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Sample records for 1b bis 1d

  1. Data of evolutionary structure change: 1B99C-2AZ1D [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available GSDS--VESAN >E --HHHHH> ATOM 316...>D 2AZ1D HGSDHEDEGANE >E HHH...pdbID>1B99 C 1B99C EELLT-EVKPN ...> - > ATOM 3319 CA GLU C 141 17.330 5.755...DChain>2AZ1D DELVDWDRDAS re>GG EEGGHcture

  2. 5-HT reuptake inhibitors with 5-HT(1B/1D) antagonistic activity: a new approach toward efficient antidepressants.

    Science.gov (United States)

    Matzen, L; van Amsterdam, C; Rautenberg, W; Greiner, H E; Harting, J; Seyfried, C A; Böttcher, H

    2000-03-23

    As part of our research program toward new, potential antidepressants, a series of unsymmetrical ureas has been prepared and evaluated as 5-HT reuptake inhibitors with 5-HT(1B/1D) antagonistic activities. The design of these compounds was based on coupling of various indole derivatives, previously shown to inhibit 5-HT reuptake, to three different aniline moieties, which are part of known 5-HT(1B/1D) ligands. Binding experiments in rat frontal cortex using [(125)I]iodocyanopindolol, in calf striatum using [(3)H]5-HT, and in rat hippocampus using [(3)H]8-OH-DPAT as radioligands, respectively, revealed significantly higher affinity at the 5-HT(1B) receptor as compared to the affinities for the 5-HT(1A) and 5-HT(1D) receptors for a number of compounds, among them 4-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide (5), the corresponding 4-fluoro-1H-indol-3-yl analogue 21a, and the corresponding 6-fluoro-1H-indol-3-yl analogue 21b. Conformational restriction of the aniline moiety in 5 only slightly enhanced the 5-HT(1B) affinity, whereas introduction of an aniline moiety with higher conformational flexibility resulted in a less potent 5-HT(1B) receptor ligand as compared to 5. The functional 5-HT(1B/1D) antagonistic activity was investigated using the rabbit saphenous vein model as well as the [(3)H]5-HT release from guinea pig cortical slices. All new compounds tested in the rabbit saphenous vein model were shown to antagonize the sumatriptan-evoked contractile responses with pA(2) values ranging from 7.3 to 8.7. These observations were consistent with the results of the cortical slice model, in which the ureas were found to block the sumatriptan-induced inhibition of potassium-evoked [(3)H]5-HT release. The 5-HT reuptake inhibition of the ureas determined in rat brain synaptosomes was found to be either increased or decreased as compared to the uncoupled indole derivatives indicating that the reuptake inhibition

  3. NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models

    DEFF Research Database (Denmark)

    Bhatt, Deepak K; Gupta, Saurabh; Jansen-Olesen, Inger;

    2013-01-01

    BackgroundNXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-...

  4. Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle.

    Science.gov (United States)

    Winter, Lilli; Kuznetsov, Andrey V; Grimm, Michael; Zeöld, Anikó; Fischer, Irmgard; Wiche, Gerhard

    2015-08-15

    Plectin, a versatile 500-kDa cytolinker protein, is essential for muscle fiber integrity and function. The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy. Besides displaying pathological desmin-positive protein aggregates and degenerative changes in the myofibrillar apparatus, skeletal muscle specimens of EBS-MD patients and plectin-deficient mice are characterized by massive mitochondrial alterations. In this study, we demonstrate that structural and functional alterations of mitochondria are a primary aftermath of plectin deficiency in muscle, contributing to myofiber degeneration. We found that in skeletal muscle of conditional plectin knockout mice (MCK-Cre/cKO), mitochondrial content was reduced, and mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions and were no longer associated with Z-disks. Additionally, decreased mitochondrial citrate synthase activity, respiratory function and altered adenosine diphosphate kinetics were characteristic of plectin-deficient muscles. To analyze a mechanistic link between plectin deficiency and mitochondrial alterations, we comparatively assessed mitochondrial morphology and function in whole muscle and teased muscle fibers of wild-type, MCK-Cre/cKO and plectin isoform-specific knockout mice that were lacking just one isoform (either P1b or P1d) while expressing all others. Monitoring morphological alterations of mitochondria, an isoform P1b-specific phenotype affecting the mitochondrial fusion-fission machinery and manifesting with upregulated mitochondrial fusion-associated protein mitofusin-2 could be identified. Our results show that the depletion of distinct plectin isoforms affects mitochondrial network organization and function in different ways.

  5. Predominance of bovine viral diarrhea virus 1b and 1d subtypes during eight years of survey in Poland.

    Science.gov (United States)

    Kuta, A; Polak, M P; Larska, M; Żmudziński, J F

    2013-10-25

    The genetic diversity of bovine viral diarrhea virus (BVDV) was determined from 65 animals persistently infected with BVDV and diagnosed between 2004 and 2011 in Poland. The samples originated from 28 herds in 12 provinces, where over 90% of the whole cattle population of Poland is reared. Phylogenetic analysis based on the fragments of two genomic regions of BVDV namely, 5'-untranslated region (5'-UTR) and N(pro) was performed. All the BVDV isolates belonged to BVDV-1 species and were further divided into four subtypes. There were 31 viruses of BVDV-1b subtype (47.6%) present in 12 herds, 24 of BVDV-1d subtype (36.9%) in 9 herds, 8 of BVDV-1f subtype (12.3%) in 5 herds and 2 BVDV-1g subtype (3.0%) in 2 herds. Neither BVDV-1a subtype, nor BVDV-2 species or any atypical bovine pestivirus were found among isolates tested. Despite increasing import of live cattle in the recent years, genetic diversity of Polish BVDV isolates was rather low.

  6. Protein kinase mediated upregulation of endothelin A, endothelin B and 5-hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Svensson, Carl-Lennart; Xu, Cang-Bao;

    2002-01-01

    had an enhancing effect on the induced changes giving rise to a 7-25% increase in E(max) in response to ET-1, S6c and 5-CT as compared to the cultured control. 5. Staurosporine inhibited the culture induced upregulation of the response of both the ET(A) and the 5-HT(1B/1D) receptors, but had...

  7. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.

    Science.gov (United States)

    Meneses, A; Terrón, J A; Hong, E

    1997-12-01

    We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.

  8. Synthesis, resolution, and applications of 2, 2'-bis(diphenylphosphino)-3,3'- binaphtho[2,1-b]furan.

    Science.gov (United States)

    Andersen, N G; Parvez, M; Keay, B A

    2000-09-07

    [structure: see text] A short five-step synthesis of (+/-)-2,2'-bis(diphenylphosphino)-3, 3'-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2-naphthoxyacetic acid is reported. The resolution of BINAPFu 1 was possible using our newly developed resolution procedure for phosphines wherein (1S)-camphorsulfonyl azide was used to prepare the bisphosphinimine of BINAPFu via the Staundinger reaction. BINAPFu consistently outperformed BINAP in an asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate.

  9. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  10. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  11. Endothelium-dependent relaxant responses to selective 5-HT(1B/1D) receptor agonists in the isolated middle cerebral artery of the rat

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Løvland Hoel, Natalie; Nilsson, Elisabeth

    2003-01-01

    perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 +/- 4, 10 +/- 2 and 13 +/- 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT(1B/1D) receptor selective antagonist GR 55562 (10(-6......)M). The use of N(omega)-nitro-L-arginine and charybdotoxin revealed that the dilatation involved both nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier demonstrated expression of 5-HT(1B/1D) immunoreactivity in the endothelium may well translate into a relaxant...... response to 5-HT and triptans. Using the vessel bath technique, MCA segments were mounted on two metal wires. The relaxant responses to sumatriptan could not be reproduced using this model; instead, weak contractile responses (6 +/- 3% of submaximal contractile capacity) were observed. The difference...

  12. Endothelium-dependent relaxant responses to selective 5-HT(1B/1D) receptor agonists in the isolated middle cerebral artery of the rat

    DEFF Research Database (Denmark)

    Hansen-Schwartz, Jacob; Løvland Hoel, Natalie; Nilsson, Elisabeth

    2003-01-01

    response to 5-HT and triptans. Using the vessel bath technique, MCA segments were mounted on two metal wires. The relaxant responses to sumatriptan could not be reproduced using this model; instead, weak contractile responses (6 +/- 3% of submaximal contractile capacity) were observed. The difference...... perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 +/- 4, 10 +/- 2 and 13 +/- 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT(1B/1D) receptor selective antagonist GR 55562 (10......(-6)M). The use of N(omega)-nitro-L-arginine and charybdotoxin revealed that the dilatation involved both nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier demonstrated expression of 5-HT(1B/1D) immunoreactivity in the endothelium may well translate into a relaxant...

  13. The relevance of preclinical research models for the development of antimigraine drugs: Focus on 5-HT1B/1D and CGRP receptors

    DEFF Research Database (Denmark)

    Gupta, S.; Villalon, C.M.

    2010-01-01

    approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT1B/1D receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development...... of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while...

  14. Autoradiographic Mapping of 5-HT(1B/1D) Binding Sites in the Rhesus Monkey Brain Using [carbonyl-C]zolmitriptan.

    Science.gov (United States)

    Lindhe, Orjan; Almqvist, Per; Kågedal, Matts; Gustafsson, Sven-Åke; Bergström, Mats; Nilsson, Dag; Antoni, Gunnar

    2011-01-01

    Zolmitriptan is a serotonin 5-HT(1B/1D) receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [(11)C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [(11)C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [(11)C]zolmitriptan as a radioligand. In saturation studies, [(11)C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95-5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT(1) receptor antagonists, [(11)C]zolmitriptan binding was blocked by selective 5-HT(1B) and 5-HT(1D) ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT(1A) receptor antagonist.

  15. Autoradiographic Mapping of 5-H T 1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

    Science.gov (United States)

    Lindhe, Örjan; Almqvist, Per; Kågedal, Matts; Gustafsson, Sven-Åke; Bergström, Mats; Nilsson, Dag; Antoni, Gunnar

    2011-01-01

    Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90%) binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM). There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist. PMID:22013519

  16. Autoradiographic Mapping of 5-HT1B/1D Binding Sites in the Rhesus Monkey Brain Using [carbonyl-11C]zolmitriptan

    Directory of Open Access Journals (Sweden)

    Örjan Lindhe

    2011-01-01

    Full Text Available Zolmitriptan is a serotonin 5-HT1B/1D receptor agonist that is an effective and well-tolerated drug for migraine treatment. In a human positron emission tomography study, [11C]zolmitriptan crossed the blood-brain barrier but no clear pattern of regional uptake was discernable. The objective of this study was to map the binding of [11C]zolmitriptan in Rhesus monkey brain using whole hemisphere in vitro autoradiography with [11C]zolmitriptan as a radioligand. In saturation studies, [11C]zolmitriptan showed specific (90% binding to a population of high-affinity binding sites (Kd 0.95–5.06 nM. There was regional distribution of binding sites with the highest density in the ventral pallidum, followed by the external globus pallidus, substantia nigra, visual cortex, and nucleus accumbens. In competitive binding studies with 5-HT1 receptor antagonists, [11C]zolmitriptan binding was blocked by selective 5-HT1B and 5-HT1D ligands in all target areas. There was no appreciable change in binding with the addition of a 5-HT1A receptor antagonist.

  17. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    Science.gov (United States)

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  18. The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin.

    Science.gov (United States)

    de Rezende, Marcos Gonçalves; Garcia-Leal, Cybele; Graeff, Frederico Guilherme; Del-Ben, Cristina Marta

    2013-12-01

    This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion.

  19. The relevance of preclinical research models for the development of antimigraine drugs: focus on 5-HT(1B/1D) and CGRP receptors.

    Science.gov (United States)

    Gupta, Saurabh; Villalón, Carlos M

    2010-10-01

    Migraine is a complex neurovascular syndrome, causing a unilateral pulsating headache with accompanying symptoms. The past four decades have contributed immensely to our present understanding of migraine pathophysiology and have led to the introduction of specific antimigraine therapies, much to the relief of migraineurs. Pathophysiological factors culminating into migraine headaches have not yet been completely deciphered and, thus, pose an additional challenge for preclinical research in the absence of any direct experimental marker. Migraine provocation experiments in humans use a head-score to evaluate migraine, as articulated by the volunteer, which cannot be applied to laboratory animals. Therefore, basic research focuses on different symptoms and putative mechanisms, one at a time or in combination, to validate the hypotheses. Studies in several species, utilizing different preclinical approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT(1B/1D) receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while incorporating the newer ideas/techniques in order to get better insights into migraine pathophysiology.

  20. 偏头痛治疗曙光初现5-HT1B/1D受体激动剂的临床应用%Clinical application of 5-HT1B/1D receptor agonist(triptan) to the treatment of migraine--a ray of sunlight

    Institute of Scientific and Technical Information of China (English)

    张石革; 马国辉

    2004-01-01

    OBJECTIVE:Migraine is a common and frequently-occurring disease in neuromedicine.with understading of mechanism of migraine,new anti-migraine drugs have been found constantly to summarize the aspect of clinical application and progress on 5-HT1B/1D receptor agonist(Triptan).METHODS: To collecte medical literatures in recent years at home and abroad.CONCLUSION:Advance in 5-HT1B/1D receptor agonist has been swiftly in recent years, it has higher selectivity to 5-HT1B/1D receptor, contraction of cerebral vessel and arteriae temporalis, efficacy being related to dosage, promoting distribution of blood flow,so 5-HT1B/1D receptor agonist(triptan) plays an important roles in treatment of migraine.

  1. Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and blood volume in normal circulation.

