extension of the dynamically supported Australian Alps and the Newer Volcanics Province. Modelled conductivities are also consistent with mantle xenolith data from central Victoria. Within the crust, the dominant trend of the data is along elongate north-eastern corridors of conductive material. These results shed new questions on the geological history of this region and the lithospheric architecture of the

Geschichtlicher Überblick

NASA Astrophysics Data System (ADS)

Bölke, Klaus-Peter

Die Nachweise einer schadlosen Ableitung von Abwässern lassen sich bis weit in die Vergangenheit zurückverfolgen. Sie waren bereits zur damaligen Zeit eine Forderung zur Pflege der öffentlichen Reinlichkeit. Der Kanalisationsbau ist auch immer ein Ausdruck der Kultur eines Volkes gewesen. So kann festgestellt werden, dass im Zusammenhang mit der Hochkultur eines Volkes auch der Kanalbau ein vorherrschendes Thema war. Der Kanalbau steht auch in einem engen Zusammenhang mit dem Wasserleitungsbau. Es ist nur logisch, dass dort wo Wasser teilweise aus großer Entfernung herangeführt worden ist, dieses dann nach Gebrauch auch wieder schadlos beseitigt werden musste.

[Leben im Eismeer - Tauchuntersuchungen zur Biologie arktischer Meerespflanzen und Meerestiere

PubMed

Lippert; Karsten; Wiencke

2000-01-01

Die Maske wird nochmals auf Dichtigkeit überprüft, der Knoten der Sicherungsleine mit zwei halben Schlägen fixiert, dann rutscht die Taucherin von der Eiskante in das kalte Wasser. Eine halbe Stunde vergeht, bevor ihr Kopf wieder aus dem Eisloch auftaucht und sie ein großes Sammelnetz nach oben reicht, gefüllt mit verschiedenen Arten von Makroalgen. Obwohl noch große Flächen des Kongsfjordes im arktischen Spitzbergen zugefroren sind und das Festland von einer dicken Schneedecke bedeckt ist, hat unter Wasser in den Algenwäldern bereits der Sommer und damit die Saison der Meeresbiologen begonnen.

Wie verstehen Schülerinnen und Schüler den Begriff der Unendlichkeit?

NASA Astrophysics Data System (ADS)

Schimmöller, Tabea

Wie Hilbert bereits feststellte, wirkt die Idee der Unendlichkeit, wie keine andere, schon seit Zeiten sehr anregend und fruchtbar auf den Verstand und bewegt das Gemüt der Menschen. Der Begriff der Unendlichkeit bedarf aber auch, wie kein anderer, der Aufklärung, denn mit ihm eröffnet sich ein weites Feld, welches nicht nur aus vielen verschiedenen Definitionen besteht, sondern auch aus völlig unterschiedlichen Disziplinen. Physiker suchen immer dringender nach einer "Theorie für Alles" oder einer "Weltformel", Kosmologen beschäftigen sich unter anderem mit der Ewigkeit des Universums, Theologen interessiert eher die Unendlichkeit Gottes, Philosophen diskutieren unter anderem Grenzfragen zwischen Naturwissenschaft und Philosophie und die Mathematiker versuchen den Paradoxien des Unendlichen einen Sinn zu geben. Und so wird ersichtlich, dass nichts abstrakter ist als das Unendliche: Obwohl die Unendlichkeit für die unterschiedlichsten Wissenschaften von großer Bedeutung ist, "[ist] in der Wirklichkeit das Unendliche nirgends zu finden, [egal] was für Erfahrungen und Beobachtungen und welcherlei Wissenschaft wir auch heranziehen".

The electric dipole moments in the ground states of gold oxide, AuO, and gold sulfide, AuS.

PubMed

Zhang, Ruohan; Yu, Yuanqin; Steimle, Timothy C; Cheng, Lan

2017-02-14

The B 2 Σ - - X 2 Π 3/2 (0,0) bands of a cold molecular beam sample of gold monoxide, AuO, and gold monosulfide, AuS, have been recorded at high resolution both field free and in the presence of a static electric field. The observed electric field induced splittings and shifts were analyzed to produce permanent electric dipole moments, μ→ el , of 2.94±0.06 D and 2.22±0.05 D for the X 2 Π 3/2 (v = 0) states of AuO and AuS, respectively. A molecular orbital correlation diagram is used to rationalize the trend in ground state μ→ el values for AuX (X = F, Cl, O, and S) molecules. The experimentally determined μ→ el are compared to those computed at the coupled-cluster singles and doubles (CCSD) level augmented with a perturbative inclusion of triple excitations (CCSD(T)) level of theory.

The Krebs cycle and mitochondrial mass are early victims of endothelial dysfunction: proteomic approach.

PubMed

Addabbo, Francesco; Ratliff, Brian; Park, Hyeong-Cheon; Kuo, Mei-Chuan; Ungvari, Zoltan; Csiszar, Anna; Ciszar, Anna; Krasnikov, Boris; Krasnikof, Boris; Sodhi, Komal; Zhang, Fung; Nasjletti, Alberto; Goligorsky, Michael S

2009-01-01

Endothelial cell dysfunction is associated with bioavailable nitric oxide deficiency and an excessive generation of reactive oxygen species. We modeled this condition by chronically inhibiting nitric oxide generation with subpressor doses of N(G)-monomethyl-L-arginine (L-NMMA) in C57B6 and Tie-2/green fluorescent protein mouse strains. L-NMMA-treated mice exhibited a slight reduction in vasorelaxation ability, as well as detectable abnormalities in soluble adhesion molecules (soluble intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1, and matrix metalloproteinase 9), which represent surrogate indicators of endothelial dysfunction. Proteomic analysis of the isolated microvasculature using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy revealed abnormal expression of a cluster of mitochondrial enzymes, which was confirmed using immunodetection. Aconitase-2 and enoyl-CoA-hydratase-1 expression levels were decreased in L-NMMA-treated animals; this phenotype was absent in nitric oxide synthase-1 and -3 knockout mice. Depletion of aconitase-2 and enoyl-CoA-hydratase-1 resulted in the inhibition of the Krebs cycle and enhanced pyruvate shunting toward the glycolytic pathway. To assess mitochondrial mass in vivo, co-localization of green fluorescent protein and MitoTracker fluorescence was detected by intravital microscopy. Quantitative analysis of fluorescence intensity showed that L-NMMA-treated animals exhibited lower fluorescence of MitoTracker in microvascular endothelia as a result of reduced mitochondrial mass. These findings provide conclusive and unbiased evidence that mitochondriopathy represents an early manifestation of endothelial dysfunction, shifting cell metabolism toward "metabolic hypoxia" through the selective depletion of both aconitase-2 and enoyl-CoA-hydratase-1. These findings may contribute to an early preclinical diagnosis of endothelial dysfunction.

MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU.

PubMed

Favaro, Elena; Ramachandran, Anassuya; McCormick, Robert; Gee, Harriet; Blancher, Christine; Crosby, Meredith; Devlin, Cecilia; Blick, Christopher; Buffa, Francesca; Li, Ji-Liang; Vojnovic, Borivoj; Pires das Neves, Ricardo; Glazer, Peter; Iborra, Francisco; Ivan, Mircea; Ragoussis, Jiannis; Harris, Adrian L

2010-04-26

Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.

Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

PubMed

Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

2010-05-31

Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumors: further evidence for a persistent truncated Krebs cycle in hepatomas.

PubMed

Parlo, R A; Coleman, P S

1986-04-29

Viable tissue slices from rat liver and Morris hepatoma 3924A were compared as to their ability to incorporate carbons from [U-14 C]pyruvate into newly synthesized cholesterol versus CO2. By 4 h, the tumor slice incubation had incorporated over 6-fold more pyruvate carbons into the sterol than into CO2, relative to the normal liver slice incubation, per g tissue protein. However, the presence of the mitochondrial citrate exchange carrier inhibitor 1,2,3-benzenetricarboxylate in the incubation inhibited the formation of [14C]cholesterol, while simultaneously leading to an increase in the rate of 14CO2 production in the tumor. In the normal liver system by contrast, benzenetricarboxylate also inhibited [14C]cholesterol formation, but had hardly any effect on the already high rate of 14CO2 production. The ability of benzenetricarboxylate to inhibit the rapid carbon flux from pyruvate to cholesterol, and to steer the metabolic flow of carbons toward oxidative decarboxylation via the Krebs cycle in whole, viable tumor tissue, indirectly emphasizes the importance of the mitochondrial citrate exchange carrier in supporting the decontrol of cholesterogenesis de novo in tumors by accelerating the supply of lipogenic precursor carbons to the tumor cytosol. These studies may be therefore interpreted as extensions, to the level of whole-cell metabolism, of the concept of a persistent 'truncated' Krebs cycle in the mitochondria of metastatic cancer tissue. This concept states, in part, that a rapid efflux of mitochondrially generated citrate would operate preferentially in tumors, and thus provide carbons continuously to the cytoplasmic compartment where the well-established deregulated pathway of cholesterogenesis occurs (Parlo, R.A. and Coleman, P.S. (1984) J. Biol. Chem. 259, 9997-10003; Coleman, P.S. and Lavietes, B.B. (1981) CRC Crit. Rev. Biochem. 11, 341-393).

[Cardiodoron® bei Patienten mit Schlafstörungen - Ergebnisse einer prospektiven Beobachtungsstudie].

PubMed

Rother, Claudia; Schnelle, Martin

Hintergrund: Schlafstörungen gehören zu den häufigsten gesundheitlichen Problemen der heutigen Zeit. Stress und die dadurch bedingte innere Anspannung sowie eine unrhythmische Lebensführung z.B. durch Schichtarbeit sind bekannte auslösende Faktoren. Weniger bekannt ist, dass auch funktionelle Herz-Kreislauf-Beschwerden zu Störungen des Schlafs führen können und dass deren Behandlung zu einer Verbesserung der Schlafqualität beiträgt. Ganzheitlich betrachtet geht es daher um die Wiederherstellung einer gesunden Rhythmik, insbesondere des Herz-/Atem- sowie des Schlaf-Wach-Rhythmus, die Cardiodoron®, eine Heilpflanzenkomposition aus Primula veris, Hyoscyamus niger und Onopordum acanthium, unterstützt. Patienten und Methoden: Mittels einer prospektiven, multizentrischen Beobachtungsstudie sollte ermittelt werden, wie sich funktionelle Herz-Kreislauf-Beschwerden und/oder Schlafstörungen unter der Behandlung mit Cardiodoron® (Dilution) über 3-6 Monate entwickeln. Im Zeitraum von September 2009 bis März 2012 dokumentierten 92 Ärzte 501 Patienten, von denen 380 über Schlafstörungen klagten und deren Daten in dieser Publikation näher betrachtet werden. Nach einer Aufnahmeuntersuchung erfolgte nach 90 Tagen eine Abschlussuntersuchung und bei Fortführung der Therapie nach nochmals 90 Tagen eine Follow-up-Untersuchung. Neben 30 ärztlicherseits bewerteten Symptomen beurteilten die Patienten ihr Befinden mittels Pittsburgh Sleep Quality Index (PSQI) nach Buysse und der Beschwerden-Liste nach von Zerssen (B-L und B-L'). Ergebnisse: Unter der Cardiodoron®-Therapie gingen bei guter Verträglichkeit sowohl die Ausprägung der Schlafstörungen (um 65% von 2,0 auf 0,7 Punkte) als auch die erfassten 30 Symptome (um 59% von 24,3 auf 9,9 Punkte) deutlich zurück (p < 0,01). Weiterhin reduzierten sich der PSQI und der Gesamtwert der Beschwerden-Liste signifikant (p < 0,0001) um 60% bzw. 56% (von 12,2 auf 4,8 bzw. von 25,6 auf 11,4 Punkte). Schlussfolgerungen: Bei

Biogeochemische Stoffkreisläufe

NASA Astrophysics Data System (ADS)

Brüggemann, Nicolas; Butterbach-Bahl, Klaus

Der Klimawandel wirkt sich auf biogeochemische Stoffkreisläufe aus. So kann davon ausgegangen werden, dass sich die ökosystemaren Kohlenstoff- und Stickstoffflüsse zwischen Biosphäre, Atmosphäre und Hydrosphäre zukünftig deutlich verändern werden, mit positiven wie auch negativen Rückkopplungseffekten auf den Klimawandel. Der Schwerpunkt dieses Kapitels liegt auf wenig intensiv bis nicht genutzten terrestrischen Ökosystemen, da intensiv landwirtschaftlich genutzte Systeme deutlich stärker von Nutzung und Management beeinflusst werden, als durch den Klimawandel. Die zu erwartenden Veränderungen für die einzelnen betroffenen terrestrischen Ökosysteme werden, soweit möglich, nach Faktoren getrennt dargestellt. Im Fokus stehen Wälder, Moore und Küstengebiete.

Wissenschaft, die unsere Kultur verändert. Tiefenschichten des Streits um die Evolutionstheorie

NASA Astrophysics Data System (ADS)

Patzelt, Werner J.

Die Evolutionstheorie ist eine der erfolgreichsten wissenschaftlichen Theorien. Sie erlaubt es, unsere Herkunft zu verstehen und riskante Merkmale gerade der menschlichen Spezies zu begreifen. Zugleich ist die Evolutionstheorie eine der umstrittensten Theorien. Das liegt nicht an ihrer empirischen Tragfähigkeit, sondern an ihrem Gegenstand. Sie handelt nämlich nicht nur - wie Hunderte andere wissenschaftliche Theorien - von der "Welt da draußen“, sondern vor allem auch von uns selbst und von unserem Platz in dieser Welt. Den einen gilt sie obendrein als Überwinderin religiösen Aberglaubens, den anderen als neuer Zugang zu Gott und seinem Wirken in der Welt. Ferner sehen die einen in der Evolution eine unbezweifelbare Tatsache gleich der Schwerkraft oder dem Holocaust, die anderen aber eine - noch oder dauerhaft - unbewiesene Hypothese oder gar eine falsche Schöpfungslehre. Und während die meisten Streitfragen solcher Art nach wechselseitig akzeptierten Regeln ‚normaler Wissenschaft‘ geklärt werden, wird bei der Frage nach dem Woher unserer Spezies und Kultur die intellektuelle Zuständigkeit von Wissenschaft mitunter überhaupt bezweifelt. Anscheinend geht es schon um recht tiefe Schichten unserer Kultur und nicht nur der wissenschaftlichen, wenn - wie seit 150 Jahren - um die Evolutionstheorie gestritten wird. Wie sehen diese Schichten aus?

Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex.

PubMed

Villa, Roberto Federico; Gorini, Antonella; Hoyer, Siegfried

2009-12-01

The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light

Establishing the Aus-ROC Australian and New Zealand out-of-hospital cardiac arrest Epistry

PubMed Central

Bray, Janet; Smith, Karen; Walker, Tony; Grantham, Hugh; Hein, Cindy; Thorrowgood, Melanie; Smith, Anthony; Smith, Tony; Dicker, Bridget; Swain, Andy; Bailey, Mark; Bosley, Emma; Pemberton, Katherine; Cameron, Peter; Nichol, Graham; Finn, Judith

2016-01-01

Introduction Out-of-hospital cardiac arrest (OHCA) is a global health problem with low survival. Regional variation in survival has heightened interest in combining cardiac arrest registries to understand and improve OHCA outcomes. While individual OHCA registries exist in Australian and New Zealand ambulance services, until recently these registries have not been combined. The aim of this protocol paper is to describe the rationale and methods of the Australian Resuscitation Outcomes Consortium (Aus-ROC) OHCA epidemiological registry (Epistry). Methods and analysis The Aus-ROC Epistry is designed as a population-based cohort study. Data collection started in 2014. Six ambulance services in Australia (Ambulance Victoria, SA Ambulance Service, St John Ambulance Western Australia and Queensland Ambulance Service) and New Zealand (St John New Zealand and Wellington Free Ambulance) currently contribute data. All OHCA attended by ambulance, regardless of aetiology or patient age, are included in the Epistry. The catchment population is approximately 19.3 million persons, representing 63% of the Australian population and 100% of the New Zealand population. Data are collected using Utstein-style definitions. Information incorporated into the Epistry includes demographics, arrest features, ambulance response times, treatment and patient outcomes. The primary outcome is ‘survival to hospital discharge’, with ‘return of spontaneous circulation’ as a key secondary outcome. Ethics and dissemination Ethics approval was independently sought by each of the contributing registries. Overarching ethics for the Epistry was provided by Monash University HREC (Approval No. CF12/3938—2012001888). A population-based OHCA registry capturing the majority of Australia and New Zealand will allow risk-adjusted outcomes to be determined, to enable benchmarking across ambulance providers, facilitate the identification of system-wide strategies associated with survival from OHCA, and

Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects?

PubMed

Xekouki, Paraskevi; Stratakis, Constantine A

2012-12-01

Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney-Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity at the SDHD locus, indicating the possibility that SDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.

Succinate dehydrogenase (SDHx) mutations in pituitary tumors: could this be a new role for mitochondrial complex II and/or Krebs cycle defects?

PubMed Central

Xekouki, Paraskevi; Stratakis, Constantine A

2013-01-01

Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role as it serves both as a critical step of the tricarboxylic acid or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney–Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal, and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity at the SDHD locus, indicating the possibility that SDHD’s loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. Although a number of other genetic defects are possible in these cases, we speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects. PMID:22889736

Manganese ions enhance mitochondrial H2O2 emission from Krebs cycle oxidoreductases by inducing permeability transition.

PubMed

Bonke, Erik; Siebels, Ilka; Zwicker, Klaus; Dröse, Stefan

2016-10-01

Manganese-induced toxicity has been linked to mitochondrial dysfunction and an increased generation of reactive oxygen species (ROS). We could recently show in mechanistic studies that Mn 2+ ions induce hydrogen peroxide (H 2 O 2 ) production from the ubiquinone binding site of mitochondrial complex II (II Q ) and generally enhance H 2 O 2 formation by accelerating the rate of superoxide dismutation. The present study with intact mitochondria reveals that manganese additionally enhances H 2 O 2 emission by inducing mitochondrial permeability transition (mPT). In mitochondria fed by NADH-generating substrates, the combination of Mn 2+ and different respiratory chain inhibitors led to a dynamically increasing H 2 O 2 emission which was sensitive to the mPT inhibitor cyclosporine A (CsA) as well as Ru-360, an inhibitor of the mitochondrial calcium uniporter (MCU). Under these conditions, flavin-containing enzymes of the mitochondrial matrix, e.g. the mitochondrial 2-oxoglutaratedehydrogenase (OGDH), were major sources of ROS. With succinate as substrate, Mn 2+ stimulated ROS production mainly at complex II, whereby the applied succinate concentration had a marked effect on the tendency for mPT. Also Ca 2+ increased the rate of H 2 O 2 emission by mPT, while no direct effect on ROS-production of complex II was observed. The present study reveals a complex scenario through which manganese affects mitochondrial H 2 O 2 emission: stimulating its production from distinct sites (e.g. site II Q ), accelerating superoxide dismutation and enhancing the emission via mPT which also leads to the loss of soluble components of the mitochondrial antioxidant systems and favors the ROS production from flavin-containing oxidoreductases of the Krebs cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

[Drug-Coated Balloons and Stents for the Treatment of Femoro-Popliteal Lesions].

PubMed

Ito, Wulf D

2017-08-01

Medikamenten-beschichtete Ballons bei femoro-poplitealen Läsionen  Medikamenten-beschichtete Ballons (DCB) führen in der Behandlung von femoro-poplitealen Läsionen zu besseren Offenheitsraten als die einfache Ballondilatation und zu ähnlichen bis besseren Offenheitsraten als die Stentimplantation. Vorteil ist die Vermeidung von permanentem Fremdmaterial in Regionen, die einer ständigen mechanischen Beanspruchung unterworfen sind und die Möglichkeit, die Prozedur an derselben Stelle wiederholen zu können bzw. chirurgische Zugangswege offenzuhalten. Bei Auftreten von Dissektionen oder einem Recoil bietet sich die fokale Implantation möglichst kurzer Stents in den betroffenen Segmenten an. Die primäre Implantation Medikamenten-beschichteter Stents zeigt darüber hinaus keinen weiteren Vorteil und ist auf längere Sicht mit den Nachteilen der Implantation von Fremdmaterial in Bewegungssegmenten behaftet. Nicht medikamentöse und medikamentöse Begleittherapie  Die Kombination aus interventioneller Behandlung und supervidiertem Gehtraining zeigt die besten Erfolgsaussichten einer dauerhaften Verbesserung der Gehstrecke bei Patienten mit femoro-poplitealen Läsionen und ist einer alleinigen interventionellen Behandlung oder einem alleinigen Gehtraining überlegen. Darüber hinaus werden aktuell große randomisierte, kontrollierte Studien durchgeführt, die den Einfluss niedrig dosierter direkter Antikoagulanzien auf die kardiovaskuläre Komplikationsrate nach Intervention untersuchen. Die Ergebnisse dieser Studien werden Aufschluss geben über die optimale antithrombotische Therapie nach Intervention im femoro-poplitealen Stromgebiet.

Thyroid hormone stimulates myoglobin expression in soleus and extensorum digitalis longus muscles of rats: concomitant alterations in the activities of Krebs cycle oxidative enzymes.

PubMed

dos Santos, R A; Giannocco, G; Nunes, M T

2001-06-01

Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15 days) rats. The fiber type composition of S muscle was also evaluated and used as control of the T3-induced effects. In the S muscle, the T3 treatment increased the Mb mRNA and protein expression, as well as the CS and SDH activity. These changes occurred parallel to the expected increase in type II (fast) and decrease in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was decreased, while the Mb expression and CS activity tended to decrease. In contrast the SDH activity was increased, probably due to the enhanced motor activity that occurs as a short-term response to the hypothermia induced by hypothyroidism. In the EDL, the alterations were milder than those in S muscle in both thyroid states. These findings show that Mb gene expression is induced by T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and provides additional evidence that thyroid hormone increases the aerobic potential of skeletal muscles, as well as the speed of muscle contraction.

CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism.

PubMed

Menazza, Sara; Wong, Renee; Nguyen, Tiffany; Wang, Guanghui; Gucek, Marjan; Murphy, Elizabeth

2013-03-01

Cyclophilin D (CypD) is a mitochondrial chaperone that has been shown to regulate the mitochondrial permeability transition pore (MPTP). MPTP opening is a major determinant of mitochondrial dysfunction and cardiomyocyte death during ischemia/reperfusion (I/R) injury. Mice lacking CypD have been widely used to study regulation of the MPTP, and it has been shown recently that genetic depletion of CypD correlates with elevated levels of mitochondrial Ca(2+). The present study aimed to characterize the metabolic changes in CypD(-/-) hearts. Initially, we used a proteomics approach to examine protein changes in CypD(-/-) mice. Using pathway analysis, we found that CypD(-/-) hearts have alterations in branched chain amino acid metabolism, pyruvate metabolism and the Krebs cycle. We tested whether these metabolic changes were due to inhibition of electron transfer from these metabolic pathways into the electron transport chain. As we found decreased levels of succinate dehydrogenase and electron transfer flavoprotein in the proteomics analysis, we examined whether activities of these enzymes might be altered. However, we found no alterations in their activities. The proteomics study also showed a 23% decrease in carnitine-palmitoyltransferase 1 (CPT1), which prompted us to perform a metabolomics analysis. Consistent with the decrease in CPT1, we found a significant decrease in C4/Ci4, C5-OH/C3-DC, C12:1, C14:1, C16:1, and C20:3 acyl carnitines in hearts from CypD(-/-) mice. In summary, CypD(-/-) hearts exhibit changes in many metabolic pathways and caution should be used when interpreting results from these mice as due solely to inhibition of the MPTP. Published by Elsevier Ltd.

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

PubMed

Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

2017-02-01

Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm ® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species.

PubMed

Lushchak, Oleh V; Piroddi, Marta; Galli, Francesco; Lushchak, Volodymyr I

2014-01-01

Aconitase, an enzyme possessing an iron-sulfur cluster that is sensitive to oxidation, is involved in the regulation of cellular metabolism. There are two isoenzymes of aconitase (Aco)--mitochondrial (mAco) and cytosolic (cAco) ones. The primary role of mAdco is believed to be to control cellular ATP production via regulation of intermediate flux in the Krebs cycle. The cytosolic Aco in its reduced form operates as an enzyme, whereas in the oxidized form it is involved in the control of iron homeostasis as iron regulatory protein 1 (IRP1). Reactive oxygen species (ROS) play a central role in regulation of Aco functions. Catalytic Aco activity is regulated by reversible oxidation of [4Fe-4S]²⁺ cluster and cysteine residues, so redox-dependent posttranslational modifications (PTMs) have gained increasing consideration as regards possible regulatory effects. These include modifications of cysteine residues by oxidation, nitrosylation and thiolation, as well as Tyr nitration and oxidation of Lys residues to carbonyls. Redox-independent PTMs such as phosphorylation and transamination also have been described. In the presence of a sustained ROS flux, redox-dependent PTMs may lead to enzyme damage and cell stress by impaired energy and iron metabolism. Aconitase has been identified as a protein that undergoes oxidative modification and inactivation in aging and certain oxidative stress-related disorders. Here we describe possible mechanisms of involvement of the two aconitase isoforms, cAco and mAco, in the control of cell metabolism and iron homeostasis, balancing the regulatory, and damaging effects of ROS.

Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

PubMed

Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

2012-10-01

It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

Automatisierung des Verfahrens nach Beyer & Schweiger (1969) zur Bestimmung von Durchlässigkeit und Porosität aus Kornverteilungskurven

NASA Astrophysics Data System (ADS)

Houben, Georg J.; Blümel, Martin

2017-11-01

Porosity is a fundamental parameter in hydrogeology. The empirical method of Beyer and Schweiger (1969) allows the calculation of hydraulic conductivity and both the total and effective porosity from granulometric data. However, due to its graphical nature with type curves, it is tedious to apply and prone to reading errors. In this work, the type curves were digitized and emulated by mathematical functions. The latter were implemented into a spreadsheet and a visual basic program, allowing the fast automated application of the method for any number of samples.

Size resolved infrared spectroscopy of Na(CH3OH)n (n = 4-7) clusters in the OH stretching region: unravelling the interaction of methanol clusters with a sodium atom and the emergence of the solvated electron.

PubMed

Forck, Richard M; Pradzynski, Christoph C; Wolff, Sabine; Ončák, Milan; Slavíček, Petr; Zeuch, Thomas

2012-03-07

Size resolved IR action spectra of neutral sodium doped methanol clusters have been measured using IR excitation modulated photoionisation mass spectroscopy. The Na(CH(3)OH)(n) clusters were generated in a supersonic He seeded expansion of methanol by subsequent Na doping in a pick-up cell. A combined analysis of IR action spectra, IP evolutions and harmonic predictions of IR spectra (using density functional theory) of the most stable structures revealed that for n = 4, 5 structures with an exterior Na atom showing high ionisation potentials (IPs) of ~4 eV dominate, while for n = 6, 7 clusters with lower IPs (~3.2 eV) featuring fully solvated Na atoms and solvated electrons emerge and dominate the IR action spectra. For n = 4 simulations of photoionisation spectra using an ab initio MD approach confirm the dominance of exterior structures and explain the previously reported appearance IP of 3.48 eV by small fractions of clusters with partly solvated Na atoms. Only for this cluster size a shift in the isomer composition with cluster temperature has been observed, which may be related to kinetic stabilisation of less Na solvated clusters at low temperatures. Features of slow fragmentation dynamics of cationic Na(+)(CH(3)OH)(6) clusters have been observed for the photoionisation near the adiabatic limit. This finding points to the relevance of previously proposed non-vertical photoionisation dynamics of this system.

Die Energiebranche am Beginn der digitalen Transformation: aus Versorgern werden Utilities 4.0

NASA Astrophysics Data System (ADS)

Doleski, Oliver D.

Die traditionelle Energieversorgung befindet sich in einer Zäsur. Das seit Jahrzehnten bewährte und stabile Geschäftsmodell einer zuverlässig planbaren, zentralen Energieerzeugung mit anschließender unidirektionaler Verteilung geriet spätestens seit der Energiewende des Jahres 2011 immer mehr unter Druck. Angesichts fortschreitender Digitalisierung und Dezentralisierung einerseits und gestiegener Erwartungshaltung der Kunden gegenüber "ihrem" Versorger andererseits sieht sich die Energiebranche heute einem epochalen Transformationsprozess gegenübergestellt. Bei diesem entwickeln sich aus den monopolistischen Versorgern des 19. und 20. Jahrhunderts (Utility 1.0), über die liberalisierten Energieversorgungsunternehmen (Utility 2.0) und Energiedienstleistungsunternehmen (Utility 3.0) heutiger Prägung, die digitalen Energiedienstleistungsunternehmen (Utility 4.0) von morgen. Oliver D. Doleski beschränkt sich in seinem Beitrag nicht auf die reine Beschreibung dieses Veränderungsprozesses an sich. Vielmehr werden darüber hinaus sowohl die mit dieser Entwicklung verbundenen übergeordneten Ziele als auch die wesentlichen Anforderungen an erfolgreiche Utilities 4.0 skizziert. Das Kapitel endet mit einem prägnanten Überblick profitabler Betätigungsfelder, die zur Sicherung der ökonomischen Zukunft von Energiekonzernen, Regionalversorgern und Stadtwerken beitragen können.

Evolving electrical SCLM models of the Australian continent - results of the South Australia AusLAMP deployment

NASA Astrophysics Data System (ADS)

Robertson, K. E.; Thiel, S.; Heinson, G. S.

2017-12-01

The Australian Lithospheric Architecture Magnetotelluric Project (AusLAMP) is an Australian initiative to map the Australian continental lithosphere using magnetotelluric (MT) stations to obtain a resistivity model of the subsurface. It is a joint project between Geoscience Australia, state surveys, and Universities. We present new MT 3D inversion results of the largest coherent array of the AusLAMP MT deployments to date covering two-thirds of South Australia, funded largely by the Geological Survey of South Australia with additional funding by Geoscience Australia and The University of Adelaide. The model extends across the South Australian Gawler Craton, including the Eucla Basin to the west of the craton and the Flinders Ranges and Curnamona Province to the east. The MT array covers parts of the Australian lithosphere, which has been largely unexplored with seismic tomography methods and provide a unique insight into the tectonic evolution of the continent. We incorporate 284 long-period (10s-10,000s) MT stations separated roughly every half degree latitude and longitude across an area spanning 1200 km x 800 km, south of latitude -28.5 degrees and from longitude 129 degrees to 141 degrees. We invert 24 discrete periods of the impedance tenor between 7 s and 13,000 s, and 22 different periods of the tipper data between 7s-8000 s period. The results show a heterogeneous lower crust and mantle lithosphere with a primarily resistive mantle (>1000 Ωm) lithosphere in the central and western part of the Gawler Craton and Eucla Domain. The model shows a generally NS oriented electric LAB offset from deeper cratonic lithosphere in the west to a shallow lithosphere along the eastern margin of the Gawler Craton extending further east towards the Proterozoic and Phanerozoic eastern part of Australia. The lower crust is generally resistive with elongated lower crustal conductivity anomalies, which are associated with major translithospheric shear zones likely existent

Radiosensibilisierung durch BRAF Inhibitoren.

PubMed

Strobel, Sophia Boyoung; Pätzold, Sylvie; Zimmer, Lisa; Jensen, Alexandra; Enk, Alexander; Hassel, Jessica Cecile

2017-07-01

In der letzten Zeit wurden in der Literatur vermehrt erhöhte Hauttoxizitäten während einer Kombinationstherapie mit BRAF Inhibitoren und Radiotherapie beschrieben. Wir berichten über sieben Melanompatienten in einem nicht resezierbaren Stadium III oder IV, die eine kombinierte Behandlung aus Bestrahlung und BRAF-Inhibitor erhielten. Bei allen Patienten konnte durch die Kombinationstherapie ein gutes lokales Ansprechen erreicht werden. Nur bei zwei Patienten wurde eine schwere Radiodermatitis (CTCAE Grad 3 bzw. 4) beobachtet. Bei diesen Patienten, die beide Vemurafenib erhielten, trat die Radiodermatitis nach ein bzw. zwei Wochen auf und resultierte in einer Unterbrechung der BRAF-Inhibitor Behandlung.. Die kumulative Dosis bis zum Zeitpunkt der Strahlendermatitis betrug 10 Gy bzw. 35 Gy. Bei allen anderen Vemurafenibpatienten konnten nur milde Reaktionen im Sinne einer Radiodermatitis CTCAE Grad 2, beim Dabrafenibpatienten CTCAE Grade 1 diagnostiziert werden. Bei einem Patienten wurde eine Recalldermatitis nach 14 Tagen einer beendeten Strahlentherapie mit einer kumulativen Dosis von 30 Gy diagnostiziert. Schwere Toxizitätsreaktionen der Haut unter einer BRAF-Inhibitionen treten nicht häufig auf und sind meistens gut therapierbar. Deshalb sollte die Kombinationstherapie bei aggressiv wachsenden Melanomen eine Therapieoption bleiben. Obwohl ein erhöhtes Risiko der Hauttoxizität unter einer Kombinationstherapie von Radiatio und BRAF-Inhibitoren besteht, wird diese von den meisten Patienten gut toleriert. Sequenzielle Therapie anstelle von gleichzeitiger Behandlung scheint die Toxizitätreaktionen nicht zu verhindern. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation.

PubMed

Samokhvalov, V; Ignatov, V; Kondrashova, M

2004-01-01

We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.

The Quintessential Bond of Modern Science. The Detection and Characterization of Diatomic Gold Sulfide, AuS.

NASA Astrophysics Data System (ADS)

Kokkin, Damian L.; Zhang, Ruohan; Steimle, Timothy; Pearlman, Bradley W.; Wyse, Ian A.; Varberg, Thomas D.

2015-06-01

The gold sulfur bond is becoming ever more important to a vast range of scientific endeavors. We have recorded the electronic spectrum of gas-phase AuS, at vibrational resolution, over the 440-740 nm wavelength range. By application of a synergy of production techniques, hot hollow-cathode sputtering source and cold laser ablation molecular beam source, excitation from both spin components of the inverted ^2Π ground state is possible. Excitation into four different excited electronic states involving approximately 100 red-degraded bands has been observed. The four excited states have been characterized as a^4σ1/2, A^2σ^+1/2, B^2σ^-1/2 and C^2Δ_i. The observed red-degraded vibronic bands where then globally analyzed to determine an accurate set of term energies and vibrational constants for the excited and ground electronic states. The electronic configurations from which these states arise will be discussed.

Low glucose level and low pH alter the electrochemical function of human parietal pleura.

PubMed

Kouritas, V K; Hatzoglou, C; Foroulis, C N; Hevas, A; Gourgoulianis, K I; Molyvdas, P A

2007-08-01

The aim of the present study was to investigate whether low glucose and pH level, which are usually measured in complicated pleural effusions, alter the electrochemical function of healthy human parietal pleura. Parietal pleural pieces were stripped from 66 patients during thoracic surgery and were mounted in Ussing chambers. Krebs' solutions containing different glucose levels (0, 40 and 100 mg) and balanced at different pH levels (7.4, 7.3 and 7.2) were added to the pleural cavity surface of the pieces. Transmesothelial potential difference was measured at various time-points as an electrophysiological variable and transmesothelial resistance (R(TM)) was calculated using Ohm's law. When normal-glucose Krebs at pH 7.45 was used, R(TM) remained unchanged over time, but when low-glucose Krebs was used, R(TM) decreased. Krebs without glucose caused the greatest decrease in R(TM). Use of low-pH Krebs decreased R(TM). The lower the pH of the Krebs, the faster the decrease in R(TM) and the greater the effect. The decrease in R(TM) was greater with low-pH than with low-glucose Krebs. Low glucose and low pH caused an additive decrease in R(TM). Low glucose concentration and low pH cause alteration of the electrochemical function of human parietal pleura and could act as agents that lead to further exudate progression.

The Role of Energy Metabolism in Cutaneous Sulfur Mustard Injury

DTIC Science & Technology

2006-11-01

have observed. They are: (a) that inhibition of mitochondrial metabolism may cause accumulation of amino acids and/or Krebs cycle intermediates...the Krebs cycle ) (Martens, 1998). The activity in untreated cells comprised only 2 - 3% of the total glucose consumption. At 300 µM HD, we...Glucose Metabolism: Oxidative metabolism of glucose via the Krebs cycle was determined as the production of 14CO2 from 6-14C-glucose (Martens, 1998

Sodium Channel Expression and Localization at Demyelinated Sites in Painful Human Dental Pulp

PubMed Central

Henry, Michael A.; Luo, Songjiang; Foley, Benjamin D.; Rzasa, Rachael S.; Johnson, Lonnie R.; Levinson, S. Rock

2009-01-01

The expression of sodium channels (NaCh(s)) change after inflammatory and nerve lesions and this change has been implicated in the generation of pain states. Here we examine NaCh expression within nerve fibers from normal and painful extracted human teeth with special emphasis on their localization within large accumulations, like those seen at nodes of Ranvier. Pulpal tissue sections from normal wisdom teeth and from teeth with large carious lesions associated with severe and spontaneous pain were double-stained with pan-specific NaCh antibody and caspr (paranodal protein used to visualize nodes of Ranvier) antibody, while additional sections were triple-stained with NaCh, caspr and myelin basic protein (MBP) antibodies. Z-series of images were obtained with the confocal microscope and evaluated with NIH ImageJ software to quantify the density and size of NaCh accumulations, and to characterize NaCh localization at caspr-identified typical and atypical nodal sites. Although the results showed variability in the overall density and size of NaCh accumulations in painful samples, a common finding included the remodeling of NaChs at atypical nodal sites. This remodeling of NaChs included prominent NaCh expression within nerve regions that showed a selective loss of MBP staining in a pattern consistent with a demyelinating process. PMID:19559391

Objectively measured sedentary time, physical activity, and metabolic risk: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).

PubMed

Healy, Genevieve N; Wijndaele, Katrien; Dunstan, David W; Shaw, Jonathan E; Salmon, Jo; Zimmet, Paul Z; Owen, Neville

2008-02-01

We examined the associations of objectively measured sedentary time and physical activity with continuous indexes of metabolic risk in Australian adults without known diabetes. An accelerometer was used to derive the percentage of monitoring time spent sedentary and in light-intensity and moderate-to-vigorous-intensity activity, as well as mean activity intensity, in 169 Australian Diabetes, Obesity and Lifestyle Study (AusDiab) participants (mean age 53.4 years). Associations with waist circumference, triglycerides, HDL cholesterol, resting blood pressure, fasting plasma glucose, and a clustered metabolic risk score were examined. Independent of time spent in moderate-to-vigorous-intensity activity, there were significant associations of sedentary time, light-intensity time, and mean activity intensity with waist circumference and clustered metabolic risk. Independent of waist circumference, moderate-to-vigorous-intensity activity time was significantly beneficially associated with triglycerides. These findings highlight the importance of decreasing sedentary time, as well as increasing time spent in physical activity, for metabolic health.

Theoretische Konzepte der Physik

NASA Astrophysics Data System (ADS)

Longair, Malcolm S.; Simon, B.; Simon, H.

"Dies ist kein Lehrbuch der theoretischen Physik, auch kein Kompendium der Physikgeschichte ... , vielmehr eine recht anspruchsvolle Sammlung historischer Miniaturen zur Vergangenheit der theoretischen Physik - ihrer "Sternstunden", wenn man so will. Frei vom Zwang, etwas Erschöpfendes vorlegen zu müssen, gelingt dem Autor etwas Seltenes: einen "lebendigen" Zugang zum Ideengebäude der modernen Physik freizulegen, ... zu zeigen, wie Physik in praxi entsteht... Als Vehikel seiner Absichten dienen dem Autor geschichtliche Fallstudien, insgesamt sieben an der Zahl. Aus ihnen extrahiert er das seiner Meinung nach Lehrhafte, dabei bestrebt, mathematische Anachronismen womöglich zu vermeiden... Als Student hätte ich mir diese gescheiten Essays zum Werden unserer heutigen physikalischen Weltsicht gewünscht. Sie sind originell, didaktisch klug und genieren sich auch nicht, von der Faszination zu sprechen, die ... von der Physik ausgeht. Unnötig darauf hinzuweisen, das sie ein gründliches "konventionelles" Studium weder ersetzen wollen noch können, sie vermögen aber, dazu zu ermuntern." #Astronomische Nachrichten (zur englischen Ausgabe)#1

Ein statistisches Modell zum Einfluß der thermischen Bewegung auf NMR-Festkörperspektren

NASA Astrophysics Data System (ADS)

Ploss, W.; Freude, D.; Pfeifer, H.; Schmiedel, H.

Es wird ein statistisches Modell zum Einfluß der thermischen Bewegung auf die NMR-Linienform vorgestellt, das die Verschmälerung von Festkörper-Spektren bei wachsender Temperatur beschreibt. Das Modell geht von der Annahme aus, daß nach einer Ortsveränderung eines Kerns infolge thermischer Bewegung jede beliebige Kernresonanzfrequenz mit der durch das Festkörperspektrum vorgegebenen Wahrscheinlichkeit angenommen werden kann. Am Beispiel der Festkörper-Gaußlinie wird der Unterschied zu dem bekannten Modell von ANDERSON und WEISS verdeutlicht.Translated AbstractA Statistical Model for the Influence of Thermal Motion on N. M. R. Spectra in SolidsA theory is proposed which allows to describe the narrowing of n. m. r.-line width in the presence of thermal motions of the spins. The model is based on the assumption, that the local resonance frequency of a given spin immediately after the jump is distributed according to the n. m. r.-line shape of the rigid lattice. The difference to the well-known ANDERSON-WEISS-model of spectral narrowing is demonstrated for a gaussian line shape.

Dual-Use Telemedicine Support System for Pathology.

DTIC Science & Technology

1998-12-01

Pathology 2.6.3 Conclusion 2.7 UMC/Cortex Medical Management Systems Demo by Judith Krebs and Mark Stevens (cyto geneticist) 2.7.1 Conclusion 2.7.2...Systems demo by Judith Krebs and Mark Stevens (cyto geneticist) Mrs. Krebs was coming into Tucson to check on the newly installed Gold Standard System at...The system uses a Novell and Ethernet networks and gives reasonably fast response. Judith has found that doctors are definitely becoming more

Prevalence, incidence, risk factors and treatment of atrial fibrillation in Australia: The Australian Diabetes, Obesity and Lifestyle (AusDiab) longitudinal, population cohort study.

PubMed

Diouf, Ibrahima; Magliano, Dianna J; Carrington, Melinda J; Stewart, Simon; Shaw, Jonathan E

2016-02-15

We sought to describe the prevalence, incidence, risk factors and treatment (according to stroke risk) of atrial fibrillation (AF) in the national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study cohort. ECG data were available from 8273/11,247 participants of AusDiab study in 1999/2000 and from 5422 participants in 2004/2005. Minnesota coding was used to identify prevalent and incident cases of AF. 90 prevalent cases of AF (14.1 per 1000) comprising 56 men (mean age 70.5 ± 1.9 years) and 34 women (aged 78.3 ± 1.2 years) were identified in 1999-2000. AF prevalence was associated with sedentary behaviour versus physically active (PR 2.0, 95% CI 1.2-3.6). 53 incident cases of AF (2.0, 95%, CI 1.5-2.6 per 1000 person-year) were subsequently identified in 2004-2005. Increased risk of incident AF was associated with male sex, obesity, history of angina, myocardial infarction and stroke. Both increased weight gain and increased weight loss appeared to be associated with increased risks of developing AF in women, while no obvious association was observed in men. Despite their high risk for stroke, anti-thrombotic therapy was observed in only 39.3% of participants with CHA2DS2-VASC scores ≥ 2. This study contributes to a better understanding of the AF burden. With the ageing population, coordinated efforts will be needed to anticipate the future health care costs related to AF and its impacts on the health care system. This will include appropriate application of anti-thrombotic therapy according to risk of thrombo-embolic events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigating the Functional Role of Prostate-Specific Membrane Antigen and Its Enzymatic Activity in Prostate Cancer Metastasis

DTIC Science & Technology

2009-11-01

24-well plates and grown for 2-3 days prior to initiating the experiments. Cells were rinsed in Krebs -Ringer buffer, and incubated with mAbs J591...J415, 7E11 at 10µg/ml in Krebs - Ringer buffer at 370C for 30 min. 3H-NAAG were co-incubated along with the respective antibody at 0.8 µci/ml for 60 min...at 370C. Cells were washed in Krebs -Ringer buffer, and lysed in 1N of NaOH. Cell lysates were counted in liquid scintillation counter. PSMA negative

Gerbstoffe aus Potentilla officinalis wirken entzündungshemmend im UV-Erythem-Test und bei Anwendung auf atopischer Haut.

PubMed

Hoffmann, Julia; Wölfle, Ute; Schempp, Christoph M; Casetti, Federica

2016-09-01

Das Rhizom von Potentilla officinalis (PO) ist reich an Gerbstoffen und wird traditionell zur äußerlichen Behandlung von Entzündungen der Haut und der Schleimhäute verwendet. Ziel der vorliegenden Arbeit war die Bestätigung der antiinflammatorischen Eigenschaften von PO mittels eines UV-Erythem-Tests und einer klinischen Anwendungsstudie bei atopischer Haut. Die antiinflammatorische Wirkung eines PO-Extrakts (standardisiert auf 2 % Trockensubstanz) wurde in einer prospektiven, randomisierten, placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV-Erythem-Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer prospektiven nicht kontrollierten Studie wurde die Wirkung und Verträglichkeit der 2 % PO-Creme an zwölf Erwachsenen und zwölf Kindern mit atopischer Haut nach Anwendung über zwei Wochen in einem definierten Testareal anhand eines Teil-SCORAD untersucht. Zusätzlich wurde die Beeinflussung der Hautrötung im Testareal photometrisch gemessen. Im UV-Erythem-Test zeigte die PO-Creme eine signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat-Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des Teil-SCORAD und des Erythems im Testareal. Es wurden keine Unverträglichkeitsreaktionen beobachtet. PO als 2%ige Zubereitung besitzt entzündungshemmende Eigenschaften und ist wirksam und gut verträglich auf atopischer Haut. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Empowering Parents of Australian Infants and Children in Hospital: Translation, Cultural Adaptation, and Validation of the EMpowerment of PArents in The Intensive Care-30-AUS Questionnaire.

PubMed

Gill, Fenella J; Wilson, Sally; Aydon, Laurene; Leslie, Gavin D; Latour, Jos M

2017-11-01

To translate, culturally adapt, and psychometrically test the EMpowerment of PArents in The Intensive Care-30 questionnaire in Australian pediatric critical care, neonatal, and pediatric ward settings. Cross-sectional, descriptive, multicenter study conducted in two phases; 1) translation and cultural adaptation and 2) validation of the EMpowerment of PArents in The Intensive Care-30 questionnaire. Two Western Australian sites, the PICU and two pediatric wards of a children's hospital and the neonatal unit of a women's and newborn hospital. Parents whose baby or child was admitted to the participating wards or units with a length of hospital stay greater than 24 hours. None. Phase 1: A structured 10-step translation process adhered to international principles of good practice for translation and cultural adaptation of patient-reported outcomes. Thirty parents participated in cognitive debriefing. Phase 2: A total of 328 parents responded to the EMpowerment of PArents in The Intensive Care-30-AUS questionnaire. Reliability was sufficient (Cronbach α at domain level 0.70 -0.82, for each clinical area 0.56-0.86). Congruent validity was adequate between the domains and three general satisfaction items (rs 0.38-0.69). Nondifferential validity showed no significant effect size between three patient or parent demographic characteristics and the domains (Cohen's d < 0.36). Between the different clinical areas, significant differences in responses were found in all domains. The translated and culturally adapted EMpowerment of PArents in The Intensive Care-30-AUS is a reliable and valid questionnaire to measure parent-reported outcomes in pediatric critical care, pediatric ward, and neonatal hospital settings. Using this questionnaire can provide a framework for a standardized quality improvement approach and identification of best practices across specialties, hospital services and for benchmarking similar health services worldwide.

Arzt und Hobby-Astronom in stürmischen Zeiten Der Büchernachlass des Doktor Johannes Häringshauser, Viertelsmedicus in Mistelbach (1630-1641) in der Melker Stiftsbibliothek.

NASA Astrophysics Data System (ADS)

Davison, Giles; Glaßner, Gottfried

2009-06-01

Auf der Suche nach astronomischer Literatur stieß Giles Davison in der Melker Stiftsbibliothek auf den Namen "Doctor Johannes Häringshauser“ als Besitzer seltener und interessanter astronomischer Werke u.a. von Johannes Regiomontan, Georg von Peuerbach, Michael Mästlin, Johannes Kepler und Daniel Sennert. Weitere in den Jahren 2007-2009 durchgeführte Nachforschungen ergaben, dass es sich um den von 1630-1641 in Mistelbach, Niederösterreich, als Landschaftsarzt tätigen Vater des Melker Konventualen und Bibliothekars Sigismund Häringshauser (1631-1698) handelt. Er wurde 1603 als Sohn des aus Magdeburg stammenden Apothekers Johannes Häringshauser geboren und starb 1642 in Mistelbach. Johannes Häringshauser Sen. bekleidete von 1613-1640 eine Reihe wichtiger Ämter in der Wiener Stadtregierung und starb 1647. Der Studienaufenthalt von Dr. Johannes Häringshauser Jun. in Padua (1624-1626) dürfte das Interesse für Astronomie geweckt haben, das sich in seiner in die Bestände der Melker Stiftsbibliothek eingegangenen Privatbibliothek widerspiegelt. Der Großteil der 10 dem Fachbereich der Astronomie und Astrologie zuzuweisenden Titel wurde von ihm in den Jahren 1636 und 1637 erworben.

Einleitung

NASA Astrophysics Data System (ADS)

Ha, Suk-Woo

Der Einsatz von Implantaten zielt auf die Unterstützung oder den Ersatz von Zelloder Gewebefunktionen im menschlichen Körper. Die Werkstoffauswahl für diese Implantate hängt dabei von der Art und der Funktion des zu ersetzenden Gewebes ab. Die Anforderungen an den Implantatwerkstoff bezüglich Eigenschaften und Struktur können je nach Implantationsort und Funktionalität ganz unterschiedlich sein. Implantate, die im Knochengewebe Funktionen der Lasteinleitung und -überleitung ausüben, sind hohen mechanischen Anforderungen (optimale Bauteilsteifigkeit, Dauerfestigkeit) unterworfen, während bei Blutgefässimplantaten die Werkstoffoberfläche, primär in ihrer chemischen Zusammensetzung derart gestaltet sein muss, dass eine minimale Thrombogenität resultiert. Für den Erfolg des Implantatwerkstoffes oder -bauteils sind folgende drei Faktoren relevant: (a) Biokompatibilität, (b) Gesundheitszustand des Patienten und (c) Verlauf der Operation und der nachfolgenden Therapie. Bei Vorliegen einer Erkrankung, wie z. B. die allergische Sensibilisierung gegenüber Metallionen (Nickelallergie) oder Osteoporose im Fall der Verankerung von Hüftprothesen, ist der Implantatwerkstoff höheren Anforderungen bezüglich der Biokompatibilität unterworfen als bei organisch gesunden Patienten.

Socio-demographic correlates of prolonged television viewing time in Australian men and women: the AusDiab study.

PubMed

Clark, Bronwyn Kay; Sugiyama, Takemi; Healy, Genevieve N; Salmon, Jo; Dunstan, David W; Shaw, Jonathan E; Zimmet, Paul Z; Owen, Neville

2010-09-01

Sedentary behaviors, particularly television viewing (TV) time, are associated with adverse health outcomes in adults, independent of physical activity levels. These associations are stronger and more consistent for women than for men. Multivariate regression models examined the sociodemographic correlates of 2 categories of TV time (≥ 2 hours/day and ≥ 4 hours/day); in a large, population-based sample of Australian adults (4950 men, 6001 women; mean age 48.1 years, range 25-91) who participated in the 1999/2000 Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Some 46% of men and 40% of women watched ≥ 2 hours TV/day; 9% and 6% respectively watched ≥ 4 hours/day. For both men and women, ≥ 2 hours TV/day was associated with less than tertiary education, living outside of state capital cities, and having no paid employment. For women, mid and older age (45-64 and 65+) were also significant correlates of ≥ 2 hours TV/day. Similar patterns of association were observed in those viewing ≥ 4 hours/day. Prolonged TV time is associated with indices of social disadvantage and older age. These findings can inform the understanding of potential contextual influences and guide preventive initiatives.

Construction of Pseudomolecule Sequences of the aus Rice Cultivar Kasalath for Comparative Genomics of Asian Cultivated Rice

PubMed Central

Sakai, Hiroaki; Kanamori, Hiroyuki; Arai-Kichise, Yuko; Shibata-Hatta, Mari; Ebana, Kaworu; Oono, Youko; Kurita, Kanako; Fujisawa, Hiroko; Katagiri, Satoshi; Mukai, Yoshiyuki; Hamada, Masao; Itoh, Takeshi; Matsumoto, Takashi; Katayose, Yuichi; Wakasa, Kyo; Yano, Masahiro; Wu, Jianzhong

2014-01-01

Having a deep genetic structure evolved during its domestication and adaptation, the Asian cultivated rice (Oryza sativa) displays considerable physiological and morphological variations. Here, we describe deep whole-genome sequencing of the aus rice cultivar Kasalath by using the advanced next-generation sequencing (NGS) technologies to gain a better understanding of the sequence and structural changes among highly differentiated cultivars. The de novo assembled Kasalath sequences represented 91.1% (330.55 Mb) of the genome and contained 35 139 expressed loci annotated by RNA-Seq analysis. We detected 2 787 250 single-nucleotide polymorphisms (SNPs) and 7393 large insertion/deletion (indel) sites (>100 bp) between Kasalath and Nipponbare, and 2 216 251 SNPs and 3780 large indels between Kasalath and 93-11. Extensive comparison of the gene contents among these cultivars revealed similar rates of gene gain and loss. We detected at least 7.39 Mb of inserted sequences and 40.75 Mb of unmapped sequences in the Kasalath genome in comparison with the Nipponbare reference genome. Mapping of the publicly available NGS short reads from 50 rice accessions proved the necessity and the value of using the Kasalath whole-genome sequence as an additional reference to capture the sequence polymorphisms that cannot be discovered by using the Nipponbare sequence alone. PMID:24578372

Umgang mit Antithrombotika bei Operationen an der Haut vor und nach Publikation der entsprechenden S3-Leitlinie.

PubMed

Gaskins, Matthew; Dittmann, Martin; Eisert, Lisa; Werner, Ricardo Niklas; Dressler, Corinna; Löser, Christoph; Nast, Alexander

2018-03-01

Laut einer Befragung im Jahre 2012 war der Umgang mit Antithrombotika bei dermatochirurgischen Eingriffen in Deutschland sehr heterogen. 2014 wurde erstmals eine evidenzbasierte Leitlinie zu diesem Thema veröffentlicht. Es wurde eine anonyme Befragung derselben Stichprobe zum Umgang mit Antithrombotika sowie zu Kenntnissen der Leitlinie durchgeführt. Die Ergebnisse wurden als relative Häufigkeiten berichtet und denen aus 2012 gegenübergestellt. 208 Antwortbögen wurden ausgewertet (Rücklaufquote: 36,6 %). Die große Mehrheit der Dermatologen erklärte, kleinere Eingriffe unter Fortführung der Therapie mit Phenprocoumon, niedrig dosierter Acetylsalicylsäure (≤ 100 mg) und Clopidogrel sowie mit direkten oralen Antikoagulanzien durchzuführen. Bei größeren Eingriffen war der Umgang hingegen weiterhin heterogen, insbesondere unter niedergelassenen Dermatologen. Der Anteil der Dermatologen, die Phenprocoumon, Acetylsalicylsäure und Clopidogrel leitlinienkonform verwendeten, hat sich insgesamt vergrößert. Führten 2012 beispielsweise 53,8 % der Klinikärzte bzw. 36,3 % der niedergelassenen Dermatologen eine große Exzision unter Fortführung der Therapie mit niedrig dosierter Acetylsalicylsäure durch, taten dies 2017 90,2 % bzw. 57,8 % (Phenprocoumon: 33,8 % bzw. 11,9 % auf 63,9 % bzw. 29,9 %; Clopidogrel: 36,9 % bzw. 23,2 % auf 63,9 % bzw. 30,6 %). Unter den Klinikärzten war ein hoher Anteil mit der Leitlinie vertraut und fand diese hilfreich. Eine Zunahme des leitlinienkonformen Verhaltens war bei allen Eingriffen zu verzeichnen. Bei größeren Eingriffen zeigte sich trotz deutlicher Verbesserung die Notwendigkeit verstärkter Anstrengungen zur Leitlinienumsetzung bzw. zur Identifizierung von Implementierungsbarrieren. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Loops D, E and G in the Drosophila Dα1 subunit contribute to high neonicotinoid sensitivity of Dα1-chicken β2 nicotinic acetylcholine receptor.

PubMed

Ihara, Makoto; Hikida, Mai; Matsushita, Hiroyuki; Yamanaka, Kyosuke; Kishimoto, Yuya; Kubo, Kazuki; Watanabe, Shun; Sakamoto, Mifumi; Matsui, Koutaro; Yamaguchi, Akihiro; Okuhara, Daiki; Furutani, Shogo; Sattelle, David B; Matsuda, Kazuhiko

2018-06-01

Neonicotinoid insecticides interact with the orthosteric site formed at subunit interfaces of insect nicotinic ACh (nACh) receptors. However, their interactions with the orthosteric sites at α-non α and α-α subunit interfaces remain poorly understood. The aim of this study was to elucidate the mechanism of neonicotinoid actions using the Drosophila Dα1-chicken β2 hybrid nACh receptor. Computer models of the (Dα1) 3 (β2) 2 nACh receptor in complex with imidacloprid and thiacloprid were generated. Amino acids in the Dα1 subunit were mutated to corresponding amino acids in the human α4 subunit to examine their effects on the agonist actions of neonicotinoids on (Dα1) 3 (β2) 2 and (Dα1) 2 (β2) 3 nACh receptors expressed in Xenopus laevis oocytes using voltage-clamp electrophysiology. The (Dα1) 3 (β2) 2 nACh receptor models indicated that amino acids in loops D, E and G probably determine the effects of neonicotinoids. The amino acid mutations tested had minimal effects on the EC 50 for ACh. However, the R57S mutation in loop G, although having minimal effect on imidacloprid's actions, reduced the affinity of thiacloprid for the (Dα1) 3 (β2) 2 nACh receptor, while scarcely affecting thiacloprid's action on the (Dα1) 2 (β2) 3 nACh receptor. Both the K140T and the combined R57S;K140T mutations reduced neonicotinoid efficacy but only for the (Dα1) 3 (β2) 2 nACh receptor. Combining the E78K mutation with the R57S;K140T mutations resulted in a selective reduction of thiacloprid's affinity for the (Dα1) 3 (β2) 2 nACh receptor. These findings suggest that a triangle of residues from loops D, E and G contribute to the selective actions of neonicotinoids on insect-vertebrate hybrid nACh receptors. This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc. © 2017 The British Pharmacological Society.

Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence in Gastrointestinal Stromal Tumor

PubMed Central

Killian, J. Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Smith, William I.; Jahromi, Mona S.; Xekouki, Paraskevi; Szarek, Eva; Walker, Robert L.; Lasota, Jerzy; Raffeld, Mark; Klotzle, Brandy; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J.; O’Sullivan, Maureen J.; Bibikova, Marina; Pacak, Karel; Stratakis, Constantine; Janeway, Katherine A.; Schiffman, Joshua D.; Fan, Jian-Bing; Helman, Lee; Meltzer, Paul S.

2014-01-01

Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway–mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH -mutant GIST with isocitrate dehydrogenase -mutant glioma, another Krebs cycle–defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance. SIGNIFICANCE This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. PMID:23550148

The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies.

PubMed

Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

2014-08-01

Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. © 2014 The British Pharmacological Society.

The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies

PubMed Central

Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

2014-01-01

BACKGROUND AND PURPOSE Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. EXPERIMENTAL APPROACHES To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. KEY RESULTS BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. CONCLUSION AND IMPLICATIONS Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. PMID:24750073

The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

PubMed

Winkelmann, Isabel; Diehl, Daniela; Oesterle, Doris; Daniel, Hannelore; Wenzel, Uwe

2007-07-01

Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism.

