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The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor ...

UK PubMed Central (United Kingdom)

IntroductionChest pain with ST-segment elevation is a rare clinical problem during dobutamine stress testing. Although beta-agonists treatment prior to dobutamine stress testing...Full Text Available

International Nuclear Information System (INIS)

Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. ["1"1C]CUMI-101, proposed as the first 5-HT_1_A receptor agonist PET ligand, has been reported to behave as a potent 5-HT_1_A agonist in a cellular system stably expressing human recombinant 5-HT_1_A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: ["3"5S]-GTP#gamma#S binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT_1_A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant ...

UK PubMed Central (United Kingdom)

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available

UK PubMed Central (United Kingdom)

In laboratory studies, hamsters (Mesocricetus spp.) exhibit intense male-male aggression, thus making them an excellent model system for studies of the functional and mechanistic...Full Text Available

UK PubMed Central (United Kingdom)

The main function of white adipose tissue is to store nutrient energy in the form of triglycerides. The mechanism by which free fatty acids (FFA) move into and out of the adipocyte has not been resolved....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCompared to outbred Sprague Dawley (SD) rats, inbred Brown Norway (BN) rats exhibit less prepulse inhibition of startle (PPI) at long prepulse intervals,...Full Text Available

Science.gov (United States)

... Page 66 List of Figures Figure II.A.1 Simple Fuel Cell Model Page 8 ... Carbon Electrodes Figure II.A.1 Simple Fuel Cell Model Page 11. 9 ...

UK PubMed Central (United Kingdom)

BackgroundType A1 Clostridium botulinum strains are a group of Gram-positive, spore-forming anaerobic bacteria that produce a genetically, biochemically, and biophysically...Full Text Available

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The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate binding sites respectively to be compared with a 62% and a 85% decrease expected from calculated q-values. K/sub A/-values ...

Science.gov (United States)

Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity for the three serotonin receptors. ...

British Library Electronic Table of Contents (United Kingdom)

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the ?-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antag...

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In rat adipocyte membranes, both beta-adrenergic agonists and beta-adrenergic antagonists competed with (--)(/sup 3/H)dihydroalprenolol for high affinity (KD 2-4 nM) and low capacity binding sites. The antagonists but not the agonists competed with (--)(/sup 3/H)dihydroalprenolol for lower affinity and higher capacity sites. The present studies were performed in order to characterize the adipocyte beta-adrenergic receptor and distinguish it from low affinity, higher capacity sites which were heat-labile and not stereoselective. When isoproterenol was used to define the nonspecific binding, saturation studies showed a single binding site with a capacity of approximately 100 fmol/mg membrane protein (corresponding to approximately 50,000 sites/adipocyte). Binding was saturated by 10 nM (--)(/sup 3/H)dihydroalprenolol. Approximate KD's of 204 nM were observed. Kinetic analysis of (--)(/sup 3/H)dihydroalprenolol binding provided an ...

UK PubMed Central (United Kingdom)

AimsRosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-γ (PPARγ) and -α (PPARα),...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X₃ and P2X_2/3 receptor agonist α,β-methyleneATP...Full Text Available

UK PubMed Central (United Kingdom)

The substantia nigra pars reticulata (SNR) controls seizures in a sex-specific manner. At postnatal day 15 (P15), SNR infusion of GABA_A receptor agonist muscimol have proconvulsant...Full Text Available

International Nuclear Information System (INIS)

Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than in the cerebellum. Both glycine antagonists and agonists ...

UK PubMed Central (United Kingdom)

TRPM7 is an unusual bifunctional protein consisting of an α-kinase...Full Text Available

UK PubMed Central (United Kingdom)

Sphingomonas paucimobilis B90A contains two variants, LinA1 and LinA2, of a dehydrochlorinase that catalyzes the first and second steps in the metabolism of hexachlorocyclohexanes (R....Full Text Available

Science.gov (United States)

Plerocercoids of the tapeworm Spirometra mansonoides produce a substance that stimulates growth of experimental hosts. We report purification of plerocercoid growth factor (PGF) to homogeneity by a process involving isolation and solubilization of plerocercoid membranes, isoelectric point selection by chromatofocusing chromatography or preparative isoelectric focusing, and anion-exchange chromatography. A radioreceptor assay (RRA) for human growth hormone (hGH) was used to detect PGF and purity of the 27.5-kDa protein was judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Proteolytic activity was detected in the 27.5-kDa protein by gelatin substrate PAGE. Characterization of PGF as a neutral cysteine proteinase was based on substrate and inhibitor specificities and dependence on pH and thiol-containing reagents. The association of hGH agonist and proteinase activities was shown by comparing RRA and hydrolytic activities in the presence ...