    Science.gov (United States)

    Okazawa, Hidehiko; Tsuchida, Tatsuro; Pagani, Marco; Mori, Tetsuya; Kobayashi, Masato; Tanaka, Fumiko; Yonekura, Yoshiharu

    2006-01-01

    To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT1B/1D) receptor agonists for migraine treatment, changes in cerebral blood flow (CBF) and blood volume induced by rizatriptan were assessed by positron emission tomography (PET). Eleven healthy volunteers underwent PET studies before and after rizatriptan administration. Dynamic PET data were acquired after bolus injection of H2(15)O to analyze CBF and arterial-to-capillary blood volume (V0) images using the three-weighted integral method. After a baseline scan, three further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug administration. Global and regional differences in CBF and V0 between conditions were compared using absolute values in the whole brain and cortical regions, as well as statistical parametric mapping (SPM) analysis. The global and regional values for CBF and V0 decreased significantly after rizatriptan administration compared with the baseline condition. However, both values recovered to baseline within 80 mins after treatment. The maximal reduction in global CBF and V0 was approximately 13% of baseline value. The greatest decrease in CBF was observed approximately 60 mins after drug administration, whereas the maximal reduction in V0 was observed approximately 5 mins earlier. Statistical parametric mapping did not highlight any regional differences between conditions. Thus, in brain circulation, rizatriptan caused significant CBF and V0 decreases, which are consistent with the vasoconstrictor effect of triptans on the large cerebral arteries. The gradual recovery in the late phase from the maximal CBF and V0 decrease suggests that rizatriptan does not affect the cerebral autoregulatory response in small arteries induced by CBF reduction.

  2. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, Dipak V; Ploug, Kenneth B; Hay-Schmidt, Anders;

    2012-01-01

    Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expres......Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the m...

  3. Antidiabetic Bis-Maltolato-OxoVanadium(IV): Conversion of inactive trans- to bioactive cis-BMOV for possible binding to target PTP-1B

    Science.gov (United States)

    Scior, Thomas; Mack, Hans-Georg; García, José Antonio Guevara; Koch, Wolfhard

    2008-01-01

    The postulated transition of Bis-Maltolato-OxoVanadium(IV) (BMOV) from its inactive trans- into its cis-aquo-BMOV isomeric form in solution was simulated by means of computational molecular modeling. The rotational barrier was calculated with DFT – B3LYP under a stepwise optimization protocol with STO-3G, 3-21G, 3-21G*, and 6-31G ab initio basis sets. Our computed results are consistent with reports on the putative molecular mechanism of BMOV triggering the insulin-like cellular response (insulin mimetic) as a potent inhibitor of the protein tyrosine phosphatase-1B (PTP-1B). Initially, trans-BMOV is present in its solid dosage form but in aqueous solution, and during oral administration, it is readily converted into a mixture of “open-type” and “closed-type” complexes of cis-aquo-BMOV under equilibrium conditions. However, in the same measure as the “closed-type” complex binds to the cytosolic PTP-1B, it disappears from solution, and the equilibrium shifts towards the “closed-type” species. In full accordance, the computed binding mode of cis-BMOV is energetically favored over sterically hindered trans-BMOV. In view of our earlier report on prodrug hypothesis of vanadium organic compounds the present results suggest that cis-BMOV is the bioactive species. PMID:19920909

  4. Anion-dependent construction of a series of fluorescent coordination polymers based on 1D zinc∩4,4‧-bis(imidazol-1-yl)-biphenyl substrates

    Science.gov (United States)

    Zou, Kang-Yu; Zou, Qian; Han, Tong; Liu, Yi-Chen; Wang, Jun-Jie; Zhang, Xue; Li, Zuo-Xi

    2016-03-01

    In this work, the rod-like ligand 4,4‧-bis(imidazol-1-yl)-biphenyl (bibp) has been utilized as a building block to carry out counterion effects on the structural diversities of coordination polymers. A series of new zinc complexes, [Zn(trans-bibp)Cl2]∞ (1), [Zn(trans-bibp)Br2]∞ (2), {[Zn(cis-bibp)(Ac)2]·(H2O)}∞ (3), [Zn(trans-bibp)SO4]∞ (4), {[Zn2(cis-bibp)2(ipa)2]·(H2O)}∞ (5, H2ipa=isophthalic acid) and {[Zn(trans-bibp)(cis-bibp)]·(ClO4)2(CHCl3)2(CH3OH)}∞ (6) have been successfully synthesized. Complexes 1 and 2 are iso-structural, which show a 1D W-type chain [Zn(trans-bibp)]∞. Complex 3 exhibits a 2D wave-like layer formed by the hydrogen bond among the 1D linear chain [Zn(cis-bibp)]∞. Complex 4 displays a 2D fish-bone lattice, which is generated from connecting the 1D W-type chain [Zn(trans-bibp)]∞ by the μ2-SO42- . Complex 5 presents an interesting 2D-3D 65·8 architecture, including two 1D chains [Zn(ipa)]∞ and [Zn(cis-bibp)]∞. Complex 6 demonstrates a 2D wave-like layer [Zn(trans-bibp)(cis-bibp)]∞. The structural diversities among 1-6 have been carefully discussed, and the role of counterion in the self-assembly of coordination polymer have also been well documented from the coordination affinity and bridging mode. Furthermore, the solid-state fluorescence properties of 1-6 at room temperature have been studied.

  5. Antidiabetic Bis-Maltolato-OxoVanadium(IV: Conversion of inactive trans- to bioactive cis-BMOV for possible binding to target PTP-1B

    Directory of Open Access Journals (Sweden)

    Thomas Scior

    2008-11-01

    Full Text Available Thomas Scior1, Hans-Georg Mack2, José Antonio Guevara García3, Wolfhard Koch41Departamento de Farmacia. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Colonia San Manuel, Puebla, Mexico; 2Institut für Physikalische Chemie, Universität Tübingen, Tübingen, Germany; 3Laboratorio de Investigación en Bioinorgánica y Biorremediación (LIByB. Departamento de Ciencias Básicas, Ingeniería y Tecnología, Universidad Autónoma de Tlaxcala, Apizaco, Tlaxcala, Mexico; 4Facultad de Estudios Superiores Zaragoza (FESZ, Universidad Nacional Autónoma de México (UNAM, Colonia Ejército de Oriente, Delegación Iztapalapa, Mexico City, MexicoAbstract: The postulated transition of Bis-Maltolato-OxoVanadium(IV (BMOV from its inactive trans- into its cis-aquo-BMOV isomeric form in solution was simulated by means of computational molecular modeling. The rotational barrier was calculated with DFT – B3LYP under a stepwise optimization protocol with STO-3G, 3-21G, 3-21G*, and 6-31G ab initio basis sets. Our computed results are consistent with reports on the putative molecular mechanism of BMOV triggering the insulin-like cellular response (insulin mimetic as a potent inhibitor of the protein tyrosine phosphatase-1B (PTP-1B. Initially, trans-BMOV is present in its solid dosage form but in aqueous solution, and during oral administration, it is readily converted into a mixture of “open-type” and “closed-type” complexes of cis-aquo-BMOV under equilibrium conditions. However, in the same measure as the “closed-type” complex binds to the cytosolic PTP-1B, it disappears from solution, and the equilibrium shifts towards the “closed-type” species. In full accordance, the computed binding mode of cis-BMOV is energetically favored over sterically hindered trans-BMOV. In view of our earlier report on prodrug hypothesis of vanadium organic compounds the present results suggest that cis-BMOV is the bioactive species

  6. Synthesis and Crystal Structure of 1D Coordination Polymer of N,N'-Bis(3-pyridylmethyl)-1,4-benzenedicarboxamide and Cobalt(II) Nitrate

    Institute of Scientific and Technical Information of China (English)

    GE,Chun-Hua(葛春华); ZHANG,Xiang-Dong(张向东); TONG,Jian(佟健); ZHANG,Peng(张鹏); GUO,Fang(郭放); LIU,Qi-Tao(刘祁涛)

    2004-01-01

    A noval cobalt(II)coordination polymer,{[Co(bpmb)(H2O)2(C2H5OH)2]·(NO3)2}∞(1),where bpmb=N,N'-bis(3-pyridylmethyl)-1,4-benzenedicarboxamide,was synthesized by self-assembly of the two topic ligands with cobalt nitrate in ethanol solution,and characterized structurally by X-ray crystallography analysis.The crystal data belong to triclinic,space group Pwith cell parameters a=0.8911(3)nm,b=0.9042(3)nm,c=1.0068(3)nm,α=73.083(5)°,β=81.069(5)°,γ=76.210(5)°,R1=0.0518,wR2=0.0947.The results of structure analysis indicate that each bpmb ligand coordinates two Co(II)atoms and each metal atom is in octahedral coordination geometry with four oxygen atoms of two ethanol and two water molecules,two nitrogen atoms from two different bpmb ligands in trans position forming an infinite 1D chain-like structure.There are hydrogen bonding and π-π stacking interaction among these chains,leading to supramolecular formation with 3D net structure.

  7. The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors.

    Science.gov (United States)

    Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Stepanović-Petrović, Radica M

    2015-12-01

    Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.

  8. 3D, 2D and 1D networks via N-H…O and N-H…N hydrogen bonding by the bis-amide analogues: Effect of chain lengths and odd-even spacers

    Indian Academy of Sciences (India)

    Gargi Mukherjee; Kumar Biradha

    2014-09-01

    The synthesis, crystal structures and hydrogen bonding networks of four members of the bis(pyridinecarboxamido)alkane and bis(pyridyl)alkanediamides series (1 ≤ ≤ 8), where the amide moieties are separated by alkyl chain (-(CH2)-) having even or odd number of -(CH2)-groups are explored and correlated with the previously reported structures. The odd members (n= odd) of both the series are found to adopt three-dimensional networks in contrast to the 1D or 2D structures of the even members (n= even). This odd-even effect on the dimensionality of the networks however disappears with increase in chain length.

  9. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on myocardial reactive hyperemic response in conscious dogs.

    Science.gov (United States)

    Lynch, Joseph J; Shen, You-Tang; Pittman, Tamara J; Anderson, Kenneth D; Koblan, Kenneth S; Gould, Robert J; Regan, Christopher P; Kane, Stefanie A

    2009-11-25

    The triptans, serotonin 5-HT(1B/1D) receptor agonists exemplified by sumatriptan, are a mainstay migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans constrict human coronary artery in vitro, and there are case reports of myocardial infarction in patients using sumatriptan. However, preclinical studies with sumatriptan in normal dogs have failed to demonstrate effects on resting coronary flow. Calcitonin gene-related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP receptor antagonist peptide CGRP(8-37), is a new antimigraine mechanism which also has been reported to have no effect on coronary flow in normal, non-stressed animals. The goal of the present studies was to compare the effects of sumatriptan (10microg/kg/min i.v.) and CGRP(8-37) (30microg/kg/min i.v.) on systemic and coronary hemodynamics in conscious dogs under resting conditions and during myocardial reactive hyperemia following a brief 15s of coronary artery occlusion. Neither CGRP(8-37) nor sumatriptan affected resting coronary flow. However, whereas CGRP(8-37) had no effect on myocardial reactive hyperemic response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow (baseline vs treatment: 75.4+/-12.7 vs 60.0+/-10.3ml/min, Ptriptan effects on coronary vascular function.

  10. Irradiation programme HFR phase 1b. Results of impact tests with the irradiated materials (2.4 dpa); Bestrahlungsprogramm HFR Phase 1b. Ergebnisse der Kerbschlagbiegeversuche mit den bis 2,4 dpa bestrahlten Werkstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, H.C.; Dafferner, B.; Ries, H.; Lautensack, S.; Romer, O.

    2004-04-01

    The irradiation project HFR phase 1b was planned and carried out in the frame of the European Long-term Fusion Materials Development Programme. It represents the continuation of the former High-Flux-Reactor irradiation programmes which are documented in detail in former FZK-reports. The problem of the irradiation induced embrittlement of possible martensitic alloy candidates is still not finally solved. After evaluation of sub-size Charpy tests with the 2.4 dpa irradiated specimens, the low activation 7-10%-Cr-W(Ge)VTa alloys showed outstandingly better characteristics compared to the modified commercial 10-11%-Cr-NiMoVNb steels. The emphasis of the phase 1b project is now on the investigation of low activating OPTIFER-alloys, which exhibit in contrast to the previously irradiated OPTIFER-steels a clearly reduced boron content in order to reduce the irradiation embrittlement. In the present report the results of instrumented impact tests within the phase 1b programme (irradiation dose 2.4 dpa, irradiation temperatures 250, 300, 350, 400, and 450 C) are analysed and assessed in comparison to the results of the MANITU- and HFR phase 1a- irradiation programmes. Herein, the OPTIFER-V steel, which is nearly identical to the industrial heat EUROFER97 (which became available after the irradiation), supplied the best results. (orig.)

  11. Glucose Uptake Activities of Bis (2, 3-Dibromo-4, 5-Dihydroxybenzyl) Ether, a Novel Marine Natural Product from Red Alga Odonthaliacorymbifera with Protein Tyrosine Phosphatase 1B Inhibition, In Vitro and In Vivo.