Biologie statt Philosophie? Evolutionäre Kulturerklärungen und ihre Grenzen

NASA Astrophysics Data System (ADS)

Illies, Christian

Vor über siebzig Jahren fand man in einer Höhle nahe Hohlenstein-Stadel, im heutigen Baden-Württemberg, eine Frau, die keiner bekannten Spezies und nicht einmal eindeutig den Hominiden zugeordnet werden konnte. Wegen ihres Aussehens wurde sie schon bald als "Löwenfrau“ bekannt (unterdessen wird sie als "Löwenmensch“ bezeichnet, da die in solchen Fragen Klarheit schaffenden Geschlechtsteile bei der Figur fehlen und in Zeiten von gender mainstreaming derartige Festlegungen gerne vermieden werden), denn sie hatte eine menschlich-aufrechte, unbehaarte Gestalt mit weiblichen Rundungen, aber zugleich eine Mähne, sowie Augen, Ohren und Schnauze eines Löwen. Eine sehr weitläufige Verwandte des Minotaurus, so schien es, und doch wesentlich älter als alle Bewohner des Olymps, denn vermutlich wurde die knapp 30 cm große Skulptur bereits in der Altsteinzeit vor etwa 32.000 Jahren aus Mammut-Elfenbein geschnitzt. Wir wissen nicht, ob sie kultischen Zwecken diente oder ein Kind mit ihr spielte, ob sie als Glücksbringer für die Jagd oder als Schamanin mit Löwenmaske verehrt und gefürchtet wurde. Aber die Löwenfrau legt nahe, dass der Mensch schon im Morgendämmern seiner Kultur über die eigene Nähe, aber auch Distanz zum Tier nachgedacht haben muss. Die Frage nach der menschlichen Selbstverortung begegnet uns in dieser Figur, und sie bestimmt viele Zeugnisse menschlichen Nachdenkens, welche uns die Altertumswissenschaften vorlegen. Mit dem Begriff "animal rationale“, wie er unter Bezug auf Aristoteles geprägt wurde, findet sie schließlich ihre klassische, für das Abendland lange Zeit maßgebliche Antwort: Der Mensch als Tier, dessen spezifisches Merkmal die Vernunftbegabtheit ist, die ihn zugleich von allen anderen Tieren abgrenzt und über sie stellt. Aber wo genau verläuft die Grenze? Und wie kann der Mensch beides zugleich sein? Die aristotelische Definition beantwortet diese Fragen nach der Doppelnatur nicht, sondern erhebt das offene R�

Epidemiologie, Prävention und Früherkennung des Zervixkarzinoms

PubMed Central

Wentzensen, Nicolas

2016-01-01

Zusammenfassung Hintergrund Persistierende Infektionen mit humanen Papillomviren sind die notwendige Ursache des Zervixkarzinoms. Die Entwicklung von HPV-basierten Präventionsverfahren, der HPV Impfung und der HPV-Testung, führt derzeit zu umfangreichen Veränderungen von Zervixkarzinom-Vorsorgeprogrammen. Eine Dekade nach Einführung der HPV-Imfpung in vielen Ländern werden bereits Reduktionen von HPV-Infektionen und Krebsvorstufen in jungen Frauen beobachtet. Der Fokus liegt jetzt auf der Integration von neuen Testverfahren im Screening von Populationen mit zunehmenden Impfraten. Ergebnisse und Schlussfolgerung Ein erfolgreiches Zervixkarzinom-Vorsorgeprogramm besteht aus verschiedenen Komponenten, vom primären Screening über die Triage zur Kolposkopie mit Biopsie, um Frauen mit Kresbvorstufen zu identifizieren, die eine therapeutische Intervention benötigen. Im primären Screening wird eine kleine Gruppe von Frauen mit erhöhtem Risiko für eine Krebsvorstufe identifiziert, während die grosse Mehrheit kein erhöhtes Risiko hat. Je nach primärem Testverfahren werden in screen-positiven Frauen zusätzliche Triage-Tests durchgeführt, um zu entscheiden, wer zur Kolposkopie überwiesen werden sollte. Derzeit gibt es drei verschiedene Ansätze für das primäre Zervixkarzinomscreening: Die Zervix-Zytologie, die HPV-Testung, und die HPV-Zytologie Ko-Testung. Zahlreiche Triage-Tests für HPV-positive Frauen werden derzeit untersucht, darunter sind die Zytologie, HPV-Genotypisierung, p16/Ki-67 Zytologie, und diverse Methylierungstests. Die steigende Anzahl an Optionen für die Früherkennung des Zervixkarzinoms stellt eine Herausforderung für klinische Leitlinien dar. Die zunehmende Komplexität von Vorsorgeprogrammen kann zur Verunsicherung von Ärzten und von am Screening teilnehmenden Frauen führen. Die Präzisions-Prävention des Zervixkarzinoms ist eine neuer Ansatz, der umfangreiche Risikodaten basierend auf der individuellen Vorgeschichte und von

Implantate für den Bandscheibenersatz (Stand 1993)

NASA Astrophysics Data System (ADS)

Mathey, Michael; Wintermantel, Erich

Die Bandscheiben sind besonders betroffen von Fehlhaltungen und -stellungen der Wirbelsäule. Sie unterliegen als grösstes zusammenhängendes, nicht vaskularisiertes Gewebe im Menschen, statisch und dynamisch extrem belastet, besonders der Alterung. Um die teilweise sehr starken Schmerzen bei Bandscheibenschädigungen zu lindern, ist eine Operation vielfach die einzige Hilfe. Bei dieser Operation (Nukleotomie) entfernt man das aus der Bandscheibe ausgetretene Gewebe des Gallertkerns (nucleus pulposus), welches durch Druck auf die Nervenstränge im Bereich der Wirbelsäule die Beschwerden (Ischias-Schmerz) verursacht hat. Nach der Entfernung des Gallertkerns werden die auftretenden Kräfte bei veränderter Biomechanik übertragen. Dabei erhalten die Zwischenwirbelgelenke (Facettengelenke) eine erheblich grössere Flächenpressung als dies bei intakter Bandscheibe der Fall war. Die höhere Flächenpressung kommt durch die Verringerung des Abstandes zwischen den oberen und unteren Deckplatten der benachbarten Wirbelkörper zustande, zwischen denen sich der Gallertkern befand. Durch geeignetes Training der Rückenmuskulatur kann eine Stabilisierung des operierten Bandscheibensegmentes erreicht werden, jedoch ist es eine klinische Erfahrung, dass die meisten Patienten, die momentan durch die Operation schmerzfrei geworden sind, keine adäquate zusätzliche sportliche Betätigung auf sich nehmen.

Validity of a multi-context sitting questionnaire across demographically diverse population groups: AusDiab3.

PubMed

Clark, Bronwyn K; Lynch, Brigid M; Winkler, Elisabeth Ah; Gardiner, Paul A; Healy, Genevieve N; Dunstan, David W; Owen, Neville

2015-12-04

Sitting time questionnaires have largely been validated in small convenience samples. The validity of this multi-context sitting questionnaire against an accurate measure of sitting time is reported in a large demographically diverse sample allowing assessment of validity in varied demographic subgroups. A subgroup of participants of the third wave of the Australian Diabetes, Obesity, and Lifestyle (AusDiab3) study wore activPAL3™ monitors (7 days, 24 hours/day protocol) and reported their sitting time for work, travel, television viewing, leisure computer use and "other" purposes, on weekdays and weekend days (n = 700, age 36-89 years, 45% men). Correlations (Pearson's r; Spearman's ρ) of the self-report measures (the composite total, contextual measures and items) with monitor-assessed sitting time were assessed in the whole sample and separately in socio-demographic subgroups. Agreement was assessed using Bland-Altman plots. The composite total had a correlation with monitor-assessed sitting time of r = 0.46 (95% confidence interval [CI]: 0.40, 0.52); this correlation did not vary significantly between demographic subgroups (all >0.4). The contextual measure most strongly correlated with monitor-assessed sitting time was work (ρ = 0.25, 95 % CI: 0.17, 0.31), followed by television viewing (ρ = 0.16, 95 % CI: 0.09, 0.24). Agreement of the composite total with monitored sitting time was poor, with a positive bias (B = 0.53, SE 0.04, p < 0.001) and wide limits of agreement (±4.32 h). This multi-context questionnaire provides a total sitting time measure that ranks participants well for the purposes of assessing health associations but has limited accuracy relative to activPAL-assessed sitting time. Findings did not differ in demographic subgroups.

Nicotine evokes kinetic tremor by activating the inferior olive via α7 nicotinic acetylcholine receptors.

PubMed

Kunisawa, Naofumi; Iha, Higor A; Shimizu, Saki; Tokudome, Kentaro; Mukai, Takahiro; Kinboshi, Masato; Serikawa, Tadao; Ohno, Yukihiro

2016-11-01

Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and immunohistochemical studies using mice and rats to elucidate the mechanisms underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5-2mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the nACh receptor antagonist mecamylamine (MEC). The specific α7 nACh receptor antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor, whereas the α4β2 nACh antagonist dihydro-β-erythroidine (DHβE) or the peripheral α3β4 nACh antagonist hexamethonium showed no effects. Mapping analysis of Fos protein expression, a biological marker of neural excitation, revealed that a tremorgenic dose (1mg/kg) of nicotine region-specifically elevated Fos expression in the piriform cortex (PirC), medial habenula, solitary nucleus and inferior olive (IO) among 44 brain regions examined. In addition, similarly to the tremor responses, nicotine-induced Fos expression in the PirC and IO was selectively antagonized by MLA, but not by DHβE. Furthermore, an electrical lesioning of the IO, but not the PirC, significantly suppressed the induction of nicotine tremor. The present results suggest that nicotine elicits kinetic tremor in rodents by activating the IO neurons via α7 nACh receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeted Zinc Delivery: A Novel Treatment for Prostate Cancer

DTIC Science & Technology

2010-06-01

aconitase, which normally functions to oxidize citrate during the Krebs cycle . Because citrate is a principle component of seminal fluid, prostate...tissue, likely due to the metabolic effects of zinc in the Krebs cycle . That is, because zinc inhibits m- aconitase, loss of zinc allows for greater...secretory cells do not complete the oxidation of citrate in the mitochondria and the zinc-mediated inhibition of m-aconitase is crucial for the

A broken krebs cycle in macrophages.

PubMed

O'Neill, Luke A J

2015-03-17

Macrophages undergo metabolic rewiring during polarization but details of this process are unclear. In this issue of Immunity, Jha et al. (2015) report a systems approach for unbiased analysis of cellular metabolism that reveals key metabolites and metabolic pathways required for distinct macrophage polarization states. Copyright © 2015 Elsevier Inc. All rights reserved.

Fine mapping of the chromosome 5B region carrying closely linked rust resistance genes Yr47 and Lr52 in wheat

USDA-ARS?s Scientific Manuscript database

The widely effective and linked rust resistance genes Yr47 and Lr52 were previously mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229 and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to generate an F6 recombinant inbred line (RIL) population t...

Windkraftanlagen

NASA Astrophysics Data System (ADS)

Surek, Dominik

Windturbinenanlagen nutzen die kinetische Energie des Windes bei Geschwindigkeiten von c=4 m/s bis 25 m/s in Nabenhöhe des Windrades zur Stromerzeugung. Die oben genannten Windgeschwindigkeiten liegen im Grenzschichtbereich der ebenen Strömung (Abb. 67.1), die bei Höhen von h=100 m bis 1000 m liegen und in Großstädten mit Skylines bis 2000 m. Die größten Windturbinentürme erreichen gegenwärtig Nabenhöhen von h=160 m und Windraddurchmesser von d=130 m, d. h. mit Flügellängen von L=65 m. Die Windturbinen werden vorrangig mit 3 Schaufeln ausgeführt. Windturbinen mit einer und zwei Schaufeln waren Versuchsgeräte. Die Drehzahl von Windturbinen für Leistungen von P_{T}=2 MW betragen n=12 bis 20 min{}^{-1}. Das Windrad entzieht dem Wind mit der Anströmgeschwindigkeit c 1 nach Betz die Geschwindigkeitsdifferenz c2=(2/3) c1. Der Rest der Windgeschwindigkeit wird für die Abströmung des Windes im Leebereich c3=c1/3 benötigt. Durch den Entzug der Geschwindigkeit im Laufrad bläht sich der Abströmdurchmesser auf d3> d1 auf, der bei der Installation von Windturbinen zu beachten ist (Abb. 67.2) [Gasch und Twele(2013)]. Um die Windturbinen bei starkem Wind von c {}1> 25 m/s zu schützen, werden die Laufschaufeln durch Pitch- oder Stall-Anlagen aus dem Wind gedreht, so dass die Strömung an den Schaufeln abreißt und das Windrad in die Ruhestellung gelangt. Bei der Windgeschwindigkeit c1=25 m/s bis 34 m/s wird der Windrotor abgeschaltet. Die zulässige Maximalgeschwindigkeit liegt aus Festigkeitsgründen etwa bei . Die aktive Blattverdrehung (Pitchregelung) stellt eine Blattwinkelregelung dar, wobei die Profilnase in die Anströmung gedreht wird. Sie benötigen für die Drehzahlreduzierung keine mechanische Bremse.

Differential Expression of Zinc Transporters in Prostate Epithelia of Racial Groups

DTIC Science & Technology

2010-09-01

mitochondria inhibits terminal oxidation, truncating the Krebs cycle , hence decreasing the ATP-based energy production and resulting in less growth...as a major component of prostatic fluid [7,10]. In addition, high Zn levels in the mitochondria inhibits terminal oxidation, truncat- ing the Krebs ...PCR (MJR/Bio-Rod – Twin Tower, PTC 200, Waltham, MA). The two cycles were programmed for 30 min at 50 C, then 95 C for 5 min (for cDNA step), and

Rapamycin impairs metabolism-secretion coupling in rat pancreatic islets by suppressing carbohydrate metabolism.

PubMed

Shimodahira, Makiko; Fujimoto, Shimpei; Mukai, Eri; Nakamura, Yasuhiko; Nishi, Yuichi; Sasaki, Mayumi; Sato, Yuichi; Sato, Hiroki; Hosokawa, Masaya; Nagashima, Kazuaki; Seino, Yutaka; Inagaki, Nobuya

2010-01-01

Rapamycin, an immunosuppressant used in human transplantation, impairs beta-cell function, but the mechanism is unclear. Chronic (24 h) exposure to rapamycin concentration dependently suppressed 16.7 mM glucose-induced insulin release from islets (1.65+/-0.06, 30 nM rapamycin versus 2.35+/-0.11 ng/islet per 30 min, control, n=30, P<0.01) without affecting insulin and DNA contents. Rapamycin also decreased alpha-ketoisocaproate-induced insulin release, suggesting reduced mitochondrial carbohydrate metabolism. ATP content in the presence of 16.7 mM glucose was significantly reduced in rapamycin-treated islets (13.42+/-0.47, rapamycin versus 16.04+/-0.46 pmol/islet, control, n=30, P<0.01). Glucose oxidation, which indicates the velocity of metabolism in the Krebs cycle, was decreased by rapamycin in the presence of 16.7 mM glucose (30.1+/-2.7, rapamycin versus 42.2+/-3.3 pmol/islet per 90 min, control, n=9, P<0.01). Immunoblotting revealed that the expression of complex I, III, IV, and V was not affected by rapamycin. Mitochondrial ATP production indicated that the respiratory chain downstream of complex II was not affected, but that carbohydrate metabolism in the Krebs cycle was reduced by rapamycin. Analysis of enzymes in the Krebs cycle revealed that activity of alpha-ketoglutarate dehydrogenase (KGDH), which catalyzes one of the slowest reactions in the Krebs cycle, was reduced by rapamycin (10.08+/-0.82, rapamycin versus 13.82+/-0.84 nmol/mg mitochondrial protein per min, control, n=5, P<0.01). Considered together, these findings indicate that rapamycin suppresses high glucose-induced insulin secretion from pancreatic islets by reducing mitochondrial ATP production through suppression of carbohydrate metabolism in the Krebs cycle, together with reduced KGDH activity.

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

Walker, T.E.; Han, C.H.; Kollman, V.H.

/sup 13/C NMR of isotopically enriched metabolites has been used to study the metabolism of Microbacterium ammoniaphilum, a bacterium which excretes large quantities of L-glutamic acid into the medium. Biosynthesis from 90% (1-/sup 13/C) glucose results in relatively high specificity of the label, with (2,4-/sup 13/C/sub 2/) glutamate as the major product. The predominant biosynthetic pathway for synthesis of glutamate from glucose was determined to be the Embden Meyerhof glycolytic pathway followed by P-enolpyruvate carboxylase and the first third of the Krebs cycle. Different metabolic pathways are associated with different correlations in the enrichment of the carbons, reflected in themore » spectrum as different /sup 13/C-/sup 13/C scalar multiplet intensities. Hence, intensity and /sup 13/C-/sup 13/C multiplet analysis allows quantitation of the pathways involved. Although blockage of the Krebs cycle at the ..cap alpha..-ketoglutarate dehydrogenase step is the basis for the accumulation of glutamate, significant Krebs cycle activity was found in glucose grown cells, and extensive Krebs cycle activity in cells metabolizing (1-/sup 13/C) acetate. In addition to the observation of the expected metabolites, the disaccharide ..cap alpha..,..cap alpha..-trehalose and ..cap alpha..,..beta..-glucosylamine were identified from the /sup 13/C NMR spectra.« less

Electrophysiological and Ultrastructural Characterization of Neuromuscular Junctions in Diaphragm Muscle of Acetylcholinesterase Knockout Mice

DTIC Science & Technology

2008-04-01

conditioned fresh air. The mice were on a 12-hr light/dark full-spectrum lighting cycle . AChE +/+ and AChE -/- mice were 58.7 ± 2.9 and 51.6 ± 3.2 days old...diaphragms were excised and pinned at resting length in Sylgard (Dow Chemical Co., Midland, MI) coated dishes containing oxygenated Krebs -Ringer solution of...measurements Hemidiaphragms with attached phrenic nerves were mounted in tissue baths at 37o C and immersed in an oxygenated Krebs -Ringer solution. To

Young investigator challenge: Atypia of undetermined significance in thyroid FNA: Standardized terminology without standardized management--a closer look at repeat FNA and quality measures.

PubMed

Brandler, Tamar C; Aziz, Mohamed S; Coutsouvelis, Constantinos; Rosen, Lisa; Rafael, Oana C; Souza, Fabiola; Jelloul, Fatima-Zahra; Klein, Melissa A

2016-01-01

The Bethesda system (TBS) for the reporting of thyroid cytopathology established the category of atypia of undetermined significance (AUS) with a 7% target rate and a 5% to 15% implied malignancy risk. Recent literature has reported a broad range of AUS rates, subsequent malignancy rates, and discrepant results from repeat fine-needle aspiration (FNA) versus surgical follow-up. Therefore, this study examined AUS data from the Hofstra North Shore-LIJ School of Medicine to determine the best clinical follow-up. Thyroid aspirates interpreted as AUS in 2012-2014 at the Hofstra North Shore-LIJ School of Medicine were collected. Repeat FNA and surgical follow-up data were tabulated to establish AUS, secondary AUS (diagnosed upon repeat FNA follow-up of a primary FNA AUS diagnosis), atypia of undetermined significance/malignancy (AUS:M) ratios (according to the TBS categories), and malignancy rates for AUS. The AUS rate was 8.5% (976/11,481), and there was follow-up data for 545 cases. The AUS:M ratio was 2.0. Repeat FNA was performed for 281 cases; 57 proceeded to surgical intervention. Repeat FNA reclassified 71.17% of the cases. The malignancy rates for AUS cases proceeding directly to surgery and for those receiving a surgical intervention after a repeat AUS diagnosis were 33.33% and 43.75%, respectively. Repeat FNA resulted in definitive diagnostic reclassification for 67.61% of primary AUS cases and reduced the number of patients triaged to surgery, with 56.58% of the cases recategorized as benign. Cases undergoing surgery after repeat AUS had a higher malignancy rate than those going straight to surgery, and this emphasizes the value of repeat FNA in selecting surgical candidates. In addition, this study highlights the utility of AUS rate monitoring as a quality measure that has contributed to the ability of the Hofstra North Shore-LIJ School of Medicine to adhere closely to TBS recommendations. © 2016 American Cancer Society.

Gender disparities in the assessment and management of cardiovascular risk in primary care: the AusHEART study.

PubMed

Turnbull, Fiona; Arima, Hisatomi; Heeley, Emma; Cass, Alan; Chalmers, John; Morgan, Claire; Patel, Anushka; Peiris, David; Weekes, Andrew; Anderson, Craig

2011-06-01

Studies indicate ongoing gender-based differences in the prevention, detection and management of cardiovascular disease. The aims of this study were to determine whether there are differences in general practitioners' (GPs') perceptions of a patient's cardiovascular risk compared with the patient's estimated risk and in the patient's subsequent medical management according to patient sex. The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey among 322 GPs. Each GP was asked to collect data on cardiovascular disease risk factors and their management in 15-20 consecutive patients (age ≥55 years) who presented between April and June, 2008. They were also asked to estimate each patient's absolute risk of a cardiovascular event in the next five years. The main outcomes were the Adjusted Framingham risk, GP estimated risk and proportion of patients receiving blood pressure-lowering, statin and antiplatelet therapy. A total of 5293 patients were recruited to the study, of whom 2968 (56%) were women. Among patients without established cardiovascular disease, the level of agreement between the GP estimated risk and the Adjusted Framingham risk was poor (<50%) and was similarly so for men (kappa coefficient 0.18; 95% confidence interval (CI) 0.14-0.21) and women (0.19; 95% CI 0.16-0.22; P homogeneity = 0.57). For patients with established cardiovascular disease, however, women were more likely to be assigned by the GP to a lower risk category (66% vs. 54%, P < 0.001) and less likely to be prescribed combination (blood pressure-lowering, statin and antiplatelet) (44% vs. 56%, P < 0.001) therapy compared with men, even after adjusting for patient age. Cardiovascular risk is underrecognized and undertreated in Australian primary care patients, with women apparently disproportionately affected. These findings underscore the importance of initiatives to raise awareness of

Update zum klinischen Einsatz von Inhibitoren mutierter Phosphokinasen beim Melanom.

PubMed

Cosgarea, Ioana; Ritter, Cathrin; Becker, Jürgen C; Schadendorf, Dirk; Ugurel, Selma

2017-09-01

Die Behandlungsstrategie beim metastasierten Melanom hat sich mit der Identifizierung therapeutisch angreifbarer molekularer Zielstrukturen innerhalb zellulärer Signalwege radikal geändert. Durch die Zulassung von Substanzen, die gezielt an den zentralen Schaltmolekülen, den Phosphokinasen, angreifen, können diese Signalwege selektiv abgeschaltet werden. Dies ist insbesondere bei denjenigen Tumoren von Interesse, deren Signalwege durch aktivierende Mutationen der für die Schaltmoleküle kodierenden Gene konstitutiv aktiviert sind. Aktuell ist diese therapeutische Strategie insbesondere für Patienten bedeutsam, deren Melanome eine Mutation im BRAF-Gen aufweisen. Diese Patienten können durch eine Kombinationstherapie aus Inhibitoren der Phosphokinasen BRAF und MEK langfristig mit sehr guter Krankheitskontrolle behandelt werden. Unter dieser Kombinationstherapie wird aktuell ein progressionsfreies Überleben von über zehn Monaten und ein Gesamtüberleben von mehr als zwei Jahren bei guter Lebensqualität erzielt. Da unter längerfristiger Therapie mit Kinaseinhibitoren jedoch bei einem Großteil der Patienten eine Resistenzbildung auftritt, sind aktuelle klinische Therapiestudien auf die Suche nach geeigneten Kombinationspartnern unter Blockierung anderer Signalwege oder unter Aktivierung der T-Zell-vermittelten Immunantwort ausgerichtet. Der vorliegende Übersichtsartikel stellt sowohl die aktuell verfügbaren als auch die in der klinischen Testung befindlichen zukünftigen Optionen der zielgerichteten Therapie des Melanoms dar. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Erhöhtes Lungenkrebs-Risiko bei Ekzempatienten: eine landesweite Kohortenstudie in Taiwan.

PubMed

Juan, Chao-Kuei; Shen, Jui-Lung; Lin, Cheng-Li; Kim, Karen Wang; Chen, Wen-Chi

2016-09-01

Der Zusammenhang zwischen Lungenkrebs und Ekzemen bleibt umstritten. Frühere Studien haben zu widersprüchlichen Ergebnissen geführt. Diese retrospektive populationsbasierte Kohortenstudie zielt darauf ab, das Risiko von Lungenkrebs im Zusammenhang mit Ekzemen abzuklären. In der Forschungsdatenbank der taiwanesischen nationalen Krankenversicherung identifizierten wir 43719 Patienten, bei denen in den Jahren 2000 bis 2010 ein Ekzem neu diagnostiziert wurde. Die Vergleichskohorte bildeten 87438 zufällig ausgewählte, altersangepasste Patienten ohne Ekzem. Die Fälle aus diesen beiden Kohorten wurden bis 2011 verfolgt. Zur Kalkulation des Lungenkrebsrisikos bei Ekzempatienten wurde die Cox-Regression verwendet. Die Datenbank enthielt keine Informationen über Raucherstatus, Alkoholkonsum, sozioökonomischen Status oder Familienanamnese. Nach der Bereinigung um Alter und Komorbidität hatte die Population mit Ekzemen ein um 2,80 erhöhtes Risiko für die Entwicklung von Lungenkrebs gegenüber der Vergleichskohorte (bereinigte Hazard-Ratio 2,80, 95 % Konfidenzinterval 2,59-3,03). Ekzempatienten mit Begleiterkrankungen, darunter Asthma, chronisch obstruktive Lungenerkrankungen, alkoholbedingten Leberschäden oder Diabetes, hatten ein höheres Lungenkrebsrisiko als Patienten ohne Ekzeme oder Komorbidität. Ekzeme gehen mit einem höheren Risiko für die Entwicklung von Lungenkrebs einher. Weitere Studien mit umfassenderen Informationen über weitere potentielle Einflussfaktoren sind sinnvoll. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)

PubMed Central

Boughey, Judy C.; Ballman, Karla V.; Hunt, Kelly K.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Le-Petross, Huong T.

2015-01-01

Purpose The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients and Methods Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Results Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. Conclusion AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. PMID:25646192

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).

PubMed

Boughey, Judy C; Ballman, Karla V; Hunt, Kelly K; McCall, Linda M; Mittendorf, Elizabeth A; Ahrendt, Gretchen M; Wilke, Lee G; Le-Petross, Huong T

2015-10-20

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. © 2015 by American Society of Clinical Oncology.

Artificial urinary sphincter

PubMed Central

Martins, Francisco E.

2017-01-01

Although currently still the gold standard treatment for post-prostatectomy urinary incontinence, the artificial urinary sphincter (AUS) (AMS800) is an invasive procedure with associated risks factors. In this paper, we aim to outline what the scientific literature and what we personally believe are the factors that are useful and/or necessary to mitigate these risks, including both patient factors and surgeon factors. We also review special populations, including transcorporal (TC) AUS approach, AUS with inflatable penile prosthesis, AUS after male urethral sling, AUS erosion management, and AUS after orthotopic urinary diversion. PMID:28904901

Metabolic remodeling triggered by salivation and diabetes in major salivary glands.

PubMed

Nogueira, Fernando N; Carvalho, Rui A

2017-02-01

The metabolic profile of major salivary glands was evaluated by 13 C nuclear magnetic resonance isotopomer analysis ( 13 C NMR-IA) following the infusion of [U- 13 C]glucose in order to define the true metabolic character of submandibular (SM) and parotid (PA) glands at rest and during salivary stimulation, and to determine the metabolic remodeling driven by diabetes. In healthy conditions, the SM gland is characterized at rest by a glycolytic metabolic profile and extensive pyruvate cycling. On the contrary, the PA gland, although also dominated by glycolysis, also possesses significant Krebs' cycle activity and does not sustain extensive pyruvate cycling. Under stimulation, both glands increase their glycolytic and Krebs' cycle fluxes, but the metabolic coupling between the two pathways is further compromised to account for the much increased biosynthetic anaplerotic fluxes. In diabetes, the responsiveness of the PA gland to a salivary stimulus is seriously hindered, mostly as a result of the incapacity to burst glycolytic activity and also an inability to improve the Krebs' cycle flux to compensate. The Krebs' cycle activity in the SM gland is also consistently compromised, but the glycolytic flux in this gland is more resilient. This diabetes-induced metabolic remodeling in SM and PA salivary glands illustrates the metabolic need to sustain adequate saliva production, and identifies glycolytic and oxidative pathways as key players in the metabolic dynamism of salivary glands. Copyright © 2016 John Wiley & Sons, Ltd.

Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism.

PubMed

Rowlands, Benjamin D; Lau, Chew Ling; Ryall, James G; Thomas, Donald S; Klugmann, Matthias; Beart, Philip M; Rae, Caroline D

2015-07-01

Silent information regulators (SIRTs) have been shown to deacetylate a range of metabolic enzymes, including those in glycolysis and the Krebs cycle, and thus alter their activity. SIRTs require NAD(+) for their activity, linking cellular energy status to enzyme activity. To examine the impact of SIRT1 modulation on oxidative metabolism, this study tests the effect of ligands that are either SIRT-activating compounds (resveratrol and SRT1720) or SIRT inhibitors (EX527) on the metabolism of (13)C-enriched substrates by guinea pig brain cortical tissue slices with (13)C and (1)H nuclear magnetic resonance spectroscopy. Resveratrol increased lactate labeling but decreased incorporation of (13)C into Krebs cycle intermediates, consistent with effects on AMPK and inhibition of the F0/F1-ATPase. By testing with resveratrol that was directly applied to astrocytes with a Seahorse analyzer, increased glycolytic shift and increased mitochondrial proton leak resulting from interactions of resveratrol with the mitochondrial electron transport chain were revealed. SRT1720, by contrast, stimulated incorporation of (13)C into Krebs cycle intermediates and reduced incorporation into lactate, although the inhibitor EX527 paradoxically also increased Krebs cycle (13)C incorporation. In summary, the various SIRT1 modulators show distinct acute effects on oxidative metabolism. The strong effects of resveratrol on the mitochondrial respiratory chain and on glycolysis suggest that caution should be used in attempts to increase bioavailability of this compound in the CNS. © 2015 Wiley Periodicals, Inc.

Spectrum of risk of malignancy in subcategories of 'atypia of undetermined significance'.

PubMed

Olson, Matthew T; Clark, Douglas P; Erozan, Yener S; Ali, Syed Z

2011-01-01

To determine if focal 'nuclear atypia' or 'microfollicular architecture' portends a higher risk of malignancy than other subcategories of atypia of undetermined significance (AUS) in thyroid fine-needle aspirations (FNAs). The frequencies of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories were calculated from 3,956 thyroid FNAs interpreted over a 26-month period at The Johns Hopkins Hospital after adoption of TBSRTC. TBSRTC criteria were applied strictly. The risk of malignancy, specifically for AUS subcategories, was analyzed by cyto-histo correlation. Of the 133 cases diagnosed as AUS, 32% were found to have stageable carcinoma (not incidental microcarcinoma) on resection. When the subset of AUS with 'nuclear atypia' (AUS-N) was separated from other AUS cases, 48% (30/62) of them had stageable carcinoma on resection; of the AUS subset with 'microfollicular architecture' (AUS-F), 27% (8/30) were malignant on resection. The 'suspicious for papillary thyroid carcinoma' (SPTC) group maintained a higher risk of malignancy versus AUS-N (relative risk, RR 1.57; 95% CI 1.23-1.81). The subcategory of 'nuclear atypia' within AUS indicates a higher risk of malignancy than other subcategories of AUS but has a lower risk of malignancy than SPTC does. Thus, it is an important distinction with potential clinical implications. Copyright © 2011 S. Karger AG, Basel.

State-dependent compound inhibition of Nav1.2 sodium channels using the FLIPR Vm dye: on-target and off-target effects of diverse pharmacological agents.

PubMed

Benjamin, Elfrida R; Pruthi, Farhana; Olanrewaju, Shakira; Ilyin, Victor I; Crumley, Gregg; Kutlina, Elena; Valenzano, Kenneth J; Woodward, Richard M

2006-02-01

Voltage-gated sodium channels (NaChs) are relevant targets for pain, epilepsy, and a variety of neurological and cardiac disorders. Traditionally, it has been difficult to develop structure-activity relationships for NaCh inhibitors due to rapid channel kinetics and state-dependent compound interactions. Membrane potential (Vm) dyes in conjunction with a high-throughput fluorescence imaging plate reader (FLIPR) offer a satisfactory 1st-tier solution. Thus, the authors have developed a FLIPR Vm assay of rat Nav1.2 NaCh. Channels were opened by addition of veratridine, and Vm dye responses were measured. The IC50 values from various structural classes of compounds were compared to the resting state binding constant (Kr)and inactivated state binding constant (Ki)obtained using patch-clamp electrophysiology (EP). The FLIPR values correlated with Ki but not Kr. FLIPRIC50 values fell within 0.1-to 1.5-fold of EP Ki values, indicating that the assay generally reports use-dependent inhibition rather than resting state block. The Library of Pharmacologically Active Compounds (LOPAC, Sigma) was screened. Confirmed hits arose from diverse classes such as dopamine receptor antagonists, serotonin transport inhibitors, and kinase inhibitors. These data suggest that NaCh inhibition is inherent in a diverse set of biologically active molecules and may warrant counterscreening NaChs to avoid unwanted secondary pharmacology.

The contributions of solar ultraviolet radiation exposure and other determinants to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD Study.

PubMed

Kimlin, Michael G; Lucas, Robyn M; Harrison, Simone L; van der Mei, Ingrid; Armstrong, Bruce K; Whiteman, David C; Kricker, Anne; Nowak, Madeleine; Brodie, Alison M; Sun, Jiandong

2014-04-01

The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation; 2) 10 days of personal ultraviolet radiation dosimetry; 3) a sun exposure and physical activity diary; and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration; modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)(2)) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.

A Reanalysis of the Need to Achieve and Its Relationship to Education. Theoretical Paper No. 42.

ERIC Educational Resources Information Center

Marliave, Richard

A review of the literature indicates that measures of the McClelland-Atkinson need-Achievement (nAch) construct are weak in terms of both reliability and validity. The most serious weakness of the model's validity is the lack of evidence for the hypothesized positive relationship between nAch and performance. In addition, the inverse relationship…

Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development.

PubMed

Heisenberg, C P; Brennan, C; Wilson, S W

1999-05-01

During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in which the expression of noi and ace is upregulated. In aus mutant embryos, ace is upregulated at many sites in the embryo, while noi expression is only upregulated in regions of the forebrain and midbrain which also express ace. Subsequent to the alterations in noi and ace expression, aus mutants exhibit defects in the differentiation of the forebrain, midbrain and eyes. Within the forebrain, the formation of the anterior and postoptic commissures is delayed and the expression of markers within the pretectal area is reduced. Within the midbrain, En and wnt1 expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth of neural retina in the temporal half of the eyes, whereas in putative homozygous aus embryos, the ventral retina is reduced and the pigmented retinal epithelium is expanded towards the midline. The observation that aus mutant embryos exhibit widespread upregulation of ace raised the possibility that aus might represent an allele of the ace gene itself. However, by crossing carriers for both aus and ace, we were able to generate homozygous ace mutant embryos that also exhibited the aus phenotype. This indicated that aus is not tightly linked to ace and is unlikely to be a mutation directly affecting the ace locus. However, increased Ace activity may underly many aspects of the aus phenotype and we show that the upregulation of noi in the forebrain of aus mutants is partially dependent upon functional Ace activity. Conversely, increased ace expression in the forebrain of aus mutants is not dependent upon functional Noi activity. We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis.

Genetic and molecular characterization of leaf rust resistance in two durum landraces against the durum- specific Puccinia triticina races

USDA-ARS?s Scientific Manuscript database

The Portuguese durum landraces, Aus26582 and Aus26579, showed resistance against two very different durum-specific Puccinia triticina (Pt) races CA 1.2 and ETH 12.5-2 collected from California and Ethiopia, respectively. Aus26582 and Aus26579 were crossed with a susceptible landrace Bansi to develop...

Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress

PubMed Central

Tretter, Laszlo; Adam-Vizi, Vera

2005-01-01

Alpha-ketoglutarate dehydrogenase (α-KGDH) is a highly regulated enzyme, which could determine the metabolic flux through the Krebs cycle. It catalyses the conversion of α-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain. α-KGDH is sensitive to reactive oxygen species (ROS) and inhibition of this enzyme could be critical in the metabolic deficiency induced by oxidative stress. Aconitase in the Krebs cycle is more vulnerable than α-KGDH to ROS but as long as α-KGDH is functional NADH generation in the Krebs cycle is maintained. NADH supply to the respiratory chain is limited only when α-KGDH is also inhibited by ROS. In addition being a key target, α-KGDH is able to generate ROS during its catalytic function, which is regulated by the NADH/NAD+ ratio. The pathological relevance of these two features of α-KGDH is discussed in this review, particularly in relation to neurodegeneration, as an impaired function of this enzyme has been found to be characteristic for several neurodegenerative diseases. PMID:16321804

The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology

PubMed Central

Dihge, Looket; Grabau, Dorthe A.; Rasmussen, Rogvi W.; Bendahl, Pär-Ola; Rydén, Lisa

2016-01-01

Abstract Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal metastatic burden and clinico-pathological characteristics. Material and methods The performance of AUS and AUS-guided FNAB for predicting nodal metastases was assessed in a prospective breast cancer cohort subjected for surgery during 2009–2012. Predictors of accuracy were included in multivariate analysis. Results AUS had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained 73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases (median four metastases) and identified patients with more extensive nodal metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were significant in the multivariate analysis. Conclusions The clinical utility of AUS in low-risk breast cancer deserves further evaluation as the accuracy decreased with a low nodal metastatic burden. The diagnostic performance is modified by tumor and clinical characteristics. Patients with nodal disease detected by AUS-FNAB represent a group for whom neoadjuvant therapy should be considered. PMID:27050668

Ustekinumab in der Therapie der Pustulosis palmoplantaris - Eine Fallserie mit neun Patienten.

PubMed

Buder, Valeska; Herberger, Katharina; Jacobi, Arnd; Augustin, Matthias; Radtke, Marc Alexander

2016-11-01

Die Pustulosis palmoplantaris ist eine chronisch entzündliche Hauterkrankung, die mit bedeutenden Einschränkungen der Lebensqualität und der Belastbarkeit einhergeht. Aufgrund von Zulassungsbeschränkungen und einem häufig therapierefraktären Verlauf sind die Behandlungsmöglichkeiten limitiert. Nach zuvor frustranen Therapien erhielten 9 Patienten mit Pustulosis palmoplantaris nach Ausschluss einer latenten Tuberkulose Ustekinumab (45 mg Ustekinumab bei < 100 kg Körpergewicht [KG], 90 mg Ustekinumab > 100 kg KG) in Woche 0, 4, 12 und 24. Reguläre Visiten erfolgten nach 4 und 12 Wochen, im weiteren Verlauf alle 12 Wochen. Das Durchschnittsalter bei Therapiebeginn betrug 48 Jahre. Drei Patienten waren männlich. Bei n  =  4 Patienten (44,4 %) wurde eine Verbesserung um 75 % des Palmoplantar-Psoriasis-Area-Severity-Index (PPPASI) erreicht. Insgesamt verbesserte sich der PPPASI nach 24 Wochen durchschnittlich um 71,6 %. Eine komplette Abheilung zeigte sich bei n  =  2 Patienten nach 24 Wochen. Bis auf lokale Injektionsreaktionen und leichte Infekte wurden keine unerwünschten Wirkungen beobachtet. Die Fallserie ist ein weiterer Beleg für die Wirksamkeit und Verträglichkeit von Ustekinumab in der Therapie der Pustulosis palmoplantaris. Zur Beurteilung der Langzeitwirkung und -sicherheit sowie der Wirksamkeit einer intermittierenden Therapie sind kontrollierte Studiendaten sowie Beobachtungen im Rahmen von Patientenregistern notwendig. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer.

PubMed

Assing, Matthew A; Patel, Bhavika K; Karamsadkar, Neel; Weinfurtner, Jared; Usmani, Omar; Kiluk, John V; Drukteinis, Jennifer S

2017-11-01

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI-RADS criteria as "suspicious" or "not suspicious" for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false-negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS. © 2017 Wiley Periodicals, Inc.

AMANDA and D0 as a Test Environment for the LHC Computing Grid (in German)

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

Harenberg, Torsten

2005-08-01

Die Suche nach den Grundbausteinen der Materie und nach den Kräften, die zwischen ihnen wirken, ist das Forschungsgebiet der Hochenergiephysik. Mit immer größer werdenden Teilchenbeschleunigern erreicht man immer tiefer gehende Erkenntnisse und dringt dabei in Energiebereiche vor, wie sie kurz nach dem Urknall herrschten. Im Moment ist das Tevatron am Fermilab der energ piereichste Teilchenbeschleuniger der Welt mit einer Schwerpunktsenergie von √s = 1, 96 TeV. Um die bei diesen hohen Energien entstehende Anzahl von Teilchen zu messen, sind auch immer höher auflösende Detektoren nötig. Dem wurde dadurch Rechnung getragen, dass mit der Steigerung der Schwerpunktsenergie am Tevatron auch diemore » Detektoren DØ und CDF1) teilweise erneuert wurden.« less

Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients with Early Stage Breast Cancer

PubMed Central

Tucker, Natalia S.; Cyr, Amy E.; Ademuyiwa, Foluso O.; Tabchy, Adel; George, Krystl; Sharma, Piyush; Jin, Linda X.; Sanati, Souzan; Aft, Rebecca; Gao, Feng; Margenthaler, Julie A.; Gillanders, William E.

2016-01-01

Objective Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. Background Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1–T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. Methods Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by two independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. Results 647 patients with clinical T1–T2, N0 breast cancer underwent AUS between January, 2008 and March, 2013. AUS had a sensitivity of 70%, NPV of 84% and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (> 2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. Conclusions AUS accurately excludes clinically significant ALN disease in patients with clinical T1–T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions. PMID:26779976

[Osteopathie bei gastroösophagealem Reflux mit Hiatushernie: Ein Fallbericht gemäß der CARE-Leitlinie].

PubMed

Rotter, Gabriele; Brinkhaus, Benno

2017-01-01

Hintergrund: Das Vorhandensein einer Hiatushernie kann das Auftreten einer gastroösophagealen Refluxerkrankung (GERD) als Komplikation bedingen. Konventionelle medizinische Therapiemaßnahmen können zu unerwünschten Ereignissen und Rezidiven führen. Bisher sind die Effekte von osteopathischen Behandlungen bei Hiatushernie und GERD nicht bekannt. Fallbericht: Eine 59-jährige Patientin mit endoskopisch diagnostizierter chronischer Gastritis, GERD und Hiatushernie beklagte einen persistierenden gastroösophagealen Reflux trotz konventionell-medizinischer konservativer Therapie. Die osteopathische Diagnostik ergab eine funktionelle Störung im Bereich des Magens und der Kardia mit einer Beteiligung zugehöriger Reflexzonen. Nach einer osteopathischen Behandlung als individuelle, befundorientierte Therapie ließen die Beschwerden erheblich nach. Die Hiatushernie war nach einer dieser Behandlung endoskopisch nicht mehr nachweisbar. Schlussfolgerungen: Dieser Fallbericht schildert die Symptomreduktion einer GERD nach osteopathischer Behandlung. In der endoskopischen Folgeuntersuchung fand sich die initial diagnostizierte Hiatushernie nicht mehr, diese Befund änderung könnte jedoch auf die unterschiedlichen Untersucher zurückgeführt werden. Prospektive kontrollierte klinische Studien sind notwendig, um den Stellenwert von osteopathischen Behandlungen bei GERD mit Hiatushernie zu untersuchen. © 2017 The Author(s). Published by S. Karger GmbH, Freiburg.

Menthol Binding and Inhibition of α7-Nicotinic Acetylcholine Receptors

PubMed Central

Ashoor, Abrar; Nordman, Jacob C.; Veltri, Daniel; Yang, Keun-Hang Susan; Al Kury, Lina; Shuba, Yaroslav; Mahgoub, Mohamed; Howarth, Frank C.; Sadek, Bassem; Shehu, Amarda; Kabbani, Nadine; Oz, Murat

2013-01-01

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl− channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing Ba2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [125I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner. PMID:23935840

Indications for axillary ultrasound use in breast cancer patients.

PubMed

Joh, Jennifer E; Han, Gang; Kiluk, John V; Laronga, Christine; Khakpour, Nazanin; Lee, M Catherine

2012-12-01

Axillary ultrasound has been adopted for preoperative planning in breast cancer. Our objective was to determine features predictive of abnormal AUS and/or positive axillary node needle biopsy (NBx). Single-institution database of breast cancer patients identified patients with preoperative AUS. Patient characteristics and outcomes were correlated with AUS and NBx. Significant features were identified using univariable and multivariable analysis and correlative statistics. Three hundred thirteen breast cancers were evaluated. Abnormal AUS was demonstrated in 250 cases (80%). Node needle biopsy was performed in 247 cases (79%). Sensitivity and specificity was 93% and 48% for AUS and 86% and 100% for NBx, respectively. Palpable axillary adenopathy was significant in logistic regression model (P < .05). There were positive correlations between tumor grade, clinical T and tumor-node-metastasis stage, invasive ductal carcinoma histology, and inflammatory breast carcinoma with AUS and NBx (P < .05). Clinicopathologic features (grade, histology, tumor size) might help guide judicious use of AUS. Copyright © 2012 Elsevier Inc. All rights reserved.

Lifetime cost of stroke subtypes in Australia: findings from the North East Melbourne Stroke Incidence Study (NEMESIS).

PubMed

Dewey, Helen M; Thrift, Amanda G; Mihalopoulos, Cathy; Carter, Robert; Macdonell, Richard A L; McNeil, John J; Donnan, Geoffrey A

2003-10-01

Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes. A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used. The present value of total lifetime costs for all strokes was Aus 1.3 billion dollars (US 985 million dollars). Total lifetime costs were greatest for ischemic stroke (72%; Aus 936.8 million dollars; US 709.7 million dollars), followed by intracerebral hemorrhage (26%; Aus 334.5 million dollars; US 253.4 million dollars) and unclassified stroke (2%; Aus 30 million dollars; US 22.7 million dollars). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus 28 266 dollars). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus 73 542 dollars), followed by total anterior circulation infarction (Aus 53 020 dollars), partial anterior circulation infarction (Aus 50 692 dollars), posterior circulation infarction (Aus 37 270 dollars), lacunar infarction (Aus 34 470 dollars), and unclassified stroke (Aus 12 031 dollars). First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.

Impaired mitochondrial energy metabolism in Alzheimer's disease: Impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape.

PubMed

Salminen, Antero; Haapasalo, Annakaisa; Kauppinen, Anu; Kaarniranta, Kai; Soininen, Hilkka; Hiltunen, Mikko

2015-08-01

The amyloid cascade hypothesis for the pathogenesis of Alzheimer's disease (AD) was proposed over twenty years ago. However, the mechanisms of neurodegeneration and synaptic loss have remained elusive delaying the effective drug discovery. Recent studies have revealed that amyloid-β peptides as well as phosphorylated and fragmented tau proteins accumulate within mitochondria. This process triggers mitochondrial fission (fragmentation) and disturbs Krebs cycle function e.g. by inhibiting the activity of 2-oxoglutarate dehydrogenase. Oxidative stress, hypoxia and calcium imbalance also disrupt the function of Krebs cycle in AD brains. Recent studies on epigenetic regulation have revealed that Krebs cycle intermediates control DNA and histone methylation as well as histone acetylation and thus they have fundamental roles in gene expression. DNA demethylases (TET1-3) and histone lysine demethylases (KDM2-7) are included in the family of 2-oxoglutarate-dependent oxygenases (2-OGDO). Interestingly, 2-oxoglutarate is the obligatory substrate of 2-OGDO enzymes, whereas succinate and fumarate are the inhibitors of these enzymes. Moreover, citrate can stimulate histone acetylation via acetyl-CoA production. Epigenetic studies have revealed that AD is associated with changes in DNA methylation and histone acetylation patterns. However, the epigenetic results of different studies are inconsistent but one possibility is that they represent both coordinated adaptive responses and uncontrolled stochastic changes, which provoke pathogenesis in affected neurons. Here, we will review the changes observed in mitochondrial dynamics and Krebs cycle function associated with AD, and then clarify the mechanisms through which mitochondrial metabolites can control the epigenetic landscape of chromatin and induce pathological changes in AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistivity Changes Due to Precipitation Effects in Fibre Reinforced Mg-Al-Zn-Mn Alloy

NASA Astrophysics Data System (ADS)

Kiehn, J.; Kainer, K. U.; Vostrý, P.; Stulíková, I.

1997-05-01

The change of electrical properties of alumina short fibre reinforced Mg-Al-Zn-Mn alloy AZ91D during isochronal annealing up to 300 °C is discussed. The Saffil® fibres were incorporated into the magnesium alloy by direct squeeze casting. The fibre distribution is random planar parallel to the flat faces of the dc four-point resistivity specimens machined from the solution treated castings. A sharp drop of resistivity between 140 and 260 °C is explained by the formation of incoherent -phase particles. Some practical recommendations concerning the use of alumina short fibre reinforced AZ91 alloy are made on the basis of the results obtained. Es werden die Änderungen der elektrischen Eigenschaften der aluminiumoxid-kurzfaserverstärkten Mg-Al-Zn-Mn Legierung AZ91D während isochroner Wärmebehandlungen bis 300 °C diskutiert. Das direkte Preßgießverfahren diente zur Herstellung der Saffil®-Faser Magnesium Verbundwerkstoffe. Die Proben zur Widerstandsmessung nach der Vier-Punkt Methode wurden durch spanende Bearbeitung aus den lösungsgeglühten Preßgußstücken herausgearbeitet, so daß sie regellose Faserverteilung in den Ebenen parallel zu den flachen Probenseiten aufwiesen. Ein starker Abfall des elektrischen Widerstands im Temperaturbereich zwischen 140 und 260 °C wird durch die Bildung inkohärenter β-Phase erklärt. Auf Grundlage der Ergebnisse werden einige Empfehlungen zur Anwendung der kurzfaserverstärkten Legierung AZ91 gegeben.

Crystallization and preliminary crystallographic analysis of latent, active and recombinantly expressed aurone synthase, a polyphenol oxidase, from Coreopsis grandiflora

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

Molitor, Christian; Mauracher, Stephan Gerhard; Rompel, Annette, E-mail: annette.rompel@univie.ac.at

2015-05-22

Latent and active aurone synthase purified from petals of C. grandiflora (cgAUS1) were crystallized. The crystal quality of recombinantly expressed latent cgAUS1 was significantly improved by co-crystallization with the polyoxotungstate Na{sub 6}[TeW{sub 6}O{sub 24}] within the liquid–liquid phase-separation zone. Aurone synthase (AUS), a member of a novel group of plant polyphenol oxidases (PPOs), catalyzes the oxidative conversion of chalcones to aurones. Two active cgAUS1 (41.6 kDa) forms that differed in the level of phosphorylation or sulfation as well as the latent precursor form (58.9 kDa) were purified from the petals of Coreopsis grandiflora. The differing active cgAUS1 forms and themore » latent cgAUS1 as well as recombinantly expressed latent cgAUS1 were crystallized, resulting in six different crystal forms. The active forms crystallized in space groups P2{sub 1}2{sub 1}2{sub 1} and P12{sub 1}1 and diffracted to ∼1.65 Å resolution. Co-crystallization of active cgAUS1 with 1,4-resorcinol led to crystals belonging to space group P3{sub 1}21. The crystals of latent cgAUS1 belonged to space group P12{sub 1}1 and diffracted to 2.50 Å resolution. Co-crystallization of recombinantly expressed pro-AUS with the hexatungstotellurate(VI) salt Na{sub 6}[TeW{sub 6}O{sub 24}] within the liquid–liquid phase separation zone significantly improved the quality of the crystals compared with crystals obtained without hexatungstotellurate(VI)« less

Lithospheric scale conductivity anomalies at the Proterozoic-Phanerozoic transition of Australia- Insights from AusLAMP MT data

NASA Astrophysics Data System (ADS)

Robertson, K. E.; Thiel, S.; Heinson, G. S.

2017-12-01

The intraplate deformation of the north-south trending Neoproterozoic Ikara-Flinders Ranges in South Australia, Australia, draws interest due to its high heat flow, elevated seismicity and the presence of diamondiferous kimberlites and mineral deposits. To the west lies the highly prospective Archean-Paleoproterozoic Gawler Craton, boasting the world's largest IOCG-U deposit, Olympic Dam. The Paleo-Mesoproterozoic Curnamona Province lies to the east, thought to have once been connected to the Gawler Craton and host to the world-class Broken Hill Ag-Pb-Zn deposit. A total of 162 long-period (10 s - 10,000 s) magnetotelluric (MT) stations from the Australia-wide AusLAMP (Australian Lithospheric Architecture Magnetotelluric Project) dataset were used to image the electrical resistivity beneath the Ikara-Flinders Ranges and adjacent Curnamona Province. The most recent acquisition extends this survey region northward to an area predominantly covered with Paleo-Mesozoic sedimentary basins including the most significant on-shore oil and gas region in Australia, the Cooper Basin. The resultant model from 3D inversions using ModEM software shows a relatively resistive Ikara-Flinders Ranges, with two parallel arcuate conductors (the WNAC and ENAC) at 20 to 80 km depth in the Nackara Arc. These conductors correlate well with locations of diamondiferous kimberlites which suggests that the conductors may have derived from the ascent of carbon-rich kimberlite-hosting magma and volatiles up large lithospheric scale structures. The conductors appear to have no correlation with regions of intraplate seismicity within the Ikara-Flinders Ranges which may mean that enhanced pore fluid pressure is not the main cause for the seismicity as was recently proposed. A large conductor covering most of the Curnamona Province (the CC) extends over depths of 10-40 km. The Curnamona Province's most recent tectonothermal activity is from Delamerian reworking during the Cambrian at its margins but

Novel management approach to connecting tube erosion of artificial urinary sphincter.

PubMed

Boateng, Akwasi A; Mohamed, Mahmoud A; Mahdy, Ayman E

2014-04-01

Artificial urinary sphincter (AUS) erosion often involve the urethral cuff and is managed by complete or partial device removal. Abdominal wall erosion of AUS tubing has not been previously reported and its management is unknown. We report tube erosion (TE) of AUS successfully managed without device explant. An 81-year-old male with AUS for post-prostatectomy incontinence presented with TE at the site of inguinal incision without signs or symptoms of infection. The exposed tube was reduced and wound was closed after copious antibiotic solution irrigation. No complications were noted at 2 month follow up. AUS-TE can be successfully managed conservatively with antiseptic wound site irrigation and reinsertion in absence of infection.

Thyroid cytopathology with an emphasis on the 'atypical cells of uncertain significance' category: a 3-year audit with cytohistologic correlation.

PubMed

Fatman, Luvo; Michelow, Pamela

2015-01-01

The National Cancer Institute meeting of 2007 resulted in the reporting terminology for thyroid cytopathology. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) aims to standardise thyroid cytopathology reporting for cytology centres and clinicians alike. To compare our laboratory's performance against TBSRTC. The second aim was to determine our laboratory's atypia of undetermined significance/follicular cells of undetermined significance (AUS/FLUS) reporting rate and malignant outcomes. Our laboratory subclassifies the AUS/FLUS category into AUS/FLUS not otherwise specified (NOS) and AUS/FLUS cannot exclude malignancy. All thyroid reports were retrieved from our computerised database for the period of January 1, 2008 to March 31, 2011. Histologic correlation was obtained where available, and cases were classified according to their original diagnosis into 1 of the 6 categories of TBSRTC. A total of 1,767 cases were retrieved. The categories were as follows: inadequate (n=415; 23%), benign (n=1,063; 60%), AUS/FLUS (n=141; 8%) [NOS (n=93; 5%) and cannot exclude malignancy (n=48; 3%)] suspicious for follicular/Hürthle cell neoplasm (n=68; 4%), suspicious for malignancy (n=37; 2%) and malignant (n=43; 2%). The malignant rates for the categories were as follows: -6 (26%), 0 (0%), 8 (40%), 9 (38%), 11 (42%), 15 (62.5%), and 15 (94%), respectively. We have shown that the AUS category carries a higher malignant rate than that of the AUS category in TBSRTC of 5-15%. We conclude that subclassifying the AUS/FLUS category into NOS and cannot exclude malignancy helps to better identify patients with an increased risk of malignancy in the AUS/FLUS cannot exclude malignancy category. © 2015 S. Karger AG, Basel.

Ecological relevance of current water quality assessment unit designations in impaired rivers

USGS Publications Warehouse

Layhee, Megan J.; Sepulveda, Adam; Ray, Andrew; Mladenka, Greg; Van Every, Lynn

2016-01-01

Managers often nest sections of water bodies together into assessment units (AUs) to monitor and assess water quality criteria. Ideally, AUs represent an extent of waters with similar ecological, watershed, habitat and land-use conditions and no overlapping characteristics with other waters. In the United States, AUs are typically based on political or hydrologic boundaries rather than on ecologically relevant features, so it can be difficult to detect changes in impairment status. Our goals were to evaluate if current AU designation criteria of an impaired water body in southeastern Idaho, USA that, like many U.S. waters, has three-quarters of its mainstem length divided into two AUs. We focused our evaluation in southeastern Idaho's Portneuf River, an impaired river and three-quarters of the river is divided into two AUs. We described biological and environmental conditions at multiple reaches within each AU. We used these data to (1) test if variability at the reach-scale is greater within or among AUs and, (2) to evaluate alternate AU boundaries based on multivariate analyses of reach-scale data. We found that some biological conditions had greater variability within an AU than between AUs. Multivariate analyses identified alternative, 2- and 3-group, AUs that reduced this variability. Our results suggest that the current AU designations in the mainstem Portneuf River contain ecologically distinct sections of river and that the existing AU boundaries should be reconsidered in light of the ecological conditions measured at the reach scale. Variation in biological integrity within designated AUs may complicate water quality and biological assessments, influence management decisions or affect where monitoring or mitigation resources are directed.

Comparison of complication rates related to male urethral slings and artificial urinary sphincters for urinary incontinence: national multi-institutional analysis of ACS-NSQIP database.

PubMed

Alwaal, Amjad; Harris, Catherine R; Awad, Mohannad A; Allen, Isabel E; Breyer, Benjamin N

2016-10-01

Male stress urinary incontinence (SUI) can significantly diminish quality of life and lead to embarrassment and social withdrawal. Surgical therapies, such as male urethral slings and artificial urinary sphincters (AUS), are considered effective and safe treatments for male SUI. Our objective is to evaluate 30-day complications in patients undergoing male slings and AUS placement from a national multicenter database. Data from the American College of Surgeons National Surgical Quality of Improvement Program for 2008-2013 were used to identify patients who underwent male slings and AUS implantation. Trained coders abstracted complication data from the patient record independent of the surgical team. We compared 30-day postoperative complications for male slings and AUS. We examined the relationship between patient factors and complication rates for each procedure type. Overall, 1205 incontinence surgeries in men were identified: 597 male sling placements and 608 AUS implantations. Male sling placement had a lower 30-day postoperative complication rate compared to AUS (2.8 vs. 5.1 %, p = 0.046). Compared to AUS, male sling was associated with fewer urinary tract infections (0.3 vs. 2.0 %, p = 0.020) and return trips to the operating room (1.0 vs. 3.0 %, p < 0.001). Patients with higher BMI were more likely to have a complication, while age, race and Charlson comorbidity index were not associated with higher or lower complication rates. Complications rates for both male sling and AUS are low. Male sling is associated with a lower rate of complications than AUS. These findings allow for better patient perioperative counseling regarding 30-day perioperative complications.

Stress urinary incontinence in female neurological patients: long-term functional outcomes after artificial urinary sphincter (AMS 800TM ) implantation.