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Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral ...

Science.gov (United States)

ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850

British Library Electronic Table of Contents (United Kingdom)

The environmental impact caused by local people (ecological footprint of consumption, EFc) and the actual environmental impact that the ecosystem burdens (ecological footprint of production, EFp) in West Jilin Province, Northeast China from 1986 to 2006 were evaluated by using ecological footprint (EF) method. And the major driving forces of EFc and EFp were analyzed by STIRPAT model. Both EFc and EFp showed increasing trends in 1986?2006, accompanied by decreasing ecological deficits but expanding ecological overshoots. Population (P), GDP per capita (A 1), quadratic term of GDP per capita (A 2), urbanization (T a1), and quadratic term of urbanization (T a2) were important influencing factors of EFc, among which T a2 and T a1 were the most dominate driving forces of EFc. A 1, A 2 and T a2...

UK PubMed Central (United Kingdom)

BACKGROUND: Epidermolysis bullosa (EB) is a group of heritable diseases that manifest as blistering and erosions of the skin and mucous membranes. In the dystrophic forms of EB (DEB), the diagnostic...Full Text Available

UK PubMed Central (United Kingdom)

Three homeologous genes encoding a sucrose (Suc) transporter (SUT) in hexaploid wheat (Triticum aestivum), TaSUT1A, 1B, and 1D, were...Full Text Available

UK PubMed Central (United Kingdom)

To gain insight into ATP-binding cassette transporter A1 (ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1...Full Text Available

Science.gov (United States)

To calibrate channels A1 to A4 for particles with Z >= 1, tests were done on the IBIS accelerator at AERE, Harwell, which gave protons up to 3 MeV. ...

Science.gov (United States)

...2010-04-01 false Sodium pentobarbital injection. 522.1704 Section...DRUGS § 522.1704 Sodium pentobarbital injection. (a)(1) Specifications. Sodium pentobarbital injection is sterile and...

International Nuclear Information System (INIS)

A method based on path integral formulation is given for obtaining exact solution of the s states for the Bargmann potentialV(r)=1ka"2#beta#(#beta#-1)e"-"2"r"/"a1-e"-"r"/"a"2-Ae"-"r"/"a1-e"-"r"/"a,where #beta# and k are parameters. The exact energy spectrum and the normalised s-state eigenfunctions are obtained from the poles of the Green function and their residues, respectively. The results are compared with their of Schrodinger formalism, special cases are also discussed.

British Library Electronic Table of Contents (United Kingdom)

Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...

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Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, ...

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During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB, like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of evaluation of quaternized mAChR ligands in the ...

International Nuclear Information System (INIS)

Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, ...

British Library Electronic Table of Contents (United Kingdom)

Mono- and disubstituted novel derivatives of the heptaene nystatin analog 28,29-didehydronystatin A1 (S44HP, 1) were obtained by chemical modification of the exocyclic C-16 carboxyl and/or an amino group of mycosamine moiety. The strategy of preparation of mono- and double-modified polyene macrolides was based on the use of intermediate hydrophobic N-Fmoc (9-fluorenylmethoxycarbonyl) derivatives that facilitated the procedures of isolation and purification of new compounds. The antifungal activity of the new derivatives was first tested in vitro against yeasts and filamentous fungi, allowing the selection of the most active compounds that were subsequently tested for acute toxicity in mice. 2-(N,N-dimethylamino)ethylamide of 1 (2) and 2-(N,N-dimethylamino)ethylamide of N-fructopyranosyl-28...

International Nuclear Information System (INIS)

By using the quark-parton-flucton and Weinberg-Salam models, effects of interactions of weak neutral quark and neutrino currents were considered in deep - inelastic neutrino (anti)-nucleus scattering #nu# (anti-#nu#) A #-># #nu# (anti-#nu#) #gamma#X. The energy spectrum and degree of photon circular polarization were obtained in present paper. In particular for the nucleon (A = 1). The theoretical results were in a good agreement with data mentioned. (author). 6 refs., 4 figs.

UK PubMed Central (United Kingdom)

PurposeOptic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular...Full Text Available

UK PubMed Central (United Kingdom)

Outbred Wistar rats were immunised with a single intraperitoneal injection of a mixture of 30 mg of A1(OH)3 and 100microng of gonococcal zeolite antigen (ZA). Ten days after immunisation, ZA prepared...Full Text Available

UK PubMed Central (United Kingdom)

Several closely related Mn(II)-oxidizing alpha-Proteobacteria were isolated from very different marine environments: strain SI85-9A1 from the oxic/anoxic interface of a stratified...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps {>=}10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1 - x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA + ...