    Science.gov (United States)

    Xu, Feng; Wang, Fang; Wang, Zhenhong; Lv, Wenshan; Wang, Wei; Wang, Yangang

    2016-01-01

    Protein tyrosine phosphatase 1B (PTP1B) is a novel therapeutic target for type-2 diabetes, which negatively regulates the insulin signaling transduction. Bis (2, 3-dibromo-4, 5-dihydroxybenzyl) ether (BDDE), a novel bromophenol isolated from the Red Alga, is a novel PTP1B inhibitor. But the anti-diabetic effects are not clear. In the present study, we evaluated the in vitro and in vivo antidiabetic effects of BDDE. The insulin-resistant HepG2 cells were used to evaluate the in vitro antidiabetic effects of BDDE. MTT assay was used to determine the safety concentrations in HepG2 cells. Glucose assay kit was used to check glucose uptake after treated with BDDE. Western blotting assay was used to explore the potent mechanisms. The db/db mice were used to evaluate the in vivo antidiabetic effects of BDDE. Body weight, blood glucose, Glycated hemoglobin (HbA1c), lipid profile, and insulin level were checked at the respective time points. Gastrocnemii were dissected and used to analyze the PTP1B and insulin receptor β (IRβ) expression. BDDE increased the insulin-resisted glucose uptake in HepG2 cells. BDDE also decreased the expression of PTP1B and activated the substrates and downstream signals in insulin signal pathway, such as IRβ, insulin receptor substrate-1/2 (IRS1/2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/Akt). In the db/db mice model, BDDE significantly decreased the blood glucose, HbA1c and triglyceride (TG) levels. BDDE also decreased the expression of PTP1B and activated the phosphorylation of IRβ in gastrocnemii. Moreover, BDDE at high doses downregulated the body weight without affecting food and water intake. Our results suggest that BDDE as a new PTP1B inhibitor improves glucose metabolism by stimulating the insulin signaling and could be used in the treatment of type-2 diabetes mellitus.

  12. Glucose Uptake Activities of Bis (2, 3-Dibromo-4, 5-Dihydroxybenzyl Ether, a Novel Marine Natural Product from Red Alga Odonthaliacorymbifera with Protein Tyrosine Phosphatase 1B Inhibition, In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Feng Xu

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a novel therapeutic target for type-2 diabetes, which negatively regulates the insulin signaling transduction. Bis (2, 3-dibromo-4, 5-dihydroxybenzyl ether (BDDE, a novel bromophenol isolated from the Red Alga, is a novel PTP1B inhibitor. But the anti-diabetic effects are not clear. In the present study, we evaluated the in vitro and in vivo antidiabetic effects of BDDE.The insulin-resistant HepG2 cells were used to evaluate the in vitro antidiabetic effects of BDDE. MTT assay was used to determine the safety concentrations in HepG2 cells. Glucose assay kit was used to check glucose uptake after treated with BDDE. Western blotting assay was used to explore the potent mechanisms. The db/db mice were used to evaluate the in vivo antidiabetic effects of BDDE. Body weight, blood glucose, Glycated hemoglobin (HbA1c, lipid profile, and insulin level were checked at the respective time points. Gastrocnemii were dissected and used to analyze the PTP1B and insulin receptor β (IRβ expression.BDDE increased the insulin-resisted glucose uptake in HepG2 cells. BDDE also decreased the expression of PTP1B and activated the substrates and downstream signals in insulin signal pathway, such as IRβ, insulin receptor substrate-1/2 (IRS1/2, phosphoinositide 3-kinase (PI3K, and protein kinase B (PKB/Akt. In the db/db mice model, BDDE significantly decreased the blood glucose, HbA1c and triglyceride (TG levels. BDDE also decreased the expression of PTP1B and activated the phosphorylation of IRβ in gastrocnemii. Moreover, BDDE at high doses downregulated the body weight without affecting food and water intake.Our results suggest that BDDE as a new PTP1B inhibitor improves glucose metabolism by stimulating the insulin signaling and could be used in the treatment of type-2 diabetes mellitus.

  13. Supramolecular chirality in organo-, hydro-, and metallogels derived from bis-amides of L-(+)-tartaric acid: formation of highly aligned 1D silica fibers and evidence of 5-c net SnS topology in a metallogel network.

    Science.gov (United States)

    Das, Uttam Kumar; Dastidar, Parthasarathi

    2012-10-01

    A series of bis-amides derived from L-(+)-tartaric acid was synthesized as potential low-molecular-weight gelators. Out of 14 bis-amides synthesized, 13 displayed organo-, hydro-, and ambidextrous gelation behavior. The gels were characterized by methods including circular dichroism, differential scanning calorimetry, optical and electron microscopy, and rheology. One of the gels derived from di-3-pyridyltartaramide (D-3-PyTA) displayed intriguing nanotubular morphology of the gel network, which was exploited as a template to generate highly aligned 1D silica fibers. The gelator D-3-PyTA was also exploited to generate metallogels by treatment with various Cu(II) /Zn(II) salts under suitable conditions. A structure-property correlation on the basis of single-crystal and powder X-ray diffraction data was attempted to gain insight into the structures of the gel networks in both organo- and metallogels. Such study led to the determination of the gel-network structure of the Cu(II) coordination-polymer-based metallogel, which displayed a 2D sheet architecture made of a chloride-bridged double helix that resembled a 5-c net SnS topology.

  14. BIS 220 Tutorials /bis220dotcom

    OpenAIRE

    ramya85

    2015-01-01

    BIS 220 Entire Course   For more course tutorials visit www.bis220.com   BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summ...

  15. BIS 220 Tutorials / bis220dotcom

    OpenAIRE

    rajitha82

    2015-01-01

    BIS 220 Entire Course   For more course tutorials visit www.bis220.com   BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summ...

  16. Interferon Gamma-1b Injection

    Science.gov (United States)

    Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with ... with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  17. Interferon Beta-1b Injection

    Science.gov (United States)

    ... medications (Avonex, Plegridy, Rebif), any other medications, human albumin, mannitol, or any of the other ingredients in ... 1b powder at room temperature and away from excess heat and moisture (not in the bathroom). If ...

  18. Synthesis, spectral and structural properties of bis-imidazoline selones

    Indian Academy of Sciences (India)

    Arruri Sathyanarayana; Katam Srinivas; Anindita Mandal; Saswati Gharami; Ganesan Prabusankar

    2014-09-01

    New biphenyl derivatives of bis-imidazoline selones were synthesized in good yield and characterized by multinuclear (1D and 2D) NMR and UV-vis studies. The solid state structures of bis-imidazoline selones were further confirmed by single crystal X ray diffraction technique.

  19. BIS 220 Uop Material-bis220dotcom

    OpenAIRE

    greenappled

    2015-01-01

    BIS 220 Entire Course For more course tutorials visit www.bis220.com BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summary BIS 220 Week 3...

  20. Main: 1B37 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B37 トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...FSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B37.jpg ...

  1. 18 CFR 1b.12 - Transcripts.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any,...

  2. 18 CFR 1b.14 - Subpoenas.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Subpoenas. 1b.14 Section 1b.14 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.14 Subpoenas. (a) Service of a...

  3. 18 CFR 1b.19 - Submissions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Submissions. 1b.19 Section 1b.19 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.19 Submissions. In the event...

  4. 18 CFR 1b.5 - Formal investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations....

  5. 18 CFR 1b.6 - Preliminary investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Preliminary investigations. 1b.6 Section 1b.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.6 Preliminary investigations....

  6. 18 CFR 1b.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part—...

  7. 18 CFR 1b.2 - Scope.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to...

  8. Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel organic anion-transporting polypeptide.

    Science.gov (United States)

    Popovic, Marta; Zaja, Roko; Fent, Karl; Smital, Tvrtko

    2013-11-22

    The organic anion-transporting polypeptide (OATP/Oatp) superfamily includes a group of polyspecific transporters that mediate transport of large amphipathic, mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are involved in the disposition and elimination of numerous physiological and foreign compounds. However, in non-mammalian species, the functional properties of Oatps remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain insights into the functional and structural evolution of the OATP1/Oatp1 superfamily. We show that diversification of the OATP1/Oatp1 family occurs after the emergence of jawed fish and that the OATP1A/Oatp1a and OATP1B/Oatp1b subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological role in transport and balance of steroid hormones. Oatp1d1 activity is dependent upon pH gradient, which could indicate bicarbonate exchange as a mode of transport. Our analysis of evolutionary conservation and structural properties revealed that (i) His-79 in intracellular loop 3 is conserved within OATP1/Oatp1 family and is crucial for the transport activity; (ii) N-glycosylation impacts membrane targeting and is conserved within the OATP1/Oatp1 family with Asn-122, Asn-133, Asn-499, and Asn-512 residues involved; (iii) the evolutionarily conserved cholesterol recognition interaction amino acid consensus motif is important for membrane localization; and (iv) Oatp1d1 is present in dimeric and possibly oligomeric form in the cell membrane. In conclusion, we describe the first detailed characterization of a new Oatp transporter in zebrafish, offering important insights into the functional evolution of the OATP1/Oatp1 family and the physiological role of Oatp1d1.

  9. 18 CFR 1b.21 - Enforcement hotline.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Enforcement hotline. 1b..., DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.21 Enforcement hotline. (a) The Hotline Staff may provide information to the public and give informal staff opinions. The opinions...

  10. One-Dimensional (1-D) Nanoscale Heterostructures

    Institute of Scientific and Technical Information of China (English)

    Guozhen SHEN; Di CHEN; Yoshio BANDO; Dmitri GOLBERG

    2008-01-01

    One-dimensional (1-D) nanostructures have been attracted much attention as a result of their exceptional properties, which are different from bulk materials. Among 1-D nanostructures, 1-D heterostructures with modulated compositions and interfaces have recently become of particular interest with respect to potential applications in nanoscale building blocks of future optoelectronic devices and systems. Many kinds of methods have been developed for the synthesis of 1-D nanoscale heterostructures. This article reviews the most recent development, with an emphasize on our own recent efforts, on 1-D nanoscale heterostructures, especially those synthesized from the vapor deposition methods, in which all the reactive precursors are mixed together in the reaction chamber. Three types of 1-D nanoscale heterostructures, defined from their morphologies characteristics, are discussed in detail, which include 1-D co-axial core-shell heterostructures, 1-D segmented heterostructures and hierarchical heterostructures. This article begins with a brief survey of various methods that have been developed for synthesizing 1-D nanoscale heterostructures and then mainly focuses on the synthesis, structures and properties of the above three types of nanoscale heterostructures. Finally, this review concludes with personal views towards the topic of 1-D nanoscale heterostructures.

  11. Selective up-regulation of 5-HT(1B/1D) receptors during organ culture of cerebral arteries

    DEFF Research Database (Denmark)

    Hoel, N L; Hansen-Schwartz, J; Edvinsson, L

    2001-01-01

    5-Hydroxytryptamine (5-HT) is thought to be involved in migraine headache and the pathophysiology of cerebrovascular diseases. Previous data show that organ culture induces a phenotypic change in cerebral vessels. Therefore we investigated if these changes also applied for the vasoconstrictive 5-HT...

  12. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

    Science.gov (United States)

    Chen, M; Qu, B X; Chen, X L; Hu, H H; Jiang, H D; Yu, L S; Zhou, Q; Zeng, S

    2016-06-01

    A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

  13. sup 1 sup 1 B nutation NMR study of powdered borosilicates

    CERN Document Server

    Woo, A J; Han, D Y

    1998-01-01

    In this work, we applied the 1D sup 1 sup 1 B nutation NMR method for the analysis of the local structural environments in powdered borosilicates (SiO sub 2 -B sub 2 O sub 3). Spin dynamics during a rf irradiation for spin I=3/2 was analytically calculated with a density matrix formalism. Spectral simulation programs were written in MATLAB on a PC. Two borosilicates prepared by the sol-gel process at different stabilization temperature were used for the 1D sup 1 sup 1 B nutation NMR experiment. The sup 1 sup 1 B NMR parameters, quadrupole coupling constants (e sup 2 qQ/h) and asymmetry parameters (eta), for each borosilicate were extracted from the nonlinear least-squares fitting. The effects of heat treatments on the local structures of boron sites in borosilicates were discussed.

  14. Could the 5-HT1B receptor inverse agonism affect learning consolidation?

    Science.gov (United States)

    Meneses, A

    2001-03-01

    Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits

  15. Bacterial Expression and Purification of an Active ω-Atracotoxin-Ar1b from Spider Atrax robustus

    Institute of Scientific and Technical Information of China (English)

    WANG Yu-qin; WANG Jue; LI Jian; LIU Qiang; HUANG Shi-di; WANG Dun

    2010-01-01

    The ω-atracotoxin-Ar1b toxin(ω-ACTX-Ar1b)is one of the arthropod-selective peptide neurotoxins from the venom of Australian funnel-web spider Atrax robustus.The gene of Ar1b was synthesized and cloned into pET-32a(+)vector to allow expression of Ar1b as a fusion protein with thioredoxin and the His-tag(rTrx-Ar1b)in E.coli BL21(DE3).The optimal condition for inducing the expression of rTrx-Ar1b was 1.0 mmol L-1 IPTG for 6 h at 28℃.The fusion protein rTrx-Ar1b was expressed in soluble form and was purified effectively by His Trap HP affinity column and rpHLPC and a final yield of purified rTrx-Ar1b was 95 mg from 1000 mL E.coli culture.The LD50 values for Mythimna separate and Tenebrio molitor were 111.66 and 11.04 μg g-1 determined by injection of the purified rTrx-Ar1b.The results indicated that the recombinant Ar1b protein was successfully expressed in E.coli and it was high toxicity against tested insects.

  16. 2000 Johnston Site 1B-P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 1B-P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on June 29, 2000. With a start point (meter 0) at...

  17. Analysis of the rotational structure in the high-resolution infrared spectra of trans-hexatriene-1,1-d2 and -cis-1-d1

    Science.gov (United States)

    Craig, Norman C.; Fuson, Hannah A.; Tian, Hengfeng; Blake, Thomas A.