PubMed

Phé, Véronique; Léon, Priscilla; Granger, Benjamin; Denys, Pierre; Bitker, Marc-Olivier; Mozer, Pierre; Chartier-Kastler, Emmanuel

2017-03-01

To report the long-term functional outcomes of artificial urinary sphincter (AUS) implantation in female adult neurological patients suffering from stress urinary incontinence (SUI) due to sphincter deficiency. Female patients with neurological disease suffering from SUI due to sphincter deficiency who underwent AUS (AMS 800 TM ) implantation between 1984 and 2011 were included. Continence rate defined as no need for pads and survival rates of the device without needing explantation or revision using Kaplan-Meier curves were reported. Overall, 26 patients, median age 49.2 years (IQR 28.5-59.7) were included. The median follow-up time was 7.5 years (IQR 3.9-23.8). At the end of follow-up period, 15 patients (57.7%) still had their primary AUS. The AUS was explanted in five women because of infection or erosion. Survival rates, without AUS explantation were 90%, 84%, 84%, and 74% at 5, 10, 15, 20 years, respectively. Survival rates without AUS revision were 75%, 51%, 51%, and 51% at 5, 10, 15, 20 years, respectively. 71.4% of patients with AUS were continent. When considering the 26 initial patients, including the patients in whom the AUS was explanted, the continence rate was 57.7%. For treating neurogenic sphincter deficiency in the long term, the AMS 800 TM can offer a satisfying rate of continence to female patients, with a tolerable rate of explantation and revision. Neurourol. Urodynam. 36:764-769, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Herstellung von Chitosan und einige Anwendungen

NASA Astrophysics Data System (ADS)

Struszczyk, Marcin Henryk

2001-05-01

1. Die Deacetylierung von crabshell - Chitosan führte gleichzeitig zu einem drastischen Abfall der mittleren viscosimetrischen Molmasse ( Mv), insbesondere wenn die Temperatur und die Konzentration an NaOH erhöht werden. Diese Parameter beeinflussten jedoch nicht den Grad der Deacetylierung (DD). Wichtig ist jedoch die Quelle des Ausgangsmaterials: Chitin aus Pandalus borealis ist ein guter Rohstoff für die Herstellung von Chitosan mit niedrigem DD und gleichzeitig hoher mittlerer Mv, während Krill-Chitin (Euphausia superba) ein gutes Ausgangsmaterial zur Herstellung von Chitosan mit hohem DD und niedrigem Mv ist. Chitosan, das aus Insekten (Calliphora erythrocephala), unter milden Bedingungen (Temperatur: 100°C, NaOH-Konzentration: 40 %, Zeit: 1-2h ) hergestellt wurde, hatte die gleichen Eigenschaften hinsichtlich DD und Mv wie das aus Krill hergestellte Chitosan. Der Bedarf an Zeit, Energie und NaOH ist für die Herstellung von Insekten-Chitosan geringer als für crabshell-Chitosan vergleichbare Resultaten für DD und Mv. 2. Chitosan wurde durch den Schimmelpilz Aspergillus fumigatus zu Chitooligomeren fermentiert. Die Ausbeute beträgt 25%. Die Chitooligomere wurden mit Hilfe von HPLC und MALDI-TOF-Massenspektrmetrie identifiziert. Die Fermentationsmischung fördert die Immunität von Pflanzen gegen Bakterien und Virusinfektion. Die Zunahme der Immunität schwankt jedoch je nach System Pflanze-Pathogen. Die Fermentation von Chitosan durch Aspergillus fumigatus könnte eine schnelle und billige Methode zur Herstellung von Chitooligomeren mit guter Reinheit und Ausbeute sein. Eine partiell aufgereinigte Fermentationsmischung dieser Art könnte in der Landwirtschaft als Pathogeninhibitor genutzt werden. Durch kontrollierte Fermentation, die Chitooligomere in definierter Zusammensetzung (d.h. definierter Verteilung des Depolymerisationsgrades) liefert, könnte man zu Mischungen kommen, die für die jeweilige Anwendung eine optimale Bioaktivität besitzen. 3

Evaluation of uterine ultrasound imaging in cervical radiotherapy; a comparison of autoscan and conventional probe

PubMed Central

Cooper, David T; Behrens, Claus F

2016-01-01

Objective: In cervical radiotherapy, it is essential that the uterine position is correctly determined prior to treatment delivery. The aim of this study was to evaluate an autoscan ultrasound (A-US) probe, a motorized transducer creating three-dimensional (3D) images by sweeping, by comparing it with a conventional ultrasound (C-US) probe, where manual scanning is required to acquire 3D images. Methods: Nine healthy volunteers were scanned by seven operators, using the Clarity® system (Elekta, Stockholm, Sweden). In total, 72 scans, 36 scans from the C-US and 36 scans from the A-US probes, were acquired. Two observers delineated the uterine structure, using the software-assisted segmentation in the Clarity workstation. The data of uterine volume, uterine centre of mass (COM) and maximum uterine lengths, in three orthogonal directions, were analyzed. Results: In 53% of the C-US scans, the whole uterus was captured, compared with 89% using the A-US. F-test on 36 scans demonstrated statistically significant differences in interobserver COM standard deviation (SD) when comparing the C-US with the A-US probe for the inferior–superior (p < 0.006), left–right (p < 0.012) and anteroposterior directions (p < 0.001). The median of the interobserver COM distance (Euclidean distance for 36 scans) was reduced from 8.5 (C-US) to 6.0 mm (A-US). An F-test on the 36 scans showed strong significant differences (p < 0.001) in the SD of the Euclidean interobserver distance when comparing the C-US with the A-US scans. The average Dice coefficient when comparing the two observers was 0.67 (C-US) and 0.75 (A-US). The predictive interval demonstrated better interobserver delineation concordance using the A-US probe. Conclusion: The A-US probe imaging might be a better choice of image-guided radiotherapy system for correcting for daily uterine positional changes in cervical radiotherapy. Advances in knowledge: Using a novel A-US probe might reduce the uncertainty in

Evaluation of uterine ultrasound imaging in cervical radiotherapy; a comparison of autoscan and conventional probe.

PubMed

Baker, Mariwan; Cooper, David T; Behrens, Claus F

2016-10-01

In cervical radiotherapy, it is essential that the uterine position is correctly determined prior to treatment delivery. The aim of this study was to evaluate an autoscan ultrasound (A-US) probe, a motorized transducer creating three-dimensional (3D) images by sweeping, by comparing it with a conventional ultrasound (C-US) probe, where manual scanning is required to acquire 3D images. Nine healthy volunteers were scanned by seven operators, using the Clarity(®) system (Elekta, Stockholm, Sweden). In total, 72 scans, 36 scans from the C-US and 36 scans from the A-US probes, were acquired. Two observers delineated the uterine structure, using the software-assisted segmentation in the Clarity workstation. The data of uterine volume, uterine centre of mass (COM) and maximum uterine lengths, in three orthogonal directions, were analyzed. In 53% of the C-US scans, the whole uterus was captured, compared with 89% using the A-US. F-test on 36 scans demonstrated statistically significant differences in interobserver COM standard deviation (SD) when comparing the C-US with the A-US probe for the inferior-superior (p < 0.006), left-right (p < 0.012) and anteroposterior directions (p < 0.001). The median of the interobserver COM distance (Euclidean distance for 36 scans) was reduced from 8.5 (C-US) to 6.0 mm (A-US). An F-test on the 36 scans showed strong significant differences (p < 0.001) in the SD of the Euclidean interobserver distance when comparing the C-US with the A-US scans. The average Dice coefficient when comparing the two observers was 0.67 (C-US) and 0.75 (A-US). The predictive interval demonstrated better interobserver delineation concordance using the A-US probe. The A-US probe imaging might be a better choice of image-guided radiotherapy system for correcting for daily uterine positional changes in cervical radiotherapy. Using a novel A-US probe might reduce the uncertainty in interoperator variability during ultrasound scanning.

Laparoscopic implantation of an artificial urinary sphincter around the prostatic urethra

PubMed Central

Chłosta, Piotr; Aboumarzouk, Omar; Bondad, Jasper; Szopiński, Tomasz; Korzelik, Ignacy; Borówka, Andrzej

2015-01-01

Objective To report the first laparoscopic periprostatic implantation of an artificial urinary sphincter (AUS) after a transurethral resection of the prostate. Background The implantation of an AUS is a standard procedure for severe urinary incontinence. In men it is usually implanted through a perineal approach, with the cuff placed around the bulbous urethra, bladder neck, or even around the prostate. Method We report a laparoscopic periprostatic implantation of an AUS after a transurethral resection of a prostate in a 72-year-old-man with incontinence. Results The operative duration was 180 min and the blood loss was 150 mL. There were no complications. After activating the AUS the patient was totally continent. Conclusion The laparoscopic periprostatic implantation of an AUS is a safe, effective and considerably less invasive procedure. PMID:26413345

Breast mass characterization using 3D automated ultrasound as an adjunct to digital breast tomosynthesis: A pilot study

PubMed Central

Padilla, Frederic; Roubidoux, Marilyn A.; Paramagul, Chintana; Sinha, Sumedha P.; Goodsitt, Mitchell M.; Le Carpentier, Gerald L.; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Fowlkes, Brian J.; Joe, Annette D.; Klein, Katherine A.; Nees, Alexis V.; Noroozian, Mitra; Patterson, Stephanie K.; Pinsky, Renee W.; Hooi, Fong Ming; Carson, Paul L.

2013-01-01

Objective To retrospectively evaluate the effect of 3D automated ultrasound (3D-AUS) as an adjunct to digital breast tomosynthesis (DBT) on radiologists’ performance and confidence in discriminating malignant and benign breast masses. Methods Two-view DBT (CC and MLO or Lateral) and single-view 3D-AUS were acquired on 51 patients with (subsequently) biopsy-proven masses (13 malignant, 38 benign). Six experienced radiologists rated, on a 13-point scale, the likelihood of malignancy of an identified mass, first by reading the DBT alone, followed immediately by reading the DBT with automatically co-registered 3D-AUS. The diagnostic performance of each method was measured using ROC analysis. and changes in sensitivity and specificity with the McNemar test. After each reading, radiologists took a survey to rate their confidence level in using DBT alone vs combined DBT/3D-AUS as potential screening modalities. Results The six radiologists had an average area under the ROC curve of 0.92 for both modalities (range 0.89–0.97 for DBT, 0.90–0.94 for DBT/3D-AUS). With BI-RADS rating of 4 as the threshold for biopsy recommendation, the average sensitivity of the radiologists increased from 96% to 100% (p>0.08) with 3D-AUS, while the specificity decreased from 33% to 25% (p>0.28). Survey responses indicated an increased confidence in potentially using DBT for screening when 3D-AUS was added (p<0.05 for each reader). Conclusions In this initial reader study, no significant difference in ROC performance was found with the addition of 3D-AUS to DBT. However, a trend to an improved discrimination of malignancy was observed when adding 3D-AUS. Radiologists’ confidence also improved with DBT/3DAUS compared to DBT alone. PMID:23269714

Survey of cytopathologists and cytotechnologists for the clinical impact of the use of atypia or follicular lesion of undetermined significance.

PubMed

Nassar, Aziza; Reynolds, Jordan P; Kerr, Sarah E; Jenkins, Sarah M; Lackore, Kandace A; Bernet, Victor

2015-01-01

The cytologic diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) is controversial because of variation in how it is applied in practice, as well as uncertainty about patient management. We aimed to assess the percentage of thyroid fine-needle aspiration biopsies (FNABs) with AUS/FLUS diagnoses in different North American and European practice settings (e.g. community, academic, etc.), assess whether patients were managed according to current guidelines, and determine patient outcomes. A detailed questionnaire survey was posted in secure websites used separately by cytopathologists and cytotechnologists. The questionnaire was posted from August 1 through December 31, 2013. Endocrinologists and cytopathologists performed 51.7% and 37.1% of thyroid FNABs, respectively. The Bethesda reporting system for thyroid FNAB was used in 90% of practices. The rate of AUS/FLUS varied widely among institutions, with 46.1% of represented institutions reporting AUS/FLUS rates of 3-10%. The median follow-up rate of patients with an initial AUS/FLUS diagnosis was 70% (range, 10-100%). For the majority of represented institutions (86.4%), patients with initial AUS/FLUS diagnosis had follow-up with endocrinologists. Of repeat AUS/FLUS thyroid FNABs, a median of 52% was considered benign, and 18% were suspicious of or positive for malignancy (median, 10% and 7.5%, respectively). Reporting of the AUS/FLUS category varied widely among different institutions. The median follow-up rate was lower than published guidelines. The most common follow-up diagnosis was benign thyroid nodule. Improved standardization of cytologic criteria should be adopted to reduce such variation.

Neuromuscular transmission failure in myasthenia gravis: decrement of safety factor and susceptibility of extraocular muscles.

PubMed

Serra, Alessandro; Ruff, Robert L; Leigh, Richard John

2012-12-01

An appropriate density of acetylcholine receptors (AChRs) and Na(+) channels (NaChs) in the normal neuromuscular junction (NMJ) determines the magnitude of safety factor (SF) that guarantees fidelity of neuromuscular transmission. In myasthenia gravis (MG), an overall simplification of the postsynaptic folding secondary to NMJ destruction results in AChRs and NaChs depletion. Loss of AChRs and NaChs accounts, respectively, for 59% and 40% reduction of the SF at the endplate, which manifests as neuromuscular transmission failure. The extraocular muscles (EOM) have physiologically less developed postsynaptic folding, hence a lower baseline SF, which predisposes them to dysfunction in MG and development of fatigue during "high performance" eye movements, such as saccades. However, saccades in MG show stereotyped, conjugate initial components, similar to normal, which might reflect preserved neuromuscular transmission fidelity at the NMJ of the fast, pale global fibers, which have better developed postsynaptic folding than other extraocular fibers. © 2012 New York Academy of Sciences.

AusEinetter, 2000.

ERIC Educational Resources Information Center

AusEinetter, 2000

2000-01-01

This document contains two issues of 2000 Australian Early Intervention Network for Mental Health in Young People newsletter. The newsletters disseminate information about the national and local initiatives for intervention and prevention of mental health problems in young children and youth. They also provide information on upcoming workshops and…

AusEinetter, 1998.

ERIC Educational Resources Information Center

AusEinetter, 1998

1998-01-01

This publication contains the 1998 issues of the Australian Early Intervention Network for Mental Health in Young People newsletters for health professionals. The newsletters disseminate information about the national and local initiatives for intervention and prevention of mental health problems in young children and youth. Each issue also offers…

Hardware-Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur

NASA Astrophysics Data System (ADS)

Flatt, H.; Tarnowsky, A.; Blume, H.; Pirsch, P.

2010-10-01

Dieser Beitrag behandelt die Abbildung eines videobasierten Verfahrens zur echtzeitfähigen Auswertung von Winkelhistogrammen auf eine modulare Coprozessor-Architektur. Die Architektur besteht aus mehreren dedizierten Recheneinheiten zur parallelen Verarbeitung rechenintensiver Bildverarbeitungsverfahren und ist mit einem RISC-Prozessor verbunden. Eine konfigurierbare Architekturerweiterung um eine Recheneinheit zur Auswertung von Winkelhistogrammen von Objekten ermöglicht in Verbindung mit dem RISC eine echtzeitfähige Klassifikation. Je nach Konfiguration sind für die Architekturerweiterung auf einem Xilinx Virtex-5-FPGA zwischen 3300 und 12 000 Lookup-Tables erforderlich. Bei einer Taktfrequenz von 100 MHz können unabhängig von der Bildauflösung pro Einzelbild in einem 25-Hz-Videodatenstrom bis zu 100 Objekte der Größe 256×256 Pixel analysiert werden. This paper presents the mapping of a video-based approach for real-time evaluation of angular histograms on a modular coprocessor architecture. The architecture comprises several dedicated processing elements for parallel processing of computation-intensive image processing tasks and is coupled with a RISC processor. A configurable architecture extension, especially a processing element for evaluating angular histograms of objects in conjunction with a RISC processor, provides a real-time classification. Depending on the configuration of the architecture extension, 3 300 to 12 000 look-up tables are required for a Xilinx Virtex-5 FPGA implementation. Running at a clock frequency of 100 MHz and independently of the image resolution per frame, 100 objects of size 256×256 pixels are analyzed in a 25 Hz video stream by the architecture.

Zu einer inhaltsorientierten Theorie des Lernens und Lehrens der biologischen Evolution

NASA Astrophysics Data System (ADS)

Wallin, Anita

Der Zweck dieser Studie (zwecks Überblick siehe dazu Abb. 9.1) war zu untersuchen, wie die Schüler der Sekundarstufe II ein Verständnis von der Theorie der biologischen Evolution entwickeln. Vom Ausgangspunkt "Vorurteile der Schüler“ ausgehend wurden Unterrichtssequenzen entwickelt und drei verschiedene Lernexperimente in einem zyklischen Prozess durchgeführt. Das Wissen der Schüler wurde vor, während und nach den Unterrichtssequenzen mit Hilfe von schriftlichen Tests, Interviews und Diskussionsrunden in kleinen Gruppen abgefragt. Etwa 80 % der Schüler hatten vor dem Unterricht alternative Vorstellungen von Evolution, und in dem Nachfolgetest erreichten circa 75 % ein wissenschaftliches Niveau. Die Argumentation der Schüler in den verschiedenen Tests wurde sorgfältig unter Rücksichtnahme auf Vorurteile, der konzeptionellen Struktur der Theorie der Evolution und den Zielen des Unterrichts analysiert. Daraus konnten Einsichten in solche Anforderungen an Lehren und Lernen gewonnen werden, die Herausforderungen an Schüler und Lehrer darstellen, wenn sie anfangen, evolutionäre Biologie zu lernen oder zu lehren. Ein wichtiges Ergebnis war, dass das Verständnis existierender Variation in einer Population der Schlüssel zum Verständnis von natürlicher Selektion ist. Die Ergebnisse sind in einer inhaltsorientierten Theorie zusammengefasst, welche aus drei verschiedenen Aspekten besteht: 1) den inhaltsspezifischen Aspekten, die einzigartig für jedes wissenschaftliche Feld sind; 2) den Aspekten, die die Natur der Wissenschaft betreffen; und 3) den allgemeinen Aspekten. Diese Theorie kann in neuen Experimenten getestet und weiter entwickelt werden.

Quantum Statistics of the Toda Oscillator in the Wigner Function Formalism

NASA Astrophysics Data System (ADS)

Vojta, Günter; Vojta, Matthias

Classical and quantum mechanical Toda systems (Toda molecules, Toda lattices, Toda quantum fields) recently found growing interest as nonlinear systems showing solitons and chaos. In this paper the statistical thermodynamics of a system of quantum mechanical Toda oscillators characterized by a potential energy V(q) = Vo cos h q is treated within the Wigner function formalism (phase space formalism of quantum statistics). The partition function is given as a Wigner- Kirkwood series expansion in terms of powers of h2 (semiclassical expansion). The partition function and all thermodynamic functions are written, with considerable exactness, as simple closed expressions containing only the modified Hankel functions Ko and K1 of the purely imaginary argument i with = Vo/kT.Translated AbstractQuantenstatistik des Toda-Oszillators im Formalismus der Wigner-FunktionKlassische und quantenmechanische Toda-Systeme (Toda-Moleküle, Toda-Gitter, Toda-Quantenfelder) haben als nichtlineare Systeme mit Solitonen und Chaos in jüngster Zeit zunehmend an Interesse gewonnen. Wir untersuchen die statistische Thermodynamik eines Systems quantenmechanischer Toda-Oszillatoren, die durch eine potentielle Energie der Form V(q) = Vo cos h q charakterisiert sind, im Formalismus der Wigner-Funktion (Phasenraum-Formalismus der Quantenstatistik). Die Zustandssumme wird als Wigner-Kirkwood-Reihe nach Potenzen von h2 (semiklassische Entwicklung) dargestellt, und aus ihr werden die thermodynamischen Funktionen berechnet. Sämtliche Funktionen sind durch einfache geschlossene Formeln allein mit den modifizierten Hankel-Funktionen Ko und K1 des rein imaginären Arguments i mit = Vo/kT mit großer Genauigkeit darzustellen.

Grundlegende Steuerungsverfahren im heterogenen Logistiknetz mit Kanban

NASA Astrophysics Data System (ADS)

Dickmann, Eva; Dickmann, Philipp; Lödding, Hermann; Möller, Niklas; Rücker, Thomas; Schneider, Herfried M.; Zäh, Michael F.

In vielen Unternehmen werden heterogene (verschiedene) Steuerungen in einem abgestimmten Konzept kombiniert. Je nach Anwendungsfall und Rahmenbedingungen werden Kombinationen allgemein bekannter Steuerungen oder Steuerungsvarianten gemischt eingesetzt, um eine optimale Steuerung für unterschiedliche Fälle zu erreichen. Hierbei stehen neben den bekannten und weit verbreiteten Methoden, wie Material Requirements Planning (MRP) oder Kanban, auch weniger bekannte oder neue Methoden zur Auswahl, wie die Produktionssteuerung mit dezentraler, bestandsorientierter Fertigungsregelung (DBF). Kanban ist ein simples und effizientes Steuerungskonzept, das in der klassischen Form für spezifische einfache Anwendungsfälle umsetzbar ist. Hochentwickelte Steuerungsalgorithmen können helfen, komplexe Abläufe optimal abzubilden. Mit einer grundlegenden Vereinfachung der Abläufe kann allerdings in vielen Fällen ein wesentlich stärkerer und umfassender Verbesserungseffekt erzielt werden. Die wesentliche Fragestellung sollte folglich lauten: Warum ist der Ablauf nicht mit einer einfachen Steuerung wie Kanban abzubilden? Um die Vorteile des Konzepts auch in untypischen Bereichen anwenden zu können, sind jedoch verschiedene Varianten oder Kanban-ähnliche Steuerungsmethoden entstanden. Darüber hinaus sind in der Praxis hybride Steuerungen im Einsatz, welche so kombiniert werden, dass die Zusammensetzung anspruchsvolle Eigenschaftsbilder noch exakt abbildet. In der Praxis basieren die Steuerungsentscheidungen nur zu einem kleinen Teil auf den eigentlichen Steuerungsalgorithmen, wie sie uns das MRP-System zur Verfügung stellt. Moderne Steuerungswelten" schließen alle relevanten Informationsquellen in eine heterogene Entscheidungsmatrix mit ein. Letztlich zählt nicht, ob die Entscheidung auf den Informationen aus dem MRP-System oder auf Softfacts basierend getroffen wurde, sondern nur, ob die Entscheidung erfolgreich war.

Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal.

PubMed

Mills, Evanna L; O'Neill, Luke A

2016-01-01

Mitochondria are master regulators of metabolism. Mitochondria generate ATP by oxidative phosphorylation using pyruvate (derived from glucose and glycolysis) and fatty acids (FAs), both of which are oxidized in the Krebs cycle, as fuel sources. Mitochondria are also an important source of reactive oxygen species (ROS), creating oxidative stress in various contexts, including in the response to bacterial infection. Recently, complex changes in mitochondrial metabolism have been characterized in mouse macrophages in response to varying stimuli in vitro. In LPS and IFN-γ-activated macrophages (M1 macrophages), there is decreased respiration and a broken Krebs cycle, leading to accumulation of succinate and citrate, which act as signals to alter immune function. In IL-4-activated macrophages (M2 macrophages), the Krebs cycle and oxidative phosphorylation are intact and fatty acid oxidation (FAO) is also utilized. These metabolic alterations in response to the nature of the stimulus are proving to be determinants of the effector functions of M1 and M2 macrophages. Furthermore, reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Here, we describe the role that metabolism plays in macrophage function in infection and immunity, and propose that reprogramming with metabolic inhibitors might be a novel therapeutic approach for the treatment of inflammatory diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reinstatement after human feature-positive discrimination learning.

PubMed

Franssen, Mathijs; Claes, Nathalie; Vervliet, Bram; Beckers, Tom; Hermans, Dirk; Baeyens, Frank

2017-04-01

In two experiments, using an online conditioned suppression task, we investigated the possibility of reinstatement of extinguished feature-target compound presentations after sequential feature-positive discrimination training in humans. Furthermore, given a hierarchical account of Pavlovian modulation (e.g., Bonardi, 1998; Bonardi and Jennings, 2009), we predicted A-US reinstatement to be stronger than US-only reinstatement. In Experiment 1, participants learned a sequential feature-positive discrimination (X→A + |A - ), which was subsequently extinguished (X→A - ). During the following reinstatement phase, group US-only received US-only presentations (not signalled), group A-US received A-US presentations, and the Control group received exposure to the context, but no CSs or USs, for an equal amount of time. Reinstatement of differential X→A/A responding was observed in the US-only group but not in the Control or A-US groups. Although differential X→A/A responding was not significant in group A-US, responding to the X→A compound was significantly stronger compared to that in group US-only. Hence, it could be the case the group A-US showed stronger reinstatement, but that differential responding was abolished due to excitation gained by A. Experiment 2 was set up to circumvent the acquired excitation of A by testing transfer of the feature after A-US reinstatement to a different target, B. Participants acquired two discriminations, X→A/A and Y→B/B, of which X→A was then extinguished. Subsequently, group A-US received reinforced presentations of A during a reinstatement phase while group Control received exposure to the context. Final testing of the novel X→B compound was hypothesized to show higher responding in group A-US than in group Control, but findings of this approach were limited due to acquired equivalence and/or perceptual factors causing a secondary extinction effect. We conclude to have obtained clear evidence in favour of

Management of the axilla in metaplastic breast carcinoma.

PubMed

Murphy, Brittany L; Fazzio, Robert T; Hoskin, Tanya L; Glazebrook, Katrina N; Keeney, Michael G; Habermann, Elizabeth B; Hieken, Tina J

2018-04-01

Metaplastic breast cancer (MBC), characterized by admixed epithelial, squamous or mesenchymal elements, constitutes <1% of breast cancers and has a poor prognosis but a paradoxically low reported rate of axillary lymph node (LN) involvement. Due to its rarity, data on appropriate axillary management is lacking, prompting this investigation of LN status and outcomes. We identified 41 MBC patients treated at our institution 2001-2011 who were followed for a median of 66 months. Statistical analyses evaluated axillary ultrasound (AUS), fine needle aspiration (FNA), and sentinel LN biopsy (SLNB) in association with LN status. Median tumor size was 2.7 cm and 76% were triple-negative. Twenty-three patients (56%) had preoperative AUS: 9 (39%) showed ≥1 suspicious LN, 6 proceeded to LN FNA and 3 were confirmed positive. Six patients had neoadjuvant chemotherapy, including 2 FNA LN+. Ten patients were LN+ at operation. Among 19 patients undergoing AUS and axillary surgery, AUS ± FNA sensitivity was 100% and specificity was 94%. LN positivity correlated with increasing tumor size, grade and angiolymphatic invasion. 16 patients recurred, 63% with distant disease (10/16) and one with isolated axillary disease after a negative SLNB not preceded by AUS. Overall SLNB accuracy was 96% (23/24), but absent preoperative AUS, 1/7 (14%) of SLNBs were falsely negative. Our study is the first to specifically address the performance and utility of AUS/FNA and SLNB for MBC patients. AUS/FNA at diagnosis followed by SLN surgery provided accurate nodal staging and critical prognostic information to inform treatment recommendations. We recommend this approach for axillary management of MBC patients.

Readiness of pharmacists and consumers for pharmacy-based chlamydia screening in Australia and Switzerland.

PubMed

Arnet, Isabelle; Gudka, Sajni; Salter, Sandra; Hersberger, Kurt E; Clifford, Rhonda

2018-06-01

To assess chlamydia knowledge, willingness to undertake pharmacy-based chlamydia testing, and facilitators and barriers to such testing in consumers and community pharmacists, in Australia (AUS) and Switzerland (CH). Statements of interest were retrieved from literature and assembled into a 12-item online survey (English and German versions). Survey was disseminated through Facebook, pharmacies' publicly available emails and professional websites (March 2015). Consumers and pharmacists (AUS: n cons  = 198, n pharm  = 162; CH: n cons  = 209, n pharm  = 223) were predominantly female (>65%). Mean chlamydia knowledge scores (maximum of 8) were higher in Australia in consumers (AUS: 6.8 ± 1.5 vs CH: 4.2 ± 2.4; p < 0.001) and in pharmacists (AUS: 7.1 ± 1.1 vs CH: 6.1 ± 1.4; p < 0.001). High willingness of consumers to seek testing (AUS: 79.3% vs CH: 83.3%, p = 0.3) and of pharmacists to provide testing (AUS: 95.7% vs CH: 80.3%, p < 0.001) was observed. Greatest barrier for consumers was "Embarrassed about asking for a test" (AUS: 47.8% vs CH: 51.2%, p = 0.7) and "No remuneration" for pharmacists (AUS: 40.7% vs CH: 31.8%, p = 0.07). The majority of consumers and pharmacists support pharmacy-based chlamydia testing. There is now emerging evidence that the policy makers in Australia and Switzerland need to develop pharmacy-based chlamydia testing as core business. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Survey of cytopathologists and cytotechnologists for the clinical impact of the use of atypia or follicular lesion of undetermined significance

PubMed Central

Nassar, Aziza; Reynolds, Jordan P.; Kerr, Sarah E.; Jenkins, Sarah M.; Lackore, Kandace A.; Bernet, Victor

2015-01-01

Background: The cytologic diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) is controversial because of variation in how it is applied in practice, as well as uncertainty about patient management. We aimed to assess the percentage of thyroid fine-needle aspiration biopsies (FNABs) with AUS/FLUS diagnoses in different North American and European practice settings (e.g. community, academic, etc.), assess whether patients were managed according to current guidelines, and determine patient outcomes. Materials and Methods: A detailed questionnaire survey was posted in secure websites used separately by cytopathologists and cytotechnologists. The questionnaire was posted from August 1 through December 31, 2013. Results: Endocrinologists and cytopathologists performed 51.7% and 37.1% of thyroid FNABs, respectively. The Bethesda reporting system for thyroid FNAB was used in 90% of practices. The rate of AUS/FLUS varied widely among institutions, with 46.1% of represented institutions reporting AUS/FLUS rates of 3–10%. The median follow-up rate of patients with an initial AUS/FLUS diagnosis was 70% (range, 10–100%). For the majority of represented institutions (86.4%), patients with initial AUS/FLUS diagnosis had follow-up with endocrinologists. Of repeat AUS/FLUS thyroid FNABs, a median of 52% was considered benign, and 18% were suspicious of or positive for malignancy (median, 10% and 7.5%, respectively). Conclusions: Reporting of the AUS/FLUS category varied widely among different institutions. The median follow-up rate was lower than published guidelines. The most common follow-up diagnosis was benign thyroid nodule. Improved standardization of cytologic criteria should be adopted to reduce such variation. PMID:26195986

Management of the axilla in metaplastic breast carcinoma

PubMed Central

Murphy, Brittany L.; Fazzio, Robert T.; Hoskin, Tanya L.; Glazebrook, Katrina N.; Keeney, Michael G.; Habermann, Elizabeth B.

2018-01-01

Background Metaplastic breast cancer (MBC), characterized by admixed epithelial, squamous or mesenchymal elements, constitutes <1% of breast cancers and has a poor prognosis but a paradoxically low reported rate of axillary lymph node (LN) involvement. Due to its rarity, data on appropriate axillary management is lacking, prompting this investigation of LN status and outcomes. Methods We identified 41 MBC patients treated at our institution 2001–2011 who were followed for a median of 66 months. Statistical analyses evaluated axillary ultrasound (AUS), fine needle aspiration (FNA), and sentinel LN biopsy (SLNB) in association with LN status. Results Median tumor size was 2.7 cm and 76% were triple-negative. Twenty-three patients (56%) had preoperative AUS: 9 (39%) showed ≥1 suspicious LN, 6 proceeded to LN FNA and 3 were confirmed positive. Six patients had neoadjuvant chemotherapy, including 2 FNA LN+. Ten patients were LN+ at operation. Among 19 patients undergoing AUS and axillary surgery, AUS ± FNA sensitivity was 100% and specificity was 94%. LN positivity correlated with increasing tumor size, grade and angiolymphatic invasion. 16 patients recurred, 63% with distant disease (10/16) and one with isolated axillary disease after a negative SLNB not preceded by AUS. Overall SLNB accuracy was 96% (23/24), but absent preoperative AUS, 1/7 (14%) of SLNBs were falsely negative. Conclusions Our study is the first to specifically address the performance and utility of AUS/FNA and SLNB for MBC patients. AUS/FNA at diagnosis followed by SLN surgery provided accurate nodal staging and critical prognostic information to inform treatment recommendations. We recommend this approach for axillary management of MBC patients. PMID:29770313

Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys

PubMed Central

Banks, Matthew L.; Smith, Douglas A.; Blough, Bruce E.

2016-01-01

The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate ‘agonist’ medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like ‘agonist’ effects remains unknown. The present aim was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. Potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, ≥90%, methamphetamine-like effects. 2R,3R-hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like ‘agonist’ effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

PubMed

Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

2016-04-01

The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out.

Risk Factors for Erosion of Artificial Urinary Sphincters: A Multicenter Prospective Study

PubMed Central

Brant, William O.; Erickson, Bradley A.; Elliott, Sean P.; Powell, Christopher; Alsikafi, Nejd; McClung, Christopher; Myers, Jeremy B.; Voelzke, Bryan B.; Smith, Thomas G.; Broghammer, Joshua A.

2015-01-01

OBJECTIVE To evaluate the short- to medium-term outcomes after artificial urinary sphincter (AUS) placement from a large, multi-institutional, prospective, follow-up study. We hypothesize that along with radiation, patients with any history of a direct surgery to the urethra will have higher rates of eventual AUS explantation for erosion and/or infection. MATERIALS AND METHODS A prospective outcome analysis was performed on 386 patients treated with AUS placement from April 2009 to December 2012 at 8 institutions with at least 3 months of follow-up. Charts were analyzed for preoperative risk factors and postoperative complications requiring explantation. RESULTS Approximately 50% of patients were considered high risk. High risk was defined as patients having undergone radiation therapy, urethroplasty, multiple treatments for bladder neck contracture or urethral stricture, urethral stent placement, or a history of erosion or infection in a previous AUS. A total of 31 explantations (8.03%) were performed during the follow-up period. Overall explantation rates were higher in those with prior radiation and prior UroLume. Men with prior AUS infection or erosion also had a trend for higher rates of subsequent explantation. Men receiving 3.5-cm cuffs had significantly higher explantation rates than those receiving larger cuffs. CONCLUSION This outcomes study confirms that urethral risk factors, including radiation history, prior AUS erosion, and a history of urethral stent placement, increase the risk of AUS explantation in short-term follow-up. PMID:25109562

75 FR 40736 - Acetic Acid; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... known as the citric acid (Ref. 1.) or krebs cycle (Ref. 2.), which is the chemical activity in all cells... as antibiotics, antibacterials and antimicrobials. Acetic acid is also the main acid in vinegars, and...

Bioindikation im Grundwasser funktioniert - Erwiderung zum Kommentar von T. Scheytt zum Beitrag "Grundwasserfauna als Indikator für komplexe hydrogeologische Verhältnisse am westlichen Kaiserstuhl" von Gutjahr, S., Bork, J. & Hahn, H.J. in Grundwasser 18 (3), 173-184 (2013)

NASA Astrophysics Data System (ADS)

Hahn, Hans Jürgen; Gutjahr, Simon

2014-09-01

In seinem Kommentar schließt Traugott Scheytt die faunistische Bioindikation über die Nutzung von Grundwassermessstellen aus methodischen Gründen aus. Er postuliert auch, dass die faunistische Indikation hydrogeologischer Zusammenhänge wegen der eingeschränkten Ausbreitungsfähigkeit der Tiere in Porengrundwasserleitern nicht möglich sei und stellt grundsätzlich die Befunde unserer Untersuchungen am Kaiserstuhl in Frage. Dabei überträgt Herr Scheytt seine Erfahrungen aus der unbelebten Hydrogeologie direkt auf den Lebensraum Grundwasser. Seine Argumentation berücksichtigt dabei weder die Prinzipien der Ökologie noch den aktuellen Stand der grundwasserökologischen Forschung. Wir gehen davon aus, dass für die Untersuchungen am Kaiserstuhl sowohl unsere Arbeitshypothese wie auch die angewandten Methoden und die Interpretation der Ergebnisse der Fragestellung angemessen sind und internationalem, wissenschaftlichem Standard entsprechen. Aus den oben benannten Gründen bleiben wir dabei: Biondikation im Grundwasser funktioniert und sie bietet hervorragende Möglichkeiten, gerade auch für die Hydrogeologie.

Differences in utilisation of gastroprotective drugs between 2001 and 2005 in Australia and Nova Scotia, Canada.

PubMed

Tett, Susan E; Sketris, Ingrid; Cooke, Charmaine; van Zanten, Sander Veldhuyzen; Barozzi, Nadia

2013-07-01

This study aimed to compare use of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), 2001-2005, in the elderly and social security beneficiaries in Australia (AUS) and Nova Scotia, Canada (NS). Prescription dispensing data were collected for all subsidised H2RAs and PPIs. In AUS, dispensing data for concession beneficiaries were obtained from the Pharmaceutical Benefits Scheme database. In NS, data were sourced from the Pharmacare database. Relevant population data were used to convert to World Health Organisation Anatomic Therapeutic Chemical defined daily doses (2005) per 1000 beneficiaries per day (DDD/1000/day). Overall use of gastroprotective agents was similar and rising in NS and AUS (100-160 DDD/1000/day) over this 5-year time window. However, the proportion of this use accounted for by PPIs was far higher in AUS (over 85% by 2005) than in NS (23% rising to 35% over the 5 years). In AUS, PPI use rose from 50 to about 140 DDD/1000/day over the 5 years, whereas PPI use in NS rose slowly to less than 60 DDD/1000/day by 2005. H2RA use in NS was always high (over 100 DDD/1000/day), whereas in AUS, H2RA use fell from 54 to around 24 DDD/1000/day over this period. AUS had much higher use of PPIs than NS over 2001-2005. The proportion of PPIs in all gastroprotective agents rose in AUS to be nearly 90%. The differences in utilisation during this time window could lead to differences in health outcomes from either lower gastro-intestinal bleeding risk or higher long-term adverse effects of PPIs. Copyright © 2013 John Wiley & Sons, Ltd.

Supplementation of Mice with Specific Nondigestible Oligosaccharides during Pregnancy or Lactation Leads to Diminished Sensitization and Allergy in the Female Offspring.

PubMed

Hogenkamp, Astrid; Knippels, Leon M J; Garssen, Johan; van Esch, Betty C A M

2015-05-01

The maternal environment and early life exposure affect immune development in offspring. We investigated whether development of food allergy in offspring is affected by supplementing pregnant or lactating sensitized or nonsensitized mice with a mixture of nondigestible oligosaccharides. Dams were sensitized intragastrically with ovalbumin before mating, with use of cholera toxin (CT) as an adjuvant. Nonsensitized dams received CT only. Dams were fed a control diet or a diet supplemented with short-chain galacto oligosaccharides (scGOSs), long-chain fructo oligosaccharides (lcFOSs), and pectin-derived acidic oligosaccharides (pAOSs) in a ratio of 9:1:2 at a dose of 2% during pregnancy or lactation, resulting in 7 experimental groups. After weaning, offspring were fed a control diet and ovalbumin-CT sensitized. Acute allergic skin responses (ASRs), shock symptoms, body temperature, and specific plasma immunoglobulins were measured upon intradermal ovalbumin challenge. Th2/Th1- and regulatory T cells were analyzed with use of quantitative polymerase chain reaction and flow cytometric analysis in spleen, mesenteric lymph nodes, and blood. Supplementing sensitized pregnant or lactating dams with scGOS/lcFOS/pAOS resulted in lower ASRs in the offspring [offspring of sensitized female mice fed experimental diet during pregnancy (S-Preg): 48 ± 2.1 μm; offspring of sensitized female mice fed experimental diet during lactation (S-Lact): 60 ± 6.2 μm] compared with the sensitized control group (119 ± 13.9 μm). In the S-Lact group, this coincided with an absence of shock symptoms compared with the offspring of sensitized female mice fed control food during pregnancy and lactation (S-Con) and S-Preg groups, and lower ovalbumin-IgG1 [S-Con: 3.8 ± 0.1 arbitrary units (AUs); S-Preg: 3.3 ± 0.1 AUs; S-Lact: 2.4 ± 0.1 AUs] and higher ovalbumin-IgG2a concentrations (S-Con: 1.1 ± 0.1 AUs; S-Preg: 0.8 ± 0.1 AUs; S-Lact: 2.0 ± 0.1 AUs). Supplementing nonsensitized pregnant or

Measurement of consumer preference for treatments used to induce labour: a willingness-to-pay approach.

PubMed

Taylor, Susan J.; Armour, Carol L.

2000-09-01

AIM: The purpose of the study was to assess the acceptability to consumers of two methods of induction of labour using a willingness-to-pay (WTP) approach. The methods compared were amniotomy plus oxytocin and prostaglandin E2 vaginal gel, followed by oxytocin if necessary. METHODS: A description of each method was presented, in questionnaire format, to pregnant women attending a public hospital ante-natal clinic. Women were asked to choose one of the two treatments, then give a valuation in dollar terms for both their preferred treatment and the alternative. RESULTS: It was found that 73.7% of patients preferred gel. The mean maximum WTP for amniotomy plus oxytocin was Aus$133 while that for gel was Aus$178 (P=0.0001). Those who chose amniotomy plus oxytocin were WTP 90% more for their preferred treatment compared with the alternative (Aus$180 vs. Aus$95). Similarly, those who preferred gel were WTP 90% more for their preferred treatment compared with the alternative (Aus$222 vs. Aus$119). CONCLUSION: Consumers were able to assess drug information provided on the two therapies, make an informed choice and to value that choice. Information obtained in this way, combined with information on costs, could be used in policy decision-making.

Measurement of consumer preference for treatments used to induce labour: a willingness‐to‐pay approach

PubMed Central

Taylor, Susan J.; Armour, Carol L.

2001-01-01

Aim The purpose of the study was to assess the acceptability to consumers of two methods of induction of labour using a willingness‐to‐pay (WTP) approach. The methods compared were amniotomy plus oxytocin and prostaglandin E2 vaginal gel, followed by oxytocin if necessary. Methods A description of each method was presented, in questionnaire format, to pregnant women attending a public hospital ante‐natal clinic. Women were asked to choose one of the two treatments, then give a valuation in dollar terms for both their preferred treatment and the alternative. Results It was found that 73.7% of patients preferred gel. The mean maximum WTP for amniotomy plus oxytocin was Aus$133 while that for gel was Aus$178 (P=0.0001). Those who chose amniotomy plus oxytocin were WTP 90% more for their preferred treatment compared with the alternative (Aus$180 vs. Aus$95). Similarly, those who preferred gel were WTP 90% more for their preferred treatment compared with the alternative (Aus$222 vs. Aus$119). Conclusion Consumers were able to assess drug information provided on the two therapies, make an informed choice and to value that choice. Information obtained in this way, combined with information on costs, could be used in policy decision‐making. PMID:11281930

Cytotechnologist performance for screening microfollicular atypia in indeterminate thyroid fine-needle aspirates.

PubMed

VandenBussche, Christopher J; Olson, Matthew T; Adams, Christina; Ali, Syed Z

2014-01-01

We previously identified a high level of accuracy among our cytotechnologists (CTs) for identifying nuclear atypia in thyroid fine-needle aspiration (FNA) specimens. Herewith, we present our CT performance at screening for microfollicular atypia. 8,814 thyroid FNA specimens were identified in our archives, all screened by 1 of 11 CTs and signed out by a cytopathologist. A subsample of cases was categorized either as atypia of uncertain significance (AUS) with microfollicular proliferation (AUS-F) or suspicious for a follicular neoplasm (SFN). The agreement rate was low between CTs and cytopathologists for SFN and AUS-F. Only 55.8% of SFN screening diagnoses were upheld; 27.9% were downgraded to AUS, 10.4% were downgraded to benign, and 5% were upgraded. Of AUS-F screening diagnoses, 35.5% were upheld, 33.7% were downgraded to benign, and 20.2% were upgraded to SFN. Among all cases, two-step discrepancies were uncommon. Most disagreements were one-category discrepancies between AUS-F and SFN. The evaluation of microfollicular atypia is challenging given that certain follicular lesions cannot be definitively diagnosed on cytology, a high level of subjectivity is involved in the interpretation of such lesions, and the presence of nuclear or Hurthle cell atypia may complicate the diagnosis. © 2014 S. Karger AG, Basel.

Participation in population-based case-control studies: does the observed decline vary by socio-economic status?

PubMed

Mazloum, Marie; Bailey, Helen D; Heiden, Tamika; Armstrong, Bruce K; de Klerk, Nicholas; Milne, Elizabeth

2012-05-01

An Australian study of childhood leukaemia (Aus-ALL) previously reported that control participation was positively associated with socio-economic status (SES). A similar study of childhood brain tumours (Aus-CBT) was carried out 4 years later, and this paper compares control participation and its relationship with SES in the two studies. To assess the representativeness of controls in terms of SES, the addresses of controls were linked to Australian Bureau of Statistics Census 2006 Collection Districts (CDs), and hence to area-based indices of SES. Independent sample t-tests and chi-squared tests were used to compare the SES indices of CDs where Aus-CBT controls lived with those where Aus-ALL controls lived and with those of all CDs where Australian families lived. The overall percentage of eligible families who agreed to participate was lower in Aus-CBT (53.9%) than in Aus-ALL (70.3%). Control families in both studies were of higher SES than the general population, while the distribution of SES among recruited controls was similar in both studies. These findings provide some reassurance that the observed decline in research participation over time may not be associated with an increasingly unrepresentative participant population. © 2012 Blackwell Publishing Ltd.

Der Begriff mathematischer Schönheit in einer empirisch informierten Ästhetik der Mathematik

NASA Astrophysics Data System (ADS)

Müller-Hill, Eva; Spies, Susanne

Dieses Zitat des britischen Mathematikers G. H. Hardy bringt pointiert die unter praktizierenden Mathematikern, aber auch unter Philosophen der Mathematik weithin akzeptierte Ansicht zum Ausdruck, dass mathematische Schönheit eine nicht zu vernachlässigende Rolle in der mathematischen Forschungspraxis spielt und sowohl interessante ästhetiktheoretische, epistemische als auch ontologische Aspekte aufweist. Danach beeinflusst also das Verständnis dessen, was mathematische Schönheit ist, auch das Verständnis dessen, was Mathematik ist: "Was sind die Träger mathematischer Schönheit?" ist die Frage nach der Art der Gegenstände, für deren Schönheit Mathematiker sich begeistern und nach der sie streben. "Was sind die Kriterien für mathematische Schönheit?" ist die Frage nach den Kategorien, unter denen Mathematiker ihre Arbeit bewerten. Egal, ob sich das Phänomen mathematischer Schönheit als Ausnahmemerkmal oder als ständiger Begleiter mathematischen Tuns erweist - ein adäquates allgemeines Mathematikverständnis sollte dieses Phänomen berücksichtigen und bestenfalls auch erklären können.

Variability of oil and gas well productivities for continuous (unconventional) petroleum accumulations

USGS Publications Warehouse

Charpentier, Ronald R.; Cook, Troy A.

2013-01-01

Over the last decade, oil and gas well productivities were estimated using decline-curve analysis for thousands of wells as part of U.S. Geological Survey (USGS) studies of continuous (unconventional) oil and gas resources in the United States. The estimated ultimate recoveries (EURs) of these wells show great variability that was analyzed at three scales: within an assessment unit (AU), among AUs of similar reservoir type, and among groups of AUs with different reservoir types. Within a particular oil or gas AU (such as the Barnett Shale), EURs vary by about two orders of magnitude between the most productive wells and the least productive ones (excluding those that are dry and abandoned). The distributions of EURs are highly skewed, with most of the wells in the lower part of the range. Continuous AUs were divided into four categories based on reservoir type and major commodity (oil or gas): coalbed gas, shale gas, other low-permeability gas AUs (such as tight sands), and low-permeability oil AUs. Within each of these categories, there is great variability from AU to AU, as shown by plots of multiple EUR distributions. Comparing the means of each distribution within a category shows that the means themselves have a skewed distribution, with a range of approximately one to two orders of magnitude. A comparison of the three gas categories (coalbed gas, shale gas, and other low-permeability gas AUs) shows large overlap in the ranges of EUR distributions. Generally, coalbed gas AUs have lower EUR distributions, shale gas AUs have intermediate sizes, and the other low-permeability gas AUs have higher EUR distributions. The plot of EUR distributions for each category shows the range of variation among developed AUs in an appropriate context for viewing the historical development within a particular AU. The Barnett Shale is used as an example to demonstrate that dividing wells into groups by time allows one to see the changes in EUR distribution. Subdivision into groups

Genetics Home Reference: hereditary paraganglioma-pheochromocytoma

MedlinePlus

... two important cellular pathways called the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. These pathways are critical in ... can use. As part of the citric acid cycle, the SDH enzyme converts a compound called succinate ...

Behaviors of active sunbeds users and their knowledge on the potential health risks; results of cross-sectional study in Poland.

PubMed

Gajda, Maksymilian; Kamińska-Winciorek, Grażyna; Wydmański, Jerzy; Tukiendorf, Andrzej; Kowalska, Małgorzata

2018-06-01

Current literature review indicates that there is an increase in risk of skin melanoma due to the use of sunbeds. To assess behaviors and opinions about health risk related to tanning. From March 2012 to June of the same year, nonrepresentative cross-sectional study was conducted online concerning knowledge and behaviors during tanning. Data from 4919 people (80% of women, median age 25 years [IQR: 20-36]) were analyzed statistically with R software (level of significance at α = .05). We used the authors "active users of sunbeds" (AUS) criterion, denoting person using it ≥2 times per year with an average sessions lasting ≥5 minutes (cutoff values above 1 quartile). The reference was those not meeting above criteria. A total of 926 persons (18.8%) stated that they use sunbeds, while 680 (13.8%) met the criterion of AUS. Within the AUS group, the median number of visits in the tanning beds rooms was 10 (IQR: 5-15) per year, with single session lasting 9 (IQR: 7-10) minutes. The majority (83.5%) of AUS tanned naked indoors, with only 47.4% to have used safety glasses. These individuals were significantly more likely to be women, better educated, and were considered outdoor tanners. AUS were less aware of the risks associated with sunburns, with equal use of sunscreen and reapplication more frequently (as non-AUS). The level of knowledge in the field of prevention of melanoma was similar in both groups; however, AUS group more frequently took risky behaviors related to sun exposure. © 2018 Wiley Periodicals, Inc.

Reproducibility of atypia of undetermined significance/follicular lesion of undetermined significance category using the bethesda system for reporting thyroid cytology when reviewing slides from different institutions: A study of interobserver variability among cytopathologists.

PubMed

Padmanabhan, Vijayalakshmi; Marshall, Carrie B; Akdas Barkan, Guliz; Ghofrani, Mohiedean; Laser, Alice; Tolgay Ocal, Idris; David Sturgis, Charles; Souers, Rhona; Kurtycz, Daniel F I

2017-05-01

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) offers a six-tiered diagnostic scheme for thyroid Fine Needle Aspiration (FNA): Benign, Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS), suspicious for follicular neoplasm, suspicious for malignancy, malignant, and unsatisfactory with an aim to standardize diagnostic criteria. Reported rate of AUS/FLUS category in the literature has varied from 3% to 20.5%. The aim of this study was to assess interobserver variability among cytopathologists to assess reproducibility of the AUS/FLUS category. Seven cytopathologists brought FNA cases (a mixture of atypical and non-atypical FNA diagnosis) diagnosed using TBSRTC from their respective institutions which were reviewed and diagnosed by the participants. The analysis assessed interobserver variability among 7 cytopathologists and determined characteristics on the slides which were associated with concordance to the institutional diagnosis. Seventy eight of 125 (62.4%) benign cases were classified as benign by the reviewers and 26 (21%) were called AUS/FLUS on review. A third of the AUS/FLUS cases were called benign on review and 28.2% were classified as suspicious for neoplasia/malignancy. Roughly a third each of the suspicious for follicular neoplasm/suspicious for malignancy cases were classified as AUS/FLUS. When pathologists from different institutions shared their slides, concordance was high for specimens with adequate cellularity and those that were clearly benign but thresholds varied for the other indeterminate categories. Most definite categorization of the AUS/FLUS category was seen on review. Diagn. Cytopathol. 2017;45:399-405. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Assessment of the mechanics of a tissue-engineered rat trachea in an image-processing environment.

PubMed

Silva, Thiago Henrique Gomes da; Pazetti, Rogerio; Aoki, Fabio Gava; Cardoso, Paulo Francisco Guerreiro; Valenga, Marcelo Henrique; Deffune, Elenice; Evaristo, Thaiane; Pêgo-Fernandes, Paulo Manuel; Moriya, Henrique Takachi

2014-07-01

Despite the recent success regarding the transplantation of tissue-engineered airways, the mechanical properties of these grafts are not well understood. Mechanical assessment of a tissue-engineered airway graft before implantation may be used in the future as a predictor of function. The aim of this preliminary work was to develop a noninvasive image-processing environment for the assessment of airway mechanics. Decellularized, recellularized and normal tracheas (groups DECEL, RECEL, and CONTROL, respectively) immersed in Krebs-Henseleit solution were ventilated by a small-animal ventilator connected to a Fleisch pneumotachograph and two pressure transducers (differential and gauge). A camera connected to a stereomicroscope captured images of the pulsation of the trachea before instillation of saline solution and after instillation of Krebs-Henseleit solution, followed by instillation with Krebs-Henseleit with methacholine 0.1 M (protocols A, K and KMCh, respectively). The data were post-processed with computer software and statistical comparisons between groups and protocols were performed. There were statistically significant variations in the image measurements of the medial region of the trachea between the groups (two-way analysis of variance [ANOVA], p<0.01) and of the proximal region between the groups and protocols (two-way ANOVA, p<0.01). The technique developed in this study is an innovative method for performing a mechanical assessment of engineered tracheal grafts that will enable evaluation of the viscoelastic properties of neo-tracheas prior to transplantation.

Cleaning of Livefront Electrical Switchgear Using Carbon Dioxide Pellets at Navy Installations

DTIC Science & Technology

1998-05-01

MÄNTENIMIENTO - REPUESTOS ADX 600/- CARATTERISTICHE - CHARACTERISTICS - CARACTERISTIQUES - MERKMALE - CARACTERISTICAS Bicilindrico - Ciclo Diesel 4...Fliehkraftregler - Drehzahlregler - Kurbelgenhäuse aus Aluminium- Druckguss - Zylinder aus Perlitguss - Oelbadluftfilter. Bicilindrico - Ciclo Diesel de

Neuropsychological functioning of siblings of children with autism, siblings of children with developmental language delay, and siblings of children with mental retardation of unknown genetic etiology.

PubMed

Pilowsky, Tammy; Yirmiya, Nurit; Gross-Tsur, Varda; Shalev, Ruth S

2007-03-01

Neuropsychological functioning of 30 siblings of children with autism (AU-S), 28 siblings of children with mental retardation of (MR-S), and 30 siblings of children with developmental language delay (DLD-S) was compared. Two siblings, both AU-S, received diagnoses of pervasive developmental disorder (PDD). More siblings with cognitive disabilities were found in DLD-S than in AU-S. However, these differences disappeared after excluding diagnosed siblings or after accounting for family membership. In sum, despite the elevated incidence of PDD among AU-S, the neuropsychological functioning of the remaining siblings did not convey specific characteristics related to the genetic risk associated with autism, in contrast to the cognitive functioning of the DLD-S, which did reflect a genetic risk.

27 CFR 9.222 - Naches Heights.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the intersection of the Burlington Northern single-track rail line and the Congdon (Schuler) Canal... a straight line approximately 0.15 mile to the Congdon (Schuler) Canal, which closely parallels the... Congdon (Schuler) Canal, onto the Selah map, approximately 3.25 miles, returning to the beginning point...

27 CFR 9.222 - Naches Heights.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the intersection of the Burlington Northern single-track rail line and the Congdon (Schuler) Canal... a straight line approximately 0.15 mile to the Congdon (Schuler) Canal, which closely parallels the... Congdon (Schuler) Canal, onto the Selah map, approximately 3.25 miles, returning to the beginning point...

27 CFR 9.222 - Naches Heights.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the intersection of the Burlington Northern single-track rail line and the Congdon (Schuler) Canal... a straight line approximately 0.15 mile to the Congdon (Schuler) Canal, which closely parallels the... Congdon (Schuler) Canal, onto the Selah map, approximately 3.25 miles, returning to the beginning point...

Risk Factors for Failure of Male Slings and Artificial Urinary Sphincters: Results from a Large Middle European Cohort Study.

PubMed

Hüsch, Tanja; Kretschmer, Alexander; Thomsen, Frauke; Kronlachner, Dominik; Kurosch, Martin; Obaje, Alice; Anding, Ralf; Pottek, Tobias; Rose, Achim; Olianas, Roberto; Friedl, Alexander; Hübner, Wilhelm; Homberg, Roland; Pfitzenmaier, Jesco; Grein, Ulrich; Queissert, Fabian; Naumann, Carsten Maik; Schweiger, Josef; Wotzka, Carola; Nyarangi-Dix, Joanne; Hofmann, Torben; Ulm, Kurt; Bauer, Ricarda M; Haferkamp, Axel

2017-01-01

We analysed the impact of predefined risk factors: age, diabetes, history of pelvic irradiation, prior surgery for stress urinary incontinence (SUI), prior urethral stricture, additional procedure during SUI surgery, duration of incontinence, ASA-classification and cause for incontinence on failure and complications in male SUI surgery. We retrospectively identified 506 patients with an artificial urinary sphincter (AUS) and 513 patients with a male sling (MS) in a multicenter cohort study. Complication rates were correlated to the risk factors in univariate analysis. Subsequently, a multivariate logistic regression adjusted to the risk factors was performed. A p value <0.05 was considered statistically significant. A history of pelvic irradiation was an independent risk factor for explantation in AUS (p < 0.001) and MS (p = 0.018). Moreover, prior urethral stricture (p = 0.036) and higher ASA-classification (p = 0.039) were positively correlated with explantation in univariate analysis for AUS. Urethral erosion was correlated with prior urethral stricture (p < 0.001) and a history of pelvic irradiation (p < 0.001) in AUS. Furthermore, infection was correlated with additional procedures during SUI surgery in univariate analysis (p = 0.037) in MS. We first identified the correlation of higher ASA-classification and explantation in AUS. Nevertheless, only a few novel risk factors had a significant influence on the failure of MS or AUS. © 2016 S. Karger AG, Basel.

Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial.

PubMed

Neldam, S; Osler, M; Hansen, P K; Nim, J; Smith, S F; Hertel, J

1986-10-01

In a prospective clinical randomized investigation 487 women had the condition of the fetus during labour supervised by means of stethoscope (AUS), while 482 women went through labour under surveillance of electronic fetal monitoring, cardiotocography (EFM). 349 women refused to participate in the investigation (NAI) and had delivery conducted according to the normal procedures of the department (70% AUS, 30% EFM). Significantly more pathological fetal heart rate patterns (FHR) were found in the EFM group compared to the AUS group in both the first and the second stage of labour. As a result significantly more vacuum extractions were performed in the EFM group than in the AUS group, while no statistical difference was found between the groups in the incidence of acute cesarean sections carried out for asphyxia. One case of intrapartum death occurred in the AUS group. No differences were found in Apgar scores after 1 and 5 min or in neonatal morbidity at examination on the 2nd and 5th days after delivery. A tendency towards more biochemically compromised children was found in the AUS group. The specificity for both methods was found to be acceptably high (80%), while the predictive value for both methods was low (50%). More research is therefore urgently needed to evaluate supplementary investigations and parameters for the evaluation of the intrapartum fetal condition.

Malformations detected by abdominal ultrasound in children with congenital heart disease.

PubMed

Rosa, Rosana Cardoso Manique; Rosa, Rafael Fabiano Machado; Flores, José Antônio Monteiro; Golendziner, Eliete; Oliveira, Ceres Andréia Vieira de; Varella-Garcia, Marileila; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo Gazzola

2012-12-01

Extracardiac malformations may be present in patients with congenital heart disease (CHD), bringing greater risk of comorbidity and mortality. Verify frequency and types of abdominal abnormalities detected in children with and without CHD through abdominal ultrasound (AUS), compare the patients in relation to their dysmorphic/cytogenetic findings and perform an estimative of the cost-effectiveness of the screening through AUS. We conducted a cross-sectional study with a control cohort. The cases consisted of patients with CHD admitted for the first time in a pediatric intensive care unit; the controls consisted of children without CHD who underwent AUS at the hospital shortly thereafter a case. All patients with CHD underwent AUS, high-resolution karyotype and fluorescence in situ hybridization (FISH) for microdeletion 22q11.2. AUS identified clinically significant abnormalities in 12.2% of the cases and 5.2% of controls (p= 0.009), with a power of significance of 76.6%. Most malformations with clinical significance were renal anomalies (10.4% in cases and 4.9% in controls; p= 0.034). In Brazil, the cost of an AUS examination for the Unified Health System is US$ 21. Since clinically significant abnormalities were observed in one in every 8.2 CHD patients, the cost to identify an affected child was calculated as approximately US$ 176. Patients with CHD present a significant frequency of abdominal abnormalities detected by AUS, an inexpensive and noninvasive diagnostic method with good sensitivity. The cost of screening for these defects is considerably lower than the cost to treat the complications of late diagnoses of abdominal malformations such as renal disease.

Der Einfluss von Alitretinoin auf die Lebensqualität bei Patienten mit schwerem chronischen Handekzem: FUGETTA - Beobachtungsstudie unter Praxisbedingungen.