DEFF Research Database (Denmark)

The temporal development of the effect of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) on the ultrastructure composition and GABA receptor expression in cerebellar granule cells was investigated by quantitative electron microscopy (morphometric analysis) and GABA binding assays. It was found that the cytoplasmic density of smooth endoplasmic reticulum was decreased, while the cytoplasmic density of rough endoplasmic reticulum, Golgi apparatus, vesicles and coated vesicles was greatly enhanced after exposure of the cells to THIP (150 microM) for only 1 hr. In cerebellar granule cells exposed to THIP (150 microM) for 3 hr low affinity GABA receptors were induced. These findings show that the effect of THIP on the ultrastructure composition and GABA receptor expression in cultured cerebellar granule cells may be interrelated and moreover it is likely that the turn-over of GABA receptors is extremely fast.

International Nuclear Information System (INIS)

Targeted studies completed include the evaluation of tritiated N-0437, evaluation of "3"5S-cysteamine, evaluation of "1"8F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic receptor analogs for heart, brain and (possible) ...

British Library Electronic Table of Contents (United Kingdom)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

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The CYP1A (EROD)-inducing potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3minutes or feet,4,4minutes or feet,5-pentachlorobiphenyl (PCB126) and benzo(k)fluoranthene (B(k)F) were studied in avian embryo livers. TCDD and PCB126 proved to be much more potent as inducers in the chicken than in the other species examined. This finding is consistent with a considerably higher sensitivity of the chicken compared with a number of other avian species to the embryotoxic effects of these compounds. Furthermore, the relative potencies of the tested Ah receptor agonists as CYP1A inducers differed substantially between species. B(k)F and PCB126 showed similar induction potencies in domestic duck embryos, whereas PCB126 is much more potent than B(k)F in the chicken. Also, the potency of PCB126,relative to that of TCDD, was much lower in quail embryo liver in vitro than in chicken embryo liver. Thus, there are large interspecific differences in birds in the sensitivity ...

Science.gov (United States)

Unfamiliar male meadow voles induce pregnancy disruptions when they are in physical contact with females, but the presence of the female's original mate partially protects her from the blocking effects of an unfamiliar male. This research examines how behavioral interactions affect pregnancy disruptions by testing two hypotheses: a) original males protect females by reducing the aggressive interactions between females and strange males; and b) administration of clonidine, an alpha 2-adrenergic receptor agonist that decreases activity, aggression, and sexual motivation, will decrease the pregnancy-blocking ability of strange males. Strange males were more aggressive when the original sire was absent, indicating that this change in behavior may be related to their greater success in disrupting pregnancy. When injected with clonidine, males were less likely to block pregnancy, and they showed less contact and mating behavior than when they received saline injections. ...

British Library Electronic Table of Contents (United Kingdom)

PurposeWe investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial. Materials and MethodsPatients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.5 mg to degarelix 240/80 mg (69) or 240/160 mg (65). Data are shown on the approved degarelix 240/80 mg dose. The primary end point was safety/tolerability and the secondary end points were testosterone, prostate specific antigen, luteinizing hormone and follicle-stimulating hormone responses, and prostate specific antigen failure and progression-free survival....

British Library Electronic Table of Contents (United Kingdom)

We examined whether or not BMD or bone markers were useful for assessing the risk of vertebral fractures in 248 Japanese men with type 2 diabetes. We analyzed the relationships between bone markers (osteocalcin [OC], bone-specific alkaline phosphatase [BAP], urinary N-terminal cross-linked telopeptide of type-I collagen) or BMD and HbA1c, urinary C-peptide, insulin-like growth factor-I (IGF-I), parathyroid hormone, 1,25(OH)2 vitamin D, and the presence of prevalent vertebral fractures. Multiple regression analysis adjusted for age, body height, weight, duration of diabetes, and serum creatinine showed that serum OC and OC/BAP ratio were correlated negatively with HbA1c (P?P?P?

Science.gov (United States)

OBJECTIVE To identify patients with gestational diabetes mellitus (GDM) who will need antenatal insulin treatment (AIT) by using a risk-prediction tool based on maternal clinical and biochemical characteristics at diagnosis. RESEARCH DESIGN AND METHODS Data from 3,009 women attending the Royal Prince Alfred Hospital GDM Clinic, Australia, between 1995 and 2010 were studied. A risk engine was developed from significant factors identified for AIT using a logistic regression model. RESULTS A total of 51% of GDM patients required AIT. Ethnicity, gestation at diagnosis, HbA(1c), fasting and 60-min glucose oral glucose tolerance test, BMI, and diabetes family history were significant independent determinants of AIT. Notably, only 9% of the attributable risk for AIT can be explained by the clinical factors studied. A modeled risk-scoring system was therefore a poor predictor of AIT. CONCLUSIONS Baseline maternal characteristics including ...