    2012-09-01

    Mixtures of trans-hexatriene-1,1-d2, -cis-1-d1, and -trans-1-d1 have been synthesized. Anharmonic frequencies and harmonic intensities were predicted with the B3LYP/cc-pVTZ model for the out-of-plane (a″) modes of the three isotopologues. Assignments are proposed for most of the a″ vibrational modes above 500 cm-1. Ground state (GS) rotational constants have been determined for the 1,1-d2 and cis-1-d1 species from the analysis of rotational structure of C-type bands in the high-resolution (0.0015 cm-1) infrared spectra in a mixture of the three isotopologues. The GS constants for the 1,1-d2 species are A0 = 0.8018850(6), B0 = 0.0418540(6), and C0 = 0.0397997(4) cm-1. The GS constants for the cis-1-d1 species are A0 = 0.809388(1), B0 = 0.043532(2), and C0 = 0.041320(1) cm-1. Small inertial defects confirm planarity for both species. These ground state rotational constants are intended for use in determining a semiexperimental equilibrium structure and evaluating the influence of chain length on π-electron delocalization in polyenes.

  18. Social exploration of 1D games

    DEFF Research Database (Denmark)

    Valente, Andrea; Marchetti, Emanuela

    2013-01-01

    In this paper the apparently meaningless concept of a 1 dimensional computer game is explored, via netnography. A small number of games was designed and implemented, in close contact with online communities of players and developers, providing evidence that 1 dimension is enough to produce...... interesting gameplay, to allow for level design and even to leave room for artistic considerations on 1D rendering. General techniques to re-design classic 2D games into 1D are also emerging from this exploration....

  19. Identifying and structurally characterizing CD1b in Aotus nancymaae owl monkeys.

    Science.gov (United States)

    Castillo, Fabio; Guerrero, Carlos; Trujillo, Esperanza; Delgado, Gabriela; Martinez, Pilar; Salazar, Luz M; Barato, Paola; Patarroyo, Manuel E; Parra-López, Carlos

    2004-10-01

    This study reports the molecular characterization and tissue expression of the non-human Aotus nancymaae primate CD1b isoform in the search for an experimental animal model to be used in evaluating the role of non-peptide antigen-presentation molecules in the immune response to infectious agents. CD1b expression on the surface of A. nancymaae peripheral blood monocyte-derived dendritic cells, shown by flow cytometry, was made possible by using human CD1b isoform antibodies. Studying the expression of CD1b-encoded transcripts revealed this molecule's broad distribution in several tissues. The A. nancymaae CD1b transcript-encoded amino-acid sequence showed 95.5% identity with the human sequence. Such high sequence homology was reflected in the identical structural conservation of how pockets A', C' and F' and tunnel T' conforming the antigen's binding site are organized, the similar arrangement of those amino-acids interacting with the T-cell receptor (TCR) during antigen presentation, and the conservation of YQNI-motif sequence in the cytoplasmatic tail (responsible for the molecule's intracellular trafficking in humans). Comparing the structure of human CD1a and CD1b and mouse CD1d proteins with CD1b structure in A. nancymaae obtained by minimization revealed that changes in the latter molecule's alpha1 and alpha2 domains imposed a narrowing of the antigen-binding groove in A. nancymaae CD1b. The high structural similarity between A. nancymaae CD1b and that from humans presented in this study leads to A. nancymaae being proposed as a suitable experimental animal model for analyzing CD1b in vivo, mainly in bacterial and parasite infections such as tuberculosis and malaria, respectively.

  20. Oleanane triterpenes as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Camellia japonica.

    Science.gov (United States)

    Uddin, Mohammad Nasir; Sharma, Govinda; Yang, Jun-Li; Choi, Hong Seok; Lim, Seong-Il; Kang, Keon Wook; Oh, Won Keun

    2014-07-01

    Protein tyrosine phosphatase 1B (PTP1B) plays a key role in metabolic signaling, thereby making it an exciting drug target for type 2 diabetes and obesity. Besides, there is substantial evidence that shows its overexpression is involved in breast cancer, which suggests that selective PTP1B inhibition might be effective in breast cancer treatment. As part of our continuous research on PTP1B inhibitors from medicinal plants, four oleanane-type triterpenes were isolated from an EtOAc-soluble extract of fruit peels of Camellia japonica (Theaceae), together with 6 previously known compounds of this class. Their structures were determined on the basis of spectroscopic data analysis (UV, IR, (1)H and (13)CNMR, HMBC, HSQC, NOESY, and MS). All isolates were evaluated for their inhibitory effects on PTP1B, as well as their cytotoxic effects against human breast cancer cell lines MCF7, MCF7/ADR, and MDA-MB-231. Several compounds with OH-3 or/and COOH-28 functionalities showed strong PTP1B inhibitory activity (IC50 values ranging from 3.77±0.11 to 6.40±0.81 μM) as well as significant cytotoxicity (IC50 values ranging from 0.51±0.05 to 13.55±1.44 μM). Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Heat Capacity of 1D Molecular Chains

    Science.gov (United States)

    Bagatskii, M. I.; Barabashko, M. S.; Sumarokov, V. V.; Jeżowski, A.; Stachowiak, P.

    2017-04-01

    The heat capacity of 1D chains of nitrogen and methane molecules (adsorbed in the outer grooves of bundles of closed-cap single-walled carbon nanotubes) has been studied in the temperature ranges 2-40 and 2-60 K, respectively. The temperature dependence of the heat capacity of 1D chains of nitrogen molecules below 3 K is close to a linear. It was found that the rotational heat capacity of methane molecules is a significant part of the total heat capacity of the chains throughout the whole investigated temperature range, whereas in the case of nitrogen, the librations are significant only above 15 K. The dependence of the heat capacity for methane below 10 K indicates the presence of a Schottky anomaly caused by the tunneling between the lowest energy levels of the CH4 molecule rotational spectra. Characteristic features observed in the temperature dependence of the heat capacity of 1D methane crystals are also discussed.

  2. First Observation of Upsilon(1D) States

    CERN Document Server

    Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; McGee, S; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Mahapatra, R; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G T; Vogel, H; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, David G; Drell, P S; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Nordberg, E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Viehhauser, G; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stöck, H; Yelton, J; Brandenburg, G; Kim, D Y J; Wilson, R; Benslama, K; Eisenstein, B I; Ernst, J; Gollin, G D; Hans, R M; Karliner, I; Lowrey, N; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Ammar, R; Besson, D; Zhao, X; Anderson, S; Frolov, V V; Kubota, Y; Lee, S J; Li, S Z; Poling, R A; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z V; Seth, K K; Tomaradze, A G; Zweber, P; Ahmed, S; Alam, M S; Jian, L; Saleem, M; Wappler, F; Eckhart, E; Gan, K K; Gwon, C; Hart, T; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pedlar, T K; Thayer, J B; Von Törne, E; Wilksen, T; Zoeller, M M; Muramatsu, H; Richichi, S J; Severini, H; Skubic, P L; Dytman, S A; Müller, J A; Nam, S; Savinov, V; Chen, S; Hinson, J W; Lee, J; Miller, D H; Pavlunin, V; Shibata, E I; Shipsey, I P J; Cronin-Hennessy, D; Lyon, A L; Park, C S; Park, W; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Maravin, Y; Stroynowski, R; Artuso, M; Boulahouache, C; Bukin, K; Dambasuren, E; Khroustalev, K; Mountain, R; Nandakumar, R; Skwarnicki, T; Stone, S; Wang, J C; Mahmood, A H

    2002-01-01

    The CLEO III experiment has recently accumulated a large statistics sample of 4.73 x 10^6 Upsilon(3S) decays. We present the first evidence for the production of the triplet Upsilon(1D) states in the four-photon cascade, Upslion(3S) -> gamma chi_b(2P), chi_b(2P) -> gamma Upsilon(1D), Upsilon(1D) -> gamma chi_b(1P), chi_b(1P) -> gamma Upsilon(1S), followed by the Upsilon(1S) annihilation to e+ e- or mu+ mu-. The signal has a significance of 9.7 standard deviations. The measured product branching ratio for these five decays, (3.3 +- 0.6 +- 0.5) x 10^{-5}, is consistent with the theoretical estimates. We see a 6.8 standard deviation signal for a state with a mass of 10162.2 +- 1.6 MeV/c^2, consistent with the Upsilon(1D_2) assignment. We also present improved measurements of the Upsilon(3S) -> pi0 pi0 Upsilon(1S) branching ratio and the associated di-pion mass distribution.

  3. DESIGN PACKAGE 1D SYSTEM SAFETY ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    L.R. Eisler

    1995-02-02

    The purpose of this analysis is to systematically identify and evaluate hazards related to the Yucca Mountain Project Exploratory Studies Facility (ESF) Design Package 1D, Surface Facilities, (for a list of design items included in the package 1D system safety analysis see section 3). This process is an integral part of the systems engineering process; whereby safety is considered during planning, design, testing, and construction. A largely qualitative approach was used since a radiological System Safety analysis is not required. The risk assessment in this analysis characterizes the accident scenarios associated with the Design Package 1D structures/systems/components in terms of relative risk and includes recommendations for mitigating all identified risks. The priority for recommending and implementing mitigation control features is: (1) Incorporate measures to reduce risks and hazards into the structure/system/component (S/S/C) design, (2) add safety devices and capabilities to the designs that reduce risk, (3) provide devices that detect and warn personnel of hazardous conditions, and (4) develop procedures and conduct training to increase worker awareness of potential hazards, on methods to reduce exposure to hazards, and on the actions required to avoid accidents or correct hazardous conditions. The scope of this analysis is limited to the Design Package 1D structures/systems/components (S/S/Cs) during normal operations excluding hazards occurring during maintenance and ''off normal'' operations.

  4. A bis-bithiophene from Tridax procumbens L. (Asteraceae).

    Science.gov (United States)

    Ali, Muhammad Shaiq; Jahangir, Muhammad

    2002-08-01

    The ethyl acetate soluble part of hexane extract of Tridax procumbens yielded a new bis-bithiophene named tridbisbithiophene along with four known terpenoids: taraxasteryl acetate, beta-amyrenone, lupeol and oleanolic acid, which have never been reported so far from Tridax procumbens. The structures of all the isolated constituents were elucidated with the aid of 1D-NMR spectroscopy whereas, the structure of new constituent tridbisbithiophene was confirmed via COSY and HMBC interactions.

  5. GIFTS SM EDU Level 1B algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-10-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) Sensor Module (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  6. GIFTS SM EDU Level 1B Algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-01-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) SensorModule (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  7. Calibration of a 1D/1D urban flood model using 1D/2D model results in the absence of field data.

    Science.gov (United States)

    Leandro, J; Djordjević, S; Chen, A S; Savić, D A; Stanić, M

    2011-01-01

    Recently increased flood events have been prompting researchers to improve existing coupled flood-models such as one-dimensional (1D)/1D and 1D/two-dimensional (2D) models. While 1D/1D models simulate sewer and surface networks using a one-dimensional approach, 1D/2D models represent the surface network by a two-dimensional surface grid. However their application raises two issues to urban flood modellers: (1) stormwater systems planning/emergency or risk analysis demands for fast models, and the 1D/2D computational time is prohibitive, (2) and the recognized lack of field data (e.g. Hunter et al. (2008)) causes difficulties for the calibration/validation of 1D/1D models. In this paper we propose to overcome these issues by calibrating a 1D/1D model with the results of a 1D/2D model. The flood-inundation results show that: (1) 1D/2D results can be used to calibrate faster 1D/1D models, (2) the 1D/1D model is able to map the 1D/2D flood maximum extent well, and the flooding limits satisfactorily in each time-step, (3) the 1D/1D model major differences are the instantaneous flow propagation and overestimation of the flood-depths within surface-ponds, (4) the agreement in the volume surcharged by both models is a necessary condition for the 1D surface-network validation and (5) the agreement of the manholes discharge shapes measures the fitness of the calibrated 1D surface-network.

  8. Glass-based 1-D dielectric microcavities

    Science.gov (United States)

    Chiasera, Alessandro; Scotognella, Francesco; Valligatla, Sreeramulu; Varas, Stefano; Jasieniak, Jacek; Criante, Luigino; Lukowiak, Anna; Ristic, Davor; Gonçalves, Rogeria Rocha; Taccheo, Stefano; Ivanda, Mile; Righini, Giancarlo C.; Ramponi, Roberta; Martucci, Alessandro; Ferrari, Maurizio

    2016-11-01

    We have developed a reliable RF sputtering techniques allowing to fabricate glass-based one dimensional microcavities, with high quality factor. This property is strongly related to the modification of the density of states due to the confinement of the gain medium in a photonic band gap structure. In this short review we present some of the more recent results obtained by our team exploiting these 1D microcavities. In particular we present: (1) Er3+ luminescence enhancement of the 4I13/2 → 4I15/2 transition; (2) broad band filters based on disordered 1-D photonic structures; (3) threshold defect-mode lasing action in a hybrid structure.

  9. YORP torques with 1D thermal model

    CERN Document Server

    Breiter, Slawomir; Czekaj, Maria

    2010-01-01

    A numerical model of the Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect for objects defined in terms of a triangular mesh is described. The algorithm requires that each surface triangle can be handled independently, which implies the use of a 1D thermal model. Insolation of each triangle is determined by an optimized ray-triangle intersection search. Surface temperature is modeled with a spectral approach; imposing a quasi-periodic solution we replace heat conduction equation by the Helmholtz equation. Nonlinear boundary conditions are handled by an iterative, FFT based solver. The results resolve the question of the YORP effect in rotation rate independence on conductivity within the nonlinear 1D thermal model regardless of the accuracy issues and homogeneity assumptions. A seasonal YORP effect in attitude is revealed for objects moving on elliptic orbits when a nonlinear thermal model is used.

  10. Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

    Science.gov (United States)

    Vieira, Marcelo N. N.; Lyra e Silva, Natalia M.; Ferreira, Sergio T.; De Felice, Fernanda G.

    2017-01-01

    Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer’s disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD. PMID:28197094

  11. Analysis of Rotational Structure in the High-Resolution Infrared Spectra of the TRANS-HEXATRIENE-1,1-D2 and -CIS-1-D1 Species

    Science.gov (United States)

    Craig, Norman C.; Fuson, Hannah A.; Tian, Hengfeng; Blake, Thomas A.