PubMed

Augustin, Matthias; Thaçi, Diamant; Kamps, Anja

2016-12-01

Alitretinoin ist die einzige zugelassene Behandlung für schweres chronisches Handekzem (CHE), das refraktär gegenüber potenten topischen Corticosteroiden ist. Bei dieser Studie (FUGETTA) wurde die Wirksamkeit von leitliniengerecht angewendetem oralem Alitretinoin sowie dessen Einfluss auf die Lebensqualität (LQ) bei Patienten mit schwerem refraktärem CHE beurteilt. Multizentrische, offene, nichtinterventionelle Beobachtungsstudie, durchgeführt in Deutschland. Die Patienten wurden nach Ermessen ihres behandelnden Arztes mit Alitretinoin 10 mg oder 30 mg einmal täglich über maximal 24 Wochen behandelt. Die Wirksamkeit wurde anhand des Physician Global Assessment (PGA) und des Dermatology Life Quality Index (DLQI) bewertet. Zudem wurden unerwünschte Ereignisse (UE) erfasst. Die Studienpopulation bestand aus 658 Patienten (30 mg: n = 581; 10 mg: n = 77). Bei Beobachtungsbeginn litten die meisten Patienten (83 %) gemäß PGA an einem schweren CHE. Bei Beobachtungsende war das Handekzem bei 48 % der Patienten gemäß PGA vollständig oder fast vollständig abgeheilt (30 mg: 49 %; 10 mg: 43 %). Die mittlere Verbesserung des DLQI-Scores in Woche 24 betrug 58 % (30 mg: mittlere [SD] Veränderung gegenüber dem Ausgangswert -10,4 [8,04]) und 70 % (10 mg: mittlere [SD] Veränderung gegenüber dem Ausgangswert -10,8 [7,29]). Die Gesamtinzidenz von NW war niedrig und in den beiden Gruppen ähnlich. Alitretinoin führte zu einer schnellen, deutlichen Verbesserung der LQ bei Patienten mit schwerem CHE. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Untersuchungen zur Entwicklung von Satellitengalaxien

NASA Astrophysics Data System (ADS)

Seidel, Björn

2002-01-01

Gleichgewichtsmodelle ein- und zweikomponentiger Satellitengalaxien werden erzeugt und die Gezeiteneinwirkungen der als starres äußeres Potential angenommenen Milchstraße auf sie betrachtet. Eine erste Reihe von Simulationen mit anfänglich kugelsymmetrischen einkomponentigen Satelliten zeigt, daß sich nach elliptischer Deformation ein Balken und Schweife ungleicher Länge ausbilden, deren Aussehen sich periodisch ändert. Mithilfe von Vergleichssimulationen wurden folgende Phänomene am Satelliten entdeckt: (1) Hochdichtebereiche in den Schweifen, (2) Niedrigdichtebereiche um den Kern bzw. Balken und (3) ein oft verdeckter Balken. Analysiert wird das Erscheinungsbild in Zeitabhängigkeit. Die Teilchen gehen dem Kern über den Balken verloren und bewegen sich entlang gewisser stets gleich aussehender charakteristischer Strukturen in die Schweife. Nach einer Herleitung allgemeiner Größen des mehrkomponentigen Kingprofils werden drei stabile Standardmodelle zweikomponentiger Satellitengalaxien mit Massenverhältnis 1:10 (baryonische zu dunkle Materie) und unterschiedlicher Verteilung der dunklen und sichtbaren Materie gefunden. Ohne die Allgemeinheit der Ergebnisse zu beeinträchtigen, wurde dabei die Große Magellanische Wolke als Grundlage der Modelle genommen. Nach geeigneter Wahl der Bahn, zu der der Gezeitenradius des verwendeten dreikomponentigen Milchstraßenpotentials sowohl analytisch als auch numerisch berechnet wird, werden Simulationen der Modelle analysiert. Hauptaugenmerk ist das unterschiedliche Verhalten der Komponenten. Hauptergebnisse: (1) Es ist möglich, große Anteile dunkler, jedoch nur geringe sichtbarer Materie abzulösen. Dunkle und sichtbare Materie können unterschiedliche morphologische Strukturen bilden. (2) Je nach Konzentration der Komponenten ist die Eigengravitation der Teilchen mehr oder weniger für das Aussehen bestimmend. (3) Die Kernauflösung des Satelliten findet im Perigalaktikum (PG), sein Zerfall aber erst im

Gluconeogenesis, non-essential amino acid synthesis and substrate partitioning in chicken embryos during later development.

PubMed

Hu, Q; Agarwal, U; Bequette, B J

2017-02-01

We aimed to quantify the rate of gluconeogenesis (GNG), non-essential amino-acid (NEAA) synthesis, and substrate partitioning to the Krebs cycle in embryonic (e) day e14 and e19 chicken embryos. An in ovo continuous tracer infusion approach was employed to test the hypotheses that GNG and NEAA synthesis in developing chicken embryo increases from e14 to e19. [ 13 C 6 ]Glucose or [ 13 C 3 ]glycerol was continuously infused (8 h) into the chorio-allantoic compartment of eggs on e14 and e19. Glucose entry rate, Cori cycling, and GNG were higher (P < 0.05) in e19 compared to e14 embryos, presumably to support higher glycogen deposition in liver and muscle. Whereas de novo synthesis of alanine, aspartate, and glutamate via glycolysis and the Krebs cycle was higher (P < 0.01) in e14 embryos, synthesis of these NEAA from glycerol was higher (P < 0.05) in e19 compared to e14 embryos. These patterns of glucose and glycerol utilization suggest a metabolic shift to conserve glucose for glycogen synthesis and an increased utilization of yolk glycerol (from triacylglyceride) after e14. Although the contribution of glycerol to GNG in e19 embryos was higher (P < 0.05) than that in e14 embryos, the contribution of glycerol to GNG (1.3 to 6.0%) was minor. Based on [ 13 C 6 ]glucose tracer kinetics, the activities of both pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) in the liver were higher (P < 0.05) in e19 embryos; whereas the higher (P < 0.01) relative activity of liver PC compared to PDH in e14 embryos suggests a greater anaplerotic flux into the Krebs cycle. In summary, the in ovo continuous tracer infusion approach allowed for a measurement of chicken embryo whole body and liver metabolism over a shorter window of development. This study provided quantitative estimates of the developmental shifts in substrate utilization, GNG, and NEAA synthesis by chicken embryos, as well as qualitative estimates of the activities of enzymes central to the Krebs cycle

Iron catalysis at the origin of life.

PubMed

Camprubi, Eloi; Jordan, Sean F; Vasiliadou, Rafaela; Lane, Nick

2017-06-01

Iron-sulphur proteins are ancient and drive fundamental processes in cells, notably electron transfer and CO 2 fixation. Iron-sulphur minerals with equivalent structures could have played a key role in the origin of life. However, the 'iron-sulphur world' hypothesis has had a mixed reception, with questions raised especially about the feasibility of a pyrites-pulled reverse Krebs cycle. Phylogenetics suggests that the earliest cells drove carbon and energy metabolism via the acetyl CoA pathway, which is also replete in Fe(Ni)S proteins. Deep differences between bacteria and archaea in this pathway obscure the ancestral state. These differences make sense if early cells depended on natural proton gradients in alkaline hydrothermal vents. If so, the acetyl CoA pathway diverged with the origins of active ion pumping, and ancestral CO 2 fixation might have been equivalent to methanogens, which depend on a membrane-bound NiFe hydrogenase, energy converting hydrogenase. This uses the proton-motive force to reduce ferredoxin, thence CO 2 . The mechanism suggests that pH could modulate reduction potential at the active site of the enzyme, facilitating the difficult reduction of CO 2 by H 2 . This mechanism could be generalised under abiotic conditions so that steep pH differences across semi-conducting Fe(Ni)S barriers drives not just the first steps of CO 2 fixation to C1 and C2 organics such as CO, CH 3 SH and CH 3 COSH, but a series of similar carbonylation and hydrogenation reactions to form longer chain carboxylic acids such as pyruvate, oxaloacetate and α-ketoglutarate, as in the incomplete reverse Krebs cycle found in methanogens. We suggest that the closure of a complete reverse Krebs cycle, by regenerating acetyl CoA directly, displaced the acetyl CoA pathway from many modern groups. A later reliance on acetyl CoA and ATP eliminated the need for the proton-motive force to drive most steps of the reverse Krebs cycle. © 2017 IUBMB Life, 69(6):373-381, 2017. �

Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer.

PubMed

Ueda, Shigeto; Tsuda, Hitoshi; Asakawa, Hideki; Omata, Jiro; Fukatsu, Kazuhiko; Kondo, Nobuo; Kondo, Tadaharu; Hama, Yukihiro; Tamura, Katsumi; Ishida, Jiro; Abe, Yoshiyuki; Mochizuki, Hidetaka

2008-06-09

Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC). One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging. In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03). The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F

Evaluation of Abdominal Ultrasonography Mass Screening for Hepatocellular Carcinoma in Taiwan

PubMed Central

Yeh, Yen-Po; Hu, Tsung-Hui; Cho, Po-Yuan; Chen, Hsiu-Hsi; Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Su, Wei-Wen; Fang, Yi-Jen; Chen, Shih-Tien; San, Hsiao-Ching; Chen, Hung-Pin; Liao, Chao-Sheng

2014-01-01

Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community-based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high-incidence area to attend a risk score-guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community-based ultrasonography screening. Among the 16 screen-detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age- and gender-adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56-0.84) and 0.63 (95% CI: 0.52-0.77), respectively. Conclusion: The residents invited to community-based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45-69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849) PMID:24002724

Model non-equilibrium molecular dynamics simulations of heat transfer from a hot gold surface to an alkylthiolate self-assembled monolayer.

PubMed

Zhang, Yue; Barnes, George L; Yan, Tianying; Hase, William L

2010-05-07

Model non-equilibrium molecular dynamics (MD) simulations are presented of heat transfer from a hot Au {111} substrate to an alkylthiolate self-assembled monolayer (H-SAM) to assist in obtaining an atomic-level understanding of experiments by Wang et al. (Z. Wang, J. A. Carter, A. Lagutchev, Y. K. Koh, N.-H. Seong, D. G. Cahill, and D. D. Dlott, Science, 2007, 317, 787). Different models are considered to determine how they affect the heat transfer dynamics. They include temperature equilibrated (TE) and temperature gradient (TG) thermostat models for the Au(s) surface, and soft and stiff S/Au(s) models for bonding of the S-atoms to the Au(s) surface. A detailed analysis of the non-equilibrium heat transfer at the heterogeneous interface is presented. There is a short time temperature gradient within the top layers of the Au(s) surface. The S-atoms heat rapidly, much faster than do the C-atoms in the alkylthiolate chains. A high thermal conductivity in the H-SAM, perpendicular to the interface, results in nearly identical temperatures for the CH(2) and CH(3) groups versus time. Thermal-induced disorder is analyzed for the Au(s) substrate, the S/Au(s) interface and the H-SAM. Before heat transfer occurs from the hot Au(s) substrate to the H-SAM, there is disorder at the S/Au(s) interface and within the alkylthiolate chains arising from heat-induced disorder near the surface of hot Au(s). The short-time rapid heating of the S-atoms enhances this disorder. The increasing disorder of H-SAM chains with time results from both disorder at the Au/S interface and heat transfer to the H-SAM chains.

Male Sling and Artificial Urethral Sphincter for Male Stress Urinary Incontinence Among Certifying American Urologists.

PubMed

Liu, Joceline S; Hofer, Matthias D; Milose, Jaclyn; Oberlin, Daniel T; Flury, Sarah C; Morey, Allen F; Gonzalez, Chris M

2016-01-01

To examine case volume characteristics among certifying urologists performing male sling and artificial urinary sphincter (AUS) procedures to evaluate practice patterns in male stress urinary incontinence (SUI). Six-month case log data of certifying urologists (2003-2013) were obtained from the American Board of Urology. Cases specifying Current Procedural Terminology code for male sling, AUS, and removal or revision of either procedure in males ≥18 years were analyzed. Among 1615 urologists (568 certifying and 1047 recertifying) logging at least 1 male incontinence procedure, 2109 (48% of all procedures) male sling and 2284 (52%) AUS cases were identified. The mean age of patients undergoing AUS was 74.9 years and the mean age of patients undergoing sling procedures was 67.3 years (P <.001). An increase in male incontinence procedures from 2003 to 2013 was demonstrated. The rate of male sling procedure increased from 32.7% of incontinence surgeries in 2004 to 45.5% in 2013 (P <.001). Academically affiliated urologists are 1.5 times more likely to perform AUS than male sling for SUI (P <.001). Median number of slings performed was 2 (range 1-40), with 32.7% placing slings exclusively. A small group of certifying urologists (3.4%) accounted for 22% of all male slings placed. This same cohort logged 10.2% of all AUS performed. Surgical management of male SUI varies widely across states (P <.001), with slings performed between 21% and 70% of the time. Overall the number of male incontinence procedures has increased over time, with a growing proportion of male slings. Most slings and AUS cases are performed by a small number of high-volume surgeons. Copyright © 2015 Elsevier Inc. All rights reserved.

Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?

PubMed

Swenson, Erik R

2018-05-01

Maintenance of intracellular pH is critical for clinical homeostasis. The metabolism of glucose, fatty acids, and amino acids yielding the generation of adenosine triphosphate in the mitochondria is accompanied by the production of acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of its disposal have been argued by two investigators with a long-abiding interest in acid-base physiology. They offer different interpretations and views of the molecular mechanism of this intracellular pH regulation during normal metabolism. Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the direct end products in the Krebs cycle. In the late 1960s, he showed in brain and brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor, reduces intracellular pH. This led him to conclude that hydrogen ion and bicarbonate are the end products, and the role of intracellular carbonic anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis. Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs cycle, a more widely accepted view, and that acetazolamide prevents rapid intracellular bicarbonate formation, which can then codiffuse with carbon dioxide to the cell surface and there be reconverted for exit from the cell. Loss of this "facilitated diffusion of carbon dioxide" leads to intracellular acidosis as the still appreciable uncatalyzed rate of carbon dioxide hydration generates more protons. This review summarizes the available evidence and determines that resolution of this question will require more sophisticated measurements of intracellular pH with faster temporal resolution.

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

PubMed Central

Lee, Ji Hyeon; Park, Sang Yoong; Park, Jae-Won

2013-01-01

Background Bupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block. Methods Fifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 µM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model. Results The combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium. Conclusions Bupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction. PMID:23646245

Kometen und Asteroiden

NASA Astrophysics Data System (ADS)

Borgeest, Ulf; Staude, Jakob; Hahn, Gerhard; Harris, Alan W.; Jaumann, Ralf; Köhler, Ulrich; Kührt, Ekkehard; Schulz, Rita; Neukum, Gerhard; Arnold, Gabriele; Keller, Horst Uwe; Denk, Tilmann; Müller, Thomas; Wulff, André; Maruhn, Nicolaus; Fischer, Daniel; Trieloff, Mario; Althaus, Tilmann

Contents: Die Kleinkörper des Sonnensystems. Kern, Koma und Schweife. Ziele der Planetenforschung. ROSETTA: Naherkundung von Kometen. Asteroiden: Trümmer aus planetarer Urzeit. Kleinkörper im Infrarotweltall. Selbs beobachten! Apocalypse - not now! Meteoriten - Boten aus der Urzeit des Sonnensystems.

Milch, Milchprodukte, Analoge und Speiseeis

NASA Astrophysics Data System (ADS)

Coors, Ursula

Die Produktpalette Milch und Erzeugnisse aus Milch beinhaltet Konsummilch, die aus Milch oder Bestandteilen der Milch hergestellten Milcherzeugnisse wie Sauermilch-, Joghurt-, Kefir-, Buttermilch-, Sahne-, Kondensmilch-, Trockenmilch- und Molkenerzeugnisse, Milchmisch- und Molkenmischprodukte (Produkte mit beigegebenen Lebensmitteln), Milchzucker, Milcheiweißerzeugnisse, Milchfette und Käse.

Bildanalyse in Medizin und Biologie

NASA Astrophysics Data System (ADS)

Athelogou, Maria; Schönmeyer, Ralf; Schmidt, Günther; Schäpe, Arno; Baatz, Martin; Binnig, Gerd

Heutzutage sind bildgebende Verfahren aus medizinischen Untersuchungen nicht mehr wegzudenken. Diverse Methoden - basierend auf dem Einsatz von Ultraschallwellen, Röntgenstrahlung, Magnetfeldern oder Lichtstrahlen - werden dabei spezifisch eingesetzt und liefern umfangreiches Datenmaterial über den Körper und sein Inneres. Anhand von Mikroskopieaufnahmen aus Biopsien können darüber hinaus Daten über die morphologische Eigenschaften von Körpergeweben gewonnen werden. Aus der Analyse all dieser unterschiedlichen Arten von Informationen und unter Konsultation weiterer klinischer Untersuchungen aus diversen medizinischen Disziplinen kann unter Berücksichtigung von Anamnesedaten ein "Gesamtbild“ des Gesundheitszustands eines Patienten erstellt werden. Durch die Flut der erzeugten Bilddaten kommt der Bildverarbeitung im Allgemeinen und der Bildanalyse im Besonderen eine immer wichtigere Rolle zu. Gerade im Bereich der Diagnoseunterstützung, der Therapieplanung und der bildgeführten Chirurgie bilden sie Schlüsseltechnologien, die den Forschritt nicht nur auf diesen Gebieten maßgeblich vorantreiben.

Summer Institute in Agricultural Mechanics Education, Southern Region, Proceedings (Blacksburg, Virginia, August 3-7, 1970).

ERIC Educational Resources Information Center

Virginia Polytechnic Inst. and State Univ., Blacksburg.

This summer institute emphasizes the establishment of minimum measurable standards of attainment in agricultural engineering phases of teacher education in agriculture. Speeches presented are: (1) "Where We Are in Agricultural Mechanics Education," by Alfred H. Krebs, (2) "Research Offerings for More Effective Teaching in Agricultural Mechanics,"…

Textbook Errors & Misconceptions in Biology: Cell Metabolism.

ERIC Educational Resources Information Center

Storey, Richard D.

1991-01-01

The idea that errors and misconceptions in biology textbooks are often slow to be discovered and corrected is discussed. Selected errors, misconceptions, and topics of confusion about cell metabolism are described. Fermentation, respiration, Krebs cycle, pentose phosphate pathway, uniformity of catabolism, and metabolic pathways as models are…

Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies.

PubMed

Moreno, Nadia; Ripollés, Tomás; Paredes, José María; Ortiz, Inmaculada; Martínez, María Jesús; López, Antonio; Delgado, Fructuoso; Moreno-Osset, Eduardo

2014-09-01

The objective of this study was to analyze the accuracy of abdominal ultrasonography (AUS) in the assessment of mucosal healing in patients with Crohn's disease (CD) receiving immunomodulators and/or biological treatment, with ileocolonoscopy as the reference standard. Thirty patients were included in a prospective longitudinal study. All patients underwent ileocolonoscopy and AUS before and after a minimum of one year of treatment. The Crohn's Disease Endoscopic Inflammatory Index of Severity (CDEIS) was used for endoscopic assessment whereas AUS was analyzed by means of bowel wall thickness, color Doppler grade and percentage of increase of parietal enhancement after contrast injection. In the segmental analysis, endoscopic healing was found in 71.2% of the segments and AUS findings were normalized in 62.8%, with a significant correlation between the two techniques (κ=0.76, p<0.001). In the overall assessment performed after treatment, 18 (60%) patients exhibited endoscopic remission (CDEIS <6 points); of these patients, 15 (83.3%) had normalized sonographic findings, with a good correlation between endoscopic remission and sonographic normalization (κ=0.73, p<0.001). Of the three variables assessed by AUS, parietal thickness was the best variable to predict mucosal healing in both analyses, segmental and global. Abdominal ultrasonography is a useful and reliable technique for the assessment of the endoscopic response to treatment with immunomodulators and/or biological drugs in Crohn's disease. AUS is a highly accurate technique for evaluating the healing of the intestinal mucosa. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Assessing the activity of perianal Crohn's disease: comparison of clinical indices and computer-assisted anal ultrasound.

PubMed

Losco, Alessandra; Viganò, Chiara; Conte, Dario; Cesana, Bruno Mario; Basilisco, Guido

2009-05-01

Assessing perianal disease activity is important for the treatment and prognosis of Crohn's disease (CD) patients, but the diagnostic accuracy of the activity indices has not yet been established. The aim of this study was to determine the accuracy and agreement of the Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI), and computer-assisted anal ultrasound imaging (AUS). Sixty-two consecutive patients with CD and perianal fistulae underwent clinical, FDA, PDAI, and AUS evaluation. Perianal disease was considered active in the presence of visible fistula drainage and/or signs of local inflammation (induration and pain at digital compression) upon clinical examination. The AUS images were analyzed by calculating the mean gray-scale tone of the lesion. The PDAI and gray-scale tone values discriminating active and inactive perianal disease were defined using receiver operating characteristics statistics. Perianal disease was active in 46 patients. The accuracy of the FDA was 87% (confidence interval [CI]: 76%-94%). A PDAI of >4 and a mean gray-scale tone value of 117 maximized sensitivity and specificity; their diagnostic accuracy was, respectively, 87% (CI: 76%-94%) and 81% (CI: 69%-90%). The agreement of the 3 evaluations was fair to moderate. The addition of AUS to the PDAI or FDA increased their diagnostic accuracy to respectively 95% and 98%. The diagnostic accuracy of the FDA, PDAI, and computer-assisted AUS imaging was good in assessing perianal disease activity in patients with CD. The agreement between the techniques was fair to moderate. Overall accuracy can be increased by combining the FDA or PDAI with AUS.

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up.

PubMed

Le Long, Erwann; Rebibo, John David; Nouhaud, Francois Xavier; Grise, Philippe

2016-01-01

to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered.

Current use of the artificial urinary sphincter and its long-term durability: a nationwide survey in Japan.

PubMed

Arai, Yoichi; Takei, Mineo; Nonomura, Katsuya; Baba, Shiro; Habuchi, Tomonori; Matsuda, Tadashi; Takahashi, Satoru; Igawa, Mikio; Kaiho, Yasuhiro; Nakagawa, Haruo

2009-01-01

Although the artificial urinary sphincter (AUS) is one of the most effective surgical treatments for severe urinary incontinence, little is known about its use in Japan. A nationwide survey was done to determine contemporary trends in AUS use and its long-term durability. Data on AUS units sold in Japan were provided directly by Takai Hospital Supply Co., Ltd., Tokyo, Japan, and a survey form was sent to all 44 institutes where AUS implantation had been carried out. The survey included various demographic and preoperative variables, surgical variables, and postoperative outcomes. Between 1994 and 2007, a total of 100 AUS devices had been provided in Japan. Of the 44 institutes, 24 responded to the survey, and a total of 64 patients were enrolled in the study. Post-urological surgery incontinence accounted for 81.3% of the indications. During the mean follow-up of 50 months, mechanical failure occurred in four (6.2%), and the device was removed in 13 (20.3%) due to infection (14.0%), erosion (4.7%), or urination difficulty (1.5%). Of the 58 patients evaluated, 91.4% reported social continence. Five- and 10-year failure-free rates were 74.8% and 70.1%, respectively. On multivariate analysis, operative time was an independent predictor of treatment failure (P = 0.0334). Considering recent trends in prostate surgery, the AUS may be significantly underused in Japan. Although excellent long-term durability has been achieved, a learning effect appears to be evident. The Japanese urological community needs to provide appropriate patients with this treatment option.

Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness

PubMed Central

Stachs, A.; Thi, A. Tra-Ha; Dieterich, M.; Stubert, J.; Hartmann, S.; Glass, Ä.; Reimer, T.; Gerber, B.

2015-01-01

Purpose: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. Materials and Methods: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). Results: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. Conclusion: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare. PMID:27689144

Uncommon pollen walls: reasons and consequences*)

PubMed Central

Pacini, Ettore; Hesse, Michael

2016-01-01

The mature pollen wall of gymnosperms and angiosperms consists in principle of two fundamentally different layers, the complex, thick sporopolleninous exine and the homogeneous, thin, single-layered pectocellulosic intine. In angiosperms, the typical exine is usually formed by a tectum, columellae, a foot layer, and an endexine. An exine reduction (minimally up to the complete absence) occurs in many unrelated seed plants, without consequences for pollen viability. The intine sometimes also deviates from its common form, being either extremely thick or appearing two- or even three-layered. Environmental factors or developmental constraints are highlighted as being responsible for the various deviating exine and intine forms. Pacini E. & Hesse M, 2012: Unkomplette Pollenwand – Gründe und Konsequenzen Die fertige Pollenwand der Gymnospermen und der Angiospermen besteht im Prinzip aus zwei fundamental verschiedenen Lagen, aus der komplexen, dicken und sporopolleninhältigen Exine, und der homogenen, dünnen, einschichtigen und überwiegend zellulosehältigen Intine. Bei Angiospermen ist die typische Exine aus einem Tectum, aus Columellae, aus einem Foot Layer und zumeist noch aus einer Endexine geformt. In vielen, nicht miteinander verwandten Angiospermen (seltener bei Gymnospermen) is die Exine mehr oder weniger stark reduziert, was allerdings keinen Einfluß auf die Keimungsfähigkeit des Pollens hat. Auch die Intine weicht manchmal von ihrer üblichen Ausbildung ab, ist entweder auffallend dick oder zwei bis dreischichtig. Sowohl Umweltfaktoren als auch embryologisch und entwicklungsgeschichtlich bedingte Hemmungen sind für die abweichenden Exine- und Intineformen verantwortlich. PMID:28904424

The binding site on cochlear stereocilia for antisera raised against renal Na+ channels is blocked by amiloride and dihydrostreptomycin.

PubMed

Furness, D N; Hackney, C M; Benos, D J

1996-04-01

The mechanoelectrical transduction channels on hair cells have been suggested to be operated by tip links that are stretched when the hair bundle is deflected in the direction of the tallest row of stereocilia. Localising these channels is therefore an important test of this hypothesis. The transduction channels are known to be amiloride-sensitive and immunogold labelling with antibodies raised against the amiloride-sensitive epithelial Na+ channel from kidney (alpha NaCh), has suggested that sites with similar characteristics are located in the region where the tips of the shorter stereocilia appear to come into contact with the sides of the adjacent taller stereocilia rather than being associated directly with the tip links. Now, further immunocytochemical experiments have been performed to determine if amiloride and dihydrostreptomycin, both of which can block transduction, can affect this labelling. Immunofluorescent labelling of the stereocilia is obtained when surface preparations of the organ of Corti are fixed and incubated with alpha NaCh followed by an appropriate secondary antibody. This labelling is abolished by trypsinization prior to fixation but retained if the tissue is pretreated with amiloride and then trypsinized in its presence. Because amiloride is known to protect amiloride-binding sites from degradation by trypsin, these results suggest that alpha NaCh is revealing amiloride-binding sites on the stereocilia. Similarly, immunofluorescent labelling of the stereocilia is abolished if cochlear tissue is pretreated with dihydrostreptomycin (DHS) and fixed in its presence prior to incubation with alpha NaCh. Quantitative analysis of colloidal gold labelling using transmission electron microscopy shows that DHS treatment produces a significant reduction in the number of gold particles on stereocilia, especially in the region of contact between them. These results suggest that anti-Na+ recognises a site with characteristics similar to the

Subclassification of the "grey zone" of thyroid cytology; a retrospective descriptive study with clinical, cytological, and histological correlation.

PubMed

Bonzanini, Mariella; Amadori, Pierluigi; Morelli, Luca; Fasanella, Silvia; Pertile, Riccardo; Mattiuzzi, Angela; Marini, Giorgio; Niccolini, Mauro; Tirone, Giuseppe; Rigamonti, Marco; Dalla Palma, Paolo

2011-01-01

Undetermined thyroid cytology precludes any definitive distinction between malignant and benign lesions. Recently several classifications have been proposed to split this category into two or more cytological subcategories related to different malignancy risk rates. The current study was performed retrospectively to investigate the results obtained separating "undetermined" cytologic reports into two categories: "follicular lesion" (FL) and "atypia of undetermined significance" (AUS). Biochemical, clinical, and echographic features of each category were also retrospectively analyzed. Altogether, 316 undetermined fine-needle aspirated cytologies (FNACs) were reclassified as 74 FL and 242 AUS. Histological control leads to a diagnosis of carcinomas, adenomas, and nonneoplastic lesions, respectively, in 42.2%, 20%, and 37.8% of AUS and in 8.3%, 69.4%, and 22.2% of FL. Among biochemical, clinical, cytological, and echographic outcomes, altered thyroid autoantibodies, multiple versus single nodule, AUS versus FL, and presence of intranodular vascular flow were statistically significant to differentiate adenoma from carcinoma and from nonneoplastic lesions, whereas no significant differences were found between carcinomas and nonneoplastic lesions for these parameters. The results of this retrospective study show that undetermined FNAC category can further be subclassified in AUS and FL, the former showing higher malignancy rate. Further prospective studies are needed to confirm our results.

Association between hyperglycaemia and fracture risk in non-diabetic middle-aged and older Australians: a national, population-based prospective study (AusDiab).

PubMed

Gagnon, C; Magliano, D J; Ebeling, P R; Dunstan, D W; Zimmet, P Z; Shaw, J E; Daly, R M

2010-12-01

The association between pre-diabetes and fracture risk remains unclear. In this large cohort of middle-aged and older Australian men and women without diabetes, elevated 2-h plasma glucose and pre-diabetes were associated with a reduced 5-year risk of low trauma and all fractures in women, independently of BMI, fasting insulin and other lifestyle factors. We aimed to (1) examine associations between fasting and 2-h plasma glucose (FPG and 2-h PG), fasting insulin and risk of low trauma and all fractures in non-diabetic adults and (2) compare fracture risk between adults with pre-diabetes (impaired glucose tolerance or impaired fasting glucose) and those with normal glucose tolerance (NGT). Six thousand two hundred fifty-five non-diabetic men and women aged ≥40 years with NGT (n = 4,855) and pre-diabetes (n = 1,400) were followed for 5 years in the AusDiab Study. Fractures were self-reported. Five hundred thirty-nine participants suffered at least one fracture (368 women, 171 men), of which the majority (318) occurred after a low-energy trauma (258 women, 60 men). In women, a 2-h PG ≥ 7.2 mmol/L (highest quartile) was associated with a decreased risk of low trauma and all fractures independent of age and BMI [OR (95% CI) for low trauma fractures, 0.59 (0.40-0.88)], but also fasting insulin, smoking, physical activity, history of fracture, dietary calcium and alcohol intake or menopausal status. There was no effect of 2-h PG on fracture risk in men [OR (95% CI), 1.39 (0.60-3.26)] or any relationship between fracture risk and quartiles of FPG or insulin in either sex. Compared to women with NGT, those with pre-diabetes had a reduced risk of fracture [OR (95% CI) for all fractures, 0.70 (0.52-0.95); for low trauma fractures, 0.75 (0.53-1.05)]. Elevated 2-h PG levels and pre-diabetes were inversely associated with low trauma and/or all fractures in non-diabetic women, independent of BMI and fasting insulin levels.

5. VIEW FROM TRACK, LOOKING NORTH THROUGH SPANS (BURLINGTON NORTHERN ...

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

5. VIEW FROM TRACK, LOOKING NORTH THROUGH SPANS (BURLINGTON NORTHERN RAILROAD BRIDGE ON RIGHT) - Yakima Valley Transportation Company Interurban Railroad, Naches River Bridge, Yakima, Yakima County, WA

Microinjection of acetylcholine into cerebellar fastigial nucleus induces blood depressor response in anesthetized rats.

PubMed

Zhang, Changzheng; Luo, Wen; Zhou, Peiling; Sun, Tingzhe

2016-08-26

It is well known that the cerebellar fastigial nucleus (FN) is involved in cardiovascular modulation, and has direct evidence of cholinergic activity; however, whether and how acetylcholine (ACh) in the FN modulates blood pressure has not been investigated. In this study, we analyzed mean arterial pressure, maximal change in mean arterial pressure, and the reaction time of blood pressure changes after microinjection of cholinergic reagents into the FN in anesthetized rats. The results showed that ACh evoked a concentration-dependent (10, 30 and 100mM) effect on blood pressure down-regulation. The muscarinic ACh (mACh) receptor antagonist atropine, but not the nicotinic ACh (nACh) receptor antagonist mecamylamine, blocked the ACh-mediated depressor response. The mACh receptor agonist oxotremorine M, rather than nACh receptor agonist nicotine, mimicked the ACh-mediated blood pressure decrease in a dose-dependent manner (10, 30 and 100mM). These results indicate that cholinergic input in the cerebellar FN exerts a depressor effect on systemic blood pressure regulation, and such effects are substantially contributed by mACh rather than nACh receptors, although the precise mechanism concerning the role of mACh receptor in FN-mediated blood pressure modulation remains to be elucidated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of abdominal ultrasound and magnetic resonance imaging for detection of abdominal lymphadenopathy in dogs with metastatic apocrine gland adenocarcinoma of the anal sac.

PubMed

Anderson, C L; MacKay, C S; Roberts, G D; Fidel, J

2015-06-01

Imaging studies in humans with anal and rectal cancer indicate that magnetic resonance imaging (MRI) is a more sensitive technique than abdominal ultrasound (AUS) for the detection of abdominal lymphadenopathy. The purpose of this retrospective study was to directly compare the efficacy of these two techniques in detecting abdominal lymphadenopathy in dogs with apocrine gland adenocarcinoma of the anal sac (AGAAS). Six dogs with histologically confirmed AGAAS and histopathologic confirmation of metastasis to abdominal lymph nodes (LNs) had AUS and abdominal MRI. AUS identified lymphadenopathy in two of six dogs, whereas MRI identified lymphadenopathy in all the six dogs. Lymphadenopathy was predominantly sacral in location, with involvement of the medial iliac and hypogastric LNs in only two cases. These data suggest that MRI is more sensitive than AUS for detecting sacral abdominal lymphadenopathy in dogs with AGAAS. As such, MRI could be considered in any patient with AGAAS for initial staging of this disease. © 2013 Blackwell Publishing Ltd.

Virtual-system-coupled adaptive umbrella sampling to compute free-energy landscape for flexible molecular docking.

PubMed

Higo, Junichi; Dasgupta, Bhaskar; Mashimo, Tadaaki; Kasahara, Kota; Fukunishi, Yoshifumi; Nakamura, Haruki

2015-07-30

A novel enhanced conformational sampling method, virtual-system-coupled adaptive umbrella sampling (V-AUS), was proposed to compute 300-K free-energy landscape for flexible molecular docking, where a virtual degrees of freedom was introduced to control the sampling. This degree of freedom interacts with the biomolecular system. V-AUS was applied to complex formation of two disordered amyloid-β (Aβ30-35 ) peptides in a periodic box filled by an explicit solvent. An interpeptide distance was defined as the reaction coordinate, along which sampling was enhanced. A uniform conformational distribution was obtained covering a wide interpeptide distance ranging from the bound to unbound states. The 300-K free-energy landscape was characterized by thermodynamically stable basins of antiparallel and parallel β-sheet complexes and some other complex forms. Helices were frequently observed, when the two peptides contacted loosely or fluctuated freely without interpeptide contacts. We observed that V-AUS converged to uniform distribution more effectively than conventional AUS sampling did. © 2015 Wiley Periodicals, Inc.

Effect of microstructure on transformation-induced plasticity of silicon-containing low-alloy steel

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

Tomita, Yoshiyuki; Morioka, Kojiro

1997-04-01

Fe-0.6C-1.5Si-0.8Mn steel was studied to determine the effect of the microstructure on transformation-induced plasticity (TRIP) of silicon-containing low-alloy steel. A remarkable increase in elongation through TRIP can develop in the steel subjected to the following heat treatments: (1) austemper combined with subcritical annealing (SA Aus-T): subcritical annealing at 993K followed by austempering at 673K and then light tempering (after austenitization at 1173K); (2) austemper coupled with interrupted quenching (IQ Aus-T): interrupted quenching at 533K followed by austempering at 673K and light tempering (after austenization at 1,173K). The SA Aus-T treatment produced the triple structures of carbide-free upper bainite, retained austenitemore » ({gamma}R), and free ferrite. As a result of the IQ Aus-T treatment, the triple structures of carbide-free upper bainite, {gamma}R, and tempered martensite appeared. The results are described and microstructural factors in TRIP are discussed.« less

Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart.

PubMed

Matsuhashi, Tomohiro; Hishiki, Takako; Zhou, Heping; Ono, Tomohiko; Kaneda, Ruri; Iso, Tatsuya; Yamaguchi, Aiko; Endo, Jin; Katsumata, Yoshinori; Atsushi, Anzai; Yamamoto, Tsunehisa; Shirakawa, Kohsuke; Yan, Xiaoxiang; Shinmura, Ken; Suematsu, Makoto; Fukuda, Keiichi; Sano, Motoaki

2015-05-01

Dichloroacetate (DCA) promotes pyruvate entry into the Krebs cycle by inhibiting pyruvate dehydrogenase (PDH) kinase and thereby maintaining PDH in the active dephosphorylated state. DCA has recently gained attention as a potential metabolic-targeting therapy for heart failure but the molecular basis of the therapeutic effect of DCA in the heart remains a mystery. Once-daily oral administration of DCA alleviates pressure overload-induced left ventricular remodeling. We examined changes in the metabolic fate of pyruvate carbon (derived from glucose) entering the Krebs cycle by metabolic interventions of DCA. (13)C6-glucose pathway tracing analysis revealed that instead of being completely oxidized in the mitochondria for ATP production, DCA-mediated PDH dephosphorylation results in an increased acetyl-CoA pool both in control and pressure-overloaded hearts. DCA induces hyperacetylation of histone H3K9 and H4 in a dose-dependent manner in parallel to the dephosphorylation of PDH in cultured cardiomyocytes. DCA administration increases histone H3K9 acetylation in in vivo mouse heart. Interestingly, DCA-dependent histone acetylation was associated with an up-regulation of 2.3% of genes (545 out of 23,474 examined). Gene ontology analysis revealed that these genes are highly enriched in transcription-related categories. This evidence suggests that sustained activation of PDH by DCA results in an overproduction of acetyl-CoA, which exceeds oxidation in the Krebs cycle and results in histone acetylation. We propose that DCA-mediated PDH activation has the potential to induce epigenetic remodeling in the heart, which, at least in part, forms the molecular basis for the therapeutic effect of DCA in the heart. Copyright © 2015 Elsevier Ltd. All rights reserved.

Superoxide anion stress attenuates the contractile response of the Guinea pig vas deferens to ATP and diadenosine tetraphosphate. Possible effect on calcium dysregulation.

PubMed

Al-Rawi, Mahmood B; Aleisa, Abdulaziz M; Khattab, Mahmoud M

2008-01-01

Induction of endogenous superoxide anion stress by the use of the superoxide dismutase inhibitor diethylthiocarbamate (DETCA; 10 mmol/l) produced a potent inhibition of the ATP (0.3-10 mmol/l) and diadenosine tetraphosphate (AP(4)A) contractile activity in the isolated vas deferens by 29-92 and 24-90%, respectively. Pyrogallol (0.1 mmol/l), the exogenous superoxide anion generator, produced a significant inhibition on the contractile activity of the vas deferens induced by ATP and AP(4)A by 33-89 and 25-82%, respectively. DETCA (10 mmol/l) and pyrogallol (0.1 mmol/l) attenuated the contractile response of isolated guinea pig vas deferens strips to the selective P2X agonist alpha,beta-methyleneATP (alpha,beta-meATP; 50 micromol/l) by 25 and 47%, respectively. In Ca(2+)-free high-K(+) (80 mmol/l) Krebs solution, pyrogallol and DETCA produced inhibition of the contractile response to alpha,beta-meATP (50 micromol/l) in similar way to that in normal Krebs solution. The further addition of CaCl(2) (1 mmol/l) abolished the inhibitory effects exerted by pyrogallol and DETCA. The control contractile response to alpha,beta-meATP (50 micromol/l) was not affected in Ca(2+)-free high-K(+) (80 mmol/l) Krebs solution. It may be concluded that superoxide anion stress produces a significant inhibitory effect on both mono- and di-nucleotide purinergic contraction of the vas deferens. Superoxide anion appears to interrupt the P2X(1)-mediated transduction cascade at some step(s) of intracellular calcium handling. Copyright 2008 S. Karger AG, Basel.

HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity.

PubMed

Murlas, C G; Murphy, T P; Lang, Z

1990-06-01

We investigated whether exposure of guinea pig tracheal tissue to hypochlorous acid (HOCl) or hydrogen peroxide (H2O2) by perfusion through the airway lumen affected the responsiveness of airway muscle to ACh, KCl, or substance P in the presence or absence of 1 microM phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Pairs of tracheal segments were immersed in a Krebs solution (pH 7.40 at 37 degrees C) and connected to perfusion circuits so that the lumen of one segment of each pair could be perfused with Krebs solution while the other was perfused for the same time (10 min) with either 0.1 microM HOCl or 10 mM H2O2. Segments after perfusion were cut into rings of similar size and placed in muscle chambers so that airway muscle force generation in vitro could be measured on stimulation by cumulative agonist doses. In addition, cell homogenates were made from other, similarly perfused tracheal segments to assess NEP activity using reverse-phase, high-pressure liquid chromatography (HPLC). We found that smooth muscle of mucosa-intact guinea pig airways perfused with HOCl, but not H2O2, was hyperresponsive to substance P but not to ACh or KCl. HOCl-perfused rings were not different from Krebs solution-exposed rings pretreated with phosphoramidon. There was no increase in substance P responsiveness of HOCl-exposed airways in which the mucosa had been removed before testing in vitro. The substance P hyperresponsiveness of HOCl-exposed, mucosa-intact airways was associated with decreased NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural variation of rice blast resistance gene Pi-d2

USDA-ARS?s Scientific Manuscript database

Studying natural variation of rice resistance (R) genes in cultivated and wild rice relatives can predict resistance stability to rice blast fungus. In the present study, the protein coding regions of rice R gene Pi-d2 in 35 rice accessions of subgroups, aus (AUS), indica (IND), temperate japonica (...

Kunststoffe (Polymere)

NASA Astrophysics Data System (ADS)

Weißbach, Wolfgang

Polymere bestehen aus Riesen- oder Makromolekülen, die durch chemische Reaktionen aus einfachen, niedermolekularen Verbindungen entstehen, den Monomeren. Ausgangsstoffe sind überwiegend Kohlenwasserstoffe (KW), die größte Gruppe der C-Verbindungen. Sie müssen reaktionsfähige Stellen besitzen, das sind OH-Gruppen oder Dopppelbindungen.

Practice patterns of post-radical prostatectomy incontinence surgery in Ontario

PubMed Central

Wallis, Christopher J.D.; Herschorn, Sender; Liu, Ying; Carr, Lesley K.; Kodama, Ronald T.; Klotz, Laurence H.; Saskin, Refik; Nam, Robert K.

2014-01-01

Introduction: We assess the practice patterns of artificial urinary sphincter (AUS) and urethral sling insertion after radical prostatectomy (RP) from a large population-based cohort. Methods: We examined 25 346 men in Ontario, Canada who underwent RP between 1993 and 2006. Using hospital and cancer registry data, we identified patients who subsequently underwent an incontinence procedure. We characterized the practice patterns of post-prostatectomy incontinence procedures across Ontario during the study interval. Results: A total of 703 (2.8%) men underwent subsequent insertion of an AUS and 282 (1.1%) underwent a urethral sling procedure (985 total incontinence procedures, 3.9%) over the study period. During the study period, 121 hospitals performed RP. Among them, 32 (26%) hospitals performed both RP and AUS/sling procedures, and 89 (74%) performed RP only. Four hospitals performed AUS/sling procedures but not RP. Of the 36 institutions that performed AUS/sling procedures, the median annual case volume was 0.29 (interquartile range: 0.083-0.75). Of all incontinence procedures, 56% were performed at 3 academic institutions. When examining observed rates of AUS/sling procedures compared with expected rates from the overall cohort, 15 of 32 hospitals (47%) performed significantly fewer incontinence procedures than expected given their RP case volume (p range: <0.0001–0.0390) and 5 (16%) performed significantly more (p range: <0.0001–0.038). Conclusions: A small number of academic institutions provide most of the surgical care for men with incontinence following RP in Ontario. Many centres that perform RP refer out to other centres to surgically manage their patients’ incontinence. PMID:25408805

Utility of Computed Tomography versus Abdominal Ultrasound Examination to Identify Iliosacral Lymphadenomegaly in Dogs with Apocrine Gland Adenocarcinoma of the Anal Sac.

PubMed

Palladino, S; Keyerleber, M A; King, R G; Burgess, K E

2016-11-01

Apocrine gland adenocarcinoma of the anal sac (AGAAS) is associated with high rates of iliosacral lymph node metastasis, which may influence treatment and prognosis. Magnetic resonance imaging (MRI) recently has been shown to be more sensitive than abdominal ultrasound examination (AUS) in affected patients. To compare the rate of detection of iliosacral lymphadenomegaly between AUS and computed tomography (CT) in dogs with AGAAS. Cohort A: A total of 30 presumed normal dogs. Cohort B: A total of 20 dogs with AGAAS that underwent AUS and CT. Using cohort A, mean normalized lymph node : aorta (LN : AO) ratios were established for medial iliac, internal iliac, and sacral lymph nodes. The CT images in cohort B then were reviewed retrospectively and considered enlarged if their LN : AO ratio measured 2 standard deviations above the mean normalized ratio for that particular node in cohort A. Classification and visibility of lymph nodes identified on AUS were compared to corresponding measurements obtained on CT. Computed tomography identified lymphadenomegaly in 13 of 20 AGAAS dogs. Of these 13 dogs, AUS correctly identified and detected all enlarged nodes in only 30.8%, and either misidentified or failed to detect additional enlarged nodes in the remaining dogs. Despite limitations in identifying enlargement in all affected lymph nodes, AUS identified at least 1 enlarged node in 100% of affected dogs. Abdominal ultrasound examination is an effective screening test for lymphadenomegaly in dogs with AGAAS, but CT should be considered in any patient in which an additional metastatic site would impact therapeutic planning. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Speaker and Accent Variation Are Handled Differently: Evidence in Native and Non-Native Listeners

PubMed Central

Kriengwatana, Buddhamas; Terry, Josephine; Chládková, Kateřina; Escudero, Paola

2016-01-01

Listeners are able to cope with between-speaker variability in speech that stems from anatomical sources (i.e. individual and sex differences in vocal tract size) and sociolinguistic sources (i.e. accents). We hypothesized that listeners adapt to these two types of variation differently because prior work indicates that adapting to speaker/sex variability may occur pre-lexically while adapting to accent variability may require learning from attention to explicit cues (i.e. feedback). In Experiment 1, we tested our hypothesis by training native Dutch listeners and Australian-English (AusE) listeners without any experience with Dutch or Flemish to discriminate between the Dutch vowels /I/ and /ε/ from a single speaker. We then tested their ability to classify /I/ and /ε/ vowels of a novel Dutch speaker (i.e. speaker or sex change only), or vowels of a novel Flemish speaker (i.e. speaker or sex change plus accent change). We found that both Dutch and AusE listeners could successfully categorize vowels if the change involved a speaker/sex change, but not if the change involved an accent change. When AusE listeners were given feedback on their categorization responses to the novel speaker in Experiment 2, they were able to successfully categorize vowels involving an accent change. These results suggest that adapting to accents may be a two-step process, whereby the first step involves adapting to speaker differences at a pre-lexical level, and the second step involves adapting to accent differences at a contextual level, where listeners have access to word meaning or are given feedback that allows them to appropriately adjust their perceptual category boundaries. PMID:27309889

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up

PubMed Central

Long, Erwann Le; Rebibo, John David; Nouhaud, Francois Xavier; Grise, Philippe

2016-01-01

ABSTRACT Purpose to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. Materials and Methods From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. Results After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. Conclusions Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered. PMID:27286112

[Laparoscopic approach for artificial urinary sphincter implantation in women with severe urinary stress incontinence].

PubMed

Trolliet, S; Mandron, E; Lang, H; Jacqmin, D; Saussine, C

2013-09-01

To evaluate, feasibility, efficacy and morbidity of laparoscopic artificial urinary sphincter (AUS) implantation in women with severe stress urinary incontinence. Twenty-six women with severe stress urinary incontinence were treated between October 2007 and January 2012 by laparoscopic implantation of an AUS AMS 800 (American medical Systems, Inc., Minnetonka, Minnesota). For 18 patients AUS was primary implanted and, for eight, AUS was revised for a mechanical failure. Three patients had a concomitant laparoscopic vaginal prolapse repair. Mean value was for age 64 years, BMI 27.8kg/m2, and mean maximal urethral closure pressure was 26.75cm of water. Most of the patients (88%) had a history of pelvic or incontinence surgery. The study was a retrospective analysis of operative parameters, complications and functional results. Three conversions in open surgery and five bladder injuries were described. Mean operative time was 149 minutes. Bladder catheter was removed at a mean of day 3.8. Mean post-operative stay was 5 days. Early postoperative complications consist in eight acute transient urinary retentions, two pump migrations, and one vaginal injury. Late post-operative complications consist in one vaginal erosion. Explantation of AUS was performed for these last two patients. Mean follow-up was 20 months. Sixteen patients are totally continent, five have a social continence (1 pad/day) and three need more than one pad/day. Our results compare favorably to literature either for laparoscopic or conventional approach with a limited learning curve. Laparoscopic implantation of AUS in women with severe stress urinary incontinence was feasible and efficient. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

New Partnerships and Education Policy in Asia and the Pacific

ERIC Educational Resources Information Center

Cassity, Elizabeth

2010-01-01

Forming more effective partnerships with national governments in the Asia-Pacific region has been an important policy focus for the Australian Agency for International Development (AusAID) since 2006. AusAID is increasingly engaging in sector-wide approaches and working through partner government systems. This paper explores how new partnerships…

The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy.

PubMed

Wu, Howard Her-Juing; Rose, Crystal; Elsheikh, Tarik M

2012-05-01

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy. Copyright © 2011 Wiley-Liss, Inc.

Long-term functional outcomes after artificial urinary sphincter implantation in women with stress urinary incontinence.

PubMed

Phé, Véronique; Benadiba, Steeve; Rouprêt, Morgan; Granger, Benjamin; Richard, François; Chartier-Kastler, Emmanuel

2014-06-01

To assess the long-term outcomes obtained after artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI). Women with SUI caused by intrinsic sphincter deficiency who underwent an AUS placement between 1984 and 1992 were included. Explantation, revision and deactivation rates of the AUS were reported. Continence, defined as no pad use, was assessed at the end of the follow-up. Kaplan-Meier survival curves were generated to evaluate the survival rate of the device without explantation or revision. A total of 34 patients were included. The median (interquartile range [IQR]) age of the patients at surgery was 56.5 (50-64.7) years and the median (IQR) follow-up was 17 (12-19) years. Overall, 26 women (74%) still had their AUS in place at the end of the follow-up, while eight patients underwent an explantation of the device. The 10-, 15- and 20-year device survival rates without explantation were 80, 80 and 74%, respectively. The 10-, 15- and 20-year survival rates of the device without revision were 79, 65 and 40%, respectively. After 20 years of follow-up, 11 women still had successful outcomes (61%). The AUS provided satisfactory very long-term functional results among women with SUI caused by intrinsic sphincter deficiency. © 2013 The Authors. BJU International © 2013 BJU International.

77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-02

... DEPARTMENT OF STATE [Public Notice: 7783] The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known as Abu Adam From Germany, also Known as Abu Adam aus... Chouka, also known as Abu Adam from Germany, also known as Abu Adam aus Deutschland, committed, or poses...

TÜV - Zertifizierungen in der Life Science Branche

NASA Astrophysics Data System (ADS)

Schaff, Peter; Gerbl-Rieger, Susanne; Kloth, Sabine; Schübel, Christian; Daxenberger, Andreas; Engler, Claus

Life Sciences [1] (Lebenswissenschaften) sind ein globales Innovationsfeld mit Anwendungen der Bio- und Medizinwissenschaften, der Pharma-, Chemie-, Kosmetik- und Lebensmittelindustrie. Diese Branche zeichnet sich durch eine stark interdisziplinäre Ausrichtung aus, mit Anwendung wissenschaftlicher Erkenntnisse und Einsatz von Ausgangsstoffen aus der modernen Biologie, Chemie und Humanmedizin sowie gezielter marktwirtschaftlich orientierter Arbeit.

SaVE Our Campus: Analyzing the Effectiveness of an Online Sexual Violence Program

ERIC Educational Resources Information Center

Draper, Jordan Leigh

2017-01-01

Nearly 20% of college females and 6% of college males will experience a form of sexual assault while enrolled in a college or university (Krebs, Lindquist, Warner, Fisher, & Martin, 2007). Sexual violence is not a new issue within college environments; however, it is rapidly gaining media attention based on victim testimonials and additional…

The Biological Fuel Cell

ERIC Educational Resources Information Center

Caccavo, Frank, Jr.; Clegern, William; Miller, Isaac; Montoya, Crystal

2003-01-01

Metabolism, the sum of all chemical reactions within a living organism, is one of the most fundamental concepts presented in introductory microbiology courses. However, it is often difficult for instructors to effectively translate perfunctory diagrams of glycolysis, the Krebs cycle, and the electron transport chain in a way that is meaningful to…

A Review of Marine Geophysical Constraints on the Motion Between East and West Antarctica in the Cenozoic (Invited)

NASA Astrophysics Data System (ADS)

Cande, S. C.; Stock, J. M.

2010-12-01

Motion between East and West Antarctica in the Late Cretaceous and Cenozoic is derived by summing the plate circuit(s) linking East Antarctica to Australia to the Lord Howe Rise to the Pacific plate to West Antarctica (the Aus-Pac plate circuit). We discuss this motion in two parts: motion before and after 42 Ma. For the younger time interval, motion is directly constrained by magnetic anomalies in the Adare Basin, which opened by ultraslow seafloor spreading between 42 and 26 Ma (anomalies 18 to 9). The Adare Basin magnetic anomaly constraints can be combined with magnetic anomaly and fracture zone data from the SEIR (Aus-East Ant to the west of the Balleny FZ and Aus - West Ant to the east) to set up an Aus-East Ant - West Ant three-plate problem. The original solution of this three-plate configuration (Cande et al., 2000) only had data from a very short section of the Adare Basin and obtained an answer with very large uncertainties on the East-West Ant rotation. Better estimates of the East-West Ant rotation have been calculated by adding constraints based on seismically controlled estimates of extension in the Victoria Land Basin (Davey et al., 2006) and constraints from Damaske et al’s (2007) detailed aeromagnetic survey of the Adare Basin and adjacent Northern Basin (Granot et al., 2010). Currently, we are working on improving the accuracy of rotations for the post-42 Ma time interval by taking advantage of an unusual plate geometry that enables us to solve a five-boundary, four-plate configuration. Specifically, motion between the four plates (East Ant, West Ant, Aus and Pac) encompasses two related triple junction systems with five spreading ridge segments (Aus-East Ant, Aus-West Ant, Aus-Pac, Pac-West Ant and East Ant-West Ant) which can be combined and solved simultaneously. For the older, pre-42 Ma time interval, the only way to calculate motion between East and West Antarctica is via the long Aus-Pac plate circuit (although it is possible that

Role of Core Needle Biopsy in the Management of Atypia/Follicular Lesion of Undetermined Significance Thyroid Nodules: Comparison with Repeat Fine-Needle Aspiration in Subcategory Nodules

PubMed Central

Na, Dong Gyu; Min, Hye Sook; Lee, Hunkyung; Won, Jae-Kyung; Seo, Hyo Bin; Kim, Ji-Hoon

2015-01-01

Background The role of repeat fine-needle aspiration (RFNA) or core needle biopsy (CNB) has not been established in nodules categorized as atypia/follicular lesion of undetermined significance (AUS/FLUS). Objective The purpose of this study was to retrospectively determine whether CNB is more useful for management decisions than RFNA at each subcategory of AUS/FLUS nodules. Methods This study included 158 AUS/FLUS nodules (≥1 cm) from 153 consecutive patients who underwent both RFNA and CNB. The AUS/FLUS nodules were subcategorized into nuclear atypia (NA) and follicular lesions with other atypia (FOA). The diagnostic results and rate of determined management by RFNA and CNB were compared at each subcategory. The diagnostic values of RFNA and CNB for malignancy were evaluated in nodules with final diagnoses. Results CNB showed a lower rate of AUS/FLUS diagnosis, higher rates of benign and follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN) diagnoses (p ≤ 0.038), and marginally higher rates of malignant diagnosis than RFNA in the NA subcategory. CNB showed a higher rate of FN/SFN (p = 0.007) than RFNA in the FOA subcategory. CNB also demonstrated a higher rate of surgery decision than RFNA in both the NA subcategory (20.2 vs. 9.6%, p < 0.001) and FOA subcategory (20.8 vs. 5.6%, p = 0.007), and a higher rate of observation decision only in the NA subcategory (48.1 vs. 35.6%, p = 0.035). CNB demonstrated a higher diagnostic performance for malignancy overall in the nodules compared with RFNA. Conclusion CNB may be more useful for management decisions than RFNA in both the NA and FOA subcategories, and has the potential to be a first-line alternative diagnostic tool in initially diagnosed AUS/FLUS nodules. PMID:26558236

First Results of GPS Time Transfer to Australia

NASA Technical Reports Server (NTRS)

Mck.luck, J.; Woodger, J. R.; Wells, J. E.; Churchill, P. N.; Clements, P. A.

1984-01-01

A global positioning system (GPS) time transfer unit was installed at Tidbinbilla Deep Space Communications Complex of the DSN in June 1983. It was used to estimate the relationship to UTC(USNO MC) of the Tidbinbilla frequency and time system TID(FTS) based on a hydrogen maser, and to estimate the performance of the Australian free-running time scale UTC(AUS). Data from the first 3 months were analyzed three ways: by two-hop common view using JPL as intermediary; by long-arc interpolation of measurements against space vehicle clocks; and by long arc interpolation of GPS-Time results. Residuals from a single quadratic fit through 3 months of UTC(USNO MC) -TID(FTS) results were white noise with standard error 15 ns, and a flying clock measurement gave 70 ns agreement. A straight line fit through results UTC(USNO MC) - UTC(AUS) gave 90 ns standard error and 120 ns agreement. It is proposed to use the GPS measurements to steer UTC(AUS) to UTC(BIH), and to rename the existing time scale TA(AUS).

77 FR 40565 - Northwest Forest Plan Provincial Advisory Committees

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

.... Addresses: 215 Melody Lane, Wenatchee, WA, 98801. For Further Information Contact: Robin DeMario, 509-664... Highway 12, Naches, WA. For Further Information Contact: Robin DeMario, 509-664-9292. Deschutes PAC...

9. Close view of gate valves (foreground), paddle wheel guard ...

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

9. Close view of gate valves (foreground), paddle wheel guard (midground), and water wheel (background), facing southeast (downstream) from drum screen cover. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

Comparing standardized measures of diligence and achievement with dental student academic performance.

PubMed

Jedrychowski, Joseph; Lindemann, Robert

2005-04-01

Utilizing a reliable and valid instrument to measure a student's application of energy and effort towards a goal (diligence) or the ability to reach goals (achievement) would enable dental educators to anticipate academic performance. This knowledge could be used to better distribute faculty and educational resources, as additional tutors could be provided for students who score low on diligence and achievement instruments. In this study, fourth-year dental students completed the Diligence Inventory and the NachNaff Scale (which measures desire to achieve) immediately prior to graduation. The scores from both inventories were correlated with nine measures of academic performance. For males, the NachNaff Scale positively correlated (p<.05) only with the quantity of exceptional performance reports (EPR) and for females negatively correlated only with science DAT scores. The modest positive correlations, which differ for gender, suggest that the NachNaff may be of limited use to predict dental student performance. For males, the Total Diligence mean positively correlated with EPR and National Board Parts I and II scores. For females, the Total Diligence mean positively correlated with EPR and a predental biology-chemistry-physics grade composite. Given the simplicity of the Diligence Inventory and its significant correlations with academic performance demonstrated in this study, it appears to be a useful tool to gain insight into students' diligence in striving to obtain goals.

Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

PubMed

Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F; Sadek, Bassem; Oz, Murat

2017-06-01

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC 50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl - channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing Conceptual Understanding of Glycolysis & the Krebs Cycle Using Role-Play

ERIC Educational Resources Information Center

Ross, Pauline M.; Tronson, Deidre A.; Ritchie, Raymond J.

2008-01-01

Cellular respiration and metabolism are topics that are reportedly poorly understood by students and judged to be difficult by many teachers. Although these topics may not be required learning areas in some high school biology curricula, a grasp of fundamental concepts of cellular metabolic processes is advantageous for students undertaking (or…

Identification of Action Units Related to Affective States in a Tutoring System for Mathematics

ERIC Educational Resources Information Center

Padrón-Rivera, Gustavo; Rebolledo-Mendez, Genaro; Parra, Pilar Pozos; Huerta-Pacheco, N. Sofia

2016-01-01

Affect is an important element of the learning process both in the classroom and with educational technology. This paper presents analyses in relation to the identification of Action Units (AUs) related to affective states and their impact on learning with a tutoring system. To assess affect, a tool was devised to identify AUs on pictures of human…

Comparative analysis of the complete genome of an epidemic hospital sequence type 203 clone of vancomycin-resistant Enterococcus faecium

PubMed Central

2013-01-01

Background In this report we have explored the genomic and microbiological basis for a sustained increase in bloodstream infections at a major Australian hospital caused by Enterococcus faecium multi-locus sequence type (ST) 203, an outbreak strain that has largely replaced a predecessor ST17 sequence type. Results To establish a ST203 reference sequence we fully assembled and annotated the genome of Aus0085, a 2009 vancomycin-resistant Enterococcus faecium (VREfm) bloodstream isolate, and the first example of a completed ST203 genome. Aus0085 has a 3.2 Mb genome, comprising a 2.9 Mb circular chromosome and six circular plasmids (2 kb–130 kb). Twelve percent of the 3222 coding sequences (CDS) in Aus0085 are not present in ST17 E. faecium Aus0004 and ST18 E. faecium TX16. Extending this comparison to an additional 12 ST17 and 14 ST203 E. faecium hospital isolate genomes revealed only six genomic regions spanning 41 kb that were present in all ST203 and absent from all ST17 genomes. The 40 CDS have predicted functions that include ion transport, riboflavin metabolism and two phosphotransferase systems. Comparison of the vancomycin resistance-conferring Tn1549 transposon between Aus0004 and Aus0085 revealed differences in transposon length and insertion site, and van locus sequence variation that correlated with a higher vancomycin MIC in Aus0085. Additional phenotype comparisons between ST17 and ST203 isolates showed that while there were no differences in biofilm-formation and killing of Galleria mellonella, ST203 isolates grew significantly faster and out-competed ST17 isolates in growth assays. Conclusions Here we have fully assembled and annotated the first ST203 genome, and then characterized the genomic differences between ST17 and ST203 E. faecium. We also show that ST203 E. faecium are faster growing and can out-compete ST17 E. faecium. While a causal genetic basis for these phenotype differences is not provided here, this study revealed conserved genetic

Positive inotropism in mammalian skeletal muscle in vitro during and after fatigue.