Science.gov (United States)

Evaluation of ageable beta alloys Ti-17V-2Fe-2Co-3Al, Ti-17V-7.5Co-3A1 and Ti-8Mo-8V-5Co-3Al continued with room and elevated temperature smooth and notched tensile tests, creep stability, oxidation and stress-corrosion tests. Ti-17V-7.5Co-3Al aged more r...

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Noninvasive and simplified methods for estimating regional cerebral blood flow (CBF) and regional partition coefficient ({lambda}) using the inhalation of stable xenon (Xe{sup s}) and computed tomographic (CT) scanning are described. Thirty percent Xe{sup s} in 70% oxygen was inhaled for 240 seconds and exhaled for 160 seconds during serial CT scanning without denitrogenation in 26 patients with cerebrovascular diseases and four volunteer controls. During the investigation, the end-tidal Xe{sup s} concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) of the artery by the curve fitting method. Calculated A and K values were corrected by the following formulae reported previously: for patients aged 0-20 years, A{sub e} = 0.75A{sub a} + 2.15, K{sub e} = 0.67K{sub a} + 0.69; 21-40 years, A{sub e} = 0.56A{sub a} + 3.24, K{sub e} = 0.38K{sub a} + ...

Science.gov (United States)

This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes. Study participants were randomly assigned to the treatment (26) and control (21) conditions. The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members. These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities.

Science.gov (United States)

Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 muM. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity relationships analysis demonstrated that hydroxyl groups at C1 or C4 but not C3 ...

International Nuclear Information System (INIS)

Full text: The maturation of chicken forebrain is protracted and occurs well after synapse formation providing a good model for studying mechanisms of brain maturation. Using microslices from immature (10 day) and adult chicken forebrain prepared after decapitation, we have examined functional properties of NMDA and AMPA receptors by measuring agonist-induced uptake of "4"5Ca"2"+ . The rate and extent of NMDA induced "4"5Ca"2"+ accumulation decreased during maturation with no change in EC_5_0. The rate and extent of the AMPA induced response also decreased with a 60-fold increase in EC_5_0. However, the total NMDA receptor content did not change as indicated by 3 H-MK801 binding and NR1 immunoreactivity in P2 fractions. Similarly, there was no change in the B_m_a_x of "3H-AMPA, though there was a two-fold increase in K_D, and little or no change in the immunoreactivity in GluR1, 2, 2/3 or 4. These results suggest that it is the regulation of receptors, their ...

International Nuclear Information System (INIS)

The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ["1"4C]AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ["1"4C]AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2#alpha#. Trace amounts of PGD2 and 6-keto-PGF1#alpha# but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10"-"7, 10"-"7M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10"-"6M) did not ...

International Nuclear Information System (INIS)

Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by ...

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Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. Heterologous ...

International Nuclear Information System (INIS)

An analysis of the total photoabsorption cross section for nuclei ranging from "4He up to "2"3"8U has been performed in the energy range 0.2-1.0 GeV. Mean total photoabsorption cross sections have been obtained by summing up the contributions from partial photoreactions, and found to follow an A"1-dependence in the 0.2-1.0 GeV range. A review of the available total photoabsorption cross section data is also presented. Comparisons have been made with cross section values calculated by considering both the quasi-deuteron and #pi#-meson photoproduction mechanism of primary nuclear photointeraction. (orig.).

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The elastic behaviour of YBaCuO specimens has been studied by very low-frequency isothermal internal-friction measurements. A relaxation peak is observed which is attributed to oxygen atom jumps, between A(1/2 0 0) and B(0 1/2 0) sites, in the CuO planes of the orthorhombic phase. A limit relaxation time {tau}{sub 0}, 2.6 {center dot} 10{sup -15}s, and an activation energy, 1.3eV, have been obtained from the shift of the maximum damping frequency observed when the measurement temperature is changed. The proposed values for the limit relaxation time and the activation energy are in good agreement with those previously proposed in the literature.

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Objective To evaluate the inhibitory property of de-glycyrrhizinated extract of Glycyrrhiza glabra root and its phytoconstituents (glabridin, isoliquiritigenin and glycyrrhizin) on LPS-induced production of pro-inflammatory mediators. Materials and methods Inhibitory effect of G. glabra extract and its phytoconstituents were studied on lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels in J774A.1 murine macrophages. Results G. glabra and isoliquiritigenin significantly inhibited LPS stimulated NO, IL-1 beta and IL-6 production. Glabridin showed significant inhibition of NO and IL-1 beta release, but failed to attenuate IL-6 levels at the tested concentrations. In addition, glycyrrhizin did not exhibit inhibitory response towar...