    2011-06-01

    Hexatriene-1,1-D2 with some admixture of the cis-1-D1 and trans-1-D1 species was synthesized by reaction of 2,4-pentadienal and (methyl-D3)-triphenylphosphonium iodide (Wittig reagent). The trans isomer was isolated by preparative gas chromatography, and the high-resolution (0.0015 Cm-1) infrared spectrum was recorded on a Bruker IFS 125HR instrument. The rotational structure in two C-type bands for the 1,1-D2 species was analyzed. For this species the bands at 902.043 and 721.864 Cm-1 yielded composite ground state rotational constants of A0 = 0.801882(1), B0 = 0.041850(2), and C0 = 0.039804(1) Cm-1. For the cis-1-D1 species the C-type band at 803.018 Cm-1 gave A0 = 0.809384(2), B0 = 0.043530(3), and C0 = 0.041321(2) Cm-1. By iodine-catalyzed isomerization, we have obtained some of the much less favored cis isomer and hope to obtain microwave spectra for its three deuterium-substituted species. The rotational constants reported here contribute to data needed for determining a semi-experimental structure for trans-hexatriene, which should show that the structural consequences of pi-electron delocalization increase with the chain length of polyenes.

  12. 1-D EQUILIBRIUM DISCRETE DIFFUSION MONTE CARLO

    Energy Technology Data Exchange (ETDEWEB)

    T. EVANS; ET AL

    2000-08-01

    We present a new hybrid Monte Carlo method for 1-D equilibrium diffusion problems in which the radiation field coexists with matter in local thermodynamic equilibrium. This method, the Equilibrium Discrete Diffusion Monte Carlo (EqDDMC) method, combines Monte Carlo particles with spatially discrete diffusion solutions. We verify the EqDDMC method with computational results from three slab problems. The EqDDMC method represents an incremental step toward applying this hybrid methodology to non-equilibrium diffusion, where it could be simultaneously coupled to Monte Carlo transport.

  13. Formation of ganglioside GD1b-lactone in rat brain from intracisternally administered GD1b

    Energy Technology Data Exchange (ETDEWEB)

    Riboni, L.; Ghidoni, R.; Tettamanti, G.

    1989-05-01

    The presence of ganglioside GD1b, in lactone form GD1b-L, was ascertained in rat brain. The possible formation of GD1b-L from GD1b in brain was explored by the intracisternal injection of GD1b, /sup 3/H-labelled at the level of the terminal galactose. This was followed by recognition of the radioactive gangliosides formed at different times (1, 3, and 7 days) after injection. Whereas at 0 time after injection the only radioactive ganglioside was GD1b, after 1, 3, and 7 days other radioactive gangliosides were also found, thus indicating GD1b penetration into the brain tissue, followed by metabolic processing. Besides GD1b, the following radioactive gangliosides were recognized: GM1 and GM2, derived from GD1b degradation; GT1b, formed by the direct sialylation of GD1b; and GD1b-L, produced by metabolic lactonization. The radioactivity carried by GD1b-L was maximal 3 days after injection; its time course was different from that of the other gangliosides, suggesting that the process of lactonization is separate from that of both degradation and glycosylation. Under the same experimental conditions, some radioactive gangliosides also appeared in the liver, although in much smaller amounts than in brain. Radioactive GD1b-L could not be detected in liver, thus indicating that metabolic lactonization is a tissue- or organ-specific process.

  14. Kinetics and Mechanism of Protein Tyrosine Phosphatase 1B (PTP1B) Inactivation by Acrolein

    Science.gov (United States)

    Seiner, Derrick R.; LaButti, Jason N.; Gates, Kent S.

    2010-01-01

    Human cells are exposed to the electrophilic α,β-unsaturated aldehyde acrolein from a variety of sources. Reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B (kinact = 0.02 ± 0.005 s−1, KI = 2.3 ± 0.6 × 10−4 M). Enzyme activity does not return upon gel filtration of the inactivated enzyme and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally-related α,β-unsaturated aldehydes. PMID:17655273

  15. Practical route to the left wing of CTX1B and total syntheses of CTX1B and 54-deoxyCTX1B.

    Science.gov (United States)

    Yamashita, Shuji; Takeuchi, Katsutoshi; Koyama, Takuya; Inoue, Masayuki; Hayashi, Yujiro; Hirama, Masahiro

    2015-02-02

    Ciguatoxins, the principal causative agents of ciguatera seafood poisoning, are extremely large polycyclic ethers. We report herein a reliable route for constructing the left wing of CTX1B, which possesses the acid/base/oxidant-sensitive bisallylic ether moiety, by a 6-exo radical cyclization/ring-closing metathesis strategy. This new route enabled us to achieve the second-generation total synthesis of CTX1B and the first synthesis of 54-deoxyCTX1B.

  16. From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines.

    Science.gov (United States)

    Landreau, Cyrille; Deniaud, David; Meslin, Jean Claude

    2003-06-13

    We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.

  17. Main: 1B5Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5Q トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...EESRRIEQQSDEQTKAEIMQVLRKMFPGKDVPDATDILVPRWWSDRFYKGTFSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B5Q.jpg ...

  18. 18 CFR 1b.11 - Limitation on participation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Limitation on participation. 1b.11 Section 1b.11 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.11 Limitation...

  19. 18 CFR 1b.3 - Scope of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope of investigations. 1b.3 Section 1b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.3 Scope of investigations....

  20. 18 CFR 1b.8 - Requests for Commission investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Requests for Commission investigations. 1b.8 Section 1b.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.8 Requests for...

  1. 18 CFR 1b.7 - Procedure after investigation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Procedure after investigation. 1b.7 Section 1b.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.7 Procedure after...

  2. 18 CFR 1b.18 - Right to submit statements.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Right to submit statements. 1b.18 Section 1b.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.18 Right to...

  3. 18 CFR 1b.9 - Confidentiality of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Confidentiality of investigations. 1b.9 Section 1b.9 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Freedom of Information Act disclosure are set forth in 18 CFR part 3b and § 1b.20. A request...

  4. 18 CFR 1b.4 - Types of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Types of investigations. 1b.4 Section 1b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.4 Types of...

  5. 18 CFR 1b.10 - By whom conducted.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false By whom conducted. 1b.10 Section 1b.10 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.10 By whom conducted....

  6. Diamond-based 1-D imaging arrays

    Energy Technology Data Exchange (ETDEWEB)

    Lansley, S.P.; Williams, O.A.; Ye, H. [Electronic and Electrical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Rizvi, N.; Whitfield, M.D.; Jackman, R.B. [Exitech Limited, Hanborough Park, Long Hanborough, Oxford OX8 8LH (United Kingdom); McKeag, R.D. [Centronic Ltd., Centronic House, King Henry' s Drive, New Addington, Croydon CR9 OBG (United Kingdom)

    2002-10-16

    Diamond has shown great promise for the fabrication of high sensitivity, low dark current, fast and visible-blind deep UV photodetectors. In addition to careful choice of substrate material, defect passivation treatments applied to the diamond after growth have been found to considerably enhance the detector characteristics achieved. In this paper we report on the first purposefully designed 1-D CVD diamond imaging array for the detection of nanosecond 193 nm excimer laser pulses using this approach. It is shown to perform extremely well, giving less than 2% pixel-to-pixel variation in signal response, and is fast enough to avoid any sign of charge build up during prolonged operation. (Abstract Copyright [2002], Wiley Periodicals, Inc.)

  7. Associations of the 5-hydroxytryptamine (Serotonin) Receptor 1B Gene (HTR1B) with Alcohol, Cocaine, and Heroin Abuse

    OpenAIRE

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-01-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To ...

  8. GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.

    Science.gov (United States)

    Yuki, Nobuhiro; Fukami, Yuki; Yanaka, Chiaki; Koike, Saiko; Hirata, Koichi

    2014-08-01

    Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

  9. Analysis list: HNF1B [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HNF1B Adipocyte,Digestive tract,Pluripotent stem cell + hg19 http://dbarchive.biosc...iencedbc.jp/kyushu-u/hg19/target/HNF1B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.5....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1B.Pluripotent_st

  10. Bis(1-adamantylammonium hexafluoridogermanate

    Directory of Open Access Journals (Sweden)

    Liying Cheng

    2008-01-01

    Full Text Available The title compound, (C10H18N2[GeF6], was obtained hydrothermally from an aqueous solution of GeO2, H3BO3, NiCl2, adamantylammonium chloride, butanol and hydrofluoric acid. The structure consists of discrete bis(1-adamantylammonium cations lying on crystallographic mirror planes and hexafluoridogermanate anions disordered about sites of 2/m point symmetry. In the latter, the Ge atom lies on the site of 2/m symmetry, one F atom lies on the mirror plane and two further F atoms are included in general positions with 50% site occupancy. The cations and anions lie in layers with N—H...F hydrogen bonds formed between them.

  11. Inhibition of bromophenols against PTP1B and anti-hyperglycemic effect of Rhodomela confervoides extract in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    SHI DaYong; XU Feng; HE Juan; LI Jing; FAN Xiao; HAN LiJun

    2008-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays an important role as s negative regulator in insulin signaling pathways.PTP1B is an effective target for the treatment of type 2 diabetes mellitus.Four bromophenol derivatives from red algae Rhodomela confervoides,2,2',3,3'-tetrabromo-4,4',5,5"-tetra-hydroxydiphenyl methane (1),3-bormo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl) pyrocatechol (2),bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (3) and 2,2",3-tribromo-3",4,4",5-tetrahydroxy-6"-ethyloxy-methyldiphenylmethane (4) showed significant inhibitory activity against PTP1B (IC50 were 2.4,1.7,1.5 and 0.84 μmol/L,respectively) as potential therapeutical agents for the treatment of type 2 diabetes mellitus.The anti-hyperglycemic effects of the ethanol extracts from R.confervoides on streptozoto-cin-induced diabetes (STZ-diabetes) in male Wistar rats fed with high fat diet were investigated.The STZ-diabetic rats treated with medium-dose and high-dose alga extracts showed remarkable reductions in fasting blood glucose (FBG) as compared with the STZ-diabetic control.The results indicate that the in vivo anti-hyperglycemic activity of the R.confervoides extracts can be partially attributed to the in-hibitory actions against PTP1B of the bromophenol derivatives and that may be of clinical importance in improving the management of type 2 diabetes mellitus.

  12. Ca(2+)-dependent anti-GQ1b antibody in GQ1b-seronegative Fisher syndrome and related disorders.

    Science.gov (United States)

    Uchibori, Ayumi; Gyohda, Atsuko; Chiba, Atsuro

    2016-09-15

    Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker for Fisher syndrome and its related disorders (FS-RD), 10%-30% of the patients are still negative in conventional assays ("GQ1b-seronegative") and the relationship between GQ1b-seropositive and -seronegative patients has been unclear. Some molecules require Ca(2+) cations to interact with their ligands (Ca(2+)-dependency). Here we have investigated whether Ca(2+)-dependency is also present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative patients and show that IgG antibodies against GQ1b-related antigens (isolated GQ1b and GQ1b-containing complexes) are detected Ca(2+)-dependently in the majority of GQ1b-seronegative patients with FS-RD. The Ca(2+)-dependent antibodies might react specifically with GQ1b-Ca(2+) conformation. This is the first demonstration of disease-related Ca(2+)-dependent antibodies in neurological field. GQ1b-related pathology would be involved in FS-RD more extensively than previously revealed.

  13. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Directory of Open Access Journals (Sweden)

    Timo H J Niedermeyer

    Full Text Available Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  14. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Science.gov (United States)

    Niedermeyer, Timo H J; Daily, Abigail; Swiatecka-Hagenbruch, Monika; Moscow, Jeffrey A

    2014-01-01

    Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  15. Extraction and PTP1B inhibitory activity of bromophenols from the marine red alga Symphyocladia latiuscula

    Science.gov (United States)

    Liu, Xu; Li, Xiaoming; Gao, Lixin; Cui, Chuanming; Li, Chunshun; Li, Jia; Wang, Bingui

    2011-05-01

    Previously, we had characterized several structurally interesting brominated phenols from the marine red alga Symphyocladia latiuscula collected from various sites. However, Phytochemical investigations on this species collected from the Weihai coastline of Shandong Province remains blank. Therefore, we characterized the chemical constituents of individuals of this species collected from the region. Eight bromophenols were isolated and identified. Using detailed spectroscopic techniques and comparisons with published data, these compounds were identified as 2,3-dibromo-4,5-dihydroxybenzyl methyl ether ( 1), 3,5-dibromo-4-hydroxybenzoic acid ( 2), 2,3,6-tribromo-4,5-dihydroxymethylbenzene ( 3), 2,3,6-tribromo-4,5-dihydroxybenzaldehyde ( 4), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether ( 5), bis(2,3,6-tribromo-4,5-dihydroxyphenyl)methane ( 6), 1,2-bis(2,3,6-tribromo-4,5-dihydroxyphenyl)-ethane ( 7), and 1-(2,3,6-tribromo-4,5-dihydroxybenzyl)-pyrrolidin-2-one ( 8). Among these compounds, 1 and 2 were isolated for the first time from S. latiuscula. Each compound was evaluated on the ability to inhibit protein tyrosine phosphatase 1B (PTP1B), which is a potential therapeutic target in the treatment of type 2 diabetes. Bromophenols 5, 6, and 7 showed strong activities with IC50 values of 3.9, 4.3, and 3.5 μmol/L, respectively. This study provides further evidence that bromophenols are predominant among the chemical constituents of Symphyocladia, and that some of these compounds may be candidates for the development of anti-diabetes drugs.