PubMed

Reading, S A; Murrant, C L; Barclay, J K

2004-04-01

We tested the hypothesis that positive inotropic factors decrease fatigue and improve recovery from fatigue in mammalian skeletal muscle in vitro. To induce fatigue, we stimulated mouse soleus and extensor digitorum longus (EDL) to perform isometric tetanic contractions (50 impulses x s(-1) for 0.5 s) at 6 contractions x min(-1) for 60 min in soleus and 3 contractions x min(-1) for 20 min in EDL. Muscles were submerged in Krebs-Henseleit bicarbonate solution (Krebs) at 27 degrees C gassed with 95% nitrogen - 5% carbon dioxide (anoxia). Before and for 67 min after the fatigue period, muscles contracted at 0.6 contractions x min(-1) in 95% oxygen - 5% carbon dioxide (hyperoxia). We added a permeable cAMP analog (N6, 2'-O-dibutyryladenosine 3':5'-cyclic monophosphate at 10(-3) mol x L(-1) (dcAMP)), caffeine (2 x 10(-3) mol x L(-1), or Krebs as vehicle control at 25 min before, during, or at the end of the fatigue period. In soleus and EDL, both challenges added before fatigue significantly increased developed force but only caffeine increased developed force when added during the fatigue period. At the end of fatigue, the decrease in force in challenged muscles was equal to or greater than in controls so that the force remaining was the same or less than in controls. EDL challenged with dcAMP or caffeine at any time recovered more force than controls. In soleus, caffeine improved recovery except when added before fatigue. With dcAMP added to soleus, recovery was better after challenges at 10 min and the end of the fatigue period. Thus, increased intracellular concentrations of cAMP and (or) Ca2+ did not decrease fatigue in either muscle but improved recovery from fatigue in EDL and, in some conditions, in soleus.

Comparisons of patch-use models for wintering American tree sparrows

USGS Publications Warehouse

Tome, M.W.

1990-01-01

Optimal foraging theory has stimulated numerous theoretical and empirical studies of foraging behavior for >20 years. These models provide a valuable tool for studying the foraging behavior of an organism. As with any other tool, the models are most effective when properly used. For example, to obtain a robust test of a foraging model, Stephens and Krebs (1986) recommend experimental designs in which four questions are answered in the affirmative. First, do the foragers play the same "game" as the model? Sec- ond, are the assumptions of the model met? Third, does the test rule out alternative possibilities? Finally, are the appropriate variables measured? Negative an- swers to any of these questions could invalidate the model and lead to confusion over the usefulness of foraging theory in conducting ecological studies. Gaines (1989) attempted to determine whether American Tree Sparrows (Spizella arborea) foraged by a time (Krebs 1973) or number expectation rule (Gibb 1962), or in a manner consistent with the predictions of Charnov's (1976) marginal value theorem (MVT). Gaines (1989: 118) noted appropriately that field tests of foraging models frequently involve uncontrollable circumstances; thus, it is often difficult to meet the assumptions of the models. Gaines also states (1989: 118) that "violations of the assumptions are also in- formative but do not constitute robust tests of predicted hypotheses," and that "the problem can be avoided by experimental analyses which concurrently test mutually exclusive hypotheses so that alter- native predictions will be eliminated if falsified." There is a problem with this approach because, when major assumptions of models are not satisfied, it is not justifiable to compare a predator's foraging behavior with the model's predictions. I submit that failing to follow the advice offered by Stephens and Krebs (1986) can invalidate tests of foraging models.

Contribution of extracellular glutamine as an anaplerotic substrate to neuronal metabolism: a re-evaluation by multinuclear NMR spectroscopy in primary cultured neurons.

PubMed

Shokati, Touraj; Zwingmann, Claudia; Leibfritz, Dieter

2005-10-01

Multinuclear NMR spectroscopy is used to investigate the effect of glutamine on neuronal glucose metabolism. Primary neurons were incubated with [1-(13C)]glucose in the absence or presence of glutamine (2 mM) and/or NH4Cl (5 mM). After ammonia-treatment, the concentrations of high-energy phosphates decreased up to 84% of control, which was aggravated in glutamine-containing medium (up to 42% of control). These effects could not be attributed to changes in mitochondrial glucose oxidation. Withdrawal of glutamine decreased amino acid concentrations, e.g. of glutamate to 53%, but also considerably lessened the 13C enrichment in [4-(13C)]glutamate to 8.3% of control, and decreased the 13C-enrichment in acetyl-CoA entering the Krebs cycle (P < 0.001). Thus, although glutamine is potent in replenishing neuronal glutamate stores, glutamate formation is mainly attributed to its de novo synthesis from glucose. Furthermore, mitochondrial glucose metabolism strongly depends on the supply of carbons from glutamine, indicating that exogenous glutamine is a well-suited substrate to replenish neuronal Krebs cycle intermediates.

Recognizing Action Units for Facial Expression Analysis

PubMed Central

Tian, Ying-li; Kanade, Takeo; Cohn, Jeffrey F.

2010-01-01

Most automatic expression analysis systems attempt to recognize a small set of prototypic expressions, such as happiness, anger, surprise, and fear. Such prototypic expressions, however, occur rather infrequently. Human emotions and intentions are more often communicated by changes in one or a few discrete facial features. In this paper, we develop an Automatic Face Analysis (AFA) system to analyze facial expressions based on both permanent facial features (brows, eyes, mouth) and transient facial features (deepening of facial furrows) in a nearly frontal-view face image sequence. The AFA system recognizes fine-grained changes in facial expression into action units (AUs) of the Facial Action Coding System (FACS), instead of a few prototypic expressions. Multistate face and facial component models are proposed for tracking and modeling the various facial features, including lips, eyes, brows, cheeks, and furrows. During tracking, detailed parametric descriptions of the facial features are extracted. With these parameters as the inputs, a group of action units (neutral expression, six upper face AUs and 10 lower face AUs) are recognized whether they occur alone or in combinations. The system has achieved average recognition rates of 96.4 percent (95.4 percent if neutral expressions are excluded) for upper face AUs and 96.7 percent (95.6 percent with neutral expressions excluded) for lower face AUs. The generalizability of the system has been tested by using independent image databases collected and FACS-coded for ground-truth by different research teams. PMID:25210210

The Rice Paradox: Multiple Origins but Single Domestication in Asian Rice

PubMed Central

Choi, Jae Young; Platts, Adrian E.; Fuller, Dorian Q.; Hsing (邢禹依), Yue-Ie; Wing, Rod A.

2017-01-01

Abstract The origin of domesticated Asian rice (Oryza sativa) has been a contentious topic, with conflicting evidence for either single or multiple domestication of this key crop species. We examined the evolutionary history of domesticated rice by analyzing de novo assembled genomes from domesticated rice and its wild progenitors. Our results indicate multiple origins, where each domesticated rice subpopulation (japonica, indica, and aus) arose separately from progenitor O. rufipogon and/or O. nivara. Coalescence-based modeling of demographic parameters estimate that the first domesticated rice population to split off from O. rufipogon was O. sativa ssp. japonica, occurring at ∼13.1–24.1 ka, which is an order of magnitude older then the earliest archeological date of domestication. This date is consistent, however, with the expansion of O. rufipogon populations after the Last Glacial Maximum ∼18 ka and archeological evidence for early wild rice management in China. We also show that there is significant gene flow from japonica to both indica (∼17%) and aus (∼15%), which led to the transfer of domestication alleles from early-domesticated japonica to proto-indica and proto-aus populations. Our results provide support for a model in which different rice subspecies had separate origins, but that de novo domestication occurred only once, in O. sativa ssp. japonica, and introgressive hybridization from early japonica to proto-indica and proto-aus led to domesticated indica and aus rice. PMID:28087768

Cytological Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma before and after the Bethesda System for Reporting Thyroid Cytopathology.

PubMed

Fazeli, Roghayeh; VandenBussche, Christopher J; Bishop, Justin A; Ali, Syed Z

2016-01-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common subtype of papillary carcinoma after the classical variant. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been introduced to standardize the practice of thyroid fine needle aspiration (FNA) reporting. We evaluated the impact of TBSRTC on the FNA interpretation of histologically proven FVPTCs. Cytology reports of 455 histologically proven FVPTCs were reviewed. The rate of each TBSRTC category was compared between pre- and post-TBSRTC eras. The distribution of FNA diagnoses for pre-TBSRTC cases included suspicious for follicular neoplasm (SFN; n = 51, 28.7%), papillary thyroid carcinoma (PTC; n = 47, 26.4%), suspicious for malignancy (SFM; n = 32, 18%), atypia of undetermined significance (AUS; n = 23, 13%), benign (n = 18, 10.1%), and nondiagnostic (ND; n = 7, 4%). Post-TBSRTC diagnoses were: AUS (n = 68, 24.6%), PTC (n = 64, 23.1%), SFM (n = 50, 18%), SFN and benign (n = 42, 15.2%) and ND (n = 11, 4%). SFN rate decreased significantly from 28.7 to 15.2% (p = 0.001) and AUS increased from 12.9 to 24.5% (p = 0.003). Following implementation of TBSRTC, the frequency of AUS diagnoses on FNA prior to surgical resection increased. Given that the rate of FVPTC diagnoses on thyroidectomy increased over the same period, this suggests that the use of AUS has resulted in greater surgical resection of FVPTC. © 2016 S. Karger AG, Basel.

Alcohol Use Severity Among Hispanic Emerging Adults in Higher Education: Understanding the Effect of Cultural Congruity.

PubMed

Cano, Miguel Ángel; Vaughan, Ellen L; de Dios, Marcel A; Castro, Yessenia; Roncancio, Angelica M; Ojeda, Lizette

2015-01-01

Identifying and understanding determinants of alcohol use behavior among Hispanic college students is an increasingly important public health issue, particularly during emerging adulthood. Studies examining ethnocultural determinants of alcohol use behavior among Hispanic college students have focused on direct associations with cultural orientation (e.g., acculturation and enculturation); yet there is a need for research that accounts for the complex interplay of other culturally relevant sociocultural factors. This study examined associations of behavioral acculturation, behavioral enculturation, and cultural congruity (perception of cultural fit between the values of the academic environment and the student's personal values) with alcohol use severity (AUS); and tested if gender moderated those associations. A hierarchical linear regression and moderation analysis were conducted on a sample of 167 Hispanic emerging adults (ages 18-25) enrolled in college. All predictor variables entered in the regression model accounted for 20.9% of the variance in AUS. After controlling for demographic variables and depressive symptoms, behavioral acculturation and enculturation did not have a statistically significant association with AUS. Further, gender did not moderate either of these associations. Conversely, greater cultural congruity was associated with lower reports of AUS. A moderation analysis suggested that cultural congruity predicted lower reports of AUS among men, but not among women. This was the first known study to examine the association of cultural congruity with alcohol use. Findings highlight the value of examining contextual factors of culture and moving beyond reductive measures of cultural orientation.

[Postoperative adjuvante Therapie mit einem Mistelextrakt (Viscum album ssp. album) bei Hündinnen mit Mammatumoren].

PubMed

Biegel, Ulrike; Stratmann, Nina; Knauf, Yvonne; Ruess, Katja; Reif, Marcus; Wehrend, Axel

2017-01-01

Hintergrund: Canine Mammatumoren (CMT) sind wegen ihrer Häufigkeit und hohen Malignitätsrate eine Herausforderung für die Veterinärmedizin. Bisher ist noch keine postoperative adjuvante Therapie als wirksamer Standard etabliert und in den nächsten Jahren wohl auch nicht zu erwarten. Zusätzlich ist die Frage nach der Verträglichkeit einer adjuvanten Therapie mit Erhaltung oder Verbesserung der Lebensqualität (LQ) wichtig. Die Therapie mit Mistelextrakten (Viscum album L.; VAE) ist in der Humanonkologie nach adjuvanter Tumorbasistherapie (Chemotherapie und Bestrahlung) eine sehr häufig verwendete, zusätzliche adjuvante Behandlungsmethode. Auch bei verschiedenen Tierarten werden inzwischen Mistelpräparate in der Onkologie erfolgreich angewendet. Methoden: Überprüfung von Wirkung und Nutzen einer postoperativen, adjuvanten Misteltherapie beim CMT sowie Erfassung der LQ unter der VAE-Behandlung. Ausgewertet wurden 56 Hündinnen mit Mammaadenokarzinom, 33 ausschließlich operierte Kontrolltiere und 23 operierte Tiere, die adjuvant VAE erhielten. Ergebnisse: Die mediane Überlebenszeit (MST) aller Tiere (n = 56) betrug 32 Monate (Interquartilbereich 13-51 Monate). Im deskriptiven Vergleich der Überlebenszeiten (ST) nach Kaplan-Meier waren nach 12, 24, 36 bzw. 48 Monaten noch 24, 20, 15 bzw. 5 Hündinnen (entsprechend 72,7%, 60,6%, 45,1%, 12,4%) der Kontrollgruppe sowie 19, 14, 11 und 1 Hündin (82,6%, 60,9%, 47,8%, 4,3%) der VAE-Gruppe am Leben. Die VAE-Therapie führte zu einem geringeren Gesamtversterberisiko, das statistisch nicht signifikant war (Hazard Ratio (HR) 0,530, 95%-Konfidenzintervall (KI) 0,222-1,262; p = 0,15). Tendenziell (p = 0,07) zeigte sich eine Verringerung des tumorbedingten Sterberisikos auf 25% (HR 0,251, 95%-KI 0,056-1,122). Schlussfolgerungen: Es kann eine Tendenz zur Senkung des tumorbedingten Sterberisikos der VAE-Gruppe bei guter Verträglichkeit der Therapie angenommen werden. Die LQ der Tiere blieb über die gesamte

Chips aus Plastik: Organische Elektronik

NASA Astrophysics Data System (ADS)

Kiy, Michael

2003-01-01

Künstliche organische Materialien werden in Zukunft vermehrt in der Elektronik eingesetzt werden. Obwohl sie gute Isolatoren sind, kann ein ausreichend großes elektrisches Feld in ihnen einen elektrischen Strom fließen lassen. Dazu injizieren Metallelektroden freie Ladungsträger wie Elektronen oder Löcher in das organische Material. Diese Ladungsträgerinjektion kann die elektrischen Eigenschaften geeigneter organischer Materialien vom Isolator bis zum Leiter steuern. Eine zukünftige Domäne solcher Kunststoffe werden einfache, billige Chips sein. Bei den Displays könnten sie bald die konventionellen Flüssigkristallanzeigen technisch überflügeln.

Low VOC Barrier Coating for Industrial Maintenance

DTIC Science & Technology

2007-11-01

Color - VOC - Total Solids (wt) - Total Solids (volume) - Percent Pigment - Stormer Viscosity - Brookfield Viscosity - Pot Life...17 NTPEP LVBC Testing (R 31-02) ●Formula - Color - VOC - Total Solids (wt) - Total Solids (volume) - Percent Pigment - Stormer ...Consistency of Paints Measuring Krebs Unit (KU) Viscosity Using the Stormer -Type Viscometer D 610 Test Method for Evaluating Degree of

Mapping wilderness character in Sequoia and Kings Canyon National Parks

Treesearch

James Tricker; Peter Landres; Gregg Fauth; Paul Hardwick; Alex Eddy

2014-01-01

The Sequoia-Kings Canyon Wilderness was established in September of 1984 when President Ronald Reagan signed the California Wilderness Act (PL 98-425). In March 2009, President Barack Obama signed the Omnibus Public Land Management Act (PL 111-11) designating the John Krebs Wilderness and the Sequoia-Kings Canyon Wilderness Addition (all wholly contained within SEKI)....

Radiobiology of Large Animals

DTIC Science & Technology

1975-06-01

efforts of James L. Thomas, Richard K. Marshall, and David E. Moore. iii L.,.„. mm mm ABSTRACT The LD5QS for sheep exposed to 60Co gamma rays at 0.9...25, 480-488 (1965). 7. J. S. Krebs, R. W. Brauer, and H. Kalbach , The estimation of the non-recuperable injury caused by ionizing radiation

Methodik und Qualität statistischer Erhebungen

NASA Astrophysics Data System (ADS)

Krug, Walter; Schmidt, Jürgen; Wiegert, Rolf

Kapitel 8 wirft einen Blick hinter die Kulissen statistischer Arbeit und ihrer Methoden, insbesondere auch hinter die der amtlichen Statistik: Wie kommen die Myriaden von Zahlen zustande, die heute aus statistischen Quellenwerken aller Art und aus Datenbanken abgerufen werden können? Dabei wird deutlich, welche Schwierigkeiten bei Erhebungen, insbesondere bei Stichprobenerhebungen, zu überwinden sind, wie man Antwortverweigerer kooperativer stimmt, wie sich auch aus kleinen Stichproben auf intelligente Weise verlässliche Ergebnisse erzielen lassen und wie Großstichproben auf europäischer Ebene harmonisiert werden. Am Beispiel des Zensus 2011 wird gezeigt, wie sich eine Kombination von Stichproben und Registerauswertungen als Ersatz für eine Volkszählung nutzen lässt. Mitglieder der Deutschen Statistischen Gesellschaft waren daran kooperativ beteiligt.

14. Charles Acey Cobb standing adjacent to the fish screen ...

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

14. Charles Acey Cobb standing adjacent to the fish screen he designed and installed in the Congdon Canal, facing southeast. Photo dates ca. late 1920's. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

Anaplerotic therapy in propionic acidemia.

PubMed

Longo, Nicola; Price, Leisa B; Gappmaier, Eduard; Cantor, Nancy L; Ernst, Sharon L; Bailey, Carrie; Pasquali, Marzia

2017-09-01

Propionic acidemia is a rare metabolic disorder caused by a deficiency of propionyl- CoA carboxylase, the enzyme converting propionyl-CoA to methylmalonyl-CoA that subsequently enters the citric acid cycle as succinyl-CoA. Patients with propionic acidemia cannot metabolize propionic acid, which combines with oxaloacetate to form methylcitric acid. This, with the defective supply of succinyl-CoA, may lead to a deficiency in citric acid cycle intermediates. The objective of this study was to determine whether supplements with glutamine (400mg/kg per day), citrate (7.5mEq/kg per day), or ornithine α-ketoglutarate (400mg/kg per day) (anaplerotic agents that could fill up the citric acid cycle) would affect plasma levels of glutamine and ammonia, the urinary excretion of Krebs cycle intermediates, and the clinical outcome in 3 patients with propionic acidemia. Each supplement was administered daily for four weeks with a two week washout period between supplements. The supplement that produced the most favorable changes was supplemented for 30 weeks following the initial study period and then for a 2 year extension. The urinary excretion of the Krebs cycle intermediates, α-ketoglutarate, succinate, and fumarate increased significantly compared to baseline during citrate supplementation, but not with the other two supplements. For this reason, citrate supplements were continued in the second part of the study. The urinary excretion of methylcitric acid and 3-hydroxypropionic acid did not change with any intervention. No significant changes in ammonia or glutamine levels were observed with any supplement. However, supplementation with any anaplerotic agents normalized the physiological buffering of ammonia by glutamate, with plasma glutamate and alanine levels significantly increasing, rather than decreasing with increasing ammonia levels. No significant side effects were observed with any therapy and safety labs (blood counts, chemistry and thyroid profile) remained

First results of GPS time transfer to Australia

NASA Technical Reports Server (NTRS)

Luck, J. M.; Woodger, J. R.; Wells, J. E.; Churchill, P. N.; Clements, P. A.

1985-01-01

A Global Positioning System time transfer unit built by NBS under contract to JPL was installed at Tidbinbilla Deep Space Communications Complex of the NASA Deep Space Network in June 1983. It has been used to estimate the relationship to UTC(USNO MC) of the Tidbinbilla frequency and time system TID(FTS) based on a hydrogen maser, and thence to estimate the performance of the Australian free-running time scale UTC(AUS). Data from the first three months has been analyzed three ways: by two-hop common view using JPL as intermediary; by long-arc interpolation of measurements against space vehicle clocks; and by long-arc interpolation of GPS-Time results. Residuals from a single quadratic fit through three months of UTC(USNO MC) - TID (FTS) results were white noise with standard error 15 ns, and a flying clock measurement gave 70 ns agreement. A straight line fit through results UTC(USNO MC) - UTC (AUS) gave 90 ns standard error and 120 bns agreement. It is proposed to use the GPS measurements to steer UTS(AUS) to UTC(BIH), and to rename the existing time scale TA(AUS).

Morphogenetic Mechanisms in the Cyclic Regeneration of Hair Follicles and Deer Antlers from Stem Cells

PubMed Central

Li, Chunyi; McMahon, Chris

2013-01-01

We have made comparisons between hair follicles (HFs) and antler units (AUs)—two seemingly unrelated mammalian organs. HFs are tiny and concealed within skin, whereas AUs are gigantic and grown externally for visual display. However, these two organs share some striking similarities. Both consist of permanent and cyclic/temporary components and undergo stem-cell-based organogenesis and cyclic regeneration. Stem cells of both organs reside in the permanent part and the growth centres are located in the temporary part of each respective organ. Organogenesis and regeneration of both organs depend on epithelial-mesenchymal interactions. Establishment of these interactions requires stem cells and reactive/niche cells (dermal papilla cells for HFs and epidermal cells for AUs) to be juxtaposed, which is achieved through destruction of the cyclic part to bring the reactive cells into close proximity to the respective stem cell niche. Developments of HFs and AUs are regulated by similar endocrine (particularly testosterone) and paracrine (particularly IGF1) factors. Interestingly, these two organs come to interplay during antlerogenesis. In conclusion, we believe that investigators from the fields of both HF and AU biology could greatly benefit from a comprehensive comparison between these two organs. PMID:24383056

Alcohol Use Severity among Hispanic Emerging Adults in Higher Education: Understanding the Effect of Cultural Congruity

PubMed Central

Cano, Miguel Ángel; Vaughan, Ellen L.; de Dios, Marcel A.; Castro, Yessenia; Roncancio, Angelica M.; Ojeda, Lizette

2016-01-01

Background Identifying and understanding determinants of alcohol use behavior among Hispanic college students is an increasingly important public health issue, particularly during emerging adulthood. Studies examining ethnocultural determinants of alcohol use behavior among Hispanic college students have focused on direct associations with cultural orientation (e.g., acculturation and enculturation); yet there is a need for research that accounts for the complex interplay of other culturally relevant sociocultural factors. Objectives This study examined associations of behavioral acculturation, behavioral enculturation, and cultural congruity (perception of cultural fit between the values of the academic environment and the student's personal values) with alcohol use severity (AUS); and tested if gender moderated those associations. Methods A hierarchical linear regression and moderation analysis were conducted on a sample of 167 Hispanic emerging adults (ages 18 to 25) enrolled in college. Results All predictor variables entered in the regression model accounted for 20.9% of the variance in AUS. After controlling for demographic variables and depressive symptoms, behavioral acculturation and enculturation did not have a statistically significant association with AUS. Further, gender did not moderate either of these associations. Conversely, greater cultural congruity was associated with lower reports of AUS. A moderation analysis suggested that cultural congruity predicted lower reports of AUS among men, but not among women. Conclusions This was the first known study to examine the association of cultural congruity with alcohol use. Findings highlight the value of examining contextual factors of culture and moving beyond reductive measures of cultural orientation. PMID:26574656

U.S. Geological Survey 2013 assessment of undiscovered resources in the Bakken and Three Forks Formations of the U.S. Williston Basin Province

USGS Publications Warehouse

Gaswirth, Stephanie B.; Marra, Kristen R.

2014-01-01

The Upper Devonian Three Forks and Upper Devonian to Lower Mississippian Bakken Formations comprise a major United States continuous oil resource. Current exploitation of oil is from horizontal drilling and hydraulic fracturing of the Middle Member of the Bakken and upper Three Forks, with ongoing exploration of the lower Three Forks, and the Upper, Lower, and Pronghorn Members of the Bakken Formation. In 2008, the U.S. Geological Survey (USGS) estimated a mean of 3.65 billion bbl of undiscovered, technically recoverable oil resource within the Bakken Formation. The USGS recently reassessed the Bakken Formation, which included an assessment of the underlying Three Forks Formation. The Pronghorn Member of the Bakken Formation, where present, was included as part of the Three Forks assessment due to probable fluid communication between reservoirs. For the Bakken Formation, five continuous and one conventional assessment units (AUs) were defined. These AUs are modified from the 2008 AU boundaries to incorporate expanded geologic and production information. The Three Forks Formation was defined with one continuous and one conventional AU. Within the continuous AUs, optimal regions of hydrocarbon recovery, or “sweet spots,” were delineated and estimated ultimate recoveries were calculated for each continuous AU. Resulting undiscovered, technically recoverable resource estimates were 3.65 billion bbl for the five Bakken continuous oil AUs and 3.73 billion bbl for the Three Forks Continuous Oil AU, generating a total mean resource estimate of 7.38 billion bbl. The two conventional AUs are hypothetical and represent a negligible component of the total estimated resource (8 million barrels of oil).

Incidence of facial clefts in Cambridge, United Kingdom.

PubMed

Bister, Dirk; Set, Patricia; Cash, Charlotte; Coleman, Nicholas; Fanshawe, Thomas

2011-08-01

The aim of this study was to determine the incidence of facial clefting in Cambridge, UK, using multiple resources of ascertainment and to relate the findings to antenatal ultrasound screening (AUS) detection rates. AUS records from an obstetric ultrasound department, post-natal records from the regional craniofacial unit, and autopsy reports of foetuses over 16 weeks' gestational age from a regional pathology department from 1993 to 1997 were retrospectively reviewed. Cross-referencing between the three data sets identified all cases of facial clefts. Of 23,577 live and stillbirths, 30 had facial clefts. AUS detected 17 of these. Sixteen of the 30 had isolated facial clefts. Others had associated anomalies, chromosomal defects, or syndromes. Percentages and confidence intervals were calculated from the above data. Twenty-one resulted in live births, seven terminations, and two foetal deaths. Overall, detection rate by AUS was 65 percent [67 percent isolated cleft lip, 93 per cent cleft lip and palate (CLP), and 22 percent isolated cleft palate], with no false positives. The incidence of facial clefts was 0.127 percent (95 percent confidence interval 0.089-0.182 percent); the incidence for isolated CLP was lower than previously reported: 0.067 percent (0.042-0.110 percent). With one exception, all terminations were in foetuses with multiple anomalies. The figures presented will enable joint CLP clinics to give parents information of termination rates. The study allows pre-pregnancy counselling of families previously affected by clefting about the reliability of AUS detection rates.

Long-term functional outcomes after artificial urinary sphincter implantation in men with stress urinary incontinence.

PubMed

Léon, Priscilla; Chartier-Kastler, Emmanuel; Rouprêt, Morgan; Ambrogi, Vanina; Mozer, Pierre; Phé, Véronique

2015-06-01

To evaluate long-term functional outcomes of artificial urinary sphincters (AUSs) and to determine how many men required explantation because of stress urinary incontinence (SUI) caused by sphincter deficiency after prostate surgery. Men who had undergone placement of an AUS (American Medical Systems AMS 800®) between 1984 and 1992 to relieve SUI caused by sphincter deficiency after prostate surgery were included. Continence, defined as no need for pads, was assessed at the end of the follow-up. Kaplan-Meier survival curves estimated the survival rate of the device without needing explantation or revision. In all, 57 consecutive patients were included with a median (interquartile range, IQR) age of 69 (64-72) years. The median (IQR) duration of follow-up was 15 (8.25-19.75) years. At the end of follow-up, 25 patients (43.8%) still had their primary AUS. The AUS was explanted in nine men because of erosion (seven) and infection (two). Survival rates, without AUS explantation, were 87%, 87%, 80%, and 80% at 5, 10, 15, and 20 years, respectively. Survival rates, without AUS revision, were 59%, 28%, 15%, and 5% at 5, 10, 15, and 20 years, respectively. At the end of the follow-up, in intention-to-treat analysis, 77.2% of patients were continent. In the long term (>10 years) the AMS 800 can offer a high rate of continence to men with SUI caused by sphincter deficiency, with a tolerable rate of explantation and revision. © 2014 The Authors. BJU International © 2014 BJU International.

Post-term surveillance and birth outcomes in South Asian-born compared with Australian-born women.

PubMed

Yim, C; Wong, L; Cabalag, C; Wallace, E M; Davies-Tuck, M

2017-02-01

To determine if apparently healthy post-term South Asian-born (SA) women were more likely to have abnormal post-term fetal surveillance than Australian- and New Zealand-born (AUS/NZ) women, whether those abnormalities were associated with increased rates of obstetric intervention and adverse perinatal outcomes, and whether SA women and their babies were at higher risk of adverse outcomes in the post-term period irrespective of their post-term surveillance outcomes. Post-term surveillance and perinatal outcomes of 145 SA and 272 AUS/NZ nulliparous women with a singleton post-term pregnancy were compared in a retrospective multicentre cohort analysis. Post-term SA women were not significantly more likely to have a low amniotic fluid index (AFI) than AUS/NZ women. However, they were nearly four times more likely (odds ratio 3.75; 95% CI 1.49-9.44) to have an abnormal CTG (P=0.005). Irrespective of maternal region of birth having an abnormal cardiotocography (CTG) or AFI was not associated with adverse intrapartum or perinatal outcomes. However, post-term SA women were significantly more likely than AUS/NZ women to have intrapartum fetal compromise (P=0.03) and an intrapartum cesarean section (P=0.002). Babies of SA women were more also significantly likely to be admitted to the Special Care Nursery or Neonatal Intensive Care Unit (P=0.02). Post-term SA women experience higher rates of fetal compromise (antenatal and intrapartum) and obstetric intervention than AUS/NZ women. Irrespective of maternal region of birth an abnormal CTG or AFI was not predictive of adverse outcomes.

Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP.

PubMed

Shirane, M; Nakamura, K

2001-10-19

Aniracetam, a cognition enhancer, has been recently found to preferentially increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the present study, we aimed to identify actually active substances among aniracetam and its major metabolites and to clarify the mode of action in DA and 5-HT release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5-HT release, respectively, in the PFC elicited by orally administered aniracetam. The effects of aniracetam were mimicked by local perfusion of N-anisoyl-gamma-aminobutyric acid [corrected] (N-anisoyl-GABA), one of the major metabolites of aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl-GABA applied to the VTA was also completely abolished by co-perfusion of mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam, and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT release in the same region, respectively. These results indicate that aniracetam enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA that targets not only somatodendritic nACh and NMDA receptors but also presynaptic nACh receptors.

Wide Area Recovery and Resiliency Program (WARRP) Knowledge Enhancement Working Group: Multi-Agency Coordination After Action Report

DTIC Science & Technology

2012-02-23

Kaski Charles Denver Office of Emergency Management Kellar Scott Arapahoe County/NCR Coordinator Krebs Kathleen Clear Creek County Krugman Jim USDA...Mower John Cubic Applications, Inc. Mueller Matt Denver Office of Emergency Management Ridley Teri WARRP Rubenstein Mike Jefferson County...Office of Emergency Management: Scott Field Denver Office of Emergency Management: Pat Williams Douglas County: Fran Santagata Douglas County: Steve

Ein Kredit für Weihnachtsbaumkugeln

NASA Astrophysics Data System (ADS)

Tutsch, Sina

Eine Mathematikerin aus dem DFG-Forschungszentrum Matheon arbeitet an Methoden zur dreidimensionalen Visualisierung. Sie hat die Geschäftsidee, Weihnachtsbaumkugeln mit bewegten Hologrammen herzustellen, die sich individuell gestalten lassen, und plant eine Existenzgründung. Aus einem öffentlichen Förderprogramm erhält sie ein günstiges Darlehen in Höhe von 50 000 Euro. Für die Startphase ihres Unternehmens benötigt sie jedoch den vierfachen Betrag.

32. AERIAL VIEW OF TIETON DAM, UPSTREAM FACE OF DAM ...

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

32. AERIAL VIEW OF TIETON DAM, UPSTREAM FACE OF DAM (Trashrack-structure for outlet at lower left in reservoir, spillway at upper left. Reservoir nearly empty due to drought.) - Tieton Dam, South & East of State Highway 12, Naches, Yakima County, WA

13. Detail view of drum screen short shaft gears, journal ...

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

13. Detail view of drum screen short shaft gears, journal bearing, rotation drive chain, upper sprocket gear, and drum screen edge in background, facing southeast (downstream) from drum screen cover. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

Gestational hypothyroidism-induced changes in L-type calcium channels of rat aorta smooth muscle and their impact on the responses to vasoconstrictors.

PubMed

Sedaghat, Katayoun; Zahediasl, Saleh; Ghasemi, Asghar

2015-02-01

Thyroid hormones play an essential role in fetal growth and maternal hypo-thyroidism which leads to cardiovascular deficiency in their offspring. Considering this, we intended to investigate the impact of gestational hypothyroidism on offspring vascular contractibility and possible underlying mechanisms. Hypothyroidism was induced in female rats by administration of 6-n-propyl-2-thiouracil in drinking water (0.02%) till delivery. The offspring aorta smooth muscle (without endothelium) contractile response to KCl (10-100 mM), KCl in the presence of nifedipine (10(-4)-10(-1) µM), phenylephrine (10(-9)-10(-6) M) and finally, phenylephrine and caffeine 100 mM in Ca(2+)-free Krebs were measured. KCl and phenylephrine-induced contractions were considerably lower in gestational hypothyroid (GH) than euthyroid offspring. GH responded to nifedipine with less sensitivity than control. The GH and control groups produced almost equal contraction in respond to phenylephrine and caffeine in Ca(2+)-free Krebs. This study suggests that in hypothyroid offspring L-type Ca(2+) channels are less functional, while intracellular Ca(2+) handling systems are less modified by low levels of maternal thyroid hormones.

Pheochromocytoma/Paraganglioma: A Poster Child for Cancer Metabolism.

PubMed

Tevosian, Sergei G; Ghayee, Hans K

2018-05-01

Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize; there are no known cures for metastasized PGLs. Original articles and reviews indexed in PubMed were identified by querying with specific PCC/PGL- and Krebs cycle pathway-related terms. Additional references were selected through the in-depth analysis of the relevant publications. We primarily discuss Krebs cycle mutations that can be instrumental in helping investigators identify key biological pathways and molecules that may serve as biomarkers of or treatment targets for PCC/PGL. The mainstay of treatment of patients with PCC/PGLs is surgical. However, the tide may be turning with the discovery of new genes associated with PCC/PGLs that may shed light on oncometabolites used by these tumors.

Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state of the art--review article.

PubMed

Harrison, A P; Pierzynowski, S G

2008-08-01

The fact that men and women are living longer than they have ever done before is something in which we can all rejoice. However, the process of ageing is associated with changes in skeletal, muscular, gastrointestinal, neural hormonal and metabolic processes that seriously affect an individual's performance and quality of life. Indeed, such changes can be contributory to a loss of independence in the elderly. This state-of-the art address highlights the main changes found to occur with ageing whilst simultaneously reporting findings of in vivo and in vitro studies designed to elucidate the potential of the Krebs cycle intermediate - alpha-ketoglutaric acid (AKG) in protecting elderly body systems from failing and degradation. The topics of paramount importance include impaired bone structure and strength, amino acid and mineral absorption, muscle performance, as well as highlighting the role of Krebs cycle intermediates in the debilitating changes that occur with end-stage renal failure and the regulation of the lipid metabolism. Finally, focus will be given to the role of 2-oxoglutarate as a potent protective factor in connection with the development of malignant cells in the body.

Phylogenetically Novel LuxI/LuxR-Type Quorum Sensing Systems Isolated Using a Metagenomic Approach

PubMed Central

Nasuno, Eri; Fujita, Masaki J.; Nakatsu, Cindy H.; Kamagata, Yoichi; Hanada, Satoshi

2012-01-01

A great deal of research has been done to understand bacterial cell-to-cell signaling systems, but there is still a large gap in our current knowledge because the majority of microorganisms in natural environments do not have cultivated representatives. Metagenomics is one approach to identify novel quorum sensing (QS) systems from uncultured bacteria in environmental samples. In this study, fosmid metagenomic libraries were constructed from a forest soil and an activated sludge from a coke plant, and the target genes were detected using a green fluorescent protein (GFP)-based Escherichia coli biosensor strain whose fluorescence was screened by spectrophotometry. DNA sequence analysis revealed two pairs of new LuxI family N-acyl-l-homoserine lactone (AHL) synthases and LuxR family transcriptional regulators (clones N16 and N52, designated AubI/AubR and AusI/AusR, respectively). AubI and AusI each produced an identical AHL, N-dodecanoyl-l-homoserine lactone (C12-HSL), as determined by nuclear magnetic resonance (NMR) and mass spectrometry. Phylogenetic analysis based on amino acid sequences suggested that AusI/AusR was from an uncultured member of the Betaproteobacteria and AubI/AubR was very deeply branched from previously described LuxI/LuxR homologues in isolates of the Proteobacteria. The phylogenetic position of AubI/AubR indicates that they represent a QS system not acquired recently from the Proteobacteria by horizontal gene transfer but share a more ancient ancestry. We demonstrated that metagenomic screening is useful to provide further insight into the phylogenetic diversity of bacterial QS systems by describing two new LuxI/LuxR-type QS systems from uncultured bacteria. PMID:22983963

The experience of artificial urinary sphincter implantation by a single surgeon in 15 years.

PubMed

Shen, Yuan-Chi; Chiang, Po-Hui

2013-03-01

Artificial urinary sphincter (AUS) is the gold standard treatment for urinary incontinence owing to sphincter incompetence. We reviewed our experience in AUS implantation. From 1995 to 2009, 19 patients underwent 25 AUS implantations performed by a single surgeon. The cause of incontinence was sphincter incompetence, which was secondary to prostate surgery, neurogenic bladder, radiation, and post-traumatic urethral lesion. Twenty-three prostheses were placed in the bulbar urethra for male patients: 11 AUS cuffs were placed through the perineal approach and 12 through the penoscrotal approach. Two procedures were applied over the bladder neck for the female patients. Through a retrospective review of charts, continence and complications were analyzed. The mean follow-up time was 50.0 ± 42.9 months (range: 2-146 months). There were 16 successful surgeries (64%), and these patients were free from the need for a pad. In eight surgeries (32%), the devices were removed due to infection, while one implantation (4%) was unsuccessful due to perforation into the bulbar urethra. There was a statistically significant difference (p = 0.024) in failure rates between patients who received radiotherapy (100%) and other patients (22.7%). There was no statistically significant difference in dry and revision rates (p > 0.05) between the perineal and penoscrotal approach. Accordingly, over half of the patients with total incontinence benefitted from AUS implantation. In consideration of the high failure rate for patients receiving radiotherapy, caution should be exercised in the use of implantation. Secondary implantation has a satisfactory success rate in selected patients. The same success rate was noted for both perineal and penoscrotal approaches. Copyright © 2013. Published by Elsevier B.V.

Combination therapy for male erectile dysfunction and urinary incontinence.

PubMed

Zafirakis, Helen; Wang, Run; Westney, O Lenaine

2008-01-01

Urinary incontinence (UI) and erectile dysfunction (ED) are both very prevalent conditions. Insertion of an artificial urinary sphincter (AUS) and penile prosthesis (PP) is an effective and proven method of treatment for both conditions. With advancing age, as well as with increasing populations of patients radically treated for prostate cancer, the occurrence of both conditions found in the same patient is increasing. The purpose of this article was to analyze the available evidence for simultaneous surgical management of male ED and UI using prosthetic devices. The existing literature pertaining to dual implantation of AUS and PP was reviewed. The concomitant insertion of the PP with the male perineal sling was also considered. Concurrent ED and UI are increasingly seen in the post radical prostatectomy population, who are often younger and less willing to suffer with these conditions. Insertion of an AUS and PP, either simultaneously or as a two-stage procedure, appears to be a safe, efficacious and long-lasting method of treatment. The improvements in design of both the AUS and PP as well as the development of the single transverse scrotal incision have made simultaneous insertion of these prostheses possible. Dual implantation of the PP and male sling looks promising in a selected population. In conclusion, the insertion of the AUS and PP for the treatment of concurrent UI and ED is safe and effective. Simultaneous insertion of these prostheses in the same patient offers potential advantages in operative and recovery time and is associated with high patient satisfaction. Combination therapy should therefore be included in the arsenal of treatment of these conditions.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

PubMed Central

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-01-01

Background Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era where tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesize that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Study Design Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (Arm 1) versus SLNB (Arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Results 68 subjects were enrolled in the pilot phase of the trial (34 subjects in Arm 1, no further staging; 32 subjects in Arm 2, SLNB, and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40-80) in Arm 1 and 59 years (range 31-81) in Arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1-32). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (> 2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Conclusions Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. PMID:27212005

The use of the Bethesda terminology in thyroid fine-needle aspiration results in a lower rate of surgery for nonmalignant nodules: a report from a reference center in Turkey.

PubMed

Ozluk, Yasemin; Pehlivan, Esmehan; Gulluoglu, Mine G; Poyanli, Arzu; Salmaslioglu, Artur; Colak, Nese; Kapran, Yersu; Yilmazbayhan, Dilek

2011-12-01

The Bethesda system (BS) for reporting thyroid fine-needle aspiration (FNA), which classifies nodules as nondiagnostic (ND), benign (B), atypia/follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm (SFN/FN), suspicious for malignancy (SFM), or malignant (M), uses clinically valuable management guidelines. The authors employed a similar in-house classification system (IS) for thyroid FNAs, using the categories of ND, B, suspicious follicular cells (SFC), follicular lesion/neoplasm (FL/FN), SFM, and M. The authors compared IS and BS, and assessed the utility of BS in clinical practice. A total of 581 nodules with cytological/histological follow-up were examined and indeterminate lesions by BS were reclassified. The sensitivity and specificity for malignancy using IS were similar to that of BS (77% vs 99%). However, when SFN/FN and SFM were both considered positive, the results for IS and BS were as follows: sensitivity, 85% versus 85%; specificity, 87% versus 94%; and diagnostic accuracy, 86% versus 90%, respectively. Discrepancies between cytological and histological data were evident in 35 cases among all categories of BS except AUS/FLUS. The rate of surgery for nonmalignant nodules was lesser (20% vs 9%) by BS. Among 34 AUS/FLUS cases with follow-up data, hypocellularity was the case in 11 (46%) nonneoplastic and 10 (100%) neoplastic nodules. The use of BS results in a lower rate of surgery for nonmalignant nodules even though patients with borderline cytopathologic features are still encountered. AUS/FLUS category can be separated into subgroups according to the factors causing difficulties in the interpretation. There is a need of accumulation of AUS/FLUS cases to do further evaluations and studies.

Comparison of outcomes after single or DOUBLE-CUFF artificial urinary sphincter insertion.

PubMed

O'Connor, R Corey; Gerber, Glenn S; Avila, Desiderio; Chen, Andrew A; Bales, Gregory T

2003-10-01

To assess the effectiveness and complications associated with single and double-cuff artificial urinary sphincter (AUS) implantation for postprostatectomy stress urinary incontinence. A retrospective study of 56 men with postprostatectomy stress urinary incontinence who underwent either single (28 patients) or double (28 patients) cuff AUS placement was performed. Patients in each cohort were matched on the basis of preoperative pad use, risk factors for complications, and age. Patient selection was blinded relative to outcome. Continence, quality of life, and complications were assessed using the Incontinence Impact Questionnaire Short Form (IIQ-7), postoperative pad use, and chart review. The mean age was 67 years for each group. Daily pad use decreased from 7.7 to 1.1 in patients treated with a single-cuff AUS and from 7.8 to 0.7 in patients with a double-cuff AUS (P = 0.25). Complete continence (0 pads daily) was reported in 3 (11%) of 28 men with single-cuff and 12 (43%) of 28 men with double-cuff sphincters (P = 0.008). The IIQ-7 scores improved from 14.8 to 3.1 after single-cuff placement and from 16.3 to 2.5 after double-cuff placement (P = 0.03). With an average follow-up of 41.3 and 21.2 months for the single and double-cuff cohorts, respectively, five complications were reported in the single-cuff recipients and four in the double-cuff patients. A significantly greater rate of complete continence and improvement in the IIQ-7 were seen in men with double-cuff AUS compared with single-cuff devices. Additional study is needed to confirm the relative advantages of double-cuff insertion.

Artificial urinary sphincter implantation in women with stress urinary incontinence: preliminary comparison of robot-assisted and open approaches.

PubMed

Peyronnet, Benoit; Vincendeau, Sébastien; Tondut, Lauranne; Bensalah, Karim; Damphousse, Mireille; Manunta, Andréa

2016-03-01

We aimed to compare outcomes of open and robot-assisted artificial urinary sphincter (AUS) implantation in female patients. The charts of all female patients who underwent an AUS implantation between 2008 and 2014 in a single center were retrospectively reviewed. From 2008 to 2012, AUS were implanted using an open approach and from 2013 to 2014 using a robot-assisted approach. Perioperative and functional parameters were compared between groups. The primary endpoint was continence status. Twenty-four women were assessed: 16 in the open group and eight in the robot-assisted group. Three patients had neurogenic stress urinary incontinence. Most patients had undergone previous procedures for urinary incontinence (15 in the open group and seven in the robotic group). Mean operative time was similar in both groups (214 vs. 211 min; p = 0.90). Postoperative complicationsrate was lower in the robot-assisted group (25 vs. 75 %; p = 0.02). There was a trend toward a lower intraoperative complication rate (37.5 vs. 62.5 %; p = 0.25), decreased blood loss (17 ml vs. 275 ml; p = 0.22), and shorter length of stay (3.5 vs. 9.3 days; p = 0.09) in the robot-assisted group. Continence rates were comparable in both groups (75 vs. 68.8 %; p = 0.75). Three AUS explantations were needed in the open group (18.8 %) compared with one in the robot-assisted group (12.5 %; p = 0.70). In female patients, the robot-assisted approach compared with open AUS implantation could decrease intraoperative and postoperative complication rates, length of hospital stay, and blood loss.

Long-term Outcomes Following Artificial Urinary Sphincter Placement: An Analysis of 1082 Cases at Mayo Clinic.

PubMed

Linder, Brian J; Rivera, Marcelino E; Ziegelmann, Matthew J; Elliott, Daniel S

2015-09-01

To evaluate long-term device outcomes following primary artificial urinary sphincter (AUS) implantation. We identified 1802 male patients with stress urinary incontinence that underwent AUS placement from 1983 to 2011. Of these, 1082 (60%) were involving primary implantations and comprise the study cohort. Multiple clinical and surgical variables were evaluated for potential association with treatment failure, defined as any secondary surgery. Patient follow-up was obtained through office examination, operative report, and written or telephone correspondence. Patients undergoing AUS implantation had a median age of 71 years (interquartile range 66-76) and median follow-up of 4.1 years (interquartile range 0.8-7.7). Overall, 338 of 1082 patients (31.2%) underwent secondary surgery, including 89 for device infection and/or erosion, 131 for device malfunction, 89 for urethral atrophy, and 29 for pump malposition or tubing complications. No patient-related risk factors were independently associated with an increased risk of secondary surgery on multivariable analysis. Secondary surgery-free survival was 90% at 1 year, 74% at 5 years, 57% at 10 years, and 41% at 15 years. Primary AUS implantation is associated with acceptable long-term outcomes. Recognition of long-term success is important for preoperative patient counseling. Copyright © 2015 Elsevier Inc. All rights reserved.

Gating of the late Na+ channel in normal and failing human myocardium.

PubMed

Undrovinas, Albertas I; Maltsev, Victor A; Kyle, John W; Silverman, Norman; Sabbah, Hani N

2002-11-01

We previously reported an ultraslow inactivating late Na+ current (INaL) in left ventricular cardiomyocytes (VC) isolated from normal (NVC) and failing (FVC) human hearts. This current could play a role in heart failure-induced repolarization abnormalities. To identify properties of NaCh contributing to INaL, we examined early and late openings in cell-attached patches of HEK293 cells expressing human cardiac NaCh alpha-subunit (alpha-HEK) and in VC of one normal and three failing human hearts. Two types of the late NaCh openings underlay INaL in all three preparations: scattered late (SLO) and bursts (BO). Amplitude analysis revealed that slope conductance for both SLO and BO was the same compared to the main level of early openings (EO) in both VC (21 vs 22.7pS, NVC; 22.7 vs 22.6pS, FVC) and alpha-HEK (23.2 vs 23pS), respectively. Analysis of SLO latencies revealed voltage-independent ultraslow inactivation in all preparations with tendency to be slower in FVC compared to NCV. EO and SLO render one open voltage-independent state (tau approximately 0.4ms) for NVC and FVC. One open (voltage-dependent) and two closed states (one voltage-dependent and another voltage-independent) were found in BO of both specimens. Burst duration tend to be longer in FVC ( approximately 50ms) than in NVC ( approximately 30ms). In FVC we found both modes SLO and BO at membrane potential of -10mV that is attribute for take-off voltages (from -18 to -2mV) for early afterdepolarizations (EAD's) in FVC. In conclusions, we found a novel gating mode SLO that manifest slow (hundreds of ms), voltage-independent inactivation in both NVC and FVC. We were unable to reliably demonstrate any differences in the properties of the late NaCh in failing vs a normal human heart. Accordingly, the late current appears to be generated by a single population of channels in normal and failing human ventricular myocardium. Both SLO and BO could be implicated in EADs in HF.

Scientific Laws, Principles and Theories: A Reference Guide by Robert E. Krebs

NASA Astrophysics Data System (ADS)

Bernal, Pedro

2001-08-01

My having made a number of negative observations, particularly about the introduction, should not obscure the fact that the entries will be useful to high school and college science students and that this book will be a good addition to science collections in libraries.

The Role of Lower Extremity Joint Powers in Successful Stair Ambulation

DTIC Science & Technology

2011-01-01

written informed consent, all subjects participated in a biomechanical gait assessment during stair ascent walking. A total of 55 markers were used...power generation and vertical COM acceleration (COMA) during stair ascent. Twenty-two healthy individuals underwent a biomechanical gait assessment...DA. An integrated biomechanical analysis of normal stair ascent and descent. J Biomech 1988;21:733–44. [6] Zachazewski JE, Riley PO, Krebs DE

Mechanisms of Mitochondrial Defects in Gulf War Syndrome

DTIC Science & Technology

2012-08-01

oxidized; POR: porin; TCA: Tricarboxylic acid cycle ( Kreb cycle ). Page 2 Body: YEAR 1 of research (10/13/2009-7/14/2010) (9 months): Human... mitochondria , fatigue, myalgias 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...abnormalities in genes that are related to mitochondrial function. Hence, investigation of mitochondrial dysfunction in GWS is a priority. Mitochondria

Metabolic and Epigenetic Interactions Regulate Vascular Phenotypic Change and Maintenance in Pulmonary Hypertension

DTIC Science & Technology

2016-10-01

Krebs cycle through the generation of alpha-ketoglutarate. However, increased oxidative stress affected oxygen consumption rates at the Complex I...machinery and respiration in PH-Fibs. The difference in endogenous respiration, (i.e., oxygen consumption ) was not statistically different compared...driven through complex I. We found a roughly17% drop in oxygen consumption in PH-Fibs versus Co-Fibs (Figure 3C), which corresponded to the down

Formation of biologically relevant carboxylic acids during the gamma irradiation of acetic acid

NASA Technical Reports Server (NTRS)

Negron-Mendoza, A.; Ponnamperuma, C.

1976-01-01

Irradiation of aqueous solutions of acetic acid with gamma rays produced several carboxylic acids in small yield. Their identification was based on the technique of gas chromatography combined with mass spectrometry. Some of these acids are Krebs Cycle intermediates. Their simultaneous formation in experiments simulating the primitive conditions on the earth suggests that metabolic pathways may have had their origin in prebiotic chemical processes.

The Effect of Acute Renal Failure on Muscle Protein Turnover in the Rat and Implications for Therapy.

DTIC Science & Technology

1984-10-01

Effect on Serum Glucose and Insulin: * a. The pattern of insulin secretion and concomitant blood suoar con- centrations are of interest in this...combat casualties suffering from extensive trauma and prolonger hypotension. Despite replacement of blood , fluids and electrolytes, expert surgical care...thin muscles ar incubated in oxygenated, buffered Krebs-Ringer medium for 2 hours. The basic media contain glucose , 14C-labeled phenylalanine. Muscle

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

PubMed Central

Zelber-Sagi, Shira; Webb, Muriel; Assy, Nimer; Blendis, Laurie; Yeshua, Hanny; Leshno, Moshe; Ratziu, Vlad; Halpern, Zamir; Oren, Ran; Santo, Erwin

2013-01-01

AIM: To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of subjects from the general population, a subgroup from the First Israeli National Health Survey, without excessive alcohol consumption or viral hepatitis. All subjects underwent anthropometric measurements and fasting blood tests. Evaluation of liver fat was performed using four noninvasive methods: the SteatoTest; the fatty liver index (FLI); regular abdominal ultrasound (AUS); and the hepatorenal ultrasound index (HRI). Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods: the HRI, the ratio between the median brightness level of the liver and right kidney cortex; and the SteatoTest, a biochemical surrogate marker of liver steatosis. The FLI is calculated by an algorithm based on triglycerides, body mass index, γ-glutamyl-transpeptidase and waist circumference, that has been validated only vs AUS. FLI < 30 rules out and FLI ≥ 60 rules in fatty liver. RESULTS: Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests. The prevalence rate of NAFLD was 31.1% according to AUS. The FLI was very strongly correlated with SteatoTest (r = 0.91, P < 0.001) and to a lesser but significant degree with HRI (r = 0.55, P < 0.001). HRI and SteatoTest were significantly correlated (r = 0.52, P < 0.001). The κ between diagnosis of fatty liver by SteatoTest (≥ S2) and by FLI (≥ 60) was 0.74, which represented good agreement. The sensitivity of FLI vs SteatoTest was 85.5%, specificity 92.6%, positive predictive value (PPV) 74.7%, and negative predictive value (NPV) 96.1%. Most subjects (84.2%) with FLI < 60 had S0 and none had S3-S4. The κ between diagnosis of fatty liver by HRI (≥ 1.5) and by FLI (≥ 60) was 0.43, which represented only moderate agreement. The sensitivity of FLI vs HRI was 56

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

PubMed Central

Kim, Seung Soo; Chung, Chan Jong; Lee, Seung-Cheol

2011-01-01

Background Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB. Methods Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine. Results Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine. Conclusions Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block

Measurement of intracellular chloride in guinea-pig vas deferens by ion analysis, 36chloride and micro-electrodes

PubMed Central

Aickin, C. Claire; Brading, Alison F.

1982-01-01

1. Cl-sensitive micro-electrodes were used to measure the intracellular Cl activity (aCli) in smooth muscle cells of the guinea-pig vas deferens. The values obtained were compared with those of intracellular Cl (Cli) found by both ion analysis and 36Cl efflux. 2. Various combinations of filling solution for recording membrane potential (Em), and type of micro-electrode were tested. The most successful, which allowed continuous recording of aCli for several hours, was a double-barrelled electrode using the reference liquid ion exchanger (RLIE; Thomas & Cohen, 1981). However, aCli measured both by simultaneous impalements of separate cells with Cl-sensitive and conventional micro-electrodes, and by double-barrelled micro-electrodes, was about 42 mM in normal Krebs solution. This is five times higher than the value from a passive distribution. ECl was about -24 mV, more than 40 mV positive to Em. 3. On complete removal of extracellular Cl (Clo), aCli fell to an apparent level of about 3 mM. If this represents interference from other anions, the maximum error in ECl measured in normal Krebs solution is 2·5 mV. Replacement of Clo caused a rapid increase in aCli. This must be caused by an active transport of Cl- ions into the cell against their electrochemical gradient. 4. The stabilized values of aCli measured at different levels of Clo agree surprisingly well with aCli estimated from ion analysis and 36Cl efflux, assuming that the intracellular activity coefficient was the same as measured in the normal Krebs solution. The relationship of aCli to Clo was hyperbolic. 5. It is concluded that Cl-sensitive micro-electrodes accurately measure aCli in smooth muscle cells. The remarkable agreement between the direct and indirect methods of measuring Cli suggests that Cl- ions are not bound to a significant extent and that the compartment seen by the micro-electrodes is probably representative of the whole cell. PMID:7108787

Aggravation of cold-induced injury in Vero-B4 cells by RPMI 1640 medium - identification of the responsible medium components.

PubMed

Pless-Petig, Gesine; Metzenmacher, Martin; Türk, Tobias R; Rauen, Ursula

2012-10-10

In modern biotechnology, there is a need for pausing cell lines by cold storage to adapt large-scale cell cultures to the variable demand for their products. We compared various cell culture media/solutions for cold storage of Vero-B4 kidney cells, a cell line widely used in biotechnology. Cold storage in RPMI 1640 medium, a recommended cell culture medium for Vero-B4 cells, surprisingly, strongly enhanced cold-induced cell injury in these cells in comparison to cold storage in Krebs-Henseleit buffer or other cell culture media (DMEM, L-15 and M199). Manufacturer, batch, medium supplements and the most likely components with concentrations outside the range of the other media/solutions (vitamin B12, inositol, biotin, p-aminobenzoic acid) did not cause this aggravation of cold-induced injury in RPMI 1640. However, a modified Krebs-Henseleit buffer with a low calcium concentration (0.42 mM), a high concentration of inorganic phosphate (5.6 mM), and glucose (11.1 mM; i.e. concentrations as in RPMI 1640) evoked a cell injury and loss of metabolic function corresponding to that observed in RPMI 1640. Deferoxamine improved cell survival and preserved metabolic function in modified Krebs-Henseleit buffer as well as in RPMI 1640. Similar Ca2+ and phosphate concentrations did not increase cold-induced cell injury in the kidney cell line LLC-PK1, porcine aortic endothelial cells or rat hepatocytes. However, more extreme conditions (Ca2+ was nominally absent and phosphate concentration raised to 25 mM as in the organ preservation solution University of Wisconsin solution) also increased cold-induced injury in rat hepatocytes and porcine aortic endothelial cells. These data suggest that the combination of low calcium and high phosphate concentrations in the presence of glucose enhances cold-induced, iron-dependent injury drastically in Vero-B4 cells, and that a tendency for this pathomechanism also exists in other cell types.

Identification and mapping of stable QTL with main and epistasis effect on rice grain yield under upland drought stress

PubMed Central

2014-01-01

Background Drought is one of the most important abiotic stresses that cause drastic reduction in rice grain yield (GY) in rainfed environments. The identification and introgression of QTL leading to high GY under drought have been advocated to be the preferred breeding strategy to improve drought tolerance of popular rice varieties. Genetic control of GY under reproductive-stage drought stress (RS) was studied in two BC1F4 mapping populations derived from crosses of Kali Aus, a drought-tolerant aus cultivar, with high-yielding popular varieties MTU1010 and IR64. The aim was to identify QTL for GY under RS that show a large and consistent effect for the trait. Bulk segregant analysis (BSA) was used to identify significant markers putatively linked with high GY under drought. Results QTL analysis revealed major-effect GY QTL: qDTY 1.2 , qDTY 2.2 and qDTY 1.3 , qDTY 2.3 (DTY; Drought grain yield) under drought consistently over two seasons in Kali Aus/2*MTU1010 and Kali Aus/2*IR64 populations, respectively. qDTY 1.2 and qDTY 2.2 explained an additive effect of 288 kg ha−1 and 567 kg ha−1 in Kali Aus/2*MTU1010, whereas qDTY 1.3 and qDTY 2.3 explained an additive effect of 198 kg ha−1 and 147 kg ha−1 in Kali Aus/2*IR64 populations, respectively. Epistatic interaction was observed for DTF (days to flowering) between regions on chromosome 2 flanked by markers RM154–RM324 and RM263–RM573 and major epistatic QTL for GY showing interaction between genomic locations on chromosome 1 at marker interval RM488–RM315 and chromosome 2 at RM324–RM263 in 2012 DS and 2013 DS RS in Kali Aus/2*IR64 mapping populations. Conclusion The QTL, qDTY 1.2 , qDTY 1.3 , qDTY 2.2 , and qDTY 2.3, identified in this study can be used to improve GY of mega varieties MTU1010 and IR64 under different degrees of severity of drought stress through marker-aided backcrossing and provide farmers with improved varieties that effectively combine high yield potential with good yield

Azelainsäure 20 % Creme: Auswirkung auf Lebensqualität und Krankheitsaktivität bei erwachsenen Patientinnen mit Acne vulgaris.