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Focussed ion beam (FIB) processing has been applied to the fabrication of novel InP-based cleaved coupled cavity (CCC) quantum cascade lasers (QCL). Gas assisted etching using XeF{sub 2} has been shown to significantly reduce the redeposition of sputtered material onto the mirror surfaces during final milling. For the unprocessed laser a broad spread of lasing peaks are observed between 9.72{mu}m to 9.78{mu}m at a current of 380mA (1kA/cm{sup -2}). After FIB processing, substantial side mode suppression is observed on applying a current of 20mA (100A/cm{sup -2}) to the short section and the main lasing peak is observed at 9.77{mu}m.

British Library Electronic Table of Contents (United Kingdom)

Abstract Background: Obstructive sleep apnea (OSA), a highly prevalent condition, is independently associated with increased risks of developing type 2 diabetes mellitus (T2D) and metabolic syndrome. It is unclear, however, if the severity of OSA has any impact on glycemic control among patients with T2D. We therefore aimed to determine the independent association between OSA severity and glycosylated hemoglobin (HbA1c) in patients with T2D. Methods: This was an observational cross-sectional study of 52 consecutive patients attending the diabetes obesity clinic between January 2008 to February 2010 with risk factors for sleep apnea and who underwent polysomnography study. Clinical, demographic, and lifestyle data were recorded using a questionnaire. Results: Prevalence of OSA in this clini...

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The preliminary design of a far-infrared free-electron laser with a Coaxial Hybrid Iron (CHI) wiggler is presented. The CHI wiggler consists of a central rod and outer ring of alternating ferrite and dielectric spacers. A periodic wiggler field is produced when the CHI structure is immersed in an axial magnetic field. The design under investigation makes use of 1A, 1MV annular electron beam interacting with the TE{sub 01} coaxial waveguide mode at approximately 1 THz ({lambda} = 300 {mu}m). The nominal wiggler period is 0.5 cm and the inner and outer waveguide radii are 0.4 and 0.8 cm, respectively. An axial guide field of 5-10 kG is used. The device performance is modeled with slow-time-scale nonlinear code. Self fields and axial velocity spread are included in the model. Theoretical results will be presented.

International Nuclear Information System (INIS)

Since the publication by the International Commission on Radiological Protection of revised recommendations which set out some general principles for intervention, some ideas have emerged which address interventions in the case of chronic exposure from contaminated lands. In the past there have been interventions proposed or carried out to rehabilitate land contaminated during the era of atmospheric nuclear weapon testing. Some of these interventions are reviewed in the context of these ideas and it is concluded that, by and large, reasonable outcomes have been achieved. The concept of a 'generic action level' (an effective dose of the order of 10 mSv#centre dot#a"-"1 to representative individuals in the critical group) may be useful in future to aid decision makers in determining whether intervention is appropriate. (author)

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Product-sum property states that an ordered pair (s"n,p"n) is unique for any ordered set a"1,a"2,...,a"n where a"i,n@?N, and s"n and p"n are the sum and product of the elements of the set, respectively. This fact has been exploited to develop an O(log(M)) time complexity algorithm for pattern searching in a large dataset, where M is the number of records in the dataset. Two potential applications (from databases and computational biology) of this property have been demonstrated to show the effectiveness and working of the proposed algorithm. The space complexity of the algorithm rises to the quadratic order.

Science.gov (United States)

AIMS: To clarify the levels of protein oxidation markers such as protein carbonyl (PCO), protein hydroperoxides (P-OOH), advanced oxidation protein products (AOPP) and nitrotyrosine (NT), as well as antioxidative enzymes such as paraoxonase (PON-1) in women with and without gestational diabetes mellitus (GDM). METHODS: The study was conducted on 23 women with GDM and 22 women without GDM. The levels of the P-OOH, AOPP, and PON-1 were determined by colorimetric methods; whereas NT and PCO levels were measured by ELISA. RESULTS: The concentrations of protein oxidation markers were significantly increased and PON1 activity was significantly decreased in GDM group compared to those of normal pregnant women. The control group showed a significant negative correlation between PON-1 and PCO (r=-0.451, p=0.027); whereas in GDM group, there was a significant positive correlation between P-OOH and HbA1c (r=0.89, p=0.001). There was no significant ...