  16. Relaxation of a 1-D gravitational system

    CERN Document Server

    Valageas, P

    2006-01-01

    We study the relaxation towards thermodynamical equilibrium of a 1-D gravitational system. This OSC model shows a series of critical energies $E_{cn}$ where new equilibria appear and we focus on the homogeneous ($n=0$), one-peak ($n=\\pm 1$) and two-peak ($n=2$) states. Using numerical simulations we investigate the relaxation to the stable equilibrium $n=\\pm 1$ of this $N-$body system starting from initial conditions defined by equilibria $n=0$ and $n=2$. We find that in a fashion similar to other long-range systems the relaxation involves a fast violent relaxation phase followed by a slow collisional phase as the system goes through a series of quasi-stationary states. Moreover, in cases where this slow second stage leads to a dynamically unstable configuration (two peaks with a high mass ratio) it is followed by a new sequence ``violent relaxation/slow collisional relaxation''. We obtain an analytical estimate of the relaxation time $t_{2\\to \\pm 1}$ through the mean escape time of a particle from its potent...

  17. The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors.

    Science.gov (United States)

    Nojimoto, F D; Mueller, A; Hebeler-Barbosa, F; Akinaga, J; Lima, V; Kiguti, L R de A; Pupo, A S

    2010-01-01

    Although it is long known that the tricyclic antidepressants amitriptyline, nortriptyline and imipramine inhibit the noradrenaline transporter and alpha(1)-adrenoceptors with similar affinities, which may lead to self-cancelling actions, the selectivity of these drugs for alpha(1)-adrenoceptor subtypes is unknown. The present study investigates the selectivity of amitriptyline, nortriptyline and imipramine for human recombinant and rat native alpha(1)-adrenoceptor subtypes. The selectivity of amitriptyline, nortriptyline and imipramine was investigated in HEK-293 cells expressing each of the human alpha(1)-subtypes and in rat native receptors from the vas deferens (alpha(1A)), spleen (alpha(1B)) and aorta (alpha(1D)) through [(3)H]prazosin binding, and noradrenaline-induced intracellular Ca(2+) increases and contraction assays. Amitriptyline, nortriptyline and imipramine showed considerably higher affinities for alpha(1A)- (approximately 25- to 80-fold) and alpha(1D)-adrenoceptors (approximately 10- to 25-fold) than for alpha(1B)-adrenoceptors in both contraction and [(3)H]prazosin binding assays with rat native and human receptors, respectively. In addition, amitriptyline, nortriptyline and imipramine were substantially more potent in the inhibition of noradrenaline-induced intracellular Ca(2+) increases in HEK-293 cells expressing alpha(1A)- or a truncated version of alpha(1D)-adrenoceptors which traffics more efficiently towards the cell membrane than in cells expressing alpha(1B)-adrenoceptors. Amitriptyline, nortriptyline and imipramine are much weaker antagonists of rat and human alpha(1B)-adrenoceptors than of alpha(1A)- and alpha(1D)-adrenoceptors. The differential affinities for these receptors indicate that the alpha(1)-adrenoceptor subtype which activation is most increased by the augmented noradrenaline availability resultant from the blockade of neuronal reuptake is the alpha(1B)-adrenoceptor. This may be important for the behavioural effects of these

  18. AMYLOID-β PEPTIDE BINDS TO MICROTUBULE-ASSOCIATED PROTEIN 1B (MAP1B)

    Science.gov (United States)

    Gevorkian, Goar; Gonzalez-Noriega, Alfonso; Acero, Gonzalo; Ordoñez, Jorge; Michalak, Colette; Munguia, Maria Elena; Govezensky, Tzipe; Cribbs, David H.; Manoutcharian, Karen

    2008-01-01

    Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer’s disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer’s disease. PMID:18079022

  19. Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions

    Directory of Open Access Journals (Sweden)

    Eleni Kotsampasakou

    2017-04-01

    Full Text Available Hyperbilirubinemia is a pathological condition, very often indicative of underlying liver condition that is characterized by excessive accumulation of conjugated or unconjugated bilirubin in sinusoidal blood. In literature there are several indications associating the inhibition of the basolateral hepatic transporters Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and 1B3 with hyperbilirubinemia. In this article, we present a curated human hyperbilirubinemia dataset and the respective OATP1B1 and 1B3 inhibition predictions obtained from an effort to generate a classification model for hyperbilirubinemia. These data originate from the research article “Linking organic anion transporting polypeptide 1b1 and 1b3 (oatp1b1 and oatp1b3 interaction profiles to hepatotoxicity- the hyperbilirubinemia use case” (E. Kotsampasakou, S.E. Escher, G.F. Ecker, 2017 [1]. We further provide the full list of descriptors used for generating the hyperbilirubinemia classification models as well as the calculated descriptors for each compound of the dataset that was used to build the classification model.

  20. Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions.

    Science.gov (United States)

    Kotsampasakou, Eleni; Escher, Sylvia E; Ecker, Gerhard F

    2017-04-01

    Hyperbilirubinemia is a pathological condition, very often indicative of underlying liver condition that is characterized by excessive accumulation of conjugated or unconjugated bilirubin in sinusoidal blood. In literature there are several indications associating the inhibition of the basolateral hepatic transporters Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and 1B3) with hyperbilirubinemia. In this article, we present a curated human hyperbilirubinemia dataset and the respective OATP1B1 and 1B3 inhibition predictions obtained from an effort to generate a classification model for hyperbilirubinemia. These data originate from the research article "Linking organic anion transporting polypeptide 1b1 and 1b3 (oatp1b1 and oatp1b3) interaction profiles to hepatotoxicity- the hyperbilirubinemia use case" (E. Kotsampasakou, S.E. Escher, G.F. Ecker, 2017) [1]. We further provide the full list of descriptors used for generating the hyperbilirubinemia classification models as well as the calculated descriptors for each compound of the dataset that was used to build the classification model.

  1. Overexpression and enhanced specific activity of aldoketo reductases (AKR1B1 & AKR1B10) in human breast cancers.

    Science.gov (United States)

    Reddy, K Ashok; Kumar, P Uday; Srinivasulu, M; Triveni, B; Sharada, K; Ismail, Ayesha; Reddy, G Bhanuprakash

    2017-02-01

    The incidence of breast cancer in India is on the rise and is rapidly becoming the primary cancer in Indian women. The aldoketo reductase (AKR) family has more than 190 proteins including aldose reductase (AKR1B1) and aldose reductase like protein (AKR1B10). Apart from liver cancer, the status of AKR1B1 and AKR1B10 with respect to their expression and activity has not been reported in other human cancers. We studied the specific activity and expression of AKR1B1 and AKR1B10 in breast non tumor and tumor tissues and in the blood. Fresh post-surgical breast cancer and non-cancer tissues and blood were collected from the subjects who were admitted for surgical therapy. Malignant, benign and pre-surgical chemotherapy samples were evaluated by histopathology scoring. Expression of AKR1B1 and AKR1B10 was carried out by immunoblotting and immunohistochemistry (IHC) while specific activity was determined spectrophotometrically. The specific activity of AKR1B1 was significantly higher in red blood cells (RBC) in all three grades of primary surgical and post-chemotherapy samples. Specific activity of both AKR1B1 and AKR1B10 increased in tumor samples compared to their corresponding non tumor samples (primary surgical and post-chemotherapy). Immunoblotting and IHC data also indicated overexpression of AKR1B1 in all grades of tumors compared to their corresponding non tumor samples. There was no change in the specific activity of AKR1B1 in benign samples compared to all grades of tumor and non-tumors.

  2. MAN1B1 deficiency: an unexpected CDG-II.

    Directory of Open Access Journals (Sweden)

    Daisy Rymen

    Full Text Available Congenital disorders of glycosylation (CDG are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD. However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.

  3. 1D-1D Coulomb drag in a 6 Million Mobility Bi-layer Heterostructure

    Science.gov (United States)

    Bilodeau, Simon; Laroche, Dominique; Xia, Jian-Sheng; Lilly, Mike; Reno, John; Pfeiffer, Loren; West, Ken; Gervais, Guillaume

    We report Coulomb drag measurements in vertically-coupled quantum wires. The wires are fabricated in GaAs/AlGaAs bilayer heterostructures grown from two different MBE chambers: one at Sandia National Laboratories (1.2M mobility), and the other at Princeton University (6M mobility). The previously observed positive and negative drag signals are seen in both types of devices, demonstrating the robustness of the result. However, attempts to determine the temperature dependence of the drag signal in the 1D regime proved challenging in the higher mobility heterostructure (Princeton), in part because of difficulties in aligning the wires within the same transverse subband configuration. Nevertheless, this work, performed at the Microkelvin laboratory of the University of Florida, is an important proof-of-concept for future investigations of the temperature dependence of the 1D-1D drag signal down to a few mK. Such an experiment could confirm the Luttinger charge density wave interlocking predicted to occur in the wires. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL8500.

  4. Aldo-Keto Reductases 1B in Endocrinology and Metabolism.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers.

  5. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  6. 18 CFR 1b.20 - Request for confidential treatment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Request for confidential treatment. 1b.20 Section 1b.20 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... disclosure requirements of the Freedom of Information Act (5 U.S.C. 552), is information referred to in 18...

  7. CYP1B1 and hormone-induced cancer.

    Science.gov (United States)

    Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-11-01

    Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.

  8. Analysis list: Nr1d2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nr1d2 Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d2.1.tsv... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d2.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d...2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d2.Liver.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  9. Analysis list: Nr1d1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nr1d1 Adipocyte,Cardiovascular,Liver,Neural + mm9 http://dbarchive.biosciencedbc.jp.../kyushu-u/mm9/target/Nr1d1.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d1.5.tsv http://db...archive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1....Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1.C...ardiovascular.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d1.Liver.tsv,http://dbarchive.biosc

  10. Gi-protein-coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming.

    Science.gov (United States)

    Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D

    2016-08-01

    We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/D Gi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/D agonist, produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε, but not a protein kinase A inhibitor attenuated the prolongation phase of PGE2 hyperalgesia. The prolongation of PGE2 hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pretreated with pertussis toxin or isolectin B4-positive nociceptor toxin, IB4-saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by coinjection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors and completely prevented by coadministration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals through Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.

  11. CYP1B1: a unique gene with unique characteristics.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.

  12. Synthesis and protein tyrosine phosphatase 1B inhibition activities of two new synthetic bromophenols and their methoxy derivatives

    Science.gov (United States)

    Cui, Yongchao; Shi, Dayong; Hu, Zhiqiang

    2011-11-01

    3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol ( 1) is a natural bromophenol isolated from the red algae Rhodomela confervoides that exhibits significant inhibition against protein tyrosine phosphatase 1B (PTP1B). Based on its activity, we synthesized two new synthetic bromophenols and their methoxy derivatives from vanillin using the structure of natural bromophenol 1 as a scaffold. The structures of these bromophenols were elucidated from 1H NMR, 13C NMR, and high resolution electron ionization mass spectrometry as 2,3-dibromo-1-(2'-bromo-6'-(3″,4″-dimethoxybenzyl)-3',4'-dimethoxybenzyl)-4,5-dimethoxybenzene ( 2), 2,3-dibromo-1-(2'-bromo-6'-(2″-bromo-4″,5″-dimethoxybenzyl)-3',4'-dimethoxybenzyl)-4,5-dimethoxybenzene ( 3), 3,4-dibromo-5-(2'-bromo-6'-(2″-bromo-4″,5″-dihydroxybenzyl)-3',4'-dihydroxybenzyl)pyrocatechol ( 4) and 3,4-dibromo-5-(2'-bromo-6'-(3″,4″-dihydroxybenzyl)-3',4'-dihydroxybenzyl)pyrocatechol ( 5). PTP1B inhibition activities of these compounds were evaluated using a colorimetric assay, and compounds 3 and 4 demonstrated interesting activity against PTP1B.

  13. [Solubilization Specificities Interferon beta-1b from Inclusion Bodies].

    Science.gov (United States)

    Zhuravko, A S; Kononova, N V; Bobruskin, A I

    2015-01-01

    A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.

  14. Reversible supra-channel effects: 3D kagome structure and catalysis via a molecular array of 1D coordination polymers.

    Science.gov (United States)

    Lee, Haeri; Noh, Tae Hwan; Jung, Ok-Sang

    2013-10-14

    Self-assembly of CuX2 (X(-) = ClO4(-) and BF4(-)) with 2,3-bis(nicotinoyloxy)naphthalene yields a 1D loop-chain skeleton. The loop-chains form an ensemble constituting a unique 3D kagome-type structure with both hexagonal and trigonal supra-channels. The unprecedented supra-channel effects on the catalytic oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylbenzoquinone were investigated.

  15. Generation of Bayesian prediction models for OATP-mediated drug-drug interactions based on inhibition screen of OATP1B1, OATP1B1∗15 and OATP1B3

    NARCIS (Netherlands)

    Steeg, E. van de; Venhorst, J.; Jansen, H.T.; Nooijen, I.H.G.; Degroot, J.; Wortelboer, H.M.; Vlaming, M.L.H.