PubMed

Kainz, Julius Thomas; Berghammer, Gabriele; Auer-Grumbach, Piet; Lackner, Verena; Perl-Convalexius, Sylvia; Popa, Rodica; Wolfesberger, Barbara

2016-12-01

Zur Wirksamkeit von Aknetherapien und deren Auswirkungen auf die Lebensqualität erwachsener Patienten liegen kaum Daten vor. ZIEL: Erhebung der Wirkung von Azelainsäure 20 % Creme (Skinoren ® ) auf Akne-Schweregrad und krankheitsbedingte Lebensqualität. Nichtinterventionelle Studie bei erwachsenen Patientinnen mit leichter bis mittelschwerer Akne. Wirksamkeitsparameter waren DLQI sowie Akne-Schweregrad im Gesicht, am Dekolleté sowie am Rücken im Gesamturteil des Prüfarztes (IGA-Skala: Grad 1 = annähernd reine Haut; 2 = leichte Akne; 3 = mittelschwere Akne). Visiten waren zu Studienbeginn sowie nach 4-8 und zwölf Wochen geplant. Von den 251 eingeschlossenen Patientinnen lag zu Studienbeginn bei 59 %, 31 % bzw. 10 % ein IGA-Grad von 1, 2 bzw. 3 vor; die am häufigsten betroffene Hautpartie war das Gesicht (IGA-Grad 2 oder 3: 79 %). Nach zwölf Behandlungswochen war eine signifikante Besserung der Acne vulgaris im Gesicht (IGA-Grad 0 oder 1: 82 %) sowie auf Dekolleté und Rücken feststellbar. Der mediane DLQI-Wert sank von neun zu Studienbeginn auf fünf nach zwölf Behandlungswochen. Neunzig Prozent der behandelnden Ärzte und Patientinnen beurteilten die Verträglichkeit der Behandlung als sehr gut oder gut. Die Anwendung von 20%iger Azelainsäure-Creme führt bei erwachsenen Frauen zu einer signifikanten Besserung der Acne vulgaris und der krankheitsbedingten Lebensqualität. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Serotonergic modulation of nicotine-induced kinetic tremor in mice.

PubMed

Kunisawa, Naofumi; Iha, Higor A; Nomura, Yuji; Onishi, Misaki; Matsubara, Nami; Shimizu, Saki; Ohno, Yukihiro

2017-06-01

We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT 1A agonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT 1A antagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT 2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT 2 antagonist). The 5-HT 3 agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT 3 antagonist) or SB-258585 (5-HT 6 antagonist). These results suggest that postsynaptic 5-HT 1A receptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT 2 receptors have an inhibitory modulatory role in induction of nicotine tremor. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

An Argument for Consolidation: The ANZUS Carrier Task Force

DTIC Science & Technology

2012-06-05

the USN, assisting U.S. and NATO forces in Operation SLIPPER 18 by providing MSO (including counter piracy and counter-terrorism) as part of the...continues to be a key foreign policy objective of AUS.” 33 At AUSMIN 2010 (AUS-US Ministerial Consultations), the principal forum for bilateral...force tailored specifically to meet the concerns of the IP at a shared price and draw up a force-structure framework. In addition to the CVN, a

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

PubMed

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-08-01

Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of diet and exercise interventions to reduce overweight and obesity.

PubMed

Forster, M; Veerman, J L; Barendregt, J J; Vos, T

2011-08-01

To analyze whether two dietary weight loss interventions--the dietary approaches to stop hypertension (DASH) program and a low-fat diet program--would be cost-effective in Australia, and to assess their potential to reduce the disease burden related to excess body weight. We constructed a multi-state life-table-based Markov model in which the distribution of body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. The target population was the overweight and obese adult population in Australia in 2003. We used a lifetime horizon for health effects and costs, and a health sector perspective for costs. We populated the model with data identified from Medline and Cochrane searches, Australian Bureau of Statistics published catalogues, Australian Institute of Health and Welfare, and Department of Health and Ageing. Disability adjusted life years (DALYs) averted, incremental cost-effectiveness ratios (ICERs) and proportions of disease burden avoided. ICERs under AUS$50,000 per DALY are considered cost-effective. The DASH and low-fat diet programs have ICERs of AUS$12,000 per DALY (95% uncertainty range: Cost-saving- 68,000) and AUS$13,000 per DALY (Cost-saving--130,000), respectively. Neither intervention reduced the body weight-related disease burden at population level by more than 0.1%. The sensitivity analysis showed that when participants' costs for time and travel are included, the ICERs increase to AUS$75,000 per DALY for DASH and AUS$49,000 per DALY for the low-fat diet. Modest weight loss during the interventions, post-intervention weight regain and low participation limit the health benefits. Diet and exercise interventions to reduce obesity are potentially cost-effective but have a negligible impact on the total body weight-related disease burden.

Co-movement measure of information transmission on international equity markets

NASA Astrophysics Data System (ADS)

Al Rahahleh, Naseem; Bhatti, M. Ishaq

2017-03-01

Recently, Bhatti and Nguyen (2012) used EVT and various stochastic copulas to study the cross-country co-movements diversification and asset pricing allocation. Weiss (2013) observed that Dynamic Conditional Correlation (DCC) models outperform various copula models. This paper attempts to contribute to the literature on multivariate models for capturing forward and backward return co-movement, spillover effects and volatility linkages. It reflects cross-country forward and backward co-movements more clearly among various coupled international stock markets relating to information transmission and price discovery for making investment decisions. Given the reality of fat-tail or skewed distribution of financial data, this paper proposes the use of VECM-DCC and VAR-DCC models which capture dynamic dependences between the Australian and other selected international financial stock markets. We observe that the return co-movement effects between Australian and Asian countries are bidirectional ((AUS ↔ Hong Kong), (AUS ↔ Japan)) with the exception of Taiwan (AUS → Taiwan). We also observe that the volatility spillover between the Australian and both the UK and the US markets are bidirectional with a larger volatility spillover from both toward the AUS market. Further, the UK market has a higher volatility spillover on the Australian market compared to the US market and the US market has a higher volatility spillover on the UK than that of the Australian market.

Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography, and ERCP.

PubMed

Buscail, L; Escourrou, J; Moreau, J; Delvaux, M; Louvel, D; Lapeyre, F; Tregant, P; Frexinos, J

1995-04-01

The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81 patients with suspected pancreatic disease. All underwent EUS, abdominal ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis of CP was established in 44 patients (CP group) including 24 with a calcified form. No pancreatic disease was observed in 18 patients (control group), and 19 patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS in visualizing the pancreas, performances of CT scan being identical to EUS in this respect. A good correlation was observed between EUS and ERCP for visualization and measurement of the Wirsung duct. The most significant changes observed by EUS in the CP group were dilatation of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good performances of EUS allow early diagnosis of CP in symptomatic patients since heterogeneous echogenicity of the pancreatic parenchyma seems to be almost specifically associated with the disease.

The nursing and financial implications of laparoscopic colorectal surgery: data from a randomized controlled trial.

PubMed

Norwood, M G A; Stephens, J H; Hewett, P J

2011-11-01

The issue of cost effectiveness of laparoscopic surgery remains uncertain and its impact on the ward nursing staff is unaddressed. This study investigated these issues using patients from a single centre admitted to a randomized controlled trial. All patients recruited into the Australasian Laparoscopic Colon Cancer Study (ALCCaS) from The Queen Elizabeth Hospital between January 1999 and March 2005 were included in this study. Data relating to hospital cost were collated from the Hospital Patient Costing System. Nursing interventions were calculated in minutes per patient, using the excelcare Software database. Data from 97 patients were analysed (laparoscopy, 53; open surgery, 44). The median number of hours of nursing input per patient was 80 (27.5-907) h in the open surgery group and 58.5 (15-684.5) h in the laparoscopy group. This difference was further increased after exclusion of patients converted from laparoscopy to open surgery. The median total cost of the procedure was AUS $9698/£ 5631 (AUS $3862-90,397) in the open surgery group and AUS $10,951/£ 6219 (AUS$2337-66,237) in the laparoscopy group. These data suggest that laparoscopic colorectal surgery is equivalent in price to open surgery and there may be added benefits in reduced nursing intensity. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Proceedings of the Annual Conference on Environmental Toxicology (8th) held at Dayton, OH, 4-6 October 1977

DTIC Science & Technology

1977-12-01

generated citrate to the cyto- plasmic fatty acid synthesizing system (Kirsten et al., 1971). As shown in Table 1 , preincubation of mitochondria ( 1 mg...fatty acid bio- synthesis is independent from aconitase in terms of metabolic pathways. 127 TABLE 1 . INHIBITION OF MITOCHONDRIAL CITRATE ENTRY AND... carboxylic acid substrates of the Krebs 132 cycle enzymes revealed that none of them formed covalent adducts with membrane proteins. It was therefore

Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the Effects of Hemoglobin-Based Oxygen Carriers

DTIC Science & Technology

2008-07-16

mitochondria through the monocarboxylate transporter and feed in to the Kreb’s cycle to yield 34 ATPs via oxidative phosphorylation as follows (assuming a... Krebs (tricarboxylic acid) cycle enzyme, and is found mainly in the mitochondrial matrix (8). Therefore, its measured enzymatic activity serves as an...APPROVAL SHEET Title of Thesis: "Use of Isolated Mitochondria and Pulmonary Artery Endothelial Cell Systems in Studies of Oxygen Utilization and the

Malonyl-CoA Decarboxylase (MCD) as a Potential Therapeutic Target for Breast Cancer

DTIC Science & Technology

2010-05-01

Kreb cycle and electron transport activity. Clinical and biochemical studies of MCD deficiency, a rare inborn error of metabolism, provide another... mitochondria and is the rate limiting enzymatic step of mitochondrial fatty acid oxidation (Figure 1) (McGarry and Brown, 1997). Indeed, the 10-fold...1 activity and fatty acid oxidation, thereby preventing a futile cycle of fatty acid synthesis and oxidation. As FAS could consume malonyl-CoA, it was

A Computational Study of Transverse Combustion Instability Mechanisms

DTIC Science & Technology

2014-07-01

April 2001. 7. Selle, L ., Benoit , L ., Poinsot, T., Nicoud, F., Krebs, W., “Joint use of compressible large-eddy simulation and Helmholtz solvers for...Mechanisms Kevin J. Shipley1, William E. Anderson2 Purdue University, West Lafayette, IN, 47906 Matthew E. Harvazinski3, and Venkateswaran Sankaran4...Lafayette, IN, August 2010. 9. Xia, G., Harvazinski, M., Anderson, W., Merkle, C. L ., “Investigation of Modeling and Physical Parameters on Instability

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes.

PubMed

Kong, C; Nimmo, L; Elatrozy, T; Anyaoku, V; Hughes, C; Robinson, S; Richmond, W; Elkeles, R S

2001-06-01

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Isomorphism and solid solutions among Ag- and Au-selenides

NASA Astrophysics Data System (ADS)

Palyanova, Galina A.; Seryotkin, Yurii V.; Kokh, Konstantin A.; Bakakin, Vladimir V.

2016-09-01

Au-Ag selenides were synthesized by heating stoichiometric mixtures of elementary substances of initial compositions Ag2-xAuxSe with a step of х=0.25 (0≤х≤2) to 1050 °С and annealing at 500 °C. Scanning electron microscopy, optical microscopy, electron microprobe analysis and X-ray powder diffraction methods have been applied to study synthesized samples. Results of studies of synthesized products revealed the existence of three solid solutions with limited isomorphism Ag↔Au: naumannite Ag2Se - Ag1.94Au0.06Se, fischesserite Ag3AuSe2 - Ag3.2Au0.8Se2 and gold selenide AuSe - Au0.94Ag0.06Se. Solid solutions and AgAuSe phases were added to the phase diagram of Ag-Au-Se system. Crystal-chemical interpretation of Ag-Au isomorphism in selenides was made on the basis of structural features of fischesserite, naumannite, and AuSe.

Digital Games and the Hero's Journey in Management Workshops and Tertiary Education

ERIC Educational Resources Information Center

Busch, Carsten; Conrad, Florian; Steinicke, Martin

2013-01-01

Joseph Campbell's Monomyth not only provides a well-proven pattern for successful storytelling, it may also help to guide teams and team leaders through the challenges of change and innovation processes. In project "HELD: Innovationsdramaturgie nach dem Heldenprinzip" researchers of the University of the Arts Berlin and the Berlin…

Phellinus rimosus improves mitochondrial energy status and attenuates nephrotoxicity in diabetic rats.

PubMed

Rony, K A; Ajith, T A; Kuttikadan, Tony A; Blaze, R; Janardhanan, K K

2017-09-26

Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation. Mitochondrial antioxidant status such as mitochondrial superoxide dismutase, glutathione peroxidase, and reduced glutathione; adenosine triphosphate level; and lipid peroxidation were measured. The activities of Krebs cycle enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, III, and IV in kidney mitochondria were also determined. Administration of P. rimosus (250 mg/kg b.wt) once daily for 30 days, significantly (p<0.05) enhanced the activities of Krebs cycle dehydrogenases, mitochondrial electron transport chain complexes, and ATP level. Further, P. rimosus had significantly protected the renal mitochondrial antioxidant status and lipid peroxidation. The results of the study concluded that by limiting the extent of renal mitochondrial damage in the hyperglycemic state, P. rimosus alleviated nephrotoxicity.

Mitochondrial Bioenergetics and Dysfunction in Failing Heart.

PubMed

Sheeran, Freya L; Pepe, Salvatore

2017-01-01

Energy insufficiency has been recognized as a key feature of systolic heart failure. Although mitochondria have long been known to sustain myocardial work energy supply, the capacity to therapeutically target mitochondrial bioenergetics dysfunction is hampered by a complex interplay of multiple perturbations that progressively compound causing myocardial failure and collapse. Compared to non-failing human donor hearts, activity rates of complexes I and IV, nicotinamide nucleotide transhydrogenase (NADPH-transhydrogenase, Nnt) and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase and aconitase are markedly decreased in end-stage heart failure. Diminished REDOX capacity with lower total glutathione and coenzyme Q 10 levels are also a feature of chronic left ventricular failure. Decreased enzyme activities in part relate to abundant and highly specific oxidative, nitrosylative, and hyperacetylation modifications. In this brief review we highlight that energy deficiency in end-stage failing human left ventricle predominantly involves concomitantly impaired activities of key electron transport chain and Krebs cycle enzymes rather than altered expression of respective genes or proteins. Augmented oxidative modification of these enzyme subunit structures, and the formation of highly reactive secondary metabolites, implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, which contribute further to progressive decreases in bioenergetic capacity and contractile function in human heart failure.

Hypoxia and GABA shunt activation in the pathogenesis of Alzheimer's disease.

PubMed

Salminen, Antero; Jouhten, Paula; Sarajärvi, Timo; Haapasalo, Annakaisa; Hiltunen, Mikko

2016-01-01

We have previously observed that the conversion of mild cognitive impairment to definitive Alzheimer's disease (AD) is associated with a significant increase in the serum level of 2,4-dihydroxybutyrate (2,4-DHBA). The metabolic generation of 2,4-DHBA is linked to the activation of the γ-aminobutyric acid (GABA) shunt, an alternative energy production pathway activated during cellular stress, when the function of Krebs cycle is compromised. The GABA shunt can be triggered by local hypoperfusion and subsequent hypoxia in AD brains caused by cerebral amyloid angiopathy. Succinic semialdehyde dehydrogenase (SSADH) is a key enzyme in the GABA shunt, converting succinic semialdehyde (SSA) into succinate, a Krebs cycle intermediate. A deficiency of SSADH activity stimulates the conversion of SSA into γ-hydroxybutyrate (GHB), an alternative route from the GABA shunt. GHB can exert not only acute neuroprotective activities but unfortunately also chronic detrimental effects which may lead to cognitive impairment. Subsequently, GHB can be metabolized to 2,4-DHBA and secreted from the brain. Thus, the activation of the GABA shunt and the generation of GHB and 2,4-DHBA can have an important role in the early phase of AD pathogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolite concentrations in skeletal muscle of different aged rats submitted to hypoxia and pharmacological treatment with nicergoline.

PubMed

Pastoris, O; Foppa, P; Catapano, M; Dossena, M

1998-06-01

The energy metabolism of the gastrocnemius and soleus muscles in young-adult, mature, and senescent rats was evaluated after 72 h of continuous exposure to normobaric hypoxia or normoxia. The effects of treatment with the alpha-adrenergic antagonist nicergoline were also investigated. In the gastrocnemius muscle we evaluated the concentrations of some significative metabolites involved in anaerobic glycolysis and the Krebs' cycle, free amino acids related to the Krebs' cycle, ammonia, some energy mediators, and the energy store creatine phosphate. In the soleus muscle a selection of these was evaluated. In both muscles aging was similarly characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential remained unchanged. Singly, some gastrocnemius muscle metabolites showed linear changes in their concentrations with aging, while for the soleus muscle the only linear change regarded glucose-6-phosphate. Continuous normobaric hypoxia induced greater changes at the age of 4 and 24 months than at 12 months. Chronic treatment with nicergoline modified the influence of hypoxic conditions on muscle metabolites concentrations only in some cases, regardless of the age of the animals. Further investigations are necessary before any firm conclusions can be drawn about the pharmacological activity of nicergoline on hypoxia in aged rats.

Parallel evolution of Batesian mimicry supergene in two Papilio butterflies, P. polytes and P. memnon

PubMed Central

Itoh, Takehiko

2018-01-01

Batesian mimicry protects animals from predators when mimics resemble distasteful models. The female-limited Batesian mimicry in Papilio butterflies is controlled by a supergene locus switching mimetic and nonmimetic forms. In Papilio polytes, recent studies revealed that a highly diversified region (HDR) containing doublesex (dsx-HDR) constitutes the supergene with dimorphic alleles and is likely maintained by a chromosomal inversion. In the closely related Papilio memnon, which exhibits a similar mimicry polymorphism, we performed whole-genome sequence analyses in 11 butterflies, which revealed a nearly identical dsx-HDR containing three genes (dsx, Nach-like, and UXT) with dimorphic sequences strictly associated with the mimetic/nonmimetic phenotypes. In addition, expression of these genes, except that of Nach-like in female hind wings, showed differences correlated with phenotype. The dimorphic dsx-HDR in P. memnon is maintained without a chromosomal inversion, suggesting that a separate mechanism causes and maintains allelic divergence in these genes. More abundant accumulation of transposable elements and repetitive sequences in the dsx-HDR than in other genomic regions may contribute to the suppression of chromosomal recombination. Gene trees for Dsx, Nach-like, and UXT indicated that mimetic alleles evolved independently in the two Papilio species. These results suggest that the genomic region involving the above three genes has repeatedly diverged so that two allelic sequences of this region function as developmental switches for mimicry polymorphism in the two Papilio species. The supergene structures revealed here suggest that independent evolutionary processes with different genetic mechanisms have led to parallel evolution of similar female-limited polymorphisms underlying Batesian mimicry in Papilio butterflies. PMID:29675466

Selectivity of antagonists for the Cys-loop native receptors for ACh, 5-HT and GABA in guinea-pig myenteric neurons.

PubMed

Juárez, E H; Ochoa-Cortés, F; Miranda-Morales, M; Espinosa-Luna, R; Montaño, L M; Barajas-López, C

2014-01-01

The three most common Cys-loop receptors expressed by myenteric neurons are nACh, 5-HT3 and GABAA . To investigate the function of these proteins researchers have used channel inhibitors such as hexamethonium (antagonist of nACh receptors), ondansetron (antagonist of 5-HT3 receptors), picrotoxin and bicuculline (both antagonists of GABAA receptors). The aim of this study was to investigate the specificity of these inhibitors on Cys-loop receptors of primary cultured neurons obtained from the guinea-pig small intestine. The whole-cell configuration of the patch clamp techniques was used to record membrane currents induced by ACh (IACh ), 5-HT (I5-HT ) and GABA (IGABA ) in the absence and the presence of various concentrations of hexamethonium, ondansetron, picrotoxin or bicuculline. The three Cys-loop receptors present in enteric neurons are expressed independently and they do not cross-desensitized. Hexamethonium inhibited IACh without affecting I5-HT and IGABA . Ondansetron inhibited I5-HT and also IACh but did not affect IGABA . Picrotoxin and bicuculline inhibited I5-HT , IACh and IGABA with different potency, being the lowest potency on 5-HT3 receptors. All these inhibitory effects were concentration dependent and reversible. Our observations showed that except for hexamethonium, all other inhibitors used here show different degrees of selectivity, which has to be considered when these antagonists are used in experimental studies aimed to investigate the functions of these receptors. In particular, in tissues expressing nACh receptors because these are the targets of all other inhibitors used here. The low potency of picrotoxin and bicuculline to inhibit 5-HT3 receptors suggests that these receptors are heteromeric proteins. © 2013 John Wiley & Sons Ltd.

Einführung

NASA Astrophysics Data System (ADS)

Wellenreuther, Günter; Zastrow, Dieter

Reale Aufgaben der Automatisierungstechnik sind im Allgemeinen sehr komplex. Als umfassender Ausdruck für Steuerungs-, Regelungs- und Visualisierungs-Vorgänge hat sich der Begriff der Automatisierung durchgesetzt. Er beinhaltet, dass Automatisierungsgeräte selbsttätig Programme befolgen und dabei Entscheidungen auf Grund vorgegebener Führungsgrößen und rückgeführter Prozessgrößen aus der Anlage sowie erforderlicher Daten aus internen Speichern des Systems treffen, um daraus notwendige Ausgangsgrößen für den Betriebsprozess zu bilden.

From Cognition To Language: The Modeling Field Theory Approach

DTIC Science & Technology

2006-10-02

emergence of cells, it is still not clear how such an assemblage could be formed and maintained starting from selfish genes (see [46] for a review). In...have been struggling with for more than three decades [39]. For example, although the coordinated work of distinct genes is germane to the...290, 2005. [19] D. K. Lewis, Convention: a Philosophical Study. Harvard University Press, Cambridge, MA, 1969. [20] R. Dawkins , J. R. Krebs, “Animal

Physik gestern und heute Spurensuche

NASA Astrophysics Data System (ADS)

Engels, Wolfgang; Heering, Peter

2005-01-01

Im Jahre 1927 erhielt Charles Thomson Rees Wilson für die von ihm entwickelte Methode zur Visualisierung der Spuren ionisierender Strahlung den Nobelpreis für Physik. Die nach ihm benannte Nebelkammer wurde in der ersten Hälfte des 20. Jahrhunderts zu einem Standardinstrument für Untersuchungen subatomarer Prozesse.

Rede und Gesinnung (Speech and Ways of Thinking)

ERIC Educational Resources Information Center

Kienzle, Bertram

1974-01-01

Analyzes some of the basic ideas in Georg Franklin's book "Versuch einer neuen Lehre von den vornehmsten Gegenstanden der deutschen Sprachlehre; nach den Regeln der Vernunftlehre in sechs Abhandlungen verfasst" (1778) and compares them to those of such modern linguists and philosophers a s Searle, Austin and Wunderlich. Concludes that…

Analog-Digital-Wandler

NASA Astrophysics Data System (ADS)

Döring, Peter

Analogsignale in digital codierter Form haben Vorteile (z. B. Speicherung, Übertragung). Ein Beispiel dafür ist die Musik-Film-CD/DVD. In diesem Kapitel werden entsprechende Verfahren vorgestellt. Themen: Grundlagen; Spannungs-Frequenz-Umsetzer: Sägezahn-Verfahren; Dual-Slope-Verfahren; Flash-Umsetzer; Umsetzer nach dem Wägeverfahren. Integrierte Umsetzer.

Thyroid fine-needle aspiration reporting rates and outcomes before and after Bethesda implementation within a combined academic and community hospital system.

PubMed

Harvey, Aaron M; Mody, Dina R; Amrikachi, Mojgan

2013-11-01

The current study compares data from our hospital system before and after the 2008 implementation of the Bethesda System for Reporting Thyroid Cytology (BSRTC). To show the effects the BSRTC has had on the reporting rates and outcomes for thyroid lesions. A search for thyroid fine-needle aspiration biopsies (FNABs) was performed for 2002-2005 (before BSRTC) and 2009-2011 (after BSRTC). Diagnostic outcomes were reviewed for cases with available follow-up. For 2002-2005, cytology reports for 3302 thyroid FNABs were reviewed, and 309 (9.4%) were classified as suspicious. For 2009-2011, cytology reports for 3432 thyroid FNABs were reviewed; 72 (2.1%) were classified as "atypia of undetermined significance or follicular lesion of undetermined significance" (AUS/FLUS), and 142 (4.1%) were classified as suspicious. Follow-up material was available for 31 AUS/FLUS cases (43.0%), and 6 of these cases (19%) were malignant. Follow-up material was available for 60 cases (42.3%) classified as suspicious, and 23 of these cases (38%) were malignant. The AUS/FLUS rate of 2.1% at our institution is at the lower range of the <7% recommended by the BSRTC, and our rate of 19% for risk of malignancy for AUS/FLUS is slightly above the BSRTC recommendation of 5% to 15%. Implementation of the BSRTC did not significantly affect our institution's reporting rates, most likely because an essentially similar classification system was employed before implementation of the BSRTC.

Der Weg Nach Europa: Bildungsreformen in Mittel- und Osteuropa

NASA Astrophysics Data System (ADS)

Steier, Sonja

2006-12-01

THE WAY TO EUROPE: EDUCATION REFORM IN CENTRAL AND EASTERN EUROPE - Since embarking for the European Union in 1989, the countries of Central and Eastern Europe have been reorganising and restructuring their educational systems. In doing so, they have not only departed from the Soviet-style education model, but also recognised that education constitutes a key issue in competition. Despite some economic problems, the education reforms in these countries have been regarded as part of a major effort at integrating themselves into the European sphere of knowledge. Many of the efforts and measures in education policy envisaged and carried out since the systemic change occurred have led not only to revitalizing national educational heritages, but also to the independent adoption of other European and international trends and topics in educational discourse. Thereby, these states have proved to be considerably more innovative and flexible than the "older" members of the EU. The prospect of being taken up into the EU has probably helped accelerate the entire process. The present study focuses on some key overarching developments in the educational landscape of states in Central and Eastern Europe, even as it is apparent that these are proceeding along different paths at different speeds.

Verbesserte Visualisierung der Koronararterien in MSCT-Daten mit direkter Vergleichbarkeit zur Angiographie

NASA Astrophysics Data System (ADS)

Lacalli, Christina; Jähne, Marion; Wesarg, Stefan

In diesem Beitrag stellen wir neue, automatisierte Verfahren zur Visualisierung der Koronararterien einerseits und für eine direkte Vergleichbarkeit mit konventionellen Angiogrammen andererseits vor. Unser Ansatz umfasst Methoden für die automatische Extraktion des Herzens aus kontrastverstärkten CT-Daten, sowie für die Maskierung grosser kontrastmittelgefüllter Kavitäten des Herzens, um die Sichtbarkeit der Koronararterien bei der Darstellung mittels Volumenrendering zu verbessern. Zum direkten Vergleich mit konventionellen Angiographien wurde ein Verfahren zur automatischen Generierung von Projektionsansichten aus den CT-Daten entwickelt.

The Impact of Diabetes Mellitus and Obesity on Artificial Urinary Sphincter Outcomes in Men.

PubMed

Viers, Boyd R; Linder, Brian J; Rivera, Marcelino E; Andrews, Jack R; Rangel, Laureano J; Ziegelmann, Matthew J; Elliott, Daniel S

2016-12-01

To evaluate the impact of diabetes and obesity on artificial urinary sphincter (AUS) outcomes. From 1987 to 2011, men with available diabetes and body mass index (BMI) information (568 of 954) undergoing primary AUS placement at our institution were evaluated. The incidence of all-cause reintervention, mechanical failure, atrophy, and erosion or infection was assessed using the Kaplan-Meier method. Multivariable analyses evaluated the association between clinical characteristics and AUS outcomes. In total, 90 (16%) men had diabetes. Median follow-up among alive men without AUS event was 5.9 years. Diabetics had a greater 5-year incidence of erosion/infection (13% vs 8%; P = .025). On multivariable analysis, diabetes was independently associated with an increased risk of erosion/infection (hazard ratio [HR] = 2.26; P = .02); whereas greater BMI was associated with a reduced risk of erosion or infection (obese: HR = 0.39; P = .02; overweight: HR = 0.57; P = .07). Accordingly, in diabetics, greater average postoperative glucose level (176 mg/dL vs 153 mg/dL; P = .04) and use of nonantibiotic coated devices (13 of 62 vs 1 of 28; P = .035) was associated with a greater incidence of erosion or infection. There was no difference in social continence (≤1 pad/day) (45% vs 57%; P = .29) or high-level satisfaction (95% vs 90%; P = .43) among diabetics vs nondiabetics. However, with greater BMI (<25, 25 to <30, and ≥30), there was a decrease in ≤1 pad/day usage (62% vs 61% vs 49%; P = .02). We found that the presence of diabetes was independently associated with a 2.3-fold increased risk of AUS erosion or infection. These findings warrant the consideration of additional periprocedural measures to reduce the risk of this devastating complication. Copyright © 2016 Elsevier Inc. All rights reserved.

Water and Proppant Requirements and Water Production Associated with Undiscovered Petroleum in the Bakken and Three Forks Formations, North Dakota and Montana, USA

NASA Astrophysics Data System (ADS)

Haines, S. S.; Varela, B. A.; Thamke, J.; Hawkins, S. J.; Gianoutsos, N. J.; Tennyson, M. E.

2017-12-01

Water is used for several stages of oil and gas production, in particular for hydraulic fracturing that is typically used during production of petroleum from low-permeability shales and other rock types (referred to as "continuous" petroleum accumulations). Proppant, often sand, is also consumed during hydraulic fracturing. Water is then produced from the reservoir along with the oil and gas, representing either a disposal consideration or a possible source of water for further petroleum development or other purposes. The U.S. Geological Survey (USGS) has developed an approach for regional-scale estimation of these water and proppant quantities in order to provide an improved understanding of possible impacts and to help with planning and decision-making. Using the new methodology, the USGS has conducted a quantitative assessment of water and proppant requirements, and water production volumes, associated with associated with possible future production of undiscovered petroleum resources in the Bakken and Three Forks Formations, Williston Basin, USA. This water and proppant assessment builds directly from the 2013 USGS petroleum assessment for the Bakken and Three Forks Formations. USGS petroleum assessments incorporate all available geologic and petroleum production information, and include the definition of assessment units (AUs) that specify the geographic regions and geologic formations for the assessment. The 2013 petroleum assessment included 5 continuous AUs for the Bakken Formation and one continuous AU for the Three Forks Formation. The assessment inputs are defined probabilistically, and a Monte Carlo approach provides outputs that include uncertainty bounds. We can summarize the assessment outputs with the mean values of the associated distributions. The mean estimated total volume of water for well drilling and cement for all six continuous AUs is 5.9 billion gallons, and the mean estimated volume of water for hydraulic fracturing for all AUs is 164

A novel coating concept for ileo-colonic drug targeting: proof of concept in humans using scintigraphy.

PubMed

Varum, F J O; Hatton, G B; Freire, A C; Basit, A W

2013-08-01

The in vivo proof of concept of a novel double-coating system, based on enteric polymers, which accelerated drug release in the ileo-colonic region, was investigated in humans. Prednisolone tablets were coated with a double-coating formulation by applying an inner layer composed of EUDRAGIT S neutralised to pH 8.0 and a buffer salt (10% KH₂PO₄), which was overcoated with layer of standard EUDRAGIT S organic solution. For comparison, a single coating system was produced by applying the same amount of EUDRAGIT S organic solution on the tablet cores. Dissolution tests on the tablets were carried out using USP II apparatus in 0.1N HCl for 2 h and subsequently in pH 7.4 Krebs bicarbonate buffer. For comparison, tablets were also tested under the USP method established for modified release mesalamine formulations. Ten fasted volunteers received the double-coated and single-coated tablets in a two-way crossover study. The formulations were radiolabelled and followed by gamma scintigraphy; the disintegration times and positions were recorded. There was no drug release from the single-coated or double-coated tablets in 0.1N HCl for 2h. The single-coated tablets showed slow release in subsequent Krebs bicarbonate buffer with a lag time of 120 min, while in contrast drug release from the double-coated tablets was initiated at 60 min. In contrast, using the USP dissolution method, normally employed for modified release mesalamine products, no discrimination was attained. The in vivo disintegration of the single-coated EUDRAGIT S tablets in the large intestine was erratic. Furthermore, in 2 volunteers, the single-coated tablet was voided intact. Double-coated tablets disintegrated in a more consistent way, mainly in the ileo-caecal junction or terminal ileum. The accelerated in vivo disintegration of the double-coating EUDRAGIT S system can overcome the limitations of conventional enteric coatings targeting the colon and avoid the pass-through of intact tablets. Moreover

Facial expressions and speech acts: experimental evidences on the role of the upper face as an illocutionary force indicating device in language comprehension.

PubMed

Domaneschi, Filippo; Passarelli, Marcello; Chiorri, Carlo

2017-08-01

Language scientists have broadly addressed the problem of explaining how language users recognize the kind of speech act performed by a speaker uttering a sentence in a particular context. They have done so by investigating the role played by the illocutionary force indicating devices (IFIDs), i.e., all linguistic elements that indicate the illocutionary force of an utterance. The present work takes a first step in the direction of an experimental investigation of non-verbal IFIDs because it investigates the role played by facial expressions and, in particular, of upper-face action units (AUs) in the comprehension of three basic types of illocutionary force: assertions, questions, and orders. The results from a pilot experiment on production and two comprehension experiments showed that (1) certain upper-face AUs seem to constitute non-verbal signals that contribute to the understanding of the illocutionary force of questions and orders; (2) assertions are not expected to be marked by any upper-face AU; (3) some upper-face AUs can be associated, with different degrees of compatibility, with both questions and orders.

Synthesis of the 1-Monoester of 2-Ketoalkanedioic Acids, e.g., Octyl α-Ketoglutarate

PubMed Central

Jung, Michael E.; Deng, Gang

2012-01-01

Oxidative cleavage of cycloalkene-1-carboxylates, made from the corresponding carboxylic acids, and subsequent oxidation of the resulting ketoaldehyde afforded the important 1-monoesters of 2-ketoalkanedioic acids. Thus ozonolysis of octyl cyclobutene-1-carboxylate followed by sodium chlorite oxidation afforded the 1-monooctyl 2-ketoglutarate. This is a cell-permeable prodrug form of α-ketoglutarate, an important intermediate in the tricarboxylic acid (TCA, Krebs) cycle and a promising therapeutic agent in its own right. PMID:23163977

Nav1.7 expression is increased in painful human dental pulp.

PubMed

Luo, Songjiang; Perry, Griffin M; Levinson, S Rock; Henry, Michael A

2008-04-21

Animal studies and a few human studies have shown a change in sodium channel (NaCh) expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1) Nav1.7, N52 and PGP9.5, and 2) Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier), and myelin basic protein (MBP), and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

ProCare Trial: a phase II randomized controlled trial of shared care for follow-up of men with prostate cancer.

PubMed

Emery, Jon D; Jefford, Michael; King, Madeleine; Hayne, Dickon; Martin, Andrew; Doorey, Juanita; Hyatt, Amelia; Habgood, Emily; Lim, Tee; Hawks, Cynthia; Pirotta, Marie; Trevena, Lyndal; Schofield, Penelope

2017-03-01

To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer. Men who had completed treatment for low- to moderate-risk prostate cancer within the previous 8 weeks were eligible. Participants were randomized to usual care or shared care. Shared care entailed substituting two hospital visits with three visits in primary care, a survivorship care plan, recall and reminders, and screening for distress and unmet needs. Outcome measures included psychological distress, prostate cancer-specific quality of life, satisfaction and preferences for care and healthcare resource use. A total of 88 men were randomized (shared care n = 45; usual care n = 43). There were no clinically important or statistically significant differences between groups with regard to distress, prostate cancer-specific quality of life or satisfaction with care. At the end of the trial, men in the intervention group were significantly more likely to prefer a shared care model to hospital follow-up than those in the control group (intervention 63% vs control 24%; P<0.001). There was high compliance with prostate-specific antigen monitoring in both groups. The shared care model was cheaper than usual care (shared care AUS$1411; usual care AUS$1728; difference AUS$323 [plausible range AUS$91-554]). Well-structured shared care for men with low- to moderate-risk prostate cancer is feasible and appears to produce clinically similar outcomes to those of standard care, at a lower cost. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

PubMed

Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

2014-07-01

Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

High submuscular placement of urologic prosthetic balloons and reservoirs via transscrotal approach.

PubMed

Morey, Allen F; Cefalu, Christopher A; Hudak, Steven J

2013-02-01

Traditional placement of inflatable penile prosthesis (IPP) reservoirs and/or artificial urinary sphincter (AUS) balloons into the space of Retzius may be challenging following major pelvic surgery. The aim of this study is to report our 1-year experience using a novel technique for high balloon/reservoir placement beneath the rectus abdominus muscle, thus completely obviating deep pelvic dissection during prosthetic urologic surgery. A retrospective review of all patients who underwent IPP and/or AUS placement between June 2011 and June 2012 was performed. All had AUS balloons and/or IPP reservoirs placed in a submuscular location by bluntly tunneling through the external inguinal ring into a potential space between the transversalis fascia and the rectus abdominus muscle using a long, angled, lung grasping clamp. Patient demographics, perioperative outcomes, and initial follow-up patient-reported outcomes were reviewed. During the study period, 120 submuscular balloons/reservoirs were inserted in 107 consecutive patients who underwent placement of an IPP (61 patients), AUS (33 patients), or both (13 patients). Among our 48 most recent patients, 41 (85%) reported they were totally unable to feel their balloon/reservoir, and all but two patients reported no bother from the submuscular balloon/reservoir placement. Of the 120 total submuscular balloons and reservoirs, surgical time and outcomes of the prosthetic procedures appeared similar to those placed using traditional methods; two reservoirs required revision surgery for repositioning. High submuscular placement of genitourinary prosthetic balloons and reservoirs via a transscrotal approach is both safely and effective, while avoiding deep retropubic dissection. © 2012 International Society for Sexual Medicine.

Artificial urinary sphincter revision for urethral atrophy: Comparing single cuff downsizing and tandem cuff placement.

PubMed

Linder, Brian J; Viers, Boyd R; Ziegelmann, Matthew J; Rivera, Marcelino E; Elliott, Daniel S

2017-01-01

To compare outcomes for single urethral cuff downsizing versus tandem cuff placement during artificial urinary sphincter (AUS) revision for urethral atrophy. We identified 1778 AUS surgeries performed at our institution from 1990-2014. Of these, 406 were first AUS revisions, including 69 revisions for urethral atrophy. Multiple clinical and surgical variables were evaluated for potential association with device outcomes following revision, including surgical revision strategy (downsizing a single urethral cuff versus placing tandem urethral cuffs). Of the 69 revision surgeries for urethral atrophy at our institution, 56 (82%) were tandem cuff placements, 12 (18%) were single cuff downsizings and one was relocation of a single cuff. When comparing tandem cuff placements and single cuff downsizings, the cohorts were similar with regard to age (p=0.98), body-mass index (p=0.95), prior pelvic radiation exposure (p=0.73) and length of follow-up (p=0.12). Notably, there was no difference in 3-year overall device survival compared between single cuff and tandem cuff revisions (60% versus 76%, p=0.94). Likewise, no significant difference was identified for tandem cuff placement (ref. single cuff) when evaluating the risk of any tertiary surgery (HR 0.95, 95% CI 0.32-4.12, p=0.94) or urethral erosion/device infection following revision (HR 0.79, 95% CI 0.20-5.22, p=0.77). There was no significant difference in overall device survival in patients undergoing single cuff downsizing or tandem cuff placement during AUS revision for urethral atrophy. Copyright® by the International Brazilian Journal of Urology.

Rice Root Architectural Plasticity Traits and Genetic Regions for Adaptability to Variable Cultivation and Stress Conditions1[OPEN

PubMed Central

Sandhu, Nitika; Raman, K. Anitha; Torres, Rolando O.; Audebert, Alain; Dardou, Audrey; Kumar, Arvind; Henry, Amelia

2016-01-01

Future rice (Oryza sativa) crops will likely experience a range of growth conditions, and root architectural plasticity will be an important characteristic to confer adaptability across variable environments. In this study, the relationship between root architectural plasticity and adaptability (i.e. yield stability) was evaluated in two traditional × improved rice populations (Aus 276 × MTU1010 and Kali Aus × MTU1010). Forty contrasting genotypes were grown in direct-seeded upland and transplanted lowland conditions with drought and drought + rewatered stress treatments in lysimeter and field studies and a low-phosphorus stress treatment in a Rhizoscope study. Relationships among root architectural plasticity for root dry weight, root length density, and percentage lateral roots with yield stability were identified. Selected genotypes that showed high yield stability also showed a high degree of root plasticity in response to both drought and low phosphorus. The two populations varied in the soil depth effect on root architectural plasticity traits, none of which resulted in reduced grain yield. Root architectural plasticity traits were related to 13 (Aus 276 population) and 21 (Kali Aus population) genetic loci, which were contributed by both the traditional donor parents and MTU1010. Three genomic loci were identified as hot spots with multiple root architectural plasticity traits in both populations, and one locus for both root architectural plasticity and grain yield was detected. These results suggest an important role of root architectural plasticity across future rice crop conditions and provide a starting point for marker-assisted selection for plasticity. PMID:27342311

Quantenwelt im Nanozylinder: Elektronische Eigenschaften von Kohlenstoff-Nanoröhrchen

NASA Astrophysics Data System (ADS)

Strunk, Christoph

2005-07-01

Kohlenstoff-Nanoröhren sind einzelne oder mehrfach ineinander gesteckte molekulare Hohlzylinder. In ihnen bilden Kohlenstoffatome ein Graphit ähnliches Kristallgitter. Diese Fullerene zeichnen sich durch eine außerordentlich hohe Elastizität und Zugfestigkeit aus. In ihren elektronischen Eigenschaften verhalten sie sich entweder wie Halbleiter oder wie metallische Leiter. Aus halbleitenden Nanoröhren konnten bereits winzige Feldeffekttransistoren hergestellt werden, ein erster Schritt hin zu einer molekularen Elektronik. Die Grundlagenforscher interessiert vor allem das Verhalten metallischer Nanoröhren bei tiefen Temperaturen. An ihren elektronischen Systemen lassen sich zum Beispiel Quanteninterferenzphänomene oder Elektron-Elektron-Wechselwirkungen untersuchen.

Flexible binding simulation by a novel and improved version of virtual-system coupled adaptive umbrella sampling

NASA Astrophysics Data System (ADS)

Dasgupta, Bhaskar; Nakamura, Haruki; Higo, Junichi

2016-10-01

Virtual-system coupled adaptive umbrella sampling (VAUS) enhances sampling along a reaction coordinate by using a virtual degree of freedom. However, VAUS and regular adaptive umbrella sampling (AUS) methods are yet computationally expensive. To decrease the computational burden further, improvements of VAUS for all-atom explicit solvent simulation are presented here. The improvements include probability distribution calculation by a Markov approximation; parameterization of biasing forces by iterative polynomial fitting; and force scaling. These when applied to study Ala-pentapeptide dimerization in explicit solvent showed advantage over regular AUS. By using improved VAUS larger biological systems are amenable.

Primary Metabolism and Medium-Chain Fatty Acid Alterations Precede Long-Chain Fatty Acid Changes Impacting Neutral Lipid Metabolism in Response to an Anticancer Lysophosphatidylcholine Analogue in Yeast.

PubMed

Tambellini, Nicolas P; Zaremberg, Vanina; Krishnaiah, Saikumari; Turner, Raymond J; Weljie, Aalim M

2017-10-06

The nonmetabolizable lysophosphatidylcholine (LysoPC) analogue edelfosine is the prototype of a class of compounds being investigated for their potential as selective chemotherapeutic agents. Edelfosine targets membranes, disturbing cellular homeostasis. Is not clear at this point how membrane alterations are communicated between intracellular compartments leading to growth inhibition and eventual cell death. In the present study, a combined metabolomics/lipidomics approach for the unbiased identification of metabolic pathways altered in yeast treated with sublethal concentrations of the LysoPC analogue was employed. Mass spectrometry of polar metabolites, fatty acids, and lipidomic profiling was used to study the effects of edelfosine on yeast metabolism. Amino acid and sugar metabolism, the Krebs cycle, and fatty acid profiles were most disrupted, with polar metabolites and short-medium chain fatty acid changes preceding long and very long-chain fatty acid variations. Initial increases in metabolites such as trehalose, proline, and γ-amino butyric acid with a concomitant decrease in metabolites of the Krebs cycle, citrate and fumarate, are interpreted as a cellular attempt to offset oxidative stress in response to mitochondrial dysfunction induced by the treatment. Notably, alanine, inositol, and myristoleic acid showed a steady increase during the period analyzed (2, 4, and 6 h after treatment). Of importance was the finding that edelfosine induced significant alterations in neutral glycerolipid metabolism resulting in a significant increase in the signaling lipid diacylglycerol.

Evaluation of General Toxicity, Anti-Oxidant Activity and Effects of Ficus Carica Leaves Extract on Ischemia/Reperfusion Injuries in Isolated Heart of Rat

PubMed Central

Allahyari, Saeideh; Delazar, Abbas; Najafi, Moslem

2014-01-01

Purpose: This study was aimed to evaluate general toxicity, anti-oxidant activity and effects of Ficus carica leaves extract on ischemia/reperfusion injuries. Methods: Antioxidant activity, total phenolic and flavonoid compounds of 70% methanolic extract of Ficus carica leaves were measured. The general toxicity test was carried out by brine shrimp lethality assay. Isolated hearts of male rats were mounted on a Langendorff apparatus and perfused with modified Krebs-Henseleit solution. In control group, the hearts were perfused with normal Krebs solution, however, treatment groups received enriched solution with the extract (0.04, 0.2 and 1 mg/ml) during stabilization and reperfusion (after 30 min global ischemia), respectively. Cardiac arrhythmias were analyzed and TTC method was used for infarct size determination. Results: The extract displayed antioxidant activity in the DPPH assay (RC50=0.06666 mg/ml). Total phenolic content was 12.29 mg GAE/100 g dry sample and the amount of flavonoids was calculated 40.729 mg/g. LD50 value by brine shrimp test was 0.158 mg/ml. The extract decreased number of VEBs, incidence and duration of Rev VF with clear reduction in infarct size and infarct volume (P<0.001). Conclusion: Ficus carica decreased ischemia/reperfusion-induced injuries. These protections are probably due to antioxidant capacity and the existence of flavonoid and phenolic compounds in the extract. PMID:25671192

The Succinated Proteome of FH-Mutant Tumours

PubMed Central

Yang, Ming; Ternette, Nicola; Su, Huizhong; Dabiri, Raliat; Kessler, Benedikt M.; Adam, Julie; Teh, Bin Tean; Pollard, Patrick J.

2014-01-01

Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succino)cysteine (2SC). Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), kelch-like ECH-associated protein 1 (KEAP1) and mitochondrial aconitase (ACO2) can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC. PMID:25105836

Prostaglandins, oxygen tension and smooth muscle tone

PubMed Central

Eckenfels, A.; Vane, J. R.

1972-01-01

1. By using indomethacin to inhibit their intramural synthesis, we have investigated the contribution of prostaglandins to the maintenance of (a) the intrinsic tone of isolated smooth muscle preparations and (b) contractions produced by drugs or high oxygen concentration. 2. When treated with indomethacin, the rat stomach strip and chick rectum preparation slowly relaxed, whether they were bathed in Krebs solution or blood. Although their sensitivity to added prostaglandin was somewhat enhanced, they became insensitive to changes in oxygen or glucose concentration. However, another smooth muscle preparation, the rat colon, was neither relaxed by indomethacin nor contracted by high oxygen concentration. 3. These results support the hypothesis that intramural generation of prostaglandin maintains the tone of some smooth muscle preparations. 4. Contractions of the guinea-pig isolated colon were induced by histamine. These contractions were normally well maintained but in Krebs solution lacking either oxygen or glucose, only the initial spike contraction remained. In the presence of indomethacin the histamine contraction was also poorly sustained, but maintenance was restored by a low concentration of prostaglandin E2. 5. Thus, the effects on smooth muscle of oxygen or glucose lack may also be mediated by reduction in the synthesis or effects of an intramural prostaglandin. Extension of this hypothesis to intestinal and vascular smooth muscle in vivo is discussed. PMID:5072227

Vasorelaxant and antihypertensive effects of methanolic fraction of the essential oil of Alpinia zerumbet.

PubMed

da Cunha, Gilmara Holanda; de Moraes, Manoel Odorico; Fechine, Francisco Vagnaldo; Frota Bezerra, Fernando Antônio; Silveira, Edilberto Rocha; Canuto, Kirley Marques; de Moraes, Maria Elisabete Amaral

2013-01-01

Alpinia zerumbet is used in folk medicine in Brazil to treat hypertension. However, several pathways involved in the mechanism of vasorelaxation are still unclear. This study was designed to verify the antihypertensive effect of the methanolic fraction of the essential oil of A. zerumbet (MFEOAz) and to characterize its mechanism of action. The thoracic aortic rings from the Wistar rats were perfused in the organ chambers filled with Kreb's solution, where the tension of each ring was measured. The antihypertensive effect of MFEOAz was assessed in rats submitted to chronic hypertension by inhibition of nitric oxide synthesis by indirect measurement of blood pressure with indirect tail cuff method. MFEOAz relaxed phenylephrine and KCl-induced contraction of either endothelium-intact or endothelium-denuded rat aortic rings in a concentration-dependent manner. Pre-incubation with MFEOAz (100 and 300 μg/mL) in Ca(2+)-free Krebs solution attenuated phenylephrine- or caffeine-induced contraction. Pre-incubation with L-NAME, ODQ, wortmannin, atropine, indomethacin, catalase, SOD, TEA, 4-aminopyridine, glibenclamide, apamin, charybdotoxin, or iberiotoxin did not affect MFEOAz-induced relaxation. The intragastric administration of MFEOAz induced an antihypertensive effect. MFEOAz it seems inhibited the calcium influx via voltage-operated calcium channels and receptor-operated calcium channels, as well as inhibition of calcium mobilization from intracellular stores. Copyright © 2013 Elsevier Inc. All rights reserved.

Factors influencing erythrocyte choline concentrations.

PubMed

Miller, B L; Jenden, D J; Tang, C; Read, S

1989-01-01

Choline concentrations in human erythrocytes increase after freezing and thawing, during incubation in Krebs-phosphate for 30 min or on storage at 0 degrees C for 3-24 hr. The increase is prevented by protein precipitation by 10% perchloric acid, 10% zinc hydroxide, 10% sodium tungstate or boiling in water. It is not prevented by EDTA (10 mM) and is increased by oleate (5 mM). We suggest that the increase is due to the action of phospholipase D on erythrocyte phospholipids.

International Conference on Coordination Chemistry (23rd) Held at Boulder, Colorado on 29 July - 3 August 1984. Abstracts of Paper.

DTIC Science & Technology

1984-08-03

KlausS Gr er let Krebs MWd Gerald lNe" Anorganlach-Chemlaches Institut der Uivesitat Maopse Corrensstr. 36, D4MO M~nster, Federal Republic of Germany In...chelates previously prepared in theme Laboratories. Also, an intense, low energy band (360 cm-1 ) in the ir spectra of all od the chloro der - ivatives...PLAnIND(II) Luther 9. Erickson, Douglas R. Wright, and Gregory S. Vignoul Grinnell College, GrIonll. lam, USA, 50112 Van der Poel, et &I.* have succeeded

Hepatic Metabolism of Perfluorinated Carboxylic Acids and Polychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in Vivo

DTIC Science & Technology

1994-01-05

1 v/v) followed by perfusion with warm, oxygenated Krebs-Ringer solution (10 mil/min). The thorax was opened to expose the heart and the inferior vena ... cava was cannulated (PE 240-1.7 mm ID) via an incision in the right atrium . Livers were excised, washed with warm saline, transferred to the...AFOSR grant. Marjorie Artz was a Ph.D. graduate student who worked in this laboratory briefly in 1992 and then left in January 1993. She was supported

Measure and Analysis of a Gaze Position Using Infrared Light Technique

DTIC Science & Technology

2001-10-25

MEASURE AND ANALYSIS OF A GAZE POSITION USING INFRARED LIGHT TECHNIQUE Z. Ramdane-Cherif1,2, A. Naït-Ali2, J F. Motsch2, M. O. Krebs1 1INSERM E 01-17...also proposes a method to correct head movements. Keywords: eye movement, gaze tracking, visual scan path, spatial mapping. INTRODUCTION The eye gaze ...tracking has been used for clinical purposes to detect illnesses, such as nystagmus , unusual eye movements and many others [1][2][3]. It is also used

Cost-Effectiveness of Interventions to Promote Physical Activity: A Modelling Study

PubMed Central

Cobiac, Linda J.; Vos, Theo; Barendregt, Jan J.

2009-01-01

Background Physical inactivity is a key risk factor for chronic disease, but a growing number of people are not achieving the recommended levels of physical activity necessary for good health. Australians are no exception; despite Australia's image as a sporting nation, with success at the elite level, the majority of Australians do not get enough physical activity. There are many options for intervention, from individually tailored advice, such as counselling from a general practitioner, to population-wide approaches, such as mass media campaigns, but the most cost-effective mix of interventions is unknown. In this study we evaluate the cost-effectiveness of interventions to promote physical activity. Methods and Findings From evidence of intervention efficacy in the physical activity literature and evaluation of the health sector costs of intervention and disease treatment, we model the cost impacts and health outcomes of six physical activity interventions, over the lifetime of the Australian population. We then determine cost-effectiveness of each intervention against current practice for physical activity intervention in Australia and derive the optimal pathway for implementation. Based on current evidence of intervention effectiveness, the intervention programs that encourage use of pedometers (Dominant) and mass media-based community campaigns (Dominant) are the most cost-effective strategies to implement and are very likely to be cost-saving. The internet-based intervention program (AUS$3,000/DALY), the GP physical activity prescription program (AUS$12,000/DALY), and the program to encourage more active transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high probability of being under a AUS$50,000 per DALY threshold. GP referral to an exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if high time and travel costs for patients in screening and consulting an exercise physiologist are considered. Conclusions

Selection of Atypia/Follicular Lesion of Unknown Significance Patients for Surgery Versus Active Surveillance, Without Using Genetic Testing: A Single Institute Experience, Prospective Analysis, and Recommendations.

PubMed

Cohen, Oded; Tzelnick, Sharon; Lahav, Yonatan; Schindel, Doron; Halperin, Doron; Yehuda, Moshe

2017-07-01

Atypia/follicular lesion of unknown significance (AUS/FLUS) has variable rates of malignancy. The recommended management includes active surveillance (AS), repeated fine-needle aspiration (RFNA), diagnostic surgery, or genetic testing for malignancy. The objective of this study was to assess the management of AUS/FLUS patients in a dedicated thyroid clinic without implementing genetic testing. This was a single institute cohort study of all patients aged ≥18 years who underwent ultrasound-guided FNA thyroid biopsies between January 2009 and January 2013 and were followed until January 2016. The median follow-up time was 4.6 years (range 3.2-6.8 years). Forty-eight (57%) patients were referred to AS, and 36 (43%) patients were referred for diagnostic surgery. Thirty-six (75%) patients from the AS group underwent RFNA. An additional eight patients from the AS group subsequently underwent diagnostic surgery. Malignancies were found in 15/44 (34%) diagnostic surgical samples, and benign cytologies were found in 61.1% of the RFNAs. Analysis of adherence to follow-up in the 36 AS patients showed an adherence rate of only 53%, with males tending to comply better than females did (31.6% vs. 5.8%, respectively; p = 0.052), especially males in their sixth decade of life. Genetic tests for AUS/FLUS patients are accepted today as complementary evaluations in many well-developed health systems. Yet, when these tests are not feasible due to financial or availability issues, careful management of AUS/FLUS patients may still offer good results in the selection of patients for surgery or AS. The present results also indicate that compliance to follow-up schedules is a major consideration when selecting patients for AS.

Using brief self-reports and clinician scales to screen for substance use disorders in psychotic patients.

PubMed

Møller, Turid; Linaker, Olav M

2010-04-01

The aims of this study were to examine evidence for the concurrent validity of two self-report measures and two staff-report measures measuring alcohol and drug problems in seriously mentally ill people and to examine if psychotic patients under-report their alcohol and drug problems in an early intervention clinic. This is a cross-sectional study of 48 patients (26 inpatients and 22 outpatients) from an early intervention clinic for psychosis. To examine the sensitivity and specificity, we compared both the staff-report measures Clinical Alcohol Use Scale (AUS) and Clinical Drug Use Scale (DUS) and the self-report measures Short Michigan Alcohol Screening Test (SMAST-13) and Drug Abuse Screening Test (DAST-20), with the current ICD-10 diagnostic criteria as the gold-standard for alcohol and drug problems. To examine whether the patients under-report their alcohol and drug problems, we also compared the self-report measures SMAST-13 and DAST-20 with the staff-report measures AUS and DUS and ICD-10 consensus substance abuse diagnoses. The results show that the concurrent validity compared with ICD-10 diagnoses was moderate for both the staff-report measures AUS and DUS and for the self-report measures SMAST-13 and DAST-20. Three out of seven patients under-report alcohol problems and one patient out of seven under-report drug use problems according to consensus ICD-10 substance abuse diagnoses. We conclude that the SMAST-13 and DAST-20 in combination with the AUS and DUS, which are easy and quick to perform, are helpful in establishing a common understanding of the patient's alcohol and drug problems in an early intervention clinic.

Revision of the types of male Sciaridae (Diptera) described from Australia by F.A.A. Skuse.

PubMed

Broadley, Adam; Kauschke, Ellen; Mohrig, Werner

2016-11-17

A total of 27 male sciarid types described by Skuse (1888 and 1890), held in the Australian National Insect Collection, Canberra, and the Australian Museum, Sydney, were remounted and examined microscopically. Of these, 25 species were described as Sciara Meigen, one as Zygoneura Meigen and one as Trichosia Winnertz. Revision of these species revealed the following: 13 species belong to the genus Bradysia Winnertz (B. amabilis, B. conjuncta, B. crassicornis, B. exsequialis, B. frequens, B. froggatti, B. luctifica, B. maesta, B. mastersi, B. ornatula, B. pernitida, B. pictipes, B. unica), 1 species to the genus Corynoptera Winnertz (C. minutela), 4 species to the genus Austrosciara Schmitz & Mjöberg (Aus. infrequens, Aus. montivaga, Aus. spectabilis, Aus. winnertzi), 2 species to the genus Pseudolycoriella Menzel & Mohrig (Psl. cavatica, Psl. ignobilis), 1 species to the genus Pseudozygomma Mohrig (Pseudoz. maculipennis), 1 species to the genus Sciara Meigen (Sc. tryoni), and 1 species to the genus Scythropochroa Enderlein (Scyth. macleayi). In total 26 species were new combinations. Eight species names were declared as new synonyms: Bradysia pictipes (Skuse, 1888) = Sciara notata Skuse, 1888 syn. n. and = Bradysia seticornis Vilkamaa, Hippa & Mohrig, 2012 (from New Caledonia) syn. n.; Bradysia conjuncta (Skuse, 1890) = Sciara serenipennis Skuse, 1890 syn. n.; Pseudolycoriella cavatica (Skuse, 1888) = Sciara familiaris Skuse, 1888 syn. n. and = Sciara festiva Skuse, 1888 syn. n.; Bradysia luctifica (Skuse, 1888) = Bradysia planistylata Vilkamaa, Hippa & Mohrig, 2012 syn. n.; Sciara tryoni Skuse, 1890 = Sciara insulana Vilkamaa, Hippa & Mohrig, 2015 syn. n. (both species are from New Caledonia); Austrosciara winnertzi (Skuse, 1888) = Sciara rufulenta Edwards, 1927 syn. n. (from New Zealand). Lectotype specimens were designated for 17 species in order to fix the names.

Streamlined research funding using short proposals and accelerated peer review: an observational study.

PubMed

Barnett, Adrian G; Herbert, Danielle L; Campbell, Megan; Daly, Naomi; Roberts, Jason A; Mudge, Alison; Graves, Nicholas

2015-02-07

Despite the widely recognised importance of sustainable health care systems, health services research remains generally underfunded in Australia. The Australian Centre for Health Services Innovation (AusHSI) is funding health services research in the state of Queensland. AusHSI has developed a streamlined protocol for applying and awarding funding using a short proposal and accelerated peer review. An observational study of proposals for four health services research funding rounds from May 2012 to November 2013. A short proposal of less than 1,200 words was submitted using a secure web-based portal. The primary outcome measures are: time spent preparing proposals; a simplified scoring of grant proposals (reject, revise or accept for interview) by a scientific review committee; and progressing from submission to funding outcomes within eight weeks. Proposals outside of health services research were deemed ineligible. There were 228 eligible proposals across 4 funding rounds: from 29% to 79% were shortlisted and 9% to 32% were accepted for interview. Success rates increased from 6% (in 2012) to 16% (in 2013) of eligible proposals. Applicants were notified of the outcomes within two weeks from the interview; which was a maximum of eight weeks after the submission deadline. Applicants spent 7 days on average preparing their proposal. Applicants with a ranking of reject or revise received written feedback and suggested improvements for their proposals, and resubmissions composed one third of the 2013 rounds. The AusHSI funding scheme is a streamlined application process that has simplified the process of allocating health services research funding for both applicants and peer reviewers. The AusHSI process has minimised the time from submission to notification of funding outcomes.

Automated and objective action coding of facial expressions in patients with acute facial palsy.