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This fourteenth quarterly technical progress report of the MHD Integrated Topping Cycle Project presents the accomplishments during the period November 1, 1990 to January 31, 1991. Testing of the High Pressure Cooling Subsystem electrical isolator was completed. The PEEK material successfully passed the high temperature, high pressure duration tests (50 hours). The Combustion Subsystem drawings were CADAM released. The procurement process is in progress. An equipment specification and RFP were prepared for the new Low Pressure Cooling System (LPCS) and released for quotation. Work has been conducted on confirmation tests leading to final gas-side designs and studies to assist in channel fabrication.The final cathode gas-side design and the proposed gas-side designs of the anode and sidewall are presented. Anode confirmation tests and related analyses of anode wear mechanisms used in the selection of the proposed anode design are presented. Sidewall confirmation tests, which were used ...

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Due to the increasingly stricter regulations for deep reduction of fuel sulfur content, development of new deep desulfurization processes for liquid transport fuels has become one of the major challenges to the refining industry and to the production of hydrocarbon fuels for fuel cell applications. The sulfur compounds in the current transport fuels corresponding to the S level of 350-500 ppm account for only about 0.12-0.25 wt % of the fuel. The conventional hydrotreating approaches will need to increase catalyst bed volume at high-temperature and high-pressure conditions for treating 100 % of the whole fuel in order to convert the fuel mass of less than 0.25 wt %. In the present study, we are exploring a novel adsorption process for desulfurization at low temperatures, which can effectively reduce the sulfur content in gasoline, jet fuel and diesel fuel at low investment and operating cost to meet the needs for ultra-clean transportation fuels and for fuel cell applications. Some ...

International Nuclear Information System (INIS)

Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great demand for developing neuroimaging agents has emerged for the diagnosis of abnormal ...

International Nuclear Information System (INIS)

The augmentation of the heat transfer by inserting different type turbulators into the channels is the conventional passive enhancement method. The coiled wire is one of the common heat transfer enhancement devices. These turbulators generate almost-periodic vortices into the flow while increasing the heat transfer rate. In this study, the properties of these vortices (i.e. the vortex shedding frequency and amplitudes of the pressure fluctuations of the vortices), flow (vortex)-acoustic coupling and the relation between entropy generation and vortex characteristics were investigated experimentally. Strouhal-Re-N_s_,_a and P_r_m_s-Re-N_s_,_a variations were presented graphically. It was observed that as the pitch increases, the vortex shedding frequencies decrease and the maximum amplitudes of pressure fluctuation of vortices produced by coiled wire turbulators occur with small pitches. In addition, the effects of the turbulators on the heat transfer, friction factor and performance ...

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US Department of Energy (DOE) facilities are required to be in full compliance with all federal and state regulations. In response to this requirement, the Oak Ridge National Laboratory (ORNL) has established a Remedial Action Program (RAP) to provide comprehensive management of areas where past and current research, development, and waste management activities have resulted in residual contamination of facilities or the environment. This report presents the RCRA Facility Assessment (RFA) required to meet the requirements of RCRA Section 3004(u). Included in the RFA are (1) a listing of all sites identified at ORNL that could be considered sources of releases or potential releases; (2) background information on each of these sites, including location, type, size, period of operation, current operational status, and information on observed or potential releases (as required in Section II.A.1 of the RCRA permit); (3) analytical results obtained ...

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Our goal was a process to convert methane to higher hydrocarbons oxidatively, since this circumvents thermodynamic yield limits of a strictly degydrogenative process. Keller and Bhasin converted thermodynamic yield limits of a strictly dehydrogenative process. Keller and Bhasin converted methane to higher hydrocarbons by using metal oxides as oxidants, without co-fed oxygen. They stated that selectivity is necessarily poor if gaseous oxygen is present. Jones and Sofranko have also used reducible metal oxides as oxidants in a group of their parents, but later used some of those materials with continuous O{sub 2} feed without much loss of selectivity. Baerns, Lunsford and Otsuka have shown that high selectivity could be possible with co-fed O{sub 2} at least for low O{sub 2} partial pressures, over PbO-A1{sub 2}O{sub 3}, Li-MgO and rare earths. The performance of a group of multicomponent oxide catalysts, containing lead and magnesium oxides, for ...