    2015-01-01

    Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of

  16. Hepatic protein tyrosine phosphatase 1B (PTP1B) deficiency protects against obesity-induced endothelial dysfunction.

    Science.gov (United States)

    Agouni, Abdelali; Tual-Chalot, Simon; Chalopin, Matthieu; Duluc, Lucie; Mody, Nimesh; Martinez, M Carmen; Andriantsitohaina, Ramaroson; Delibegović, Mirela

    2014-12-15

    Growing evidence suggests that hepatic-insulin resistance is sufficient to promote progression to cardiovascular disease. We have shown previously that liver-specific protein-tyrosine-phosphatase 1B (PTP1B) deficiency improves hepatic-insulin sensitivity and whole-body glucose homeostasis. The aim of this study was to investigate the impact of liver-specific PTP1B-deficiency (L-PTP1B-/-) on cardiac and peripheral vascular function, with special emphasis on endothelial function in the context of high-fat diet (HFD)-induced obesity. L-PTP1B-/- mice exhibited an improved glucose and lipid homeostasis and increased insulin sensitivity, without changes in body weight. HFD-feeding increased systolic blood pressure (BP) in both L-PTP1B-/- and control littermates; however, this was significantly lower in L-PTP1B-/- mice. HFD-feeding increased diastolic BP in control mice only, whilst the L-PTP1B-/- mice were completely protected. The analysis of the function of the left ventricle (LV) revealed that HFD-feeding decreased LV fractional shortening in control animals, which was not observed in L-PTP1B-/- mice. Importantly, HFD feeding significantly impaired endothelium-dependent vasorelaxation in response to acetylcholine in aortas from control mice, whilst L-PTP1B-/- mice were fully protected. This was associated with alterations in eNOS phosphorylation. Selective inhibition of COX-2, using NS-398, decreased the contractile response in response to serotonin (5-HT) only in vessels from control mice. HFD-fed control mice released enhanced levels of prostaglandin E, a vasoconstrictor metabolite; whilst both chow- and HFD-fed L-PTP1B-/- mice released higher levels of prostacylin, a vasorelaxant metabolite. Our data indicate that hepatic-PTP1B inhibition protects against HFD-induced endothelial dysfunction, underscoring the potential of peripheral PTP1B inhibitors in reduction of obesity-associated cardiovascular risk in addition to its anti-diabetic effects.

  17. TES/Aura L1B Spectra Limb V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Limb granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for an entire Global Survey &...

  18. TES/Aura L1B Spectra Limb V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Limb granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for an entire Global Survey &...

  19. TES/Aura L1B Spectra Nadir V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  20. TES/Aura L1B Spectra Nadir V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  1. 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

    DEFF Research Database (Denmark)

    Knight, Y E; Edvinsson, L; Goadsby, P J

    2001-01-01

    )-mediated effects, that was developed as an anti-migraine drug, and thus was suitable to test whether higher doses of such conformationally restricted triptan analogues could inhibit trigeminal-evoked CGRP release. The superior sagittal sinus (SSS) was stimulated in 14 anaesthetised cats and external jugular vein...

  2. Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

    NARCIS (Netherlands)

    Boshuisen, ML; den Boer, JA

    2000-01-01

    Rationale: Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible

  3. Effects of avitriptan, a new 5 HT(1B/1D) receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential

    NARCIS (Netherlands)

    P.R. Saxena (Pramod Ranjan); P.A.M. de Vries (Peter); W. Wang (Wei); J.P. Heiligers (Jan); A. Maassen VanDenBrink (Antoinette); W.A. Bax (Willem); F.D. Yocca (Frank)

    1997-01-01

    markdownabstractAbstract Several acutely acting antimigraine drugs, including ergotamine and sumatriptan, have the ability to constrict porcine arteriovenous anastomoses as well as the human isolated coronary artery. These two experimental models seem to serve as indicators, respectively, for the

  4. The relevance of preclinical research models for the development of antimigraine drugs: Focus on 5-HT1B/1D and CGRP receptors

    DEFF Research Database (Denmark)

    Gupta, S.; Villalon, C.M.

    2010-01-01

    Migraine is a complex neurovascular syndrome, causing a unilateral pulsating headache with accompanying symptoms. The past four decades have contributed immensely to our present understanding of migraine pathophysiology and have led to the introduction of specific antimigraine therapies, much......-score to evaluate migraine, as articulated by the volunteer, which cannot be applied to laboratory animals. Therefore, basic research focuses on different symptoms and putative mechanisms, one at a time or in combination, to validate the hypotheses. Studies in several species, utilizing different preclinical...... to the relief of migraineurs. Pathophysiological factors culminating into migraine headaches have not yet been completely deciphered and, thus, pose an additional challenge for preclinical research in the absence of any direct experimental marker. Migraine provocation experiments in humans use a head...

  5. CIAE Signs Contract on B1/B2 Project

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    CIAE signed Contract on Design,Commissioning and Technology Service for B1/B2 Project of Birine Reactor with CZEC in December,2015.The B1/B2 project which was won over by CZEC is PhaseⅠand PhaseⅡof an Algeria project which aimed to upgrade and rebuild Algeria Birine Nuclear Research Center.According to the contract with total fund amounting to 110million Yuan,CIAE will provide

  6. Aldo-keto reductases 1B in adrenal cortex physiology

    Directory of Open Access Journals (Sweden)

    Emilie PASTEL

    2016-07-01

    Full Text Available Aldose reductase proteins are cytosolic monomeric enzymes, belonging to the aldo-keto reductase (AKR superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates such as aliphatic and aromatic aldehydes or ketones. The Aldose reductase subgroup (AKR1B is one of the most characterized because of its involvement in human diseases such as diabetic complications resulting from the ability of its human archetype AKR1B1 to reduce glucose into sorbitol. However the issue of AKR1B function in non pathologic condition remains poorly resolved. Adrenal steroidogenesis is strongly associated with high production of endogenous harmful lipid aldehyde by-products including isocaproaldehyde (4-methylpentanal derived from cholesterol side chain cleavage (the first step of steroid synthesis and 4-hydroxynonenal (4- HNE that can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase activity, suggesting that in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, previous studies have established that the adrenal gland is one of the major site for human and murine AKR1B expression suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms.This review presents the molecular mechanisms accounting for the adrenal specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  7. Association of transcription factor gene LMX1B with autism.

    Directory of Open Access Journals (Sweden)

    Ismail Thanseem

    Full Text Available Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217 showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008. Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049. Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  8. Association of transcription factor gene LMX1B with autism.

    Science.gov (United States)

    Thanseem, Ismail; Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Tsujii, Masatsugu; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Iwata, Keiko; Sugiyama, Toshiro; Yoshikawa, Takeo; Mori, Norio

    2011-01-01

    Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  9. PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

    Science.gov (United States)

    Li, Jin-Long; Gao, Li-Xin; Meng, Fan-Wang; Tang, Chun-Lan; Zhang, Ru-Jun; Li, Jing-Ya; Luo, Cheng; Li, Jia; Zhao, Wei-Min

    2015-01-01

    Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.

  10. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Qadri, Rizwana; Dada, Tanuj

    2015-01-01

    CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80.

  11. Encapsulated discrete octameric water cluster, 1D water tape, and 3D water aggregate network in diverse MOFs based on bisimidazolium ligands

    Science.gov (United States)

    Shi, Ruo-Bing; Pi, Min; Jiang, Shuang-Shuang; Wang, Yuan-Yuan; Jin, Chuan-Ming

    2014-08-01

    Four new metal-organic frameworks, [Zn(2-mBIM)2(SO3CF3)2·(H2O)4] (1), [Zn(BMIE)(1,4-BDC)]·(H2O)3 (2), [Cd(BIM)2(OH)(H2O)2(PF6)]·(H2O)4 (3), and [Cd(PA-BIM)2 (ClO4)2]·11.33H2O (4) (2-mBIM = bis(2-methylimidazol-1-yl)methane, BMIE = 1,2-bis[1-(2-methylimidazole)-diethoxy]ethane, BIM = bis(imidazol-1-yl)methane, and PA-BIM = 1,1-bis [(2-phenylazo)imidazol-1-yl]methane) have been prepared and structurally characterized. Complex 1 exhibits an infinite 1D cationic beaded-chain structure, which encapsulated discrete octameric water clusters that are comprised of a chair-like hexameric water cluster with two extra water molecules dangling on two diagonal vertices of the chair. Complex 2 forms a 1D infinite zigzag metal-organic chain structure with a 1D T4(0)A(4) water tape. Complexes 3 show a 2D grid-like sheet structure with the 1D water tape T4(0)A(0)2(0) motif. Complex 4 is a porous 3D MOF with tetrahedron-coordinated Cd(II) centers and trans-conformation PA-BIM ligands. These holes are occupied by a fascinating three-dimensional water clathrate network, which consists of cage-shaped structural tetradecameric water cluster (H2O)14 units and six independent bridged water molecules. The results suggest that the bisimidazolium ligands and anions play crucial roles in the formation of the different host structures and different guest water aggregations. Additionally, the thermal stabilities and photoluminescence spectra of the complexes have been discussed.

  12. A 1D version of EllipSys

    DEFF Research Database (Denmark)

    van der Laan, Paul; Sørensen, Niels N.

    2017-01-01

    A one-dimensional version of EllipSys, labeled as EllipSys1D is presented. Three atmospheric boundary layer test cases are used to show that results of EllipSys1D are exactly the same or very similar as results of EllipSys3D, while EllipSys1D uses 3 to 4 orders of magnitude less CPU hours compared...

  13. Bis[μ-3,5-bis(pyridin-2-ylpyrazolato]bis[(hexafluorophosphatocopper(II

    Directory of Open Access Journals (Sweden)

    Satoshi Kawata

    2013-08-01

    Full Text Available The title dinuclear complex molecule, [Cu2(C13H9N42(PF62], lies about an inversion center. The CuII atom shows a square-pyramidal coordination geometry with the basal plane formed by four N atoms of the two bis-chelating 3,5-bis(pyridin-2-ylpyrazolate ions and with one F atom of the hexafluorophosphate ion in the apical position. Molecules are stacked in a column along the a axis through C—H...F hydrogen bonds. The columns are further linked by other C—H...F hydrogen bonds, forming a three-dimensional network.

  14. [1,2-Bis(diphenylphosphinoethane]{2-[bis(diphenylphosphinomethylamino]pyridinium}fluoridohydrazidatomolybdenum(IV bis(tetrafluoridoborate

    Directory of Open Access Journals (Sweden)

    Felix Tuczek

    2008-05-01

    Full Text Available In the crystal structure of the title compound, [MoF(N2H2(C31H29N2P2(C26H24P2](BF42, each Mo atom is surrounded by four P atoms of one 1,2-bis(diphenylphosphinoethane and one 2-[bis(diphenylphosphinomethylamino]pyridinium ligand. The remaining binding sites of the distorted octahedron are occupied by a hydrazidate (NNH22− and a fluoride ligand. Two F atoms of an anion are disordered over two positions; the site occupancy factors are ca 0.7 and 0.3.

  15. Diffusion and particle mobility in 1D system

    NARCIS (Netherlands)

    Borman, V. D.; Johansson, B.; Skorodumova, N. V.; Tronin, I. V.; Tronin, V. N.; Troyan, V. I.

    2006-01-01

    The transport properties of one-dimensional (1D) systems have been studied theoretically. Contradictory experimental results on molecular transport in quasi-1D systems, such as zeolite structures, when both diffusion transport acceleration and the existence of the diffusion mode with lower particle

  16. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  17. LMX1B Mutations Cause Hereditary FSGS without Extrarenal Involvement

    Science.gov (United States)

    Boyer, Olivia; Woerner, Stéphanie; Yang, Fan; Oakeley, Edward J.; Linghu, Bolan; Gribouval, Olivier; Tête, Marie-Josèphe; Duca, José S.; Klickstein, Lloyd; Damask, Amy J.; Szustakowski, Joseph D.; Heibel, Françoise; Matignon, Marie; Baudouin, Véronique; Chantrel, François; Champigneulle, Jacqueline; Martin, Laurent; Nitschké, Patrick; Gubler, Marie-Claire; Johnson, Keith J.; Chibout, Salah-Dine

    2013-01-01

    LMX1B encodes a homeodomain-containing transcription factor that is essential during development. Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM). By linkage analysis and exome sequencing, we unexpectedly identified an LMX1B mutation segregating with disease in a pedigree of five patients with autosomal dominant FSGS but without either extrarenal features or ultrastructural abnormalities of the GBM suggestive of nail-patella–like renal disease. Subsequently, we screened 73 additional unrelated families with FSGS and found mutations involving the same amino acid (R246) in 2 families. An LMX1B in silico homology model suggested that the mutated residue plays an important role in strengthening the interaction between the LMX1B homeodomain and DNA; both identified mutations would be expected to diminish such interactions. In summary, these results suggest that isolated FSGS could result from mutations in genes that are also involved in syndromic forms of FSGS. This highlights the need to include these genes in all diagnostic approaches to FSGS that involve next-generation sequencing. PMID:23687361

  18. Synthesis, characterization, and reactivity of furan- and thiophene-functionalized bis(n-heterocyclic carbene) complexes of iron(II)

    KAUST Repository

    Rieb, Julia

    2014-09-15

    The synthesis of iron(II) complexes bearing new heteroatom-functionalized methylene-bridged bis(N-heterocyclic carbene) ligands is reported. All complexes are characterized by single-crystal X-ray diffraction (SC-XRD), nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Tetrakis(acetonitrile)-cis-[bis(o-imidazol-2-ylidenefuran)methane]iron(II) hexafluorophosphate (2a) and tetrakis(acetonitrile)-cis-[bis(o-imidazol-2-ylidenethiophene)methane]iron(II) hexafluorophosphate (2b) were obtained by aminolysis of [Fe{N(SiMe3)2}2(THF)] with furan- and thiophene-functionalized bis(imidazolium) salts 1a and 1b in acetonitrile. The SC-XRD structures of 2a and 2b show coordination of the bis(carbene) ligand in a bidentate fashion instead of a possible tetradentate coordination. The four other coordination sites of these distorted octahedral complexes are occupied by acetonitrile ligands. Crystallization of 2a in an acetone solution by the slow diffusion of Et2O led to the formation of cisdiacetonitriledi[ bis(o-imidazol-2-ylidenefuran)methane]iron(II) hexafluorophosphate (3a) with two bis(carbene) ligands coordinated in a bidentate manner and two cis-positioned acetonitrile molecules. Compounds 2a and 2b are the first reported iron(II) carbene complexes with four coordination sites occupied by solvent molecules, and it was demonstrated that those solvent ligands can undergo ligand-exchange reactions.