PubMed

Haase, Daniel; Minnigerode, Laura; Volk, Gerd Fabian; Denzler, Joachim; Guntinas-Lichius, Orlando

2015-05-01

Aim of the present observational single center study was to objectively assess facial function in patients with idiopathic facial palsy with a new computer-based system that automatically recognizes action units (AUs) defined by the Facial Action Coding System (FACS). Still photographs using posed facial expressions of 28 healthy subjects and of 299 patients with acute facial palsy were automatically analyzed for bilateral AU expression profiles. All palsies were graded with the House-Brackmann (HB) grading system and with the Stennert Index (SI). Changes of the AU profiles during follow-up were analyzed for 77 patients. The initial HB grading of all patients was 3.3 ± 1.2. SI at rest was 1.86 ± 1.3 and during motion 3.79 ± 4.3. Healthy subjects showed a significant AU asymmetry score of 21 ± 11 % and there was no significant difference to patients (p = 0.128). At initial examination of patients, the number of activated AUs was significantly lower on the paralyzed side than on the healthy side (p < 0.0001). The final examination for patients took place 4 ± 6 months post baseline. The number of activated AUs and the ratio between affected and healthy side increased significantly between baseline and final examination (both p < 0.0001). The asymmetry score decreased between baseline and final examination (p < 0.0001). The number of activated AUs on the healthy side did not change significantly (p = 0.779). Radical rethinking in facial grading is worthwhile: automated FACS delivers fast and objective global and regional data on facial motor function for use in clinical routine and clinical trials.

Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium

PubMed Central

Buultjens, Andrew H.; Lam, Margaret M.C.; Ballard, Susan; Monk, Ian R.; Mahony, Andrew A.; Grabsch, Elizabeth A.; Grayson, M. Lindsay; Pang, Stanley; Coombs, Geoffrey W.; Robinson, J. Owen; Seemann, Torsten; Howden, Benjamin P.

2017-01-01

From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments. PMID:28149688

Cost effectiveness of brief interventions for reducing alcohol consumption.

PubMed

Wutzke, S E; Shiell, A; Gomel, M K; Conigrave, K M

2001-03-01

The direct costs and health effects of a primary-care-based brief intervention for hazardous alcohol consumption were examined. The total cost of the intervention was calculated from costs associated with: marketing the intervention programme; providing training and support in the use of the intervention materials; physician time required for providing brief advice for 'at-risk' drinkers. The effect of the intervention on health outcomes was expressed in terms of number of life years saved by preventing alcohol-related deaths. This was derived by combining estimates of the impact of the programme if it were implemented nationally with available evidence on the health effects of excess alcohol consumption. Results are based on international trial evidence showing the physical resources required by the intervention and its effectiveness combined with Australian price data. The costs associated with screening and brief advice using the current intervention programme range from Aus$19.14 to Aus$21.50. The marginal costs per additional life year saved were below Aus$1873. The robustness of the model used is supported by an extensive sensitivity analysis. In comparison with existing health promotion strategies the costs and effects of the current intervention are highly encouraging.

A SERS characterization of the stability of polythionates at the gold-electrolyte interface

NASA Astrophysics Data System (ADS)

Mirza, Jeff; Smith, Scott R.; Baron, Janet Y.; Choi, Yeonuk; Lipkowski, Jacek

2015-01-01

A gold nanorod (AuNR) array electrode was employed to record SERS spectra as a function of immersion time in electrolyte solutions of tetrathionate, trithionate, the [Au(S2O3)2]3- complex, sulfide and thiosulfate. The generalized two-dimensional correlation spectroscopy was employed to deconvolute broad bands in the SERS spectra. The results show that the polythionates, tetrathionate and trithionate, sulfide, and the [Au(S2O3)2]3- complex decompose to form cyclo-S8, polymeric and monoatomic sulfur at the gold surface. The relative amount of these different forms of sulfur in the film formed at the surface depends on the nature of the electrolyte species. The decomposition of tetrathionate leads predominantly to the formation of cyclo-S8. Comparable amounts of all three forms of sulfur are formed in the solution of the [Au(S2O3)2]3- complex. Monoatomic sulfur is formed predominantly at the gold surface in solutions of trithionate and thiosulfate. In contrast to the previous suggestions, the results of this study demonstrate that polythionates are not present in the passive layer during gold leaching from thiosulfate solutions at a prolonged leaching times.

PubMed

Schützenberger, Anne; Hammer, Georg Philipp

2018-06-01

Sanuki T et al. Long-term Evaluation of Type 2 Thyroplasty with Titanium Bridges for Adductor Spasmodic Dysphonia. Otolaryngol Head Neck Surg 2017; 157: 80–84 JAPANISCHE ÄRZTE FüR HALS-, NASEN- UND OHRENHEILKUNDE SOWIE KOPF- UND HALSCHIRURGIE BERICHTETEN üBER STIMMLICHE LANGZEITERGEBNISSE NACH DURCHFüHRUNG EINER THYROPLASTIK TYP 2 ZUR BEHANDLUNG DER SPASMODISCHEN DYSPHONIE VOM ADDUKTOR TYP.

Grundlagen der zeichnerischen Darstellung

NASA Astrophysics Data System (ADS)

Döring, Peter

Eine Technische Zeichnung muss nach DIN 6774 Teil 1 in der Weise angefertigt werden, dass sie übersichtlich, unmissverständlich, auch in verkleinertem Maßstab lesbar bleibt, kostengünstig reproduzierbar und dauerhaft archivierbar ist. Zu dem Zweck benötigt man entsprechendes Papier und angepasstes Zeichengerät. Heute ist die Anfertigung mit entsprechenden Rechnerprogrammen möglich.

Stabilität

NASA Astrophysics Data System (ADS)

Horn, Joachim

Für die Stabilität eines linearen, zeitinvarianten Übertragungsgliedes existieren verschiedene Definitionen. Bei der asymptotischen Stabilität wird gefordert, dass der Systemausgang nach einer kurzzeitigen Systemanregung mit wachsender Zeit wieder gegen Null geht. Bei der BIBO-Stabilität (Bounded Input-Bounded Output) wird gefordert, dass bei einem beschränkten Systemeingang der Systemausgang ebenfalls beschränkt ist.

Die Baukastensystematik in der Fördertechnik

NASA Astrophysics Data System (ADS)

Sebulke, Johannes

In der Fördertechnik wird kaum ein größerer Einsatzfall so dem anderen gleichen, dass man zwei Anlagen nach denselben Zeichnungen fertigen kann. Konstruktionszeiten, Rüst- und Umstellungszeiten der Fertigung sind hoch; der Kunde muss bei Einzelanfertigung lange Lieferzeiten in Kauf nehmen. In der Fördertechnik haben sich daher Baukastenprinzip, Standardisierung und die Konstruktion von Erzeugnisreihen weitgehend durchgesetzt.

Theory of Non-First Norman Form Relational Databases

DTIC Science & Technology

1986-01-01

741. [BR] Benn, W. and B. Radig, "Erweiterte Anfragen nach Relationenge- bilden in Form nichtnormlalisierter Relationen." In Datenbank - Systeme fur...Relationenmodells." In Datenbank -Systeme far Biro, Technik und Wissenschaft, A. Blaser, P. Pistor, Eds., Informatik-Fachberichte Nr. 94, Springer...Versionenbe- hafteter, Hierarchisch Strukturierter Tupel." In Datenbank -Systeme fur Biro, Technik und Wissenschaft, A. Blaser, P. Pistor, Eds

Analysis of meteorological conditions for the Yakima Smoke Intrusion Case Study, 28 September 2009

Treesearch

Miriam Rorig; Robert Solomon; Candace Krull; Janice Peterson; Julia Ruthford; Brian Potter

2013-01-01

On 28 September 2009, the Naches Ranger District on the Okanogan-Wenatchee National Forest in south-central Washington state ignited an 800-ha prescribed fire. Later that afternoon, elevated PM2.5 concentrations and visible smoke were reported in Yakima, Washington, about 40 km east of the burn unit. The U.S. National Weather Service forecast for the day had predicted...

Trends in der IT-Sicherheit

NASA Astrophysics Data System (ADS)

Eckert, Claudia

Ich möchte Ihnen einen Überblick geben über Trends, Challenges, offene Fragestellungen sowie Lösungsansätze aus dem Bereich der IT-Sicherheit. Meine Vorredner haben mir schon eine wunderbare Basis dafür geschaffen, indem sie wichtige Trends im Bereich IT bereits angesprochen haben. Deshalb werde ich auf diese Trends, nämlich das Internet of Things and Services nur noch einmal kurz eingehen, um daran dann die IT-Sicherheitsthemen, die sich aus diesen IT-Trends ergeben, zu skizzieren und anschließend Lösungen vorstellen, die insbesondere im Forschungsumfeld entwickelt werden, aber schon reif sind, auch in die unternehmerische Praxis übernommen zu werden.

Astronomie für Alle. Einführung in die Himmelsbeobachtung

NASA Astrophysics Data System (ADS)

Neckel, Thorsten; Neumann, Martin; Staude, Jakob

2002-12-01

Contents: Abenteuer Astronomie - Aufbruch zu fremden Welten. Orientierung am Himmel. Das Teleskop - Dein Blick ins All. Der Erdmond. Wir beobachten unseren Mond. Planeten - Unsere Nachbarn im All. Himmelsleuchten in dunkler Nacht - Das Zodiakallicht. Vagabunden im Sonnensystem. Meteore und Feuerkugeln. Meteorite - Faszinierende Materie aus dem Weltall. Kometen - Eisige Zeugen der Urzeit. Der hellste Stern an unserem Himmel. Auf der Sonne ist 'was los! Kosmische Schattenspiele - Sonnen- und Mondfinsternisse. Ferne Sonnen. Die Tiefen des Kosmos - Sternhaufen, Gasnebel und Galaxien. Astrophotographie mit stehender Kamera. Astrophotographie mit nachgeführter Kamera. Der Kosmos im Computer - Software für Hobbyastronomen. Signale aus dem Kosmos - Radioastronomie für Einsteiger.

Meilensteine in der Erforschung der kompakten Objekte

NASA Astrophysics Data System (ADS)

Camenzind, Max

Kompakte Objekte besitzen zum einen eine sehr hohe Dichte, und zum anderen sind sie durch die Tatsache charakterisiert, dass keine nuklearen Reaktionen mehr in ihrem Inneren stattfinden können. Aus diesem Grund können sie im Unterschied zu gewöhnlichen Sternen der Gravitation nicht mehr mit dem Druck des thermischen Gases widerstehen. In den Weißen Zwergen bzw. Neutronensternen wird der Gravitation der Quantendruck eines Elektronengases bzw. einer Neutronenflüssigkeit entgegengesetzt. Ein solches Gas besteht aus Elektronen bzw. Neutronen, die auf ihr niedrigstes Energieniveau zusammengepresst wurden. Durch die daraus resultierende hohe Bewegungsenergie der Fermionen wird der sogenannte Quantendruck erzeugt.

Musik einpacken

NASA Astrophysics Data System (ADS)

Loos, Andreas

Wer schon einmal Nudeln selbst gemacht hat, der weiß: Frische Pasta kann ganz schön pappen. Das ist ein Problem für die Nudelindustrie, denn es ist nicht leicht, mit unregelmäßigen und klebrigen Nudel-Klumpen 500-Gramm-Beutel genau zu füllen. Einige Hersteller verwenden daher "Teilmengenwaagen". Die besitzen bis zu hundert kleineWaagschalen, die über ein Förderband mit jeweils ungefähr 50 Gramm Nudel-Klumpen befüllt werden. Dann kommt Mathematik ins Spiel: Ein Computer wählt die zehn Waagschalen aus, deren Inhalt zusammen die 500 Gramm genau erreicht, und leert sie in einen Beutel aus.

Unfälle mit Kleintransportern

NASA Astrophysics Data System (ADS)

Tschirschwitz, Christian

Auf einer außerörtlichen Bundesstraße geriet ein mit vier Personen besetzter Pkw Toyota Corolla aus letztlich nicht vollständig geklärten Gründen ins Schleudern. Nachdem sich das Fahrzeug beträchtlich entgegen dem Uhrzeigersinn ausgedreht hatte, prallte ein entgegenkommender Kleintransporter VW T4 frontal an die rechte Flanke des Toyota. Der Transporter wurde gedreht, ausgehoben und durch einen Pkw Ford Escort unterfahren. Alle Fahrzeuge kamen in Kollisionsortnähe zum Endstand. Die vier Toyota-Insassen wurden getötet. Aus den anderen Fahrzeugen wurden sechs Personen überwiegend schwer verletzt. Unbeteiligte Zeugen waren nicht vorhanden.

76 FR 77696 - Establishment of the Naches Heights Viticultural Area

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... origin of their wines and to allow consumers to better identify wines they may purchase. DATES: Effective... of the Treasury to prescribe regulations for the labeling of wine, distilled spirits, and malt... appellations of origin on wine labels and in wine advertisements. Part 9 of the TTB regulations (27 CFR part 9...

Die Verlegung der Berliner Sternwarte nach Babelsberg - ein konservativer Neubeginn.

NASA Astrophysics Data System (ADS)

Dick, W. R.

In 1913 the Berlin Observatory was moved from the center of the city to Babelsberg on the outskirts of Berlin, now part of Potsdam. The new observatory was considerably larger in size and with respect to its staff, and it had got a completely new equipment. At that time it was the most modern astronomical observatory in Germany and possibly even in Europe. However, the scientific results achieved afterward were not comparable to that of other institutions, especially in the USA. A main reason was the conservative concept for the observatory, drawn up by Wilhelm Foerster and his colleagues, and restricting the work to classical fields of astronomy. Foerster's successor Hermann Struve tried to follow rather strictly this concept as well as the traditions of his family of astronomers. This led to conflicts with his collaborators Eugen Goldstein, Erwin Finlay Freundlich and Paul Guthnick, who were interested rather in astrophysics than in the classical problems.

Sony’s Nightmare before Christmas: The 2014 North Korean Cyber Attack on Sony and Lessons for US Government Actions in Cyberspace

DTIC Science & Technology

2018-02-01

4,  2014), http://www.businessinsider.com/ experts-the-sony-hack-looks-a-lot-like-previous-attacks-on- south-korea-2014-12. 39 Kim Zetter, “Logic Bomb ...Set Off South Korea Cyberattack,” Wired (March 21, 2013), https://www.wired.com/2013/03/logic- bomb -south-korea-attack/. 40 Brian Krebs, “The Case...Agency (March  21,  2013), http://english.yonhapnews.co.kr/ national/2013/03/21/55/0302000000AEN20130321003552315F. HTML. 47 Kim Zetter, “Logic Bomb

Macromolecules and Enzymes: The Geneva Heritage from Kurt H. Meyer and Edmond H. Fischer.

PubMed

Fischer, Edmond H; Piguet, Alfred

2009-12-01

On the 26th May 2009, Edmond Fischer, winner with Ed Krebs of the Nobel prize in physiology or medicine in 1992, and his colleague at the time of his research activities at the Ecole de chimie of the University of Geneva, Alfred Piguet, met with Andreas Hauser, Claude Piguet and Howard Riezman of the Section de chimie et biochimie of the University of Geneva to talk about how they became scientists under the impetus of Kurt H. Meyer and what became of them thereafter.

Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease

PubMed Central

Mochel, Fanny; Duteil, Sandrine; Marelli, Cécilia; Jauffret, Céline; Barles, Agnès; Holm, Janette; Sweetman, Lawrence; Benoist, Jean-François; Rabier, Daniel; Carlier, Pierre G; Durr, Alexandra

2010-01-01

We previously identified a systemic metabolic defect associated with early weight loss in patients with Huntington's disease (HD), suggesting a lack of substrates for the Krebs cycle. Dietary anaplerotic therapy with triheptanoin is used in clinical trials to promote energy production in patients with peripheral and brain Krebs cycle deficit, as its metabolites – C5 ketone bodies – cross the blood–brain barrier. We conducted a short-term clinical trial in six HD patients (UHDRS (Unified Huntington Disease Rating Scale)=33±13, 15–49) to monitor the tolerability of triheptanoin. We also assessed peripheral markers of short-term efficacy that were shown to be altered in the early stages of HD, that is, low serum IGF1 and 31P-NMR spectroscopy (NMRS) in muscle. At baseline, 31P-NMRS displayed two patients with end-exercise muscle acidosis despite a low work output. On day 2, the introduction of triheptanoin was well tolerated in all patients, and in particular, there was no evidence of mitochondrial overload from triheptanoin-derived metabolites. After 4 days of triheptanoin-enriched diet, muscle pH regulation was normalized in the two patients with pretreatment metabolic abnormalities. A significant increase in serum IGF1 was also observed in all patients (205±60 ng/ml versus 246±68 ng/ml, P=0.010). This study provides a rationale for extending our anaplerotic approach with triheptanoin in HD. PMID:20512158

Intracellular pH in rat isolated superior cervical ganglia in relation to nicotine-depolarization and nicotine-uptake

PubMed Central

Brown, D. A.; Halliwell, J. V.

1972-01-01

1. The intracellular pH (pHi) of rat isolated superior cervical ganglia incubated in normal Krebs solution (pHo=7·37) was estimated to be 7·33 from the uptake of a weak acid, 14C-5,5-dimethyloxazolidine-2,4-dione (DMO). Addition of 30 μM nicotine for 30 min reduced the DMO-estimated pHi by 0·15 units to 7·18. This effect was prevented by hexamethonium (2·5 mM) or by depolarizing the ganglion with K+ (124 mM). 2. 3H-Nicotine (30 μM) was concentrated within the ganglia to an intracellular/extracellular concentration ratio (Ci/Co) of 5·54 in normal Krebs solution and 4·61 in 2·5 mM hexamethonium. This would suggest an intracellular pH of 6·54 and 6·63 respectively. In ganglia previously depolarized by K+ the corresponding values for Ci/Co were 4·02 (minus hexamethonium, estimated pHi 6·95) and 4·17 (plus hexamethonium, estimated pHi 6·94). 3. A multicompartment cell interior comprising an acid cytoplasm (pH∼6·6) and more alkaline nucleus and mitochondria is proposed to explain the difference between the values of pHi estimated from the uptake of DMO and nicotine. It is suggested that the fall in pHi during nicotine-depolarization results from metabolic stimulation following Na+ entry. PMID:5048652

Enhanced 5-hydroxytryptamine (5-HT) release from vascular adrenergic nerves in spontaneously hypertensive rats

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

Kawasaki, H.; Urabe, M.; Takasaki, K.

1986-03-01

The release of 5-HT from vascular adrenergic nerves was compared between normotensive Wistar Kyoto rats (WKY) and SHR. The mesenteric vascular bed isolated from WKY and SHR was perfused with Krebs solution at a constant flow rate of 5 ml/min. Periarterial nerve stimulation (PNS) was delivered at 4 to 16 Hz for 30 sec. In the SHR preparation, the pressor response to PNS, previously decreased by prazonsin (50 nM), was greatly potentiated after treatment with 5-HT(1 ..mu..M) for 15 min and a frequency-dependent pressor response to PNS reappeared, whereas the 5-HT treatment did not alter the pressor response to exogenousmore » norepinephrine (1 nmol) previously reduced by prazonsin. The potentiation of pressor response to PNS after 5-HT treatment was small in the WKY preparation. This potentiation in both WKY and SHR did not occur in the presence of ketanserin (10 nM). In the preparation labeled with (/sup 3/H)-5-HT, PNS (4-16 Hz) evoked a frequency-dependent increase of (/sup 3/H)-efflux, which was abolished by treatment with tetrodotoxin (100 nM) or 6-hydroxydopamine (50 mg/kg i.p. x 2) and in calcium-free Krebs solution. The PNS evoked-(/sup 3/H)-efflux was much greater in SHR than WKY. These results suggest that the release of 5-HT from vascular adrenergic nerves by PNS is enhanced in the SHR preparation.« less

Sensors, transmitters, and targets in mitochondrial oxygen shortage-a hypoxia-inducible factor relay story.

PubMed

Dehne, Nathalie; Brüne, Bernhard

2014-01-10

Cells sense and respond to a shortage of oxygen by activating the hypoxia-inducible transcription factors HIF-1 and HIF-2 and evoking adaptive responses. Mitochondria are at the center of a hypoxia sensing and responding relay system. Under normoxia, reactive oxygen species (ROS) and nitric oxide (NO) are HIF activators. As their individual flux rates determine their diffusion-controlled interaction, predictions how these radicals affect HIF appear context-dependent. Considering that the oxygen requirement for NO formation limits its role in activating HIF to conditions of ambient oxygen tension. Given the central role of mitochondrial complex IV as a NO target, especially under hypoxia, allows inhibition of mitochondrial respiration by NO to spare oxygen thus, raising the threshold for HIF activation. HIF targets seem to configure a feedback-signaling circuit aimed at gradually adjusting mitochondrial function. In hypoxic cancer cells, mitochondria redirect Krebs cycle intermediates to preserve their biosynthetic ability. Persistent HIF activation lowers the entry of electron-delivering compounds into mitochondria to reduce Krebs cycle fueling and β-oxidation, attenuates the expression of electron transport chain components, limits mitochondria biosynthesis, and provokes their removal by autophagy. Mitochondria can be placed central in a hypoxia sensing-hypoxia responding circuit. We need to determine to which extent and how mitochondria contribute to sense hypoxia, explore whether modulating their oxygen-consuming capacity redirects hypoxic responses in in vivo relevant disease conditions, and elucidate how the multiple HIF targets in mitochondria shape conditions of acute versus chronic hypoxia.

Two protein kinase C isoforms, δ and ε, regulate energy homeostasis in mitochondria by transmitting opposing signals to the pyruvate dehydrogenase complex.

PubMed

Gong, Jianli; Hoyos, Beatrice; Acin-Perez, Rebeca; Vinogradov, Valerie; Shabrova, Elena; Zhao, Feng; Leitges, Michael; Fischman, Donald; Manfredi, Giovanni; Hammerling, Ulrich

2012-08-01

Energy production in mitochondria is a multistep process that requires coordination of several subsystems. While reversible phosphorylation is emerging as the principal tool, it is still unclear how this signal network senses the workloads of processes as different as fuel procurement, catabolism in the Krebs cycle, and stepwise oxidation of reducing equivalents in the electron transfer chain. We previously proposed that mitochondria use oxidized cytochrome c in concert with retinol to activate protein kinase Cδ, thereby linking a prominent kinase network to the redox balance of the ETC. Here, we show that activation of PKCε in mitochondria also requires retinol as a cofactor, implying a redox-mechanism. Whereas activated PKCδ transmits a stimulatory signal to the pyruvate dehdyrogenase complex (PDHC), PKCε opposes this signal and inhibits the PDHC. Our results suggest that the balance between PKCδ and ε is of paramount importance not only for flux of fuel entering the Krebs cycle but for overall energy homeostasis. We observed that the synthetic retinoid fenretinide substituted for the retinol cofactor function but, on chronic use, distorted this signal balance, leading to predominance of PKCε over PKCδ. The suppression of the PDHC might explain the proapoptotic effect of fenretinide on tumor cells, as well as the diminished adiposity observed in experimental animals and humans. Furthermore, a disturbed balance between PKCδ and PKCε might underlie the injury inflicted on the ischemic myocardium during reperfusion. dehydrogenase complex.

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

PubMed Central

Sellers, Katherine; Fox, Matthew P.; Bousamra, Michael; Slone, Stephen P.; Higashi, Richard M.; Miller, Donald M.; Wang, Yali; Yan, Jun; Yuneva, Mariia O.; Deshpande, Rahul; Lane, Andrew N.; Fan, Teresa W.-M.

2015-01-01

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non–small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation. PMID:25607840

Impedance spectroscopy measurements as a tool for distinguishing different luminal content during bolus transit studies.

PubMed

Ruiz-Vargas, A; Mohd Rosli, R; Ivorra, A; Arkwright, J W

2018-01-08

Intraluminal electrical impedance is a well-known diagnostic tool used to study bolus movement in the human esophagus. However, it is use in the human colon it is hindered by the fact that the content cannot be controlled and may include liquid, gas, solid, or a mixture of these at any one time. This article investigates the use of complex impedance spectroscopy to study different luminal content (liquid and gas). An excised section of guinea pig proximal colon was placed in an organ bath with Krebs solution at 37°C and a custom built bioimpedance catheter was placed in the lumen. Liquid (Krebs) and gas (air) content was pumped through the lumen and the intraluminal impedance was measured at five different frequencies (1, 5.6, 31.6, 177.18 kHz and 1 MHz) at 10 samples per second. A numerical model was created to model the passage of bolus with different content and compared to the experimental data. Differences in mean impedance magnitude and phase angle were found (from 1 to 177.18 kHz) for different contents. The numerical results qualitatively agreed with those in the experimental study. Conductivities of bolus had an effect on detecting its passage. Complex impedance spectroscopy can distinguish between different luminal content within a range of measuring frequencies. The numerical model showed the importance of bolus conductivities for bolus transit studies in those where the bolus is controlled. © 2018 John Wiley & Sons Ltd.

A cost effectiveness analysis of midwife psycho-education for fearful pregnant women - a health system perspective for the antenatal period.

PubMed

Toohill, J; Callander, E; Gamble, J; Creedy, D K; Fenwick, J

2017-07-11

Psycho-education can reduce childbirth fear and caesarean section numbers. This study determines the cost-effectiveness of a midwife-led psycho-education intervention for women fearful of birth. One thousand four hundred ten pregnant women in south-east Queensland, Australia were screened for childbirth fear (W-DEQ A ≥ 66). Women with high scores (n = 339) were randomised to the BELIEF Study (Birth Emotions and Looking to Improve Expectant Fear) to receive psycho-education (n = 170) at 24 and 34 weeks of pregnancy or to the control group (n = 169). Women in both groups were surveyed 6 weeks postpartum with total cost for health service use during pregnancy calculated. Logistic regression models assessed the odds ratio of having vaginal birth or caesarean section in the study groups. Of 339 women randomised, 184 (54%) women returned data at 6 weeks postpartum (Intervention Group n = 91; Control Group n = 93). Women receiving psycho-education had a higher likelihood of vaginal birth compared to controls (n = 60, 66% vs. n = 54, 58%; OR 2.34). Mean 'treatment' cost for women receiving psycho-education was AUS$72. Mean cost for health services excluding the cost of psycho-education, was less in the intervention group (AUS$1193 vs. AUS$1236), but not significant (p = 0.78). For every five women who received midwife counselling, one caesarean section was averted. The incremental healthcare cost to prevent one caesarean section using this intervention was AUS$145. Costs of delivering midwife psycho-education to women with childbirth fear during pregnancy are offset by improved vaginal birth rates and reduction in caesarean section numbers. Australian New Zealand Controlled Trials Registry ACTRN12612000526875 , 17th May 2012 (retrospectively registered one week after enrolment of first participant).

Can patient safety indicators monitor medical and surgical care at New Zealand public hospitals?

PubMed

Hider, Phil; Parker, Karl; von Randow, Martin; Milne, Barry; Lay-Yee, Roy; Davis, Peter

2014-11-07

Increasing interest has focused on the safety of hospital care. The AusPSIs are a set of indicators developed from Australian administrative data to reliably identify inpatient adverse events in hospitals. The main aim of this study was to explore the application of the AHRQ/AusPSIs to New Zealand administrative hospital data related to medical and surgical care. Variation over time and across hospitals were also considered for a subset of the more common indicators. AHRQ/AusPSIs were adapted for use with New Zealand National Minimum Dataset administrative data for the period 2001-9. Crude positive event rates for each of the 16 indicators were assessed across New Zealand public hospitals. Variation over time for six more common indicators is presented using statistical control charts. Variation between hospitals was explored using rates adjusted for differences in patient variables including age, sex, ethnicity, rurality of residence, NZDep score and comorbidities. The AHRQ/AusPSIs were applied to New Zealand administrative hospital data and some 99,366 admissions were associated with a positive indicator event. However rates for some indicators were low (<1% of denominator admissions). Over the study period considerable variation in the rate of positive events was evident for the six most common indicators. Likewise there was substantial variation between hospitals in relation to risk adjusted positive event rates Patient safety indicators can be applied to New Zealand administrative hospital data. While infrequent rates hinder the use of some of the indicators, several could now be readily employed as warning flags to help monitor rates of adverse events at particular hospitals. In conjunction with other established or emerging tools, such as audit and trigger tools, the PSIs are now available to promote ongoing quality improvement activities in New Zealand hospitals.

Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.

PubMed

Phan, Thanh G; Beare, Richard; Chen, Jian; Clissold, Benjamin; Ly, John; Singhal, Shaloo; Ma, Henry; Srikanth, Velandai

2017-05-01

There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km 2 and MMC 1164 km 2 ) or with AUS (model 1c, RMH 1244 km 2 and AUS 1685 km 2 ), with no statistical difference between models ( P =0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km 2 and ALF 676 km 2 ), significantly different from both models 1a and 1c (both P <0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c ( P <0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs. © 2017 American Heart Association, Inc.

[Non-muscle-invasive bladder cancer: Information transfer from the clinic to the doctor's office : Results of a questionnaire study and presentation of a software solution].

PubMed

Lebentrau, S; May, M; Weckermann, D; Speck, T; Wick, A-K; Mathew, M; Schostak, M

2017-02-01

The adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) is based on the individual risk profile (RP) and its sufficient transfer from the clinic to the doctor's office. The objectives of our study were to verify the importance and degree of transfer of RP and recommendation for risk-adapted adjuvant treatment (RAAT) in patients with NMIBC as well as to develop appropriate tools for this purpose, if necessary. An email-based survey distributed to urologists in Brandenburg, Berlin, Bavaria and Lower Saxony explored the questions mentioned above. In addition, a tool for risk stratification and information transfer for patients with NMIBC was developed and validated. From a total of 134 questionnaires analyzed, 55 were from clinic urologists (CUs) and 79 were from ambulant urologists (AUs). Although 9 out of 10 urologists considered the RP of importance, only 29 % of CUs and 24 % of AUs (p = 0.553) confirmed that the RP was always mentioned in medical reports. The recommendation for RAAT was confirmed from 62 % of CUs and 20 % of AUs (p < 0.001). A recommendation for RAAT in the medical report was requested by 86 % of AUs. The risk calculator presented here - to our knowledge the first with integration of the 2004 WHO grading - is delivered in all mathematically possible constellations a RP, according to guideline recommendations. Urologists in the clinic and doctor's office both attach considerable importance to the determination and transfer of RP and the recommendation for RAAT. There was evidence to suggest an overestimation of the quality of medical reports by the CU. The risk calculator provides an easy and cost-neutral option to improve risk stratification and information transfer from the clinic to the doctor's office.

Participation in paediatric cancer studies: timing and approach to recruitment

PubMed Central

2013-01-01

Background Participation in epidemiological studies has fallen significantly over the past 30 years; this has been attributed to a busier lifestyle and longer working hours. In case–control studies, participation among cases is usually higher than among controls due to the personal relevance. In Australia, between 2003 and 2011, we conducted three national population-based case–control studies of risk factors for childhood cancers; brain tumors, acute leukemia and neuroblastoma and Wilms’ tumor. In this sub-study, we aimed to investigate factors that may have influenced study participation and completeness of survey completion. Findings The proportion of incident cases that were eligible to participate was lowest in the brain tumor study (Aus-CBT) (83.1%), as was the proportion of eligible families that consented (57%). The percentage of eligible cases that consented was highest in the leukemia study (Aus-ALL) (80.2%). The mode of invitation used was associated with families’ consent in each of the studies. Families invited in person, at clinic appointments, were more likely to consent than families invited by letter or phone. Timing of invitation following the child’s diagnosis differed among studies but, the likelihood of consent did not appear to be directly related to this. The return of questionnaires, completion of interview, and provision of DNA (blood sample) was highest in Aus-ALL (93%) and lowest in Aus-CBT (81%). Conclusions Studies of childhood cancer, and possibly other childhood diseases, should arrange for the family to be invited in person and, where possible, by a doctor with whom they are familiar. Whilst telephone interviews are time consuming and costly, particularly for large studies, they should be preferred over questionnaires for obtaining complete data. PMID:23656733

Ist da jemand? Wie Außerirdische uns entdecken können

NASA Astrophysics Data System (ADS)

Heller, R.

2016-06-01

Astronomen schlagen vor, sich bei der Suche nach Signalen außerirdischer Zivilisationen auf einen schmalen Bereich am Himmel zu konzentrieren. Von Planeten um Sterne, die in diesem Streifen liegen, würde sich die Erde vergleichsweise leicht entdecken lassen. Sollte es dort intelligentes Leben geben, könnte uns dieses schon längst aufgespürt und eine Botschaft Richtung Erde geschickt haben.

Tabellenanhang

NASA Astrophysics Data System (ADS)

Krieger, Hanno

Wichtiger Hinweis: Die Korrektur- und Umrechnungsfaktoren für die verschiedenen Dosimetrieaufgaben in diesem Tabellenanhang sind vom Autor mit Sorgfalt recherchiert und zusammengestellt. Der Anwender wird darauf hingewiesen, dass er für die Beschaffung und Überprüfung der Richtigkeit der Dosimetriefaktoren selbst die Verantwortung trägt, zumal je nach Normung und internationaler Festlegung von Zeit zu Zeit mit Änderungen zu rechnen ist.

Acta Aeronautica et Astronautica Sinica,

DTIC Science & Technology

1983-07-28

substructural analysis in modal synthesis - two improved substructural assembling techniques 49 9-node quadrilateral isoparametric element 64 Application of laser...Time from Service Data, J. Aircraft, Vol. 15, No. 11, 1978. 48 MULTI-LEVEL SUBSTRUCTURAL ANALYSIS IN MODAL SYNTHESIS -- TWO IMPROVED SUBSTRUCTURAL...34 Modal Synthesis in Structural Dynamic Analysis ," Naching Institute of Aeronautics and Astronautics, 1979. 62a 8. Chang Te-wen, "Free-Interface Modal

Identification of an ovarian voltage-activated Na+-channel type: hints to involvement in luteolysis.

PubMed

Bulling, A; Berg, F D; Berg, U; Duffy, D M; Stouffer, R L; Ojeda, S R; Gratzl, M; Mayerhofer, A

2000-07-01

An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA. Although the mechanism of channel activity under physiological conditions is not clear, it may include persistent Na+ currents. As observed in GC in culture, abundant secondary lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh activity and this form of cellular regression in vivo. Our results identify eNaCh in ovarian endocrine cells and demonstrate that their expression is under the inhibitory control of hCG. Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to decreased CL function, a process that involves lysosomal activation and autophagy. These results imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ CL in the primate ovary during the menstrual cycle. Because commonly used drugs, including phenytoin, target NaChs, these results

Monovalent and divalent cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic ganglia

PubMed Central

1995-01-01

Acetylcholine-evoked currents mediated by activation of nicotinic receptors in rat parasympathetic neurons were examined using whole-cell voltage clamp. The relative permeability of the neuronal nicotinic acetylcholine (nACh) receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements. The channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Cs+ > K+ > Rb+ > Na+ > Li+, and permeability ratios relative to Na+ (Px/PNa) ranging from 1.27 to 0.75. The selectivity of the alkaline earths was also weak, with the sequence of Mg2+ > Sr2+ > Ba2+ > Ca2+, and relative permeabilities of 1.10 to 0.65. The relative Ca2+ permeability (PCa/PNa) of the neuronal nACh receptor channel is approximately fivefold higher than that of the motor endplate channel (Adams, D. J., T. M. Dwyer, and B. Hille. 1980. Journal of General Physiology. 75:493-510). The transition metal cation, Mn2+ was permeant (Px/PNa = 0.67), whereas Ni2+, Zn2+, and Cd2+ blocked ACh-evoked currents with half-maximal inhibition (IC50) occurring at approximately 500 microM, 5 microM and 1 mM, respectively. In contrast to the muscle endplate AChR channel, that at least 56 organic cations which are permeable to (Dwyer et al., 1980), the majority of organic cations tested were found to completely inhibit ACh- evoked currents in rat parasympathetic neurons. Concentration-response curves for guanidinium, ethylammonium, diethanolammonium and arginine inhibition of ACh-evoked currents yielded IC50's of approximately 2.5- 6.0 mM. The organic cations, hydrazinium, methylammonium, ethanolammonium and Tris, were measureably permeant, and permeability ratios varied inversely with the molecular size of the cation. Modeling suggests that the pore has a minimum diameter of 7.6 A. Thus, there are substantial differences in ion permeation and block between the nACh receptor channels of mammalian parasympathetic neurons and amphibian

Turbulenzübergang in der Rohrströmung: Die Lösung eines alten Rätsels

NASA Astrophysics Data System (ADS)

Eckhardt, Bruno; Hof, Björn; Faisst, Holger

2006-09-01

Die Strömung von Flüssigkeiten und Gasen durch eine Röhre kann zwei Zustände annehmen. Einer ist laminar, also gleichmäßig geordnet, einer ist zeitlich-räumlich verwirbelt und turbulent. Mit dem Übergang zur Turbulenz nimmt der Strömungswiderstand drastisch zu. Vor etwa 120 Jahren beschrieb Osborne Reynolds bereits das Verhalten der Rohrströmung sehr genau. Er beobachtete, dass der Turbulenzübergang sehr empfindlich von äußeren Störungen abhängt, was bislang rätselhaft blieb. Dieses Rätsel konnte nun mit einer Kombination aus Computerstudien, Konzepten aus der nichtlinearen Dynamik und speziell entwickelten Experimenten gelöst werden.

Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action.

DTIC Science & Technology

1985-10-01

regions one hour 26 following microinjection of YH- choline into the right parietal cortex. II Effect of atropine sulfate (0.3 mg/kg i.v.) on the...Harvard Apparatus model 940). The superfusate consisted of a modified Kreb’s- bicarbonate buffer containing physostigmine to inhibit ACh degradation...in mM: NaCl, 118; CaCI 2 , 1.2; KC01, 4.8; MgSO4, 1.2; NaH 2 PO 4 , 1.2; NaHCO 3 , 25; choline chloride, 0.001; physostigmine, 0.1). The area of the

Gamma irradiation of isocitric and citric acid in aqueous solution: Relevance in prebiotic chemistry

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

Negrón-Mendoza, A., E-mail: negron@nucleares.unam.mx; Ramos-Bernal, S.

The radiation chemistry of hydroxy acids like citric and isocitric acids is rather scarce, even though they are crucial compounds in biological systems and for food irradiation. The aim of this work is to study the radiolytic behavior of these acids focused on the interconversion induced by radiation of citric and isocitric acid into other members of the Krebs cycle. The results showed that among the products formed were succinic, malonic, malic and other acids related to metabolic pathways, and these results are correlated with its possible role in chemical evolution processes.

Chapter 48: Geology and petroleum potential of the Eurasia Basin

USGS Publications Warehouse

Moore, Thomas E.; Pitman, Janet K.

2011-01-01

The Eurasia Basin petroleum province comprises the younger, eastern half of the Arctic Ocean, including the Cenozoic Eurasia Basin and the outboard part of the continental margin of northern Europe. For the USGS petroleum assessment (CARA), it was divided into four assessment units (AUs): the Lena Prodelta AU, consisting of the deep-marine part of the Lena Delta; the Nansen Basin Margin AU, comprising the passive margin sequence of the Eurasian plate; and the Amundsen Basin and Nansen Basin AUs which encompass the abyssal plains north and south of the Gakkel Ridge spreading centre, respectively. The primary petroleum system thought to be present is sourced in c. 50–44 Ma (Early to Middle Eocene) condensed pelagic deposits that could be widespread in the province. Mean estimates of undiscovered, technically recoverable petroleum resources include <1 billion barrels of oil (BBO) and about 1.4 trillion cubic feet (TCF) of nonassociated gas in Lena Prodelta AU, and <0.4 BBO and 3.4 TCF nonassociated gas in the Nansen Basin Margin AU. The Nansen Basin and Amundsen Basin AUs were not quantitatively assessed because they have less than 10% probability of containing at least one accumulation of 50 MMBOE (million barrels of oil equivalent).

Assessment of Appalachian basin oil and gas resources: Utica-Lower Paleozoic Total Petroleum System: Chapter G.10 in Coal and petroleum resources in the Appalachian basin: distribution, geologic framework, and geochemical character

USGS Publications Warehouse

Ryder, Robert T.; Ruppert, Leslie F.; Ryder, Robert T.

2014-01-01

Both conventional oil and gas resources and continuous (unconventional) gas resources are present in the UticaLower Paleozoic TPS. Conventional oil and gas resources in the Utica-Lower Paleozoic TPS were assessed by the U.S. Geological Survey (USGS) in 2002 in the following assessment units (AU): (1) the Lower Paleozoic Carbonates in Thrust Belt AU, (2) the Knox Unconformity AU, (3) the Black River-Trenton Hydrothermal Dolomite AU, and (4) the Lockport Dolomite AU. The total estimated undiscovered oil and gas resources for these four AUs, at a mean value, was about 46 million barrels of oil (MMBO) and about 3 trillion cubic feet of gas (TCFG), respectively. In contrast, continuous (unconventional) gas resources in the TPS were assessed by the USGS in 2002 in four AUs associated with the “Clinton” sandstone, Medina sandstone, Medina Group sandstones, Tuscarora Sandstone, and sandstones in the Queenston Shale. The total estimated undiscovered gas for these four AUs, at a mean value, was about 26.8 TCFG. A hypothetical Utica Shale AU for oil(?) and continuous gas is identified in this report. In 2012, the Utica Shale was recognized by the USGS as a continuous AU and was assessed by Kirschbaum and others (2012).

Genetic variation in resistance to blast (Pyricularia oryzae Cavara) in rice (Oryza sativa L.) germplasms of Bangladesh

PubMed Central

Khan, Mohammad Ashik Iqbal; Latif, Mohammad Abdul; Khalequzzaman, Mohammad; Tomita, Asami; Ali, Mohammad Ansar; Fukuta, Yoshimichi

2017-01-01

Genetic variation in blast resistance was clarified in 334 Bangladesh rice accessions from 4 major ecotypes (Aus, Aman, Boro and Jhum). Cluster analysis of polymorphism data of 74 SSR markers separated these accessions into cluster I (corresponding to the Japonica Group) and cluster II (corresponding to the Indica Group). Cluster II accessions were represented with high frequency in all ecotypes. Cluster II was further subdivided into subclusters IIa and IIb. Subcluster IIa accessions were represented with high frequency in only Aus and Jhum ecotypes. Cluster I accessions were more frequent in the Aman ecotype than in other ecotypes. Distinct variations in resistance were found, and accessions were classified into 4 groups (A1, A2, B1 and B2) based on their reactions to standard differential blast isolates. The most susceptible group was A2 (which included susceptible variety Lijiangxintuanheigu, most of the differential varieties, and a few Bangladesh accessions), followed in order by A1, B2 and B1 (the most resistant). Accessions from 4 ecotypes fell with different frequencies into each of these resistance groups. These results demonstrated that Japonica Group accessions were found mainly in Aman, and Indica Group accessions were distributed across all ecotypes. Susceptible accessions were limited in Aus and Aman. PMID:29398943

The low-bias conducting mechanism of single-molecule junctions constructed with methylsulfide linker groups and gold electrodes

NASA Astrophysics Data System (ADS)

Wang, Minglang; Wang, Yongfeng; Sanvito, Stefano; Hou, Shimin

2017-08-01

The atomic structure and electronic transport properties of two types of molecular junctions, in which a series of saturated and conjugated molecules are symmetrically connected to gold electrodes through methylsulfide groups, are investigated using the non-equilibrium Green's function formalism combined with density functional theory. Our calculations show that the low-bias junction conductance is determined by the electronic tunneling between the two Au-S donor-acceptor bonds formed at the molecule-electrode interfaces. For alkanes with 4, 6, and 8 carbon atoms in the chain, the Au-S bonds moderately couple with the σ-type frontier molecular orbitals of the alkane backbone and thus prefer to be coplanar with the alkane backbone in the junction. This results in an exponential decrease of the junction conductance as a function of the number of methylene groups. In contrast, the Au-S bonds couple strongly with the π-type orbitals of the 1,4'-bis(methylsulfide)benzene and 4,4'-bis(methylsulfide)biphenyl molecules and thus tend to be perpendicular to the neighboring benzene rings, leading to the rather large junction conductance. Our findings contribute to the understanding of the low-bias conducting mechanism and facilitate the design of molecular electronic devices with methylsulfide groups and gold electrodes.

Montreal electronic artificial urinary sphincters: Our futuristic alternatives to the AMS800™.

PubMed

Biardeau, Xavier; Hached, Sami; Loutochin, Oleg; Campeau, Lysanne; Sawan, Mohamad; Corcos, Jacques

2017-10-01

We aimed to present three novel remotely controlled hydromechanical artificial urinary sphincters (AUSs) and report their in-vitro and ex-vivo results. We successively developed three distinct hydromechanical AUSs on the basis of the existing AMS800 ™ device by incorporating an electronic pump. No changes were made to the cuff and balloon. The AUS#1 was designed as an electromagnetically controlled device. The AUS#2 and AUS#3 were conceived as Bluetooth 2.1 remotely controlled and Bluetooth 4.0 remotely-controlled, adaptive devices, respectively. In-vitro experiments profiled occlusive cuff pressure (OCP) during a complete device cycle, with different predetermined OCP. Ex-vivo experiments were performed on a fresh pig bladder with 4 cm cuff placed around the urethra. Leak point pressure with different predetermined OCP values was successively measured during cystometry via a catheter at the bladder dome. Our in-vitro and ex-vivo experiments demonstrated that these three novel AUSs provided stable and predetermined OCP - within the physiological range - and completely deflated the cuff, when required, in a limited time compatible with physiological voiding cycles. Our three novel, remotely controlled AUSs showed promising results that should be confirmed by in-vivo experiments focusing on efficacy and safety.

Purification and characterisation of the yeast plasma membrane ATP binding cassette transporter Pdr11p

PubMed Central

Laub, Katrine Rude; Marek, Magdalena; Stanchev, Lyubomir Dimitrov; Herrera, Sara Abad; Kanashova, Tamara; Bourmaud, Adèle; Dittmar, Gunnar

2017-01-01

The ATP binding cassette (ABC) transporters Pdr11p and its paralog Aus1p are expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and are required for sterol uptake. However, the precise mechanism by which these ABC transporters facilitate sterol movement is unknown. In this study, an overexpression and purification procedure was developed with the aim to characterise the Pdr11p transporter. Engineering of Pdr11p variants fused at the C terminus with green fluorescent protein (Pdr11p-GFP) and containing a FLAG tag at the N terminus facilitated expression analysis and one-step purification, respectively. The detergent-solubilised and purified protein displayed a stable ATPase activity with a broad pH optimum near 7.4. Mutagenesis of the conserved lysine to methionine (K788M) in the Walker A motif abolished ATP hydrolysis. Remarkably, and in contrast to Aus1p, ATPase activity of Pdr11p was insensitive to orthovanadate and not specifically stimulated by phosphatidylserine upon reconstitution into liposomes. Our results highlight distinct differences between Pdr11p and Aus1p and create an experimental basis for further biochemical studies of both ABC transporters to elucidate their function. PMID:28922409

Sonnenfinsternis 21. Juni 2001

NASA Astrophysics Data System (ADS)

Laager, Erich; Kocher, Peter; Slobins, Robert B.; Nufer, Robert; Bersinger, Walter; Schmitz-Scherzer, R.

2001-10-01

Contents: Eine Reise nach Madagaskar. Sonnenfinsternis am 21. Juni 2001 in Lusaka/Sambia. The 21 June 2001 total solar eclipse, as viewed from Kamilonga Farm, Zambia. Das Flash-Spektrum der Sonne während der totalen Sonnenfinsternis am 21. Juni 2001 in Sambia. Lufttemperatur und relative Luftfeuchtigkeit während der totalen Sonnenfinsternis am 21. Juni 2001 in Sambia. Schattenbänder fürs Fotoalbum. Totale Sonnenfinsternis.

Enhancing the Efficacy of Chemotherapeutic Breast Cancer Treatment with Nonanticoagulant Heparins

DTIC Science & Technology

2010-05-01

studies to investigate possible mechanisms associated with LMWH improvement of Dox anti-tumor activity focused on cell migration, proliferation and...tested to evaluate their effects on TFPI-1/-2 and sirt1 expression by Western blotting and real-time RT-PCR. We will evaluate the functional...without encapsulation in nanoparticles, suggesting that LMWH or NACH can improve the anti- tumor activity of Dox, even in a drug-resistant tumor. One

Sternbilder und ihre Mythen

NASA Astrophysics Data System (ADS)

Fasching, Gerhard

Aus den Besprechungen: "... Wem bei seinen philosophischen Höhenflügen allerdings die einfachsten Grundlagen fehlen, wer sich am Himmel ähnlich zurechtfindet wie ein Amazonasindianer im Großstadtverkehr, dem seien die Sternbilder und ihre Mythen ans Herz gelegt, die der Wiener Universitätsprofessor Gerhard Fasching zusammengestellt hat... Da werden Wegweiser-Sternkarten für das ganze Jahr gezeigt, die auch einem astronomischen Ignoranten die nächtliche Orientierung ermöglichen. Daneben werden die Sternsagen des Ovid opulent ausgebreitet, das überlieferte Wissen aus verschiedenen Kulturkreisen zitiert und wissenschaftliche Erklärungsmodelle zusammengetragen. Die moderne Weltsicht erscheint dabei nicht als der Weisheit letzter Schluß, sondern nur als derzeit anerkanntes Abbild der Wirklichkeit..." #Ulrich Schnabel/Die Zeit#

Untersuchung der Störwirkung von LTE auf SRD Anwendungen bei 868 MHz

NASA Astrophysics Data System (ADS)

Welpot, M.; Wunderlich, S.; Gaspard, I.

2014-11-01

Moderne Hausautomatisierungssysteme, Alarmanlagen oder auch Funk-Zugangssysteme in Haus und Automobil setzen auf frei nutzbare Frequenzen in ISM/SRD-Bändern. Die rasante Zunahme an privaten und kommerziell genutzten Applikationen im SRD-Band bei 868 MHz und der Ausbau der LTE-Mobilfunknetze im Frequenzbereich unterhalb von 1 GHz ("Digital Dividend") wirft zunehmend die Frage nach der Funkverträglichkeit dieser Systeme untereinander auf. Während die SRD-Funkmodule auf eine geringe Sendeleistung von ~ +14 dBm beschränkt sind (Ralf and Thomas, 2009), beträgt die maximale LTE-Sendeleistung im Uplink nach (ETSI-Norm, 2011) +23 dBm. Zusammen mit der Einführung von LTE im Frequenzbereich unterhalb 1 GHz als DSL-Ersatz vor allem in ländlichen Gebieten, ergibt sich damit als mögliches Störszenario, dass durch die Aussendung des LTE-Endgerätes im Bereich von ca. 850 MHz die SRD-Funkverbindungen bei 868 MHz insbesondere dann gestört werden, wenn die Antennen beider Funksysteme räumlich nahe zueinander angeordnet sind und folglich nur eine geringe zusätzliche Entkopplung der Systeme bieten. In der vorliegenden Arbeit wird das LTE-Störpotential auf SRD-Empfänger praxisnah untersucht.

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior

PubMed Central

Notarangelo, Francesca M.; Pocivavsek, Ana

2016-01-01

The kynurenine pathway (KP) of tryptophan degradation contains several neuroactive metabolites that may influence brain function in health and disease. Mounting focus has been dedicated to investigating the role of these metabolites during neurodevelopment and elucidating their involvement in the pathophysiology of psychiatric disorders with a developmental component, such as schizophrenia. In this review, we describe the changes in KP metabolism in the brain from gestation until adulthood and illustrate how environmental and genetic factors affect the KP during development. With a particular focus on kynurenic acid, the antagonist of α7 nicotinic acetylcholine (α7nACh) and N-methyl-D-aspartate (NMDA) receptors, both implicated in modulating brain development, we review animal models designed to ascertain the role of perinatal KP elevation on long-lasting biochemical, neuropathological, and behavioral deficits later in life. We present new data demonstrating that combining perinatal choline-supplementation, to potentially increase activation of α7nACh receptors during development, with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring. With these findings in mind, we conclude the review by discussing the advancement of therapeutic interventions that would target not only symptoms, but potentially the root cause of central nervous system diseases that manifest from a perinatal KP insult. PMID:26944732

Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

PubMed

Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu

2012-05-01

To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

Effect of (+)-usnic acid on mitochondrial functions as measured by mitochondria-specific oligonucleotide microarray in liver of B6C3F1 mice.

PubMed

Joseph, Ajay; Lee, Taewon; Moland, Carrie L; Branham, William S; Fuscoe, James C; Leakey, Julian E A; Allaben, William T; Lewis, Sherry M; Ali, Akhtar A; Desai, Varsha G

2009-04-01

Usnic acid is a lichen metabolite used as a weight-loss dietary supplement due to its uncoupling action on mitochondria. However, its use has been associated with severe liver disorders in some individuals. Animal studies conducted thus far evaluated the effects of usnic acid on mitochondria primarily by measuring the rate of oxygen consumption and/or ATP generation. To obtain further insight into usnic acid-mediated effects on mitochondria, we examined the expression levels of 542 genes associated with mitochondrial structure and functions in liver of B6C3F(1) female mice using a mitochondria-specific microarray. Beginning at 8 weeks of age, mice received usnic acid at 0, 60, 180, and 600 ppm in ground, irradiated 5LG6 diet for 14 days. Microarray analysis showed a significant effect of usnic acid on the expression of several genes only at the highest dose of 600 ppm. A prominent finding of the study was a significant induction of genes associated with complexes I through IV of the electron transport chain. Moreover, several genes involved in fatty acid oxidation, the Krebs cycle, apoptosis, and membrane transporters were over-expressed. Usnic acid is a lipophilic weak acid that can diffuse through mitochondrial membranes and cause a proton leak (uncoupling). The up-regulation of complexes I-IV may be a compensatory mechanism to maintain the proton gradient across the mitochondrial inner membrane. In addition, induction of fatty acid oxidation and the Krebs cycle may be an adaptive response to uncoupling of mitochondria.

Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes

PubMed Central

Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James A.; Thorpe, Suzanne R.; Baynes, John W.

2009-01-01

S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219–34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. PMID:19592500

Omega-3 Fatty Acids Attenuate Brain Alterations in High-Fat Diet-Induced Obesity Model.

PubMed

de Mello, Aline Haas; Schraiber, Rosiane de Bona; Goldim, Mariana Pereira de Souza; Garcez, Michelle Lima; Gomes, Maria Luiza; de Bem Silveira, Gustavo; Zaccaron, Rubya Pereira; Schuck, Patrícia Fernanda; Budni, Josiane; Silveira, Paulo Cesar Lock; Petronilho, Fabricia; Rezin, Gislaine Tezza

2018-05-04

This study evaluated the effects of omega-3 on inflammation, oxidative stress, and energy metabolism parameters in the brain of mice subjected to high-fat diet-induced obesity model. Body weight and visceral fat weight were evaluated as well. Male Swiss mice were divided into control (purified low-fat diet) and obese (purified high-fat diet). After 6 weeks, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + OMEGA-3. Fish oil (400 mg/kg/day) or saline solution was administrated orally, during 4 weeks. When the experiment completed 10 weeks, the animals were euthanized and the brain and visceral fat were removed. The brain structures (hypothalamus, hippocampus, prefrontal cortex, and striatum) were isolated. Treatment with omega-3 had no effect on body weight, but reduced the visceral fat. Obese animals showed increased inflammation, increased oxidative damage, decreased antioxidant enzymes activity and levels, changes in the Krebs cycle enzyme activities, and inhibition of mitochondrial respiratory chain complexes in the brain structures. Omega-3 treatment partially reversed the changes in the inflammatory and in the oxidative damage parameters and attenuated the alterations in the antioxidant defense and in the energy metabolism (Krebs cycle and mitochondrial respiratory chain). Omega-3 had a beneficial effect on the brain of obese animals, as it partially reversed the changes caused by the consumption of a high-fat diet and consequent obesity. Our results support studies that indicate omega-3 may contribute to obesity treatment.

First prize: Chitosan and the urothelial barrier: effects on ureteral intraluminal drug penetration and peristalsis.

PubMed

Pick, Donald L; Shelkovnikov, Stanislav; Canvasser, Noah; Louie, Michael K; Tongson-Ignacio, Jane; McDougall, Elspeth M; Clayman, Ralph V

2011-03-01

Relaxing the ureter prior to endourologic procedures could ease instrument access. In an ex-vivo model, intraluminal nifedipine has been shown to relax the ureter. Chitosan is the deacetylation product of chitin and can alter bladder urothelium. This study examines the effect of nifedipine on peristalsis before and after pretreating the ureter with chitosan. Intact 4-cm tubular porcine ureteral segments were placed in a novel organ bath. To induce peristalsis, phenylephrine (10 μM) was added. Chitosan (0.5% [w/v], 30 minutes) or Krebs (control) was then used to treat the urothelium. The rate and amplitude of ureteral peristalsis was then measured. Intraluminal nifedipine (1 μM) was then added to the intraluminal reservoir. Peristaltic rate and amplitude and the time to aperistalsis were measured. Methylene blue was then added after treatment with chitosan or control to measure diffusion. After Krebs pretreatment, intraluminal nifedipine (1 μM) significantly reduced peristaltic frequency (p = 0.0184) but did not stop peristalsis after 60 minutes of exposure in six trials. After chitosan, nifedipine (1 μM) stopped ureteral peristalsis within an average of 12.30 ± 4.72 minutes. Chitosan alone did not cause aperistalsis. Intraluminal methylene blue did not diffuse into the extraluminal bath after saline or chitosan pretreatment. Histological analysis of the ureter before and after pretreatment with chitosan showed no urothelial disruption. By pretreating the intraluminal surface of the ureter with chitosan, nifedipine blocks ureteral peristalsis at low concentrations. Chitosan changes ureteral urothelial permeability without barrier disruption and has no observed effect on ureteral contraction.

Atomic structure of a peptide coated gold nanocluster identified using theoretical and experimental studies

NASA Astrophysics Data System (ADS)

Wang, Hui; Li, Xu; Gao, Liang; Zhai, Jiao; Liu, Ru; Gao, Xueyun; Wang, Dongqi; Zhao, Lina

2016-06-01

Peptide coated gold nanoclusters (AuNCs) have a precise molecular formula and atomic structure, which are critical for their unique applications in targeting specific proteins either for protein analysis or drug design. To date, a study of the crystal structure of peptide coated AuNCs is absent primarily due to the difficulty of obtaining their crystalline phases in an experiment. Here we study a typical peptide coated AuNC (Au24Peptide8, Peptide = H2N-CCYKKKKQAGDV-COOH, Anal. Chem., 2015, 87, 2546) to figure out its atomic structure and electronic structure using a theoretical method for the first time. In this work, we identify the explicit configuration of the essential structure of Au24Peptide8, Au24(Cys-Cys)8, using density functional theory (DFT) computations and optical spectroscopic experiments, where Cys denotes cysteine without H bonded to S. As the first multidentate ligand binding AuNC, Au24(Cys-Cys)8 is characterized as a distorted Au13 core with Oh symmetry covered by two Au(Cys-Cys) and three Au3(Cys-Cys)2 staple motifs in its atomic structure. The most stable configuration of Au24(Cys-Cys)8 is confirmed by comparing its UV-vis absorption spectrum from time-dependent density-functional theory (TDDFT) calculations with optical absorption measurements, and these results are consistent with each other. Furthermore, we carry out frontier molecular orbital (FMO) calculations to elucidate that the electronic structure of Au24(Cys-Cys)8 is different from that of Au24(SR)20 as they have a different Au/S ratio, where SR represents alkylthiolate. Importantly, the different ligand coatings, Cys-Cys and SR, in Au24(Cys-Cys)8 and Au24(SR)20 cause the different Au/S ratios in the coated Au24. The reason is that the Au/S ratio is crucial in determining the size of the Au core of the ligand protected AuNC, and the size of the Au core corresponds to a specific electronic structure. By the adjustment of ligand coatings from alkylthiolate to peptide, the Au/S ratio

Autoimmune Retinopathy: Current Concepts and Practices (An American Ophthalmological Society Thesis).

PubMed

Sen, H Nida; Grange, Landon; Akanda, Marib; Fox, Austin

2017-08-01

To elicit and evaluate opinions in the diagnosis and management of nonparaneoplastic autoimmune retinopathy (npAIR) among members of the American Uveitis Society (AUS) and to further the development of consensus and criteria in the diagnosis and management of npAIR. We hypothesize that despite lack of any clear guidelines, a general consensus in the clinical diagnosis and treatment of npAIR exists among uveitis experts. A literature review was performed and a panel of uveitis experts was consulted to formulate a survey regarding the diagnosis and management of npAIR. An online survey of 10 questions was developed, and a link was distributed through the AUS membership discussion list. We defined "general consensus" as meaning that a majority (>50%) of the respondents provided the same answer to a question. Fifty-four members of the AUS responded to the survey. Thirty-eight members (70.4%) see one to three AIR patients per year. Greater than 50% consensus was reached on most items, particularly items relating to diagnostic features and tests (up to 96% consensus). The diagnosis and management of npAIR is challenging, as standardized clinical and laboratory diagnostic criteria have yet to be established. The results of this study support the presence of consensus regarding certain aspects of npAIR, but also indicate the need for developing clear clinical diagnostic criteria and treatment guidelines.