International Nuclear Information System (INIS)

The energy E(c/a) for a bcc element stretched along its [001] axis (the Bain path) has a minimum at c/a=1, a maximum at c/a=#sq root#(2), and an elastically unstable local minimum at c/a>#sq root#(2). An alternative path connecting the bcc and fcc structures is the rhombohedral lattice. The primitive lattice has R3m symmetry, with the angle #alpha# changing from 109.4 deg. (bcc), to 90 deg. (simple cubic), to 60 deg. (fcc). We study this path for the non-magnetic bcc transition metals (V, Nb, Mo, Ta, and W) using both all-electron linearized augmented plane wave and projector augmented wave VASP codes. Except for Ta, the energy E(#alpha#) has a local maximum at #alpha#=60 deg., with local minima near 55 deg. and 70 deg., the latter having lower energy, suggesting the possibility of a metastable rhombohedral state for these materials. We first examine the elastic stability of the 70 deg. minimum structure, and determine that only W is ...

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Technologies producing high power negative ion beams have been highly developed in these years at JAERI for use in neutral beam injectors for heating the thermonuclear fusion plasmas. At present, it is possible to produce multi-ampere H-/D- ion beams quasi-continuously at energies more than a few hundred keV with a good beam optics of beamlet divergence of a few milli-radian. Based on these technologies, two R and D projects have been initiated; one is to develop a 22A/500keV/10s D- ion source for the neutral beam injector for JT-60U, and the other is to develop a 1A/1MeV/60s H- ion source to demonstrate high current negative ion acceleration up to the energy of 1MeV, the energy required for the neutral beam injector for International Thermonuclear Experimental Reactor (ITER). (author).

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Abstract Four new dimeric naphtho--pyrones, named rubasperone D (1), rubasperone E (2), rubasperone F (3), and its atropisomer rubasperone G (4), together with four known monomeric naphtho--pyrones, TMC 256 A1 (5), rubrofusarin B (6), fonsecin (7), and flavasperone (8), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D- and 2D-NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF-7, MDA-MB-435, Hep3B, Huh7, SNB19, and U87-MG with IC50 values between 19.92 and 47.98-M. Compounds 1, 6, and 8 also showed mild cytotoxic activity.

International Nuclear Information System (INIS)

The devised radionuclide analyzer for the determination of total sulfur in coal includes two radionuclide sources with different energies, which are accommodated in collimators fitted with adjustable diaphramgs. The sample compartment is located between the two sources. Moreover, an X-ray fluorescence standard can be slid into the sample compartment. A proportional detector for X-ray fluorescence and scattered gamma radiation is located off the sample compartment. The input of the proportional detector is interfaced to the output of a high-voltage supply, the output, to the information input of a control-and-evaluation unit. One of the control outputs of the control-and-evaluation unit is connected to the input of the sliding mechanism for the X-ray fluorescence standard. This arrangement enables automatic energy calibration of the analyzer. The analyzer can measure not only total sulfur in coal by radionuclide X-ray fluorescence analysis but also ash in coal by the method of ...

International Nuclear Information System (INIS)

The objectives of this research were to investigate the possibility of controlling the #alpha#'/#beta#' phase ratio and morphology in Sialon ceramics. These objectives have been sought by the control of the starting composition, and by post sintering heat treatment. The main emphasis has been on the production of a series of #alpha#' and (#alpha#'+#beta#') Sialon ceramics with a minimum amount of the glass phase by the pressureless sintering technique and using ytterbium (Yb) as an #alpha#' stabilising element. The Yb additions were made via the oxide or the alumino- silicate presynthesised glass; the latter was found to improve the density. The XRD analysis of the as sintered materials revealed #alpha#' to be the dominant phase with minor contributions from #beta#' sialon and/ or 12H A1N polytype. Additions of SiO_2 or #beta#-Si_3N_4 were made to various materials to assess potential mechanisms for obtaining control over the microstructural ...

International Nuclear Information System (INIS)

A multielement apparatus for the removal of aerosols formed in the vitrification of simulated high-activity accident wastes from the decommissioned nuclear power plant A-1 has been designed, manufactured and tested. The apparatus consists of two cooling and condensing steps connected in series, and of five filtration steps also connected in series. The five filtration steps allowed to achieve a decontamination factor of 1x10"5 in the case of removal of a NaCl("2"4Na) testing model aerosol. The decontamination factor for removal of the cesium aerosol by the whole apparatus was 3.3x10"6. In the first filtration step the aerosols are removed by the cartridge with a filtration fabric made of polyethylene fibers, in the second step by the cartridge with a granulated natural material, in the third step by the cartridge with glass-fiber filtration paper, in the fourth and fifth steps by the cartridge with high-efficiency filtration paper made of glass ...