Does abdominal sonography provide additional information over abdominal plain radiography for diagnosis of necrotizing enterocolitis in neonates?

PubMed

Dilli, Dilek; Suna Oğuz, S; Erol, Reyhan; Ozkan-Ulu, Hülya; Dumanlı, Hüseyin; Dilmen, Uğur

2011-03-01

To explore whether addition of abdominal sonography (AUS) to plain radiography is helpful in the management of premature newborns with necrotizing enterocolitis (NEC). This study is a prospective analysis of 93 premature neonates with NEC who were followed-up in our neonatal intensive care unit between October 2007 and April 2009. Patients were classified into two groups; group I with suspected NEC (stage I) (n = 54) and group II with definite NEC (stage ≥II) (n = 39). Pneumatosis intestinalis (PI) (n = 29), free air (n = 9), and portal venous gas (PVG) (n = 1) were observed in group II on plain radiography. In the same group, echoic free fluid (EFF) (n = 9), PVG (n = 6), PI (n = 5), and focal fluid collection (n = 3) were the most prominent sonographic findings. In patients with intestinal perforation, whereas EFF and bowel wall thinning were observed on AUS, free air was not detected on plain radiography as a sign of intestinal perforation. Our results suggest AUS to be superior to plain radiography on early detection of intestinal perforation by demonstrating PVG and EFF collection. Therefore, it may be life-saving by directing the surgeon to perform surgical intervention in the case of clinical deterioration in the course of NEC.

Sterblichkeit: der paradoxe Kunstgriff des Lebens - Eine Betrachtung vor dem Hintergrund der modernen Biologie

NASA Astrophysics Data System (ADS)

Verbeek, Bernhard

Leben gibt es auf der Erde seit fast 4 Mio. Jahren, trotz allen Katastrophen. Die Idee des Lebens scheint unsterblich. Der Tod aber offenbar auch. Jedes Lebewesen ist davon bedroht, ja für Menschen und andere "höhere“ Lebewesen ist er im Lebensprogramm eingebaut - todsicher. Diese Tatsache ist alles andere als selbstverständlich. Ist sie überhaupt kompatibel mit dem Prinzip der Evolution, nach dem der am besten Angepasste überlebt?

Prostaglandin release from in vitro guinea-pig gallbladder.

PubMed

Booker, M L; LaMorte, W W

1983-02-01

In order to study prostaglandin release from guinea pig gallbladder, full thickness tissue sections were incubated for one hour in Krebs solution. Extraction and two dimensional chromatography of incubation media obtained in the presence of radio-labelled arachidonic acid demonstrated the presence of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. These results were supported by radioimmunoassay of incubations conducted in the absence of exogenous arachidonate and in the presence of varying concentrations of unlabelled exogenous arachidonate. The previously reported predominance of PGE2 was only seen at high concentrations of exogenous arachidonate.

Mitochondria are the powerhouses of immunity.

PubMed

Mills, Evanna L; Kelly, Beth; O'Neill, Luke A J

2017-04-18

Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells. These discoveries are revealing mitochondrial targets that could potentially be exploited for therapeutic gain in inflammation and cancer.

Yakima/Klickitat Fisheries Project Genetic Studies; Yakima/Klickitat Fisheries Project Monitoring and Evaluation Report 1 of 7, 2003-2004 Annual Report.

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

Busack, Craig A.; Frye, Alice; Kassler, Todd

2004-05-01

Genetic work for 2003, as in previous years, was quite diverse. In chapter 1 we report on the use of DNA microsatellite markers to sex spring chinook collected at Roza. We have learned through comparison of sex determinations at Roza and then at CESRF that sexing green fish on the basis of morphology is somewhat inaccurate, and accurate sexing of fish at Roza is needed to estimate sex ratios of fish on the spawning grounds. Using DNA microsatellite markers, sexing accuracy was high, but not perfect. In chapter 2 we report on new genetic risk concepts currently being developed andmore » their implications for the YKFP spring chinook program. The impact on domestication of gene flow between the natural and hatchery spawning components is now much better understood. It is now possible to compare the risk of different hatchery programs much more quantitatively in the past. Thus, we can now make good predictions of how much less domesticating the Yakima spring chinook supplementation effort is than other programs. In chapter 3 we present the initial results of morphological comparisons of adult (1) hatchery-origin Upper Yakima spring chinook, (2) natural-origin U. Yakima spring chinook, and (3) Naches spring chinook. Canonical variate analysis allowed both sexes of the three groups to be classified correctly with over accuracy. The differences are subtle, but hatchery-origin fish appear to be someone thinner than natural-origin fish. This is consistent with observations of hatchery vs wild morphology in coho. In chapter 4 we describe the ongoing work to refine the Domestication Research/Monitoring Plan. Work for last year included analysis of the impact of HC line precocious males spawning in the wild, development of a misting incubation system for off-site incubation of Naches eggs, and refinement of some aspects of experimental design. The misting incubation system has broad applicability outside the project. The most recent version of the domestication monitoring

Web-based Recruiting for a Survey on Knowledge and Awareness of Cervical Cancer Prevention Among Young Women Living in Kanagawa Prefecture, Japan

PubMed Central

Miyagi, Etsuko; Motoki, Yoko; Asai-Sato, Mikiko; Taguri, Masataka; Morita, Satoshi; Hirahara, Fumiki; Wark, John D.; Garland, Suzanne M.

2014-01-01

Objectives Cervical cancer (CC) incidence and mortality among young women have been increasing in Japan. To develop effective measures to combat this, we assessed the feasibility of using a social networking site (SNS) to recruit a representative sample of young women to conduct a knowledge and attitude study about CC prevention via an internet-based questionnaire. Methods From July 2012 to March 2013, advertising banners targeting women aged 16 to 35 years in Kanagawa Prefecture were placed on Facebook in a similar manner as an Australian (AUS) study conducted in 16- to 25-year-olds in 2010 and on a homepage to advertise our CC advocacy activities. Eligible participants were emailed instructions for accessing our secure Web site where they completed an online survey including demographics, awareness, and knowledge of human papillomavirus (HPV) and CC. Data for the study population were compared with the general Japanese population and the AUS study. Results Among 394 women who expressed interest, 243 (62%) completed the survey, with 52% completing it via Facebook. Women aged 26 to 35 years, living in Yokohama City, with an education beyond high school, were overrepresented. Participants had high awareness and knowledge of HPV and CC, comparable with the AUS study participants. However, the self-reported HPV vaccination rate (22% among participants aged 16–25 years) and the recognition rate of the link between smoking and CC (31%) were significantly lower than in the AUS study (58% and 43%, respectively) (P < 0.05). Significant predictors of high knowledge scores about HPV included awareness of HPV vaccine (P < 0.001) and self-reported HPV vaccination (P < 0.05). Conclusions The SNS and homepage are efficient methods to recruit young women into health surveys, which can effectively be performed online. A nationwide survey using SNSs would be an appropriate next step to better understand the current lack of uptake of the national HPV vaccine program by young women

Characterization of G2P[4] rotavirus strains associated with increased detection in Australian states using the RotaTeq® vaccine during the 2010-2011 surveillance period.

PubMed

Donato, Celeste M; Zhang, Zheng Andrew; Donker, Nicole C; Kirkwood, Carl D

2014-12-01

The introduction of rotavirus vaccines Rotarix® and RotaTeq® into the Australian National Immunisation Program in July 2007 has resulted in a dramatic decrease in the burden of rotavirus disease. G2P[4] strains became the dominant genotype Australia-wide during the 2010-2011 surveillance period and for the first time since vaccine introduction, a higher proportion were isolated in jurisdictions using RotaTeq® vaccine compared to locations using Rotarix®. Phylogenetic analysis of the VP7 gene of 32 G2P[4] strains identified six genetic clusters, these distinct clusters were also observed in the VP4 gene for a subset of 12 strains. The whole genome was determined for a representative strain of clusters; A (RVA/Human-wt/AUS/SA066/2010/G2P[4]), B (RVA/Human-wt/AUS/WAPC703/2010/G2P[4]), C (RVA/Human-wt/AUS/MON008/2010/G2P[4]) and E (RVA/Human-wt/AUS/RCH041/2010/G2P[4]). All of the strains possessed the archetypal DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Three of the strains, SA066, MON008 and WAPC703 clustered together and were distinct to RCH041 for all 11 genes. The VP7 genes of 31/32 of the strains characterized in this study possessed five conserved amino acid substitutions when compared to the G2 VP7 gene present in the RotaTeq® vaccine. Three of the substitutions were in the VP7 antigenic regions A and C, the substitutions A87T, D96N and S213D have been reported in the majority of G2P[4] strains circulating globally over the previous decade. These changes may have improved the ability of strains to circulate in settings of high vaccine use. Copyright © 2014 Elsevier B.V. All rights reserved.

Web-based recruiting for a survey on knowledge and awareness of cervical cancer prevention among young women living in Kanagawa prefecture, Japan.

PubMed

Miyagi, Etsuko; Motoki, Yoko; Asai-Sato, Mikiko; Taguri, Masataka; Morita, Satoshi; Hirahara, Fumiki; Wark, John D; Garland, Suzanne M

2014-09-01

Cervical cancer (CC) incidence and mortality among young women have been increasing in Japan. To develop effective measures to combat this, we assessed the feasibility of using a social networking site (SNS) to recruit a representative sample of young women to conduct a knowledge and attitude study about CC prevention via an internet-based questionnaire. From July 2012 to March 2013, advertising banners targeting women aged 16 to 35 years in Kanagawa Prefecture were placed on Facebook in a similar manner as an Australian (AUS) study conducted in 16- to 25-year-olds in 2010 and on a homepage to advertise our CC advocacy activities. Eligible participants were emailed instructions for accessing our secure Web site where they completed an online survey including demographics, awareness, and knowledge of human papillomavirus (HPV) and CC. Data for the study population were compared with the general Japanese population and the AUS study. Among 394 women who expressed interest, 243 (62%) completed the survey, with 52% completing it via Facebook. Women aged 26 to 35 years, living in Yokohama City, with an education beyond high school, were overrepresented. Participants had high awareness and knowledge of HPV and CC, comparable with the AUS study participants. However, the self-reported HPV vaccination rate (22% among participants aged 16-25 years) and the recognition rate of the link between smoking and CC (31%) were significantly lower than in the AUS study (58% and 43%, respectively) (P < 0.05). Significant predictors of high knowledge scores about HPV included awareness of HPV vaccine (P < 0.001) and self-reported HPV vaccination (P < 0.05). The SNS and homepage are efficient methods to recruit young women into health surveys, which can effectively be performed online. A nationwide survey using SNSs would be an appropriate next step to better understand the current lack of uptake of the national HPV vaccine program by young women in Japan.

Suggesting the cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A retrospective analysis of atypical and suspicious nodules.

PubMed

Strickland, Kyle C; Howitt, Brooke E; Barletta, Justine A; Cibas, Edmund S; Krane, Jeffrey F

2018-02-01

The term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) has replaced a subset of follicular variant of papillary thyroid carcinoma due to the indolent behavior of such tumors. NIFTPs are most often classified in an "indeterminate" diagnostic category. In the current study, the authors sought to identify cytologic features helpful in distinguishing NIFTP from other entities in these categories, particularly benign nodules. The authors retrospectively evaluated a consecutive cohort of 130 thyroid fine-needle aspiration (FNA) specimens with an indeterminate diagnosis and available histopathologic follow-up. All FNA specimens were evaluated using the ThinPrep method. Each FNA was blindly reviewed by 2 board-certified cytopathologists, who assessed overall cellularity; architectural parameters; and nuclear features, including nuclear pallor and fine chromatin, distinct nucleoli, and irregular nuclear membranes. Each case received a score of 0 to 3, based on the presence or absence of these 3 nuclear features. Nuclear but not architectural features appeared to distinguish NIFTP from benign nodules. Ninety-one percent of the NIFTPs (32 of 35 NIFTPs) received a score of ≥2, compared with 35% of benign nodules (23 of 66 benign nodules) (P<.0001). In contrast, NIFTP could not be differentiated from the invasive/infiltrative follicular variant of papillary thyroid carcinoma using these criteria (P = 1.000). Nuclear scoring was found to be especially useful in atypia of undetermined significance/follicular lesion of undetermined significance (AUS); a score ≥2 enriched for NIFTP (39% vs 3% of AUS cases with a score <2), whereas a score <2 was more likely benign (85% vs 50% of AUS cases with a score ≥2). In indeterminate FNA specimens, the distinction of a possible NIFTP from a benign thyroid nodule can be suggested using a simple nuclear scoring system that is most valuable in AUS aspirates. Cancer Cytopathol 2018;126:86-93. © 2017

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

PubMed Central

Isnard, Christophe; Cosquer, Thibaud; Odhiambo, Arlène; Bucquet, Fiona; Guérin, François; Giard, Jean-Christophe

2014-01-01

Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in Enterococcus faecium. Using the serial passage method, in vitro mutant AusTig and in vitro mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 μg/ml) were obtained from strains E. faecium Aus0004 and HM1070 (MICs, 0.03 μg/ml), respectively. In addition, two vancomycin-resistant E. faecium clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 μg/ml, respectively) were studied. Compared to the wild-type strains, the in vitro mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the rpsJ gene (efau004_00094, coding for the S10 protein of the 30S ribosomal subunit), efau004_01228 (encoding a cation transporter), efau004_01636 (coding for a hypothetical protein), and efau004_02455 (encoding the l-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein. In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci. PMID:25348531

Genomic analysis of reduced susceptibility to tigecycline in Enterococcus faecium.

PubMed

Cattoir, Vincent; Isnard, Christophe; Cosquer, Thibaud; Odhiambo, Arlène; Bucquet, Fiona; Guérin, François; Giard, Jean-Christophe

2015-01-01

Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in Enterococcus faecium. Using the serial passage method, in vitro mutant AusTig and in vitro mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 μg/ml) were obtained from strains E. faecium Aus0004 and HM1070 (MICs, 0.03 μg/ml), respectively. In addition, two vancomycin-resistant E. faecium clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 μg/ml, respectively) were studied. Compared to the wild-type strains, the in vitro mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the rpsJ gene (efau004_00094, coding for the S10 protein of the 30S ribosomal subunit), efau004_01228 (encoding a cation transporter), efau004_01636 (coding for a hypothetical protein), and efau004_02455 (encoding the l-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein. In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Estimating the recreational-use value for hiking in Bellenden Ker National Park, Australia.

PubMed

Nillesen, Eleonora; Wesseler, Justus; Cook, Averil

2005-08-01

The recreational-use value of hiking in the Bellenden Ker National Park, Australia has been estimated using a zonal travel cost model. Multiple destination visitors have been accounted for by converting visitors' own ordinal ranking of the various sites visited to numerical weights, using an expected-value approach. The value of hiking and camping in this national park was found to be dollar AUS 250,825 per year, or dollar AUS 144,45 per visitor per year, which is similar to findings from other studies valuing recreational benefits. The management of the park can use these estimates when considering the introduction of a system of user pays fees. In addition, they might be important when decisions need to be made about the allocation of resources for maintenance or upgrade of tracks and facilities.

Process for Assessing the Stability of HAN (Hydroxylamine)-Based Liquid Propellants.

DTIC Science & Technology

1987-07-29

liquid propellants on the basis of HAN according to Fig. 1 can be determined directly by Fischer titration. This method requires a special unit, as the...Wasserreagenzien nach Eugen Scholz fUr die Karl - Fischer -Titration (Guidelines by Messrs. Riedel-de Haen for Titration according to the Karl Fischer ...Propellant components 2 2.2 Methods of determination 3 2.3 Acid/base titration and pK values 4 2.4 The Titroprozessor 636 8 2.5 Propellant analyses 10

Extrasolare Monde - schöne neue Welten?

NASA Astrophysics Data System (ADS)

Heller, René

2013-10-01

Während mittlerweile rund 950 Planeten außerhalb des Sonnensystems gefunden wurden, steht der Nachweis von extrasolaren Monden noch aus. Aktuelle Studien zeigen, dass dies mit der heutigen Technologie zum ersten Mal möglich ist.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

PubMed Central

Kuo, Ming-Jeng; Chen, Hsiu-Hsi; Chen, Chi-Ling; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Lin, Yu-Min; Liao, Chao-Sheng; Chang, Hung-Chuen; Lin, Yueh-Shih; Yen, Amy Ming-Fang

2016-01-01

AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval. PMID:27022228

Trizentrische Analyse von Kofaktoren und Komorbidität des Pyoderma gangraenosum.

PubMed

Jockenhöfer, Finja; Herberger, Katharina; Schaller, Jörg; Hohaus, Katja Christina; Stoffels-Weindorf, Maren; Ghazal, Philipp Al; Augustin, Matthias; Dissemond, Joachim

2016-10-01

Das Pyoderma gangraenosum (PG) ist eine seltene, inflammatorische destruktiv-ulzerierende neutrophile Erkrankung mit weitgehend unklarer Pathophysiologie. In dieser Studie wurden die potenziell relevanten Kofaktoren und Begleiterkrankungen von Patienten mit PG aus drei dermatologischen Wundzentren in Deutschland differenziert ausgewertet. Von den insgesamt 121 analysierten Patienten waren Frauen (66,9 %) häufiger betroffen als Männer. Das Alter der Patienten war 18-96 Jahre (Mittelwert [MW]: 59,8); die Wunden hatten eine Größe von 1-600 cm² (MW: 65,6 cm²) und waren überwiegend sehr schmerzhaft (VAS 1-10, MW: 7). Die Unterschenkel waren am häufigsten (71,9 %) betroffen. Bei 12 (9,9 %) Patienten bestanden chronisch entzündliche Darmerkrankungen (5,8 % Colitis ulcerosa; 4,1 % Morbus Crohn), bei 14,1 % der Patienten wurde eine Begleiterkrankung aus dem rheumatischen Formenkreis beschrieben. Neoplasien bestanden bei 20,6 % der Patienten, von denen 6,6 % als hämatologische und 14,1 % als solide Neoplasien klassifiziert wurden. Aus dem Kreis des metabolischen Syndroms wurde bei 69,4 % Patienten eine Adipositas, bei 57,9 % eine arterielle Hypertonie und bei 33,9 % ein Diabetes mellitus diagnostiziert. Diese Datenanalyse bestätigt Assoziationen des PG mit dem metabolischen Syndrom und mit Neoplasien, die zukünftig frühzeitig bei einer zielgerichteten Diagnostik der Patienten beachtet und behandelt werden sollten. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Economic burden of toxicities associated with treating metastatic melanoma in eight countries.

PubMed

Wehler, Elizabeth; Zhao, Zhongyun; Pinar Bilir, S; Munakata, Julie; Barber, Beth

2017-01-01

Information on costs of managing adverse events (AEs) associated with current treatments in metastatic melanoma is limited. This study estimates costs of AEs in eight countries: Australia (AU), Canada (CA), France (FR), Germany (GE), Italy (IT), the Netherlands (NL), Spain (ES), and the UK. A literature search was conducted to identify grade 3/4 AEs from product label, published trials, conference abstracts, and treatment guidelines. Resource utilization for the management of each type of AE was determined via interviews with 5 melanoma clinicians in each country. Outpatient and inpatient costs were estimated for each type of AE using country-specific tariffs or government/published sources. In outpatient settings, the most costly AEs per incident included cutaneous squamous cell carcinoma (CSCC) (€1063, £720; NL/UK), anemia (€1443, €1329, €1285; ES/IT/FR), peripheral neuropathy (€1289; ES), and immune-related diarrhea (AUS$1,121; AU). In inpatient settings, the most costly AEs per hospitalization included hypophysitis (€10,265; €5316; CAN$9735; AUS$7231: ES/FR/CA/AU), dyspnea (€9077; GE), elevated liver enzymes (€6913, CAN$8030, AUS$6594; FR/CA/AU), CSCC (CAN$8934; CA), peripheral neuropathy (€6977, €4144, CAN$9472; NL/ES/CA), and diarrhea (£4284, €4113; UK/ES). Costs of managing AEs can be significant, and thus effective treatments with lower rates of severe AEs would be valuable.

Metabolomics reveals the key role of oxygen metabolism in the heat susceptibility of an alpine dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae).

PubMed

Zhu, Wei; Meng, Qian; Zhang, Huan; Wang, Meng-Long; Li, Xuan; Wang, Hong-Tuo; Zhou, Gui-Ling; Miao, Lin; Qin, Qi-Lian; Zhang, Ji-Hong

2018-05-23

Ghost moths inhabiting the alpine meadows of the Tibetan Plateau are cold-adapted stenothermal organisms that are susceptible to heat (dead within 7 days of 27 °C exposure). Exploring the metabolic basis of their heat susceptibility would extend our understanding of the thermal biology of alpine dwelling invertebrates. Here, gas chromatography-mass spectrometry-based metabolomics was combined with physiological and transcriptional approaches to determine the metabolic mechanisms of heat susceptibility in Thitarodes xiaojinensis larvae. The metabolomics results showed that 27 °C heat stress impaired the Krebs cycle and lipolysis in T. xiaojinensis larvae, as demonstrated by the accumulation of intermediary metabolites. In addition, carbohydrate reserves were highly and exclusively consumed, and an anaerobic product, lactate, accumulated. This evidence suggested a strong reliance on glycolysis to generate energy anaerobically. The respiration rate and enzymatic activity test results indicated a deficiency in O 2 metabolism; in addition, the Krebs cycle capacity was not lowered, and the metabolic flux through aerobic pathways was limited. These findings were further supported by the occurrence of hypoxia symptoms in midgut mitochondria (vacuolation and swelling) and increased transcription of hypoxia-induced factor 1-α. Overall, heat stress caused O 2 limitation and depressed the overall intensity of aerobic metabolism in ghost moths, and less efficient anaerobic glycolysis was activated to sustain their energy supply. After the carbohydrates became limited, the energy supply became deficient. Our study presented a comprehensive metabolic explanation for the heat susceptibility of ghost moths and revealed the relationship between O 2 metabolism and heat susceptibility in these larvae. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Oligo-carrageenan kappa increases NADPH, ascorbate and glutathione syntheses and TRR/TRX activities enhancing photosynthesis, basal metabolism, and growth in Eucalyptus trees.

PubMed

González, Alberto; Moenne, Fabiola; Gómez, Melissa; Sáez, Claudio A; Contreras, Rodrigo A; Moenne, Alejandra

2014-01-01

In order to analyze the effect of OC kappa in redox status, photosynthesis, basal metabolism and growth in Eucalyptus globulus, trees were treated with water (control), with OC kappa at 1 mg mL(-1), or treated with inhibitors of NAD(P)H, ascorbate (ASC), and glutathione (GSH) syntheses and thioredoxin reductase (TRR) activity, CHS-828, lycorine, buthionine sulfoximine (BSO), and auranofin, respectively, and with OC kappa, and cultivated for 4 months. Treatment with OC kappa induced an increase in NADPH, ASC, and GSH syntheses, TRR and thioredoxin (TRX) activities, photosynthesis, growth and activities of basal metabolism enzymes such as rubisco, glutamine synthetase (GlnS), adenosine 5'-phosphosulfate reductase (APR), involved in C, N, and S assimilation, respectively, Krebs cycle and purine/pyrimidine synthesis enzymes. Treatment with inhibitors and OC kappa showed that increases in ASC, GSH, and TRR/TRX enhanced NADPH synthesis, increases in NADPH and TRR/TRX enhanced ASC and GSH syntheses, and only the increase in NADPH enhanced TRR/TRX activities. In addition, the increase in NADPH, ASC, GSH, and TRR/TRX enhanced photosynthesis and growth. Moreover, the increase in NADPH, ASC and TRR/TRX enhanced activities of rubisco, Krebs cycle, and purine/pyrimidine synthesis enzymes, the increase in GSH, NADPH, and TRR/TRX enhanced APR activity, and the increase in NADPH and TRR/TRX enhanced GlnS activity. Thus, OC kappa increases NADPH, ASC, and GSH syntheses leading to a more reducing redox status, the increase in NADPH, ASC, GSH syntheses, and TRR/TRX activities are cross-talking events leading to activation of photosynthesis, basal metabolism, and growth in Eucalyptus trees.

Lipoic acid reduces ischemia-reperfusion injury in animal models.

PubMed

Freisleben, H J

2000-08-07

Hypoxia and reoxygenation were studied in rat hearts and ischemia and reperfusion in rat hindlimbs. Free radicals are known to be generated through these events and to propagate complications. In order to reduce hypoxic/ischemic and especially reoxygenation/reperfusion injury the (re)perfusion conditions were ameliorated including the treatment with antioxidants (lipoate or dihydrolipoate). In isolated working rat hearts cardiac and mitochondrial parameters are impaired during hypoxia and partially recover in reoxygenation. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7. 15) during hypoxia as compared to controls (6.98). The compound accelerates the recovery of the aortic flow and stabilizes it during reoxygenation. With dihydrolipoate, ATPase activity is reduced, ATP synthesis is increased and phosphocreatine contents are higher than in controls. Creatine kinase activity is maintained during reoxygenation in the dihydrolipoate series. Isolated rat hindlimbs were stored for 4 h in a moist chamber at 18 degrees C. Controls were perfused for 30 min with a modified Krebs-Henseleit buffer at 60 mmHg followed by 30 min Krebs-Henseleit perfusion at 100 mmHg. The dihydrolipoate group contained 8.3 microM in the modified reperfusate (controlled reperfusion). With dihydrolipoate, recovery of the contractile function was 49% (vs. 34% in controls) and muscle flexibility was maintained whereas it decreased by 15% in the controls. Release of creatine kinase was significantly lower with dihydrolipoate treatment. Dihydrolipoate effectively reduces reoxygenation injury in isolated working rat hearts. Controlled reperfusion, including lipoate, prevents reperfusion syndrome after extended ischemia in exarticulated rat hindlimbs and in an in vivo pig hindlimbs model.

Cooling-induced contraction in ovine airways smooth muscle.

PubMed

Mustafa, S M; Pilcher, C W; Williams, K I

1999-02-01

The mechanism of cold-induced bronchoconstriction is poorly understood. This prompted the present study whose aim was to determine the step-wise direct effect of cooling on smooth muscle of isolated ovine airways and analyse the role of calcium in the mechanisms involved. Isolated tracheal strips and bronchial segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling induced a rapid and reproducible contraction proportional to cooling temperature in ovine tracheal and bronchial preparations which was epithelium-independent. On readjustment to 37 degrees C the tone returned rapidly to basal level. Maximum contraction was achieved at a temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling-induced contractions (CIC) was resistant to tetrodotoxin (1; 10 micrometer), and not affected by the muscarinic antagonist atropine (1 micrometer) or the alpha-adrenergic antagonist phentolamine (1 micrometer), or the histamine H1-antagonist mepyramine (1 micrometer) or indomethacin (1 micrometer). Ca2+ antagonists (nifedipine and verapamil) and Mn2+ raised tracheal but not bronchiolar tone and augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min had no effect on CIC, although it significantly reduced KCl-induced contraction by up to 75%. Cooling inhibited Ca2+ influx measured using 45Ca2+ uptake. Caffeine (100 micrometer) significantly inhibited CIC. The results show that cooling-induced contractions do not appear to involve activation of nerve endings, all surface reception systems or Ca2+ influx. However, CIC is mainly dependent on release of intracellular Ca2+. Copyright 1999 The Italian Pharmacological Society.

Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.

PubMed

Zhang, Li; He, Huamei; Balschi, James A

2007-07-01

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor: it responds to an increase in AMP concentration ([AMP]) or the AMP-to-ATP ratio (AMP/ATP). Metformin and phenformin, which are biguanides, have been reported to increase AMPK activity without increasing AMP/ATP. This study tests the hypothesis that these biguanides increase AMPK activity in the heart by increasing cytosolic [AMP]. Groups of isolated rat hearts (n = 5-7 each) were perfused with Krebs-Henseleit buffer with or without 0.2 mM phenformin or 10 mM metformin, and (31)P-NMR-measured phosphocreatine, ATP, and intracellular pH were used to calculate cytosolic [AMP]. At various times, hearts were freeze-clamped and assayed for AMPK activity, phosphorylation of Thr(172) on AMPK-alpha, and phosphorylation of Ser(79) on acetyl-CoA carboxylase, an AMPK target. In hearts treated with phenformin for 18 min and then perfused for 20 min with Krebs-Henseleit buffer, [AMP] began to increase at 26 min and AMPK activity was elevated at 36 min. In hearts treated with metformin, [AMP] was increased at 50 min and AMPK activity, phosphorylated AMPK, and phosphorylated acetyl-CoA carboxylase were elevated at 61 min. In metformin-treated hearts, HPLC-measured total AMP content and total AMP/ATP did not increase. In summary, phenformin and metformin increase AMPK activity and phosphorylation in the isolated heart. The increase in AMPK activity was always preceded by and correlated with increased cytosolic [AMP]. Total AMP content and total AMP/ATP did not change. Cytosolic [AMP] reported metabolically active AMP, which triggered increased AMPK activity, but measures of total AMP did not.

Effects of nifedipine on anorectal smooth muscle in vitro.

PubMed

Cook, T A; Brading, A F; Mortensen, N J

1999-06-01

Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas.

PubMed

Casar-Borota, Olivera; Øystese, Kristin Astrid Berland; Sundström, Magnus; Melchior, Linea; Popovic, Vera

2016-08-01

Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas. We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses. In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses. IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.

National Assessment of Oil and Gas Project: Petroleum Systems and Geologic Assessment of Undiscovered Oil and Gas, Hanna, Laramie, and Shirley Basins Province, Wyoming

USGS Publications Warehouse

U.S. Geological Survey Hanna, Laramie

2007-01-01

INTRODUCTION The purpose of the U.S. Geological Survey?s (USGS) National Oil and Gas Assessment is to develop geologically based hypotheses regarding the potential for additions to oil and gas reserves in priority areas of the United States. The U.S. Geological Survey (USGS) recently completed an assessment of the undiscovered oil and gas potential of the Hanna, Laramie, and Shirley Basins Province in Wyoming and northeastern Colorado. The assessment is based on the geologic elements of each total petroleum system (TPS) defined in the province, including hydrocarbon source rocks (source-rock maturation, hydrocarbon generation, and migration), reservoir rocks (sequence stratigraphy and petrophysical properties), and hydrocarbon traps (trap formation and timing). Using this geologic framework, the USGS defined three TPSs and seven assessment units (AUs) within them; undiscovered resources for three of the seven AUs were quantitatively assessed.

Energiewende 4.0 - Chancen, Erfolgsfaktoren, Herausforderungen, Barrieren für Stadtwerke und Verteilnetzbetreiber

NASA Astrophysics Data System (ADS)

Rieger, Volker; Weber, Sven

Energiewende und Digitalisierung transformieren die Energiewirtschaft in noch nicht da gewesenem Maße. Durch den Wandel des linearen, vertikalen Geschäftsmodells in ein horizontales und vernetztes entstehen neue Geschäftsmodelle, in die vermehrt neue Anbieter aus anderen Branchen und Start-ups eintreten. Auf Basis langjähriger Beratungserfahrung erläutern die Autoren die zukünftige Geschäftslogik der Energiewelt 4.0. Anhand von Beispielen aus anderen Branchen zeigen sie dabei wesentliche Handlungsfelder speziell für regionale Energieunternehmen auf. Um in der neuen Energiewelt relevant zu bleiben, müssen Energieversorger ihre Kunden in den Fokus rücken, sich für Partnerschaften öffnen, in die Leistungsfähigkeit ihrer Infrastruktur investieren und v. a. einen Kulturwandel hin zu mehr Agilität und Offenheit vollführen.

Mikrodaten und statistische Auswertungsmethoden

NASA Astrophysics Data System (ADS)

Hujer, Reinhard

Mit der zunehmenden Verfügbarkeit immer größerer Querschnitts- und Längschnittsdatensätze für Personen, Haushalte und Betriebe sowie deren Verknüpfungen hat sich die mikroökonometrische Forschung in den vergangenen Jahren rasant weiterentwickelt. Dies gilt sowohl aus methodischer als auch aus empirischer, anwendungsorientierter Sicht. Mikrodaten und mikroökonometrische Ansätze dienen dazu, aktuelle, politikrelevante Fragen aufzugreifen, sie zu analysieren und fundierte politische Empfehlungen zu geben, beispielsweise im Rahmen der Arbeitsmarkt- und Sozialpolitik, der Finanzanalyse und der Marketingforschung. Die Deutsche Statistische Gesellschaft (DStatG) und deren Mitglieder haben sich in den Ausschüssen und in Hauptversammlungen kontinuierlich mit den Weiterentwicklungen der mikroökonometrischen Methodik und den empirischen Anwendungen befasst. Zahlreiche Publikationen von Mitgliedern der DStatG haben entscheidend zum kritischen Diskurs und zum wissenschaftlichen Fortschritt in diesem Bereich beigetragen.

Statistik in Naturwissenschaft und Technik

NASA Astrophysics Data System (ADS)

Wilrich, Peter-Theodor

Mit dem Aufschwung von Naturwissenschaft und Technik zu Beginn des 19. Jahrhunderts entstand die mathematische Statistik, angeregt aus der Geodäsie (wie die Methode der kleinsten Quadrate) und der Anthropologie (wie die statistische Analyse mehrdimensionaler Beobachtungen und ihrer stochastischen Abhängigkeiten). Im Gegensatz zu den Wirtschafts- und Sozialwissenschaften, in denen Daten vorwiegend aus Beobachtungsstudien gewonnen werden, stehen in den Naturwissenschaften Experimente im Vordergrund. Daher gehört die statistische Versuchsplanung zu den insbesondere in Naturwissenschaft und Technik angewendeten statistischen Methoden, aber auch die Extremwertstatistik und Lebensdaueranalysen sowie die Methoden der räumlichen Statistik (insbesondere in der Umweltforschung). Im 20. Jahrhundert wurden Stichprobenpläne und Regelkarten (Kontrollkarten) zur Prozessregelung als Hilfsmittel der statistischen Qualitätssicherung entwickelt. Diese Methodenbündel, mit denen sich der Ausschuss Statistik in Naturwissenschaft und Technik immer wieder befasst, werden im Folgenden vorgestellt.

Individuelle Templates für Rekonstruktionen des linken Herzventrikels

NASA Astrophysics Data System (ADS)

Feder, Stefan; Falk, Volkmar; Gutberiet, Matthias; Bartz, Dirk

Bei krankhaften Vergrößerungen des linken Herzventrikels kann eine chirurgische Ventrikelrekonstruktion zur Verbesserung der Herzleistung beitragen. Die dabei erstellte Ventrikelgeometrie ist von entscheidender Bedeutung. Diese Studie befasst sich mit der computerbasierten Planung von individuellen Schablonen (Templates) für Ventrikelrekonstruktionen. Ziel ist es aus Cardio-CT-Daten, präoperativ, patientenindividuelle 3D-Modelle für Ventrikeltemplates zu erstellen. Hierfür wird aus CT-Daten der linksventrikuläre Blutpool segmentiert und daraus das Ventrikeltemplate modelliert. Dies geschieht anhand von zwei Kriterien: dem physiologischen Ventrikelfüllungsvolumen und der hämodynamisch günstigen ellipsoiden Form. Es konnten 20 3D-Templatemodelle mit einem durchschnittlichen Volumen von 144 ml erstellt werden. Die ellipsoide Form konnte durch manuelle Modellierung erreicht werden. Der Nachweis verbesserter Operationsergebnisse muss in nachfolgenden klinischen Studien erbracht werden.

[COPD und Klangtherapie: Pilotstudie zur Wirksamkeit einer Behandlung mit Körpertambura bei COPD-Patienten].

PubMed

Hartwig, Bernhard; Schmidt, Stefan; Hartwig, Isabella

2016-01-01

Hintergrund: Erkrankungen der Atemorgane treten mit steigendem Alter öfter auf, nehmen weltweit zu und sind häufige Ursachen für Morbidität und Mortalität. In dieser Pilotstudie wurde der Frage nachgegangen, ob eine einmalige 10-minütige Behandlung mit einer Körpertambura eine signifikante und effektive Verbesserung der Lungenfunktion von Patienten mit chronisch-obstruktiver Lungenerkrankung (COPD; GOLD-Stadium A oder B) erbringen kann. Patienten und Methoden: 54 Probanden konnten je zur Hälfte in eine Behandlungsgruppe (Körpertambura) und eine aktive Kontrollgruppe (Atemtherapie) randomisiert werden. Eine Bestimmung der Lungenfunktionsmessparameter «Einsekundenkapazität» (FEV1) und «inspiratorische Vitalkapazität» (IVC) zu den Zeitpunkten T1 (Baseline), T2 (direkt nach Behandlung) und als Follow-up etwa 3 Wochen nach T1 (T3). Ergebnisse: Die Behandlungsgruppe zeigte sich der Kontrollgruppe in beiden Werten signifikant überlegen. Die Zeit-×-Gruppe-Interaktion (Varianzanalyse) ergab p = 0,001 (FEV1) bzw. p = 0,04 (IVC). Die Behandlungsgruppe zeigte bei beiden Werten eine Verbesserung von klinischer Relevanz. Schlussfolgerung: Diese Ergebnisse zeigen, dass die Klangbehandlung mittels einer Körpertambura - neben den schulmedizinischen, leitliniengerechten Therapien - eine zusätzliche, nebenwirkungsarme, aber durchaus klinisch wirksame Option für die Behandlung von COPD-Patienten darstellen kann, um deren Lebensqualität zu stabilisieren und zu verbessern. © 2016 S. Karger GmbH, Freiburg.

Preliminary investigation of the control of a gas-turbine engine for a helicopter / Richard P. Krebs

NASA Technical Reports Server (NTRS)

Krebs, Richard P

1951-01-01

An analog investigation of the power plant for a gas-turbine powered helicopter indicates that currently proposed turbine-propeller engine controls are satisfactory for helicopter application. Power increases from one-half to full rated at altitudes from sea level to 15,000 feet could be made in less than 4 seconds with either the rotor or propellers absorbing the engine power.

The History and Use of Our Earth's Chemical Elements: A Reference Guide (by Robert E. Krebs)

NASA Astrophysics Data System (ADS)

Bracken, Reviewed By Jeffrey D.

1999-04-01

Greenwood Press: Westport, CT, 1998. 282 pp + 25 pp glossary + 37 pp index. 15.9 x 24.1 cm. ISBN 0-313-30123-9. $39.95. This book is an excellent resource for chemical educators at the high school and college levels. The format of the text is consistent and the writing style is clear and concise, making it ideally suited for student use also. The first three chapters serve to introduce the reader to a brief history of chemistry, early models of the atom, and the development of the periodic table. Names of the contributing scientists are mentioned whenever necessary, but the overall purpose of these introductory chapters is simply to lay a foundation for the subsequent seven chapters. A complete glossary of important scientific terms mentioned in the text should allow beginning students to use this book without feeling overwhelmed. Each entry for the 112 elements contains the following information: elemental symbol, atomic number, period, common valence, atomic weight, natural state, common isotopes, properties, characteristics, abundance, natural sources, history, common uses and compounds, and safety hazards. This information is well organized, with clear headings and separate sections making the book extremely user-friendly. Readers can easily obtain the information they desire without having to skim the full entry for a chosen element. One very nice feature of this book is that the elements entries are arranged by their locations in the periodic table. For example, chapter 4 contains the alkali metals and alkaline earth metals. This organizational scheme allows one to quickly see the patterns and trends within groups of elements. This format is significantly better than arranging the elements in alphabetical order, which places the entry for sodium far removed from the entries for lithium and potassium. I would highly recommend this book to high school teachers and college chemistry professors. It is well written and is an excellent source of information for both students and educators.

Gas Metal Arc Welding Process Modeling and Prediction of Weld Microstructure in MIL A46100 Armor-Grade Martensitic Steel

DTIC Science & Technology

2013-06-01

acicular/Widmanstatten ferrite (a version of ferrite possessing an acicular/ lenticular - plate morphology which grows into the untransformed aus- tenite...boundary regions which have been transformed into allotriomorphic ferrite, as well as lenticular -shaped Widmanstatten plates advancing from the

Quantitative analysis of serotonin secreted by human embryonic stem cells-derived serotonergic neurons via pH-mediated online stacking-CE-ESI-MRM.

PubMed

Zhong, Xuefei; Hao, Ling; Lu, Jianfeng; Ye, Hui; Zhang, Su-Chun; Li, Lingjun

2016-04-01

A CE-ESI-MRM-based assay was developed for targeted analysis of serotonin released by human embryonic stem cells-derived serotonergic neurons in a chemically defined environment. A discontinuous electrolyte system was optimized for pH-mediated online stacking of serotonin. Combining with a liquid-liquid extraction procedure, LOD of serotonin in the Krebs'-Ringer's solution by CE-ESI-MS/MS on a 3D ion trap MS was0.15 ng/mL. The quantitative results confirmed the serotonergic identity of the in vitro developed neurons and the capacity of these neurons to release serotonin in response to stimulus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aconitase couples metabolic regulation to mitochondrial DNA maintenance.

PubMed

Chen, Xin Jie; Wang, Xiaowen; Kaufman, Brett A; Butow, Ronald A

2005-02-04

Mitochondrial DNA (mtDNA) is essential for cells to maintain respiratory competency and is inherited as a protein-DNA complex called the nucleoid. We have identified 22 mtDNA-associated proteins in yeast, among which is mitochondrial aconitase (Aco1p). We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. Regulation of ACO1 expression by the HAP and retrograde metabolic signaling pathways directly affects mtDNA maintenance. When constitutively expressed, Aco1p can replace the mtDNA packaging function of the high-mobility-group protein Abf2p. Thus, Aco1p may integrate metabolic signals and mtDNA maintenance.

Crystallization of Mitochondrial Respiratory Complex II from Chicken Heart: a Membrane Protein Complex Diffracting to 2.0 Å.

PubMed Central

Huang, Li-shar; Borders, Toni M.; Shen, John T.; Wang, Chung-Jen; Berry, Edward

2006-01-01

Synopsis A multi-subunit mitochondrial membrane protein complex involved in the Krebs Cycle and respiratory chain has been crystallized in a form suitable for near-atomic resolution structure determination. A procedure is presented for preparation of diffraction-quality crystals of a vertebrate mitochondrial respiratory Complex II. The crystals have the potential to diffract to at least 2.0 Å with optimization of post-crystal-growth treatment and cryoprotection. This should allow determination of the structure of this important and medically relevant membrane protein complex at near-atomic resolution and provide great detail of the mode of binding of substrates and inhibitors at the two substrate-binding sites. PMID:15805592

Micromethods for determining activities of energy-producing and non-energy-producing pathways in myocardial tissue.

PubMed Central

King, J. W.; Kennedy, F. S.; Hanley, H. G.; Lierl, J. J.; Fowler, M. R.; White, M. C.

1986-01-01

The increasingly frequent use of endomyocardial biopsies for diagnosis has provided the opportunity to study myocardial metabolism in patients with cardiac diseases. The authors have tested microassays of the hexose monophosphate shunt, glycolytic pathway, and Krebs cycle and demonstrated that they are easily and reproducibly performed on small pieces of cardiac tissue. They have also used these assays to study myocardial metabolism in 2 patients with endocarditis uncomplicated by congestive heart failure and in 2 patients with congestive heart failure due to idiopathic dilated cardiomyopathy. The ability to quantitate myocardial metabolism in biopsies from patients with a variety of cardiac diseases may enhance our understanding of cardiac pathophysiology. PMID:3706492

[Kombinierte Anwendung von Strahlentherapie und adjuvanter Therapie mit einem Mistelextrakt (Viscum album L.) zur Behandlung des oralen malignen Melanoms beim Hund: Eine retrospektive Studie].

PubMed

von Bodungen, Uta; Ruess, Katja; Reif, Marcus; Biegel, Ulrike

2017-01-01

Hintergrund: Orale maligne Melanome (OMM) des Hundes zeichnen sich durch schnelles Wachstum, lokale Invasion und hohe Metastasierungsraten aus. Extrakte auf Basis von Viscum album L. (VAE) werden zunehmend in der Krebstherapie sowohl in der Human- als auch in der Veterinärmedizin eingesetzt. Ziel unserer Studie war es zu untersuchen, inwieweit die adjuvante Therapie mit VAE eine therapeutische Option zur Behandlung von OMM ist. Besonderes Augenmerk galt dabei der Überlebenszeit und möglichen Nebenwirkungen. Tiere und Methoden: 26 Hunde mit OMM, die in einem der größten veterinäronkologischen Zentren der Schweiz allesamt eine Strahlentherapie erhielten (teilweise nach operativer Tumorresektion) wurden in die retrospektive Studie eingeschlossen: 18 Hunde wurden mit VAE behandelt (1 ml VAE (Iscador®) in ansteigenden Konzentrationen von 0,1 bis 20 mg/ml subkutan 3-mal pro Woche (VAE-Gruppe), 8 erhielten keine adjuvante Behandlung (Vergleichsgruppe). Wir verglichen die Größenentwicklung der OMM sowie die Überlebenszeit. Ergebnisse: Patienten mit Bestrahlung und adjuvanter VAE-Therapie zeigten mit 236 Tagen eine signifikant längere mediane Überlebenszeit im Vergleich zu Patienten mit Bestrahlung, aber ohne adjuvante VAE-Therapie (49 Tage; Log-Rank-Test: p = 0,0047). Die VAE-Therapie verlängerte die Überlebenszeit um mehr als zwei Drittel (Hazard Ratio (HR) = 0,30, 95%-Konfidenzintervall (KI) 0,11-0,86; p = 0,024), während ein höheres Tumorstadium gemäß UICC (Union internationale contre le cancer) einen statistischen Trend zur Verdopplung des Sterberisikos zeigte (UICC-Stadium III/IV vs. I/II: HR = 2,12, 95%-KI 0,88-5,12; p = 0,095). Zwei Patienten zeigten milde Nebenwirkungen während der VAE-Behandlung. Einer der beiden zeigte 1 Tag lang ein selbstlimitiertes Fieber, bei dem anderen Patienten reduzierten wir die Dosis von einem konzentrierteren zu einem weniger konzentrierten VAE (Serie 0) aufgrund von Müdigkeit, die daraufhin verschwand

Male synthetic sling versus artificial urinary sphincter trial for men with urodynamic stress incontinence after prostate surgery (MASTER): study protocol for a randomised controlled trial.

PubMed

Constable, Lynda; Cotterill, Nikki; Cooper, David; Glazener, Cathryn; Drake, Marcus J; Forrest, Mark; Harding, Chris; Kilonzo, Mary; MacLennan, Graeme; McCormack, Kirsty; McDonald, Alison; Mundy, Anthony; Norrie, John; Pickard, Robert; Ramsay, Craig; Smith, Rebecca; Wileman, Samantha; Abrams, Paul

2018-02-21

Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to

Three Plate Reconstruction in the Eastern Indian Ocean: New Constraints on Wharton and Australian-Antarctic basins

NASA Astrophysics Data System (ADS)

Jacob, J.; Dyment, J.

2012-12-01

Understanding the continuous seismicity and repeated occurrence of major earthquakes in Sumatra and the neighboring area requires detailed constrains on the subducting plate. In this study we analyze the past plate kinematics evolution of the Wharton basin, eastern Indian Ocean through a three plate reconstruction involving Australia (AUS), Antarctica (ANT), and India (IND). We compile marine magnetic identifications in the Australian-Antarctic Basin [1,2], the Crozet and Central Indian basins (Yatheesh et al, in prep.) and the Wharton Basin [3]. The Wharton Basin is characterized by an extinct spreading center dated by anomaly 18 (38 Ma). The southern flank of the basin exhibits a continuous sequence of anomalies 20n (42 Ma) to 34n (84 Ma), whereas the northern flank lacks some of the older anomalies because a significant part has been subducted in the Sunda Trench. The three-plate reconstructions have provided set of rotation parameters describing the evolution of IND-AUS. Using these parameters, we have reconstructed the missing isochrons of the northern flank and the detailed geometry of the subducted part of the Wharton basin. Such an exercise provides useful constraints on the age and structure of the plate in subduction under Indonesia. As a byproduct, the three plate reconstruction provided set of rotation parameters for AUS-ANT as well, which constrains the conjugate fit between the basins. Previous studies [1,2,4,5] have achieved such a fit on the base of ill-defined fracture zones. We consider the well-defined fracture zones from the Crozet, Central Indian, and Wharton basins, but avoid using the poor fracture zone imprints from the Australian-Antarctic Basin. As a result from this approach, we conclude that the relative motion of AUS with respect to ANT initially followed a north-south direction, then changed to northwest-southeast at anomaly 32ny, and reverted to northeast southwest at anomaly 24no prior to the establishment of the Southeast Indian

Fine needle aspiration of thyroid nodules in the pediatric population: a 12-year cyto-histological correlation experience at North Shore-Long Island Jewish Health System.

PubMed

Lale, Seema A; Morgenstern, Nora N; Chiara, Sugrue; Wasserman, Patricia

2015-08-01

Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature. 13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology-surgical follow-up. Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U-category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy-four children had surgical follow-up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category. To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to "follow-up and repeat" may not apply to the pediatric population

Population structure of the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae) assessed on a global scale using Amplified Fragment Length Polymorphism

USDA-ARS?s Scientific Manuscript database

The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), is a major pest of livestock in the United States and worldwide. To assess the genetic variability in geographically distant stable flies, samples were obtained from four biogeographical regions: Nearctic, Neotropical, Palearctic, and Aus...

Unlocking the variation hidden in rice germplasm collections with genomics

USDA-ARS?s Scientific Manuscript database

Cultivated Asian rice (Oryza sativa) was domesticated from O. rufipogon (O. nivara). The O. sativa subspecies indica and japonica diverged in ancient times, and based on DNA markers, further subdivided into the five major subpopulations, aus, indica, aromatic, tropical japonica and temperate japoni...

Informal Institutions and the Weaknesses of Human Behavior

DTIC Science & Technology

2005-01-01

der Wirtschafispolitik 2, 2001, S.185-210. * Haucap, Justus, Uwe Pauly & Christian Wey, Collective Wage Setting When Wages Are Generally Binding: An...in an Overlapping Generations Model, Nr. 8/1999. " Henning, Andreas & Wolfgang Greiner, Organknappheit im Transplantationswesen - L6sungs- ansditze aus

Joint Patch and Multi-label Learning for Facial Action Unit Detection

PubMed Central

Zhao, Kaili; Chu, Wen-Sheng; De la Torre, Fernando; Cohn, Jeffrey F.; Zhang, Honggang

2016-01-01

The face is one of the most powerful channel of nonverbal communication. The most commonly used taxonomy to describe facial behaviour is the Facial Action Coding System (FACS). FACS segments the visible effects of facial muscle activation into 30+ action units (AUs). AUs, which may occur alone and in thousands of combinations, can describe nearly all-possible facial expressions. Most existing methods for automatic AU detection treat the problem using one-vs-all classifiers and fail to exploit dependencies among AU and facial features. We introduce joint-patch and multi-label learning (JPML) to address these issues. JPML leverages group sparsity by selecting a sparse subset of facial patches while learning a multi-label classifier. In four of five comparisons on three diverse datasets, CK+, GFT, and BP4D, JPML produced the highest average F1 scores in comparison with state-of-the art. PMID:27382243

Virtue Quadratic Male Sling for stress incontinence—surgical guide for placement and delayed revision

PubMed Central

Rubin, Rachel S.; Xavier, Keith R.

2017-01-01

The algorithm for surgical management of post prostatectomy incontinence classically includes male slings and artificial urinary sphincter (AUS) placement. The Virtue Quadratic Male Sling was designed to provide both urethral elevation and prepubic compression making it a viable option for a wider spectrum of incontinent men whose symptoms range from mild to severe. With a focus on two key steps of the surgery, (I) sling fixation (II) use of intraoperative retrograde leak point pressure (RLPP), this guide is intended to outline a safe and efficacious treatment for post-prostatectomy incontinence. Intriguingly, the sling can be revised in the event of refractory or worsening leakage, and does not preclude the placement of an AUS should it be needed. This paper describes a step by step approach to performing the procedure as well as expert tips to improve outcomes and avoid/manage complications that have been learned over the years. PMID:28904899

Aurone synthase is a catechol oxidase with hydroxylase activity and provides insights into the mechanism of plant polyphenol oxidases

PubMed Central

Molitor, Christian; Mauracher, Stephan Gerhard

2016-01-01

Tyrosinases and catechol oxidases belong to the family of polyphenol oxidases (PPOs). Tyrosinases catalyze the o-hydroxylation and oxidation of phenolic compounds, whereas catechol oxidases were so far defined to lack the hydroxylation activity and catalyze solely the oxidation of o-diphenolic compounds. Aurone synthase from Coreopsis grandiflora (AUS1) is a specialized plant PPO involved in the anabolic pathway of aurones. We present, to our knowledge, the first crystal structures of a latent plant PPO, its mature active and inactive form, caused by a sulfation of a copper binding histidine. Analysis of the latent proenzyme’s interface between the shielding C-terminal domain and the main core provides insights into its activation mechanisms. As AUS1 did not accept common tyrosinase substrates (tyrosine and tyramine), the enzyme is classified as a catechol oxidase. However, AUS1 showed hydroxylase activity toward its natural substrate (isoliquiritigenin), revealing that the hydroxylase activity is not correlated with the acceptance of common tyrosinase substrates. Therefore, we propose that the hydroxylase reaction is a general functionality of PPOs. Molecular dynamics simulations of docked substrate–enzyme complexes were performed, and a key residue was identified that influences the plant PPO’s acceptance or rejection of tyramine. Based on the evidenced hydroxylase activity and the interactions of specific residues with the substrates during the molecular dynamics simulations, a novel catalytic reaction mechanism for plant PPOs is proposed. The presented results strongly suggest that the physiological role of plant catechol oxidases were previously underestimated, as they might hydroxylate their—so far unknown—natural substrates in vivo. PMID:26976571

Pocket ultrasound device as a complement to physical examination for ascites evaluation and guided paracentesis.

PubMed

Keil-Ríos, Daniel; Terrazas-Solís, Hiram; González-Garay, Alejandro; Sánchez-Ávila, Juan Francisco; García-Juárez, Ignacio

2016-04-01

The pocket ultrasound device (PUD) is a new tool that may be of use in the early detection of ascites. Abdominal ultrasound-guided paracentesis has been reported to decrease the rate of complications due to the procedure, but must be performed in a healthcare setting; this new tool may be a useful on an ambulatory basis. The aim of this study was to determine the diagnostic usefulness of the PUD in the diagnosis of ascites and the safety of guided paracentesis. We conducted a retrospective study that included adult patients suspected of having ascites and in whom an evaluation was performed with the PUD to identify it. Concordance with abdominal ultrasound (AUS) was determined with the Kappa coefficient. Sensitivity (Se), specificity (Sp) and likelihood ratios (LR) were determined and compared with physical examination, AUS, computed tomography and procurement of fluid by paracentesis. Complications resulting from the guided paracentesis were analyzed. 89 participants were included and 40 underwent a paracentesis. The PUD for ascites detection had 95.8 % Se, 81.8 % Sp, 5.27 +LR and 0.05 -LR. It had a concordance with AUS of 0.781 (p < 0.001). Technical problems during the guided paracentesis were present in only two participants (5 %) and three patients (7.5 %) developed minor complications that required no further intervention. There were no severe complications or deaths. This study suggests that the PUD is a reliable tool for ascites detection as a complement to physical examination and appears to be a safe method to perform guided paracentesis.

Complications and Short-Term Explantation Rate Following Artificial Urinary Sphincter Implantation: Results from a Large Middle European Multi-Institutional Case Series.

PubMed

Kretschmer, Alexander; Hüsch, Tanja; Thomsen, Frauke; Kronlachner, Dominik; Obaje, Alice; Anding, Ralf; Pottek, Tobias; Rose, Achim; Olianas, Roberto; Friedl, Alexander; Hübner, Wilhelm; Homberg, Roland; Pfitzenmaier, Jesco; Grein, Ulrich; Queissert, Fabian; Naumann, Carsten Maik; Schweiger, Josef; Wotzka, Carola; Nyarangi-Dix, Joanne N; Hofmann, Torben; Seiler, Roland; Haferkamp, Axel; Bauer, Ricarda M

2016-01-01

Background/Aims/Objectives: To analyze perioperative complication and short-term explantation rates after perineal or penoscrotal single-cuff and double-cuff artificial urinary sphincter (AUS) implantation in a large middle European multi-institutional patient cohort. 467 male patients with stress urinary incontinence underwent implantation of a perineal single-cuff (n = 152), penoscrotal single-cuff (n = 99), or perineal double-cuff (n = 216) AUS between 2010 and 2012. Postoperative complications and 6-month explantation rates were assessed. For statistical analysis, Fisher's exact test and Kruskal-Wallis rank sum test, and a multiple logistic regression model were used (p < 0.05). Compared to perineal single-cuff AUS, penoscrotal single-cuff implantation led to significantly increased short-term explantation rates (8.6% (perineal) vs. 19.2% (penoscrotal), p = 0.019). The postoperative infection rate was significantly higher after double-cuff compared to single-cuff implantation (6.0% (single-cuff) vs. 13.9% (double-cuff), p = 0.019). The short-term explantation rate after primary double-cuff placement was 6.5% (p = 0.543 vs. perineal single-cuff). In multivariate analysis, the penoscrotal approach (p = 0.004), intraoperative complications (p = 0.005), postoperative bleeding (p = 0.011), and perioperative infection (p < 0.001) were independent risk factors for short-term explantation. Providing data from a large contemporary multi-institutional patient cohort from high-volume and low-volume institutions, our results reflect the current standard of care in middle Europe. We indicate that the penoscrotal approach is an independent risk factor for increased short-term explantation rates. © 2016 S. Karger AG, Basel.

Continuing Professional Development via Social Media or Conference Attendance: A Cost Analysis

PubMed Central

Tunnecliff, Jacqueline; Morgan, Prue; Gaida, James; Keating, Jennifer; Clearihan, Lyn; Sadasivan, Sivalal; Ganesh, Shankar; Mohanty, Patitapaban; Weiner, John; Rivers, George; Ilic, Dragan

2017-01-01

Background Professional development is essential in the health disciplines. Knowing the cost and value of educational approaches informs decisions and choices about learning and teaching practices. Objective The primary aim of this study was to conduct a cost analysis of participation in continuing professional development via social media compared with live conference attendance. Methods Clinicians interested in musculoskeletal care were invited to participate in the study activities. Quantitative data were obtained from an anonymous electronic questionnaire. Results Of the 272 individuals invited to contribute data to this study, 150 clinicians predominantly from Australia, United States, United Kingdom, India, and Malaysia completed the outcome measures. Half of the respondents (78/150, 52.0%) believed that they would learn more with the live conference format. The median perceived participation costs for the live conference format was Aus $1596 (interquartile range, IQR 172.50-2852.00). The perceived cost of participation for equivalent content delivered via social media was Aus $15 (IQR 0.00-58.50). The majority of the clinicians (114/146, 78.1%, missing data n=4) indicated that they would pay for a subscription-based service, delivered by social media, to the median value of Aus $59.50. Conclusions Social media platforms are evolving into an acceptable and financially sustainable medium for the continued professional development of health professionals. When factoring in the reduced costs of participation and the reduced loss of employable hours from the perspective of the health service, professional development via social media has unique strengths that challenge the traditional live conference delivery format. PMID:28360023

Halorubrum chaoviator sp. nov., a haloarchaeon isolated from sea salt in Baja California, Mexico, Western Australia and Naxos, Greece

PubMed Central

Mancinelli, Rocco L.; Landheim, Ragnhild; Sanchez-Porro, Cristina; Dornmayr-Pfaffenhuemer, Marion; Gruber, Claudia; Legat, Andrea; Ventosa, Antonio; Radax, Christian; Ihara, Kunio; White, Melisa R.; Stan-Lotter, Helga

2011-01-01

Three halophilic isolates, strains Halo-G*T, AUS-1 and Naxos II, were compared. Halo-G* was isolated from an evaporitic salt crystal from Baja California, Mexico, whereas AUS-1 and Naxos II were isolated from salt pools in Western Australia and the Greek island of Naxos, respectively. Halo-G*T had been exposed previously to conditions of outer space and survived 2 weeks on the Biopan facility. Chemotaxonomic and molecular comparisons suggested high similarity between the three strains. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the strains clustered with Halorubrum species, showing sequence similarities of 99.2–97.1 %. The DNA–DNA hybridization values of strain Halo-G*T and strains AUS-1 and Naxos II are 73 and 75 %, respectively, indicating that they constitute a single species. The DNA relatedness between strain Halo-G*T and the type strains of 13 closely related species of the genus Halorubrum ranged from 39 to 2 %, suggesting that the three isolates constitute a different genospecies. The G+C content of the DNA of the three strains was 65.5–66.5 mol%. All three strains contained C20C20 derivatives of diethers of phosphatidylglycerol, phosphatidylglyceromethylphosphate and phosphatidylglycerolsulfate, together with a sulfated glycolipid. On the basis of these results, a novel species that includes the three strains is proposed, with the name Halorubrum chaoviator sp. nov. The type strain is strain Halo-G*T (=DSM 19316T =NCIMB 14426T =ATCC BAA-1602T). PMID:19567575