Science.gov (United States)

Antiquitin (ATQ) deficiency is the main cause of pyridoxine dependent epilepsy characterized by early onset epileptic encephalopathy responsive to large dosages of pyridoxine. Despite seizure control most patients have intellectual disability. Folinic acid responsive seizures (FARS) are genetically identical to ATQ deficiency. ATQ functions as an aldehyde dehydrogenase (ALDH7A1) in the lysine degradation pathway. Its deficiency results in accumulation of ?-aminoadipic semialdehyde (AASA), piperideine-6-carboxylate (P6C) and pipecolic acid, which serve as diagnostic markers in urine, plasma, and CSF. To interrupt seizures a dose of 100mg of pyridoxine-HCl is given intravenously, or orally/enterally with 30mg/kg/day. First administration may result in respiratory arrest in responders, and thus treatment should be performed with support of respiratory management. To make sure that late and masked response is not missed, treatment with oral/enteral ...

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The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as potent submicromolar ...

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An x-ray diffraction approach has been developed for determination of the kinetics of growth of Pd/sub 2/Si layers. Epitaxial Pd/sub 2/Si films were grown on Si(111) substrates over a temperature range of 160-222/sup 0/C by a solid-state reaction between the substrates and the Pd overlayers. The parabolic rate equation was verified and rate constants showed Arrhenius behavior with an activation energy E/sub a/ = 1.06 eV and prefactor k/sub 0/ = 7 x 10/sup -4/ cm/sup 2//s. The low value of E/sub a/ suggests a short-circuit diffusion mechanism. It is reasonable to expect that impurities and microstructure may play important roles in the growth process. Impurity levels in the specimens were evaluated by analytic techniques suited to thin-film study: Rutherford backscattering spectrometry, secondary ion mass spectrometry, and Auger electron spectrometry. No impurities were present at concentrations approaching 1 at. %. Some O, C, and F were ...

International Nuclear Information System (INIS)

Half-Heusler phases XYZ (Pearson symbol cF12) are chemically versatile and rich in physical properties. The half-Heusler phase in the Fe-Zn-Sb ternary system was reported in the year 2000. In this work, two new ternary phases are identified in the vicinity of the equiatomic composition FeZnSb in the same system: Fe1-xZnSb (tetragonal, space group P4/nmm, Pearson symbol tP6-?, Z=2: a=4.1113(6) A, c=6.0127(12) A for x=0.08 (1), and a=4.1274(6) A, c=6.0068(12) A for x=0.12 (2)); and Fe7.87Zn6.72Sb8 (Fe0.98Zn0.84Sb) (3) (cubic, space group Fm-3m, Pearson symbol cF96-?, Z=4, a=11.690(13) A). 1 and 2 crystallize in the PbFCl-type structure, and 3 adopts a unique 2x2x2 supercell of a normal half-Heusler structure. The structures of both the tetragonal and cubic phases can be described as assemblies of half-Heusler structure related subunits. Electrical resistivity measurement on the pure sample of 2 shows it has metallic-like behavior, and its thermal ...

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Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes ...

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 ...

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Toxic studies were conducted with rats, mice, and guinea pigs to determine acute effects from single exposures to M60A1-tank-generated DF2 and DF1 (diesel fuel) smoke and/or exhaust clouds under static airflow conditions. Emissions were disseminated with the Vehicle Engine Exhaust Smoke System (VEESS) and exposure periods ranged from 15 to 300 minutes. At attempted airborne concentrations of 10.0 to 12.0 mg/i (10,000 cu.m to 12,000 cu.m) of the DF2 and DF1 smoke/exhaust mixtures and 0.2 mg/1 (200 mg/cu.m) of the exhausts, toxic signs (excluding death) and lung compliance changes were observed after 15-minute exposures. Death and pathological abnormalities of the lung were seen after 16-minute exposures to DF2 smoke and/or exhaust. Exposures to DF1 smoke/exhaust showed lung pathology and death by 120 minutes while death and turbinate lesions were observed in animals exposed to DF1 exhaust for 60 minutes. Experimental evidence suggests that a ...

Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization ...

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The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-{alpha} antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-{alpha} antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the ...

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One of the aims in the safety assessment of SFR-1 is to estimate the release to the environment. In order to make these calculations there is a need to describe the inventory in greater detail. The new computerised database of waste in SFR-1 gives a good possibility to achieve this. The aim for project SAFE is to make both conservative and realistic radionuclide transport calculations. To achieve this goal there must be two inventories. The conservative inventory is the inventory used in the design of the repository, which in most parts is identical with the limits in the licence for SFR-1. There is a great interest to have good estimates of the volumes of the different waste types. A thorough prognosis should be made in 1999, but until then the latest one from 1995 could be used in the calculations. The total (actual) inventory of nuclides is calculated from the measurements of the easy-to-measure nuclides since, in principle, all hard-to-measure nuclides are calculated by correlation ...