  19. Fluorescent sensing and electrocatalytic properties of three Zn(II)/Co(II) coordination complexes containing two different dicarboxylates and two various bis(pyridyl)-bis(amide) ligands

    Science.gov (United States)

    Lin, Hongyan; Rong, Xing; Liu, Guocheng; Wang, Xiang; Wang, Xiuli; Duan, Surui

    2016-09-01

    Three new transition metal(II) coordination complexes constructed from two different dicarboxylates (1,3-H2BDC = 1,3-benzenedicarboxylic acid, 1,4-H2NDC = 1,4-naphthalenedicarboxylic acid) and two bis(pyridyl)-bis(amide) ligands (3-bpcd = N,N‧-bis(3-pyridyl)cyclohexane-1,4-dicarboxamide, 3-bpod = N,N‧-bis(3-pyridyl)octandiamide), [Zn(1,3-BDC)(3-bpcd)0.5(H2O)]·H2O (1), [Zn(1,3-BDC)(3-bpod)0.5(H2O)] (2) and [Co(1,4-NDC)(3-bpod)1.5(H2O)] (3) have been synthesized in the hydrothermal environments and structurally characterized by IR, TG and single crystal X-ray diffraction. Complexes 1 and 2 possess the similar 1D ladder-like chain based on [Zn(1,3-BDC)]n zigzag chain and the bidentate ligands 3-bpcd/or 3-bpod. Complex 3 shows a 2D layered structure with a 5-connected {410} topology, which consists of 1D linear [Co(1,4-NDC)]n chain and [Co(3-bpod)1.5]n chain with alternating arrangement of 3-bpod ligands and Co2(3-bpod)2 dinuclear loops. The adjacent 1D chains for 1-2 or the 2D layers for 3 are further extended into 2D or 3D supramolecular frameworks through the hydrogen bonding interactions. Additionally, the solid state fluorescent properties for the title complexes 1-3, the fluorescent sensing behaviors of complexes 1-2 and the electrochemical behaviour of complex 3 have been investigated.

  20. Interaction of environmental contaminants with zebrafish organic anion transporting polypeptide, Oatp1d1 (Slco1d1)

    Energy Technology Data Exchange (ETDEWEB)

    Popovic, Marta; Zaja, Roko [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia); Fent, Karl [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich (Switzerland); Smital, Tvrtko, E-mail: smital@irb.hr [Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10 000 Zagreb (Croatia)

    2014-10-01

    Polyspecific transporters from the organic anion transporting polypeptide (OATP/Oatp) superfamily mediate the uptake of a wide range of compounds. In zebrafish, Oatp1d1 transports conjugated steroid hormones and cortisol. It is predominantly expressed in the liver, brain and testes. In this study we have characterized the transport of xenobiotics by the zebrafish Oatp1d1 transporter. We developed a novel assay for assessing Oatp1d1 interactors using the fluorescent probe Lucifer yellow and transient transfection in HEK293 cells. Our data showed that numerous environmental contaminants interact with zebrafish Oatp1d1. Oatp1d1 mediated the transport of diclofenac with very high affinity, followed by high affinity towards perfluorooctanesulfonic acid (PFOS), nonylphenol, gemfibrozil and 17α-ethinylestradiol; moderate affinity towards carbaryl, diazinon and caffeine; and low affinity towards metolachlor. Importantly, many environmental chemicals acted as strong inhibitors of Oatp1d1. A strong inhibition of Oatp1d1 transport activity was found by perfluorooctanoic acid (PFOA), chlorpyrifos-methyl, estrone (E1) and 17β-estradiol (E2), followed by moderate to low inhibition by diethyl phthalate, bisphenol A, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4 tetrahydronapthalene and clofibrate. In this study we identified Oatp1d1 as a first Solute Carrier (SLC) transporter involved in the transport of a wide range of xenobiotics in fish. Considering that Oatps in zebrafish have not been characterized before, our work on zebrafish Oatp1d1 offers important new insights on the understanding of uptake processes of environmental contaminants, and contributes to the better characterization of zebrafish as a model species. - Highlights: • We optimized a novel assay for determination of Oatp1d1 interactors • Oatp1d1 is the first SLC characterized fish xenobiotic transporter • PFOS, nonylphenol, diclofenac, EE2, caffeine are high affinity Oatp1d1substrates • PFOA, chlorpyrifos

  1. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

    Science.gov (United States)

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-03-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

  2. Origin of vestibular dysfunction in Usher syndrome type 1B.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by

  3. Origin of vestibular dysfunction in Usher syndrome type 1B.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by in

  4. RELAP5 Calculations of Bethsy 9.1b Test

    Directory of Open Access Journals (Sweden)

    Andrej Prošek

    2012-01-01

    Full Text Available Recently, several advanced computational tools for simulating reactor system behavior during real and hypothetical transient scenarios were developed. The TRAC/RELAP Advanced Computational Engine (TRACE is the latest in a series of advanced, best-estimate reactor system codes developed by the United States Nuclear Regulatory Commission (US NRC. Nevertheless, the RELAP5/MOD3.3 computer code will be maintained in the next years. The purpose of the present study was to assess how the accuracy of Bethsy 9.1b test calculation depends on the US NRC RELAP5 code version used. Bethsy 9.1b test (International Standard Problem no. 27 was 5.08 cm equivalent diameter cold leg break without high-pressure safety injection and with delayed ultimate procedure. Seven different RELAP5 code versions were used and as much as possible the same input model. The obtained results indicate that the results obtained by the oldest and latest RELAP5 versions are in general comparable for Bethsy 9.1b test. This is very important for the validity of the results, obtained in the past with older RELAP5 versions. Due to the fact that observation was restricted to Bethsy 9.1b posttest, with its own physical phenomena, this conclusion could be generalized only for scenarios having similar range of the considered Bethsy transient conditions.

  5. PTP1B targets the endosomal sorting machinery

    DEFF Research Database (Denmark)

    Stuible, Matthew; Abella, Jasmine V; Feldhammer, Matthew;

    2010-01-01

    STAM2 specifically suppressed Akt activation, and a phosphorylation-deficient STAM2 mutant displayed prolonged localization on endosomes following EGF stimulation. These results reveal a novel link between the dephosphorylation and endocytic machinery and suggest that PTP1B can affect RTK signaling...

  6. Solid-state phosphorescence of trans-bis(salicylaldiminato)platinum(II) complexes bearing long alkyl chains: morphology control towards intense emission.

    Science.gov (United States)

    Komiya, Naruyoshi; Itami, Nao; Naota, Takeshi

    2013-07-15

    Morphology control for intense solid-state phosphorescence of non-emissive, but potentially emissive crystals of platinum complexes and the mechanistic rationale are described. A series of trans-bis(salicylaldiminato)platinum(II) complexes bearing linear alkyl chains (1a: n=5; 1b: n=8; 1c: n=12; 1d: n=14; 1e: n=16; 1f: n=18) was synthesized and the solid-state emission properties were examined by using crystals/aggregates prepared under various precipitation conditions. Crystals of 1e, prepared using "kinetic" conditions including rapid cooling, high concentrations, and poor solvents, emit intensive yellow phosphorescence (λ(max)=545 nm) under UV irradiation at 298 K with an absolute quantum efficiency of 0.36, whereas all the crystals of 1a-1f prepared using "thermodynamic" conditions including slow cooling, low concentrations, and good solvents were either non- or less emissive with Φ(298K) values of 0.12 (1a), 0.11 (1b), 0.10 (1c), 0.07 (1d), 0.02 (1e), and 0.02 (1f) under the same measurement conditions. The amorphous solid 1e, prepared by rapid cooling and freeze-drying, was also non-emissive (Φ(298K)=0.02, 0.02). Temperature-dependent emission spectra showed that the kinetic crystals of 1e exhibit high heat-resistance towards emission decay with increasing temperature, whereas the amorphous solid 1e is entirely heat-quenchable. This is a rare example of the change from a non-emissive crystal into a highly emissive crystal by morphology control through crystal engineering. Emission spectra and powder X-ray diffraction (XRD) patterns of the emissive, kinetic crystals of 1e are clearly distinct from those of the less emissive, thermodynamic crystals of 1a-1f. Single-crystal XRD unequivocally establishes that the thermodynamic crystals of 1d have a multilayered lamellar structure supported by highly regulated, consecutive π-stacking interactions between imine moieties, whereas the kinetic crystals of 1e have a face-to-edge lamellar structure with less

  7. The Gain Properties of 1-D Active Photonic Crystal

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The terminology 'ID frequency'(w ID) is proposed after analyzing the 1D active photonic crystal based on the transfer matrix method. The relationship between wID and the structure parameters of the photonic crystal is investigated.

  8. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

    Science.gov (United States)

    Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

    2016-04-01

    High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone.

  9. IMPROVEMENTS OF RIVER MODELING 1D DATA PREPARATION

    Directory of Open Access Journals (Sweden)

    ION-MARIAN MOISOIU

    2012-11-01

    Full Text Available Improvements of river modeling 1D data preparation. The importance of hydrographical networks data and the need for detailed studies do generate an increase of projects in this specialized area and a diversification of river mathematical modeling software. River mathematical modeling can be done in two ways, namely; the "2D mode" and the “1D mode”. The “2D mode” is where a digital terrain model of a full hydrographical basin must be produced and "1D mode" is where only cross sections, long sections and structures elevations needs to be presented in a graphical environment and in a specific formats for the mathematical modeling software. This paper will show the principle of a custom built GIS, specially created to help the preparation of 1D river modeling data. The benefits are; elimination of human errors, automated processing, increasing productivity, flexible output and cost reduction.

  10. Self-assembly, structures and properties of three new Ni(II) coordination polymers derived from two different bis-pyridyl-bis-amide ligands and two aromatic polycarboxylates

    Indian Academy of Sciences (India)

    HONGYAN LIN; JUNJUN SUN; GUOCHENG LIU; XIANG WANG; PANWEN CHEN

    2017-01-01

    Three new Ni(II) coordination polymers exhibiting different 1D and 2D framework structures have been hydrothermally synthesized: [Ni(L ¹)(1,3-BDC)(H ₂O) ₃]•H ₂O (1), [Ni(L ¹)(1,3,5-HBTC)(H ₂O) ₃] (2), [Ni ₃ (L ²)3(1,3,5-BTC) ₂ (H ₂O)8]•12H ₂ ₂O (3) [L ¹ = N,N_-bis(pyridin-3-yl)cyclohexane-1,4-dicarboxamide, L ² = N,N’-bis(3-pyridyl)octandiamide, 1,3-H ₂BDC = 1,3-benzenedicarboxylic acid, 1,3,5-H3BTC = 1,3,5- benzenetricarboxylic acid]. X-ray single crystal diffraction analyses revealed that polymer 1 is a 2D interlaced layer based on the 1D [Ni(L ¹)(1,3-BDC)(H ₂O) ₃] meso-helical chains. Polymer 2 is a 1D wave-shaped chain derived from the 1D [Ni(L ¹)]n chain and monodentate coordinated 1,3,5-HBTC anions. Polymer 3 possesses an interesting 2D layer containing the trinuclear [Ni ₃ (1,3,5-BTC) ₂] substructural unit and 1D zigzag [Ni(L ²)]n chain, representing a 3,4-connected {6•8 ²} ₂{6 ² •8 ² • 10• 12} topology. Finally, the adjacent 1D chains or the 2D layers are connected through hydrogen bonding interactions to construct 3D supramolecular networks. Further, the thermal stability, solid state fluorescent property and photocatalytic activity of 1–3 have been investigated.

  11. Supported plasma-made 1D heterostructures: perspectives and applications

    OpenAIRE

    Borras, Ana; Macias-Montero, Manuel; Romero-Gomez, Pablo; Gonzalez-Elipe, Agustin R.

    2011-01-01

    Abstract Plasma related methods have been widely used in the fabrication of carbon nanotubes and nanofibres and semiconducting inorganic nanowires. A natural progression of the research in the field of 1D nanostructures is the synthesis of multicomponent nanowires and nanofibres. In this article we review the state of the art of the fabrication by plasma methods of 1D heterostructures including applications and perspectives. Furthermore, recent developments on the use of metal seeds (Ag, A...

  12. 1D photonic crystal sensor integrated in a microfluidic system

    DEFF Research Database (Denmark)

    Nunes, Pedro; Mortensen, Asger; Kutter, Jörg Peter

    2009-01-01

    A refractive index sensor was designed as a 1D resonator incorporated in a microfluidic channel, where aqueous solutions were injected. A sensitivity of 480 nm/RIU and a minimum difference of Deltan = 0.002 were determined.......A refractive index sensor was designed as a 1D resonator incorporated in a microfluidic channel, where aqueous solutions were injected. A sensitivity of 480 nm/RIU and a minimum difference of Deltan = 0.002 were determined....

  13. TBC1D24 genotype–phenotype correlation

    Science.gov (United States)

    Balestrini, Simona; Milh, Mathieu; Castiglioni, Claudia; Lüthy, Kevin; Finelli, Mattea J.; Verstreken, Patrik; Cardon, Aaron; Stražišar, Barbara Gnidovec; Holder, J. Lloyd; Lesca, Gaetan; Mancardi, Maria M.; Poulat, Anne L.; Repetto, Gabriela M.; Banka, Siddharth; Bilo, Leonilda; Birkeland, Laura E.; Bosch, Friedrich; Brockmann, Knut; Cross, J. Helen; Doummar, Diane; Félix, Temis M.; Giuliano, Fabienne; Hori, Mutsuki; Hüning, Irina; Kayserili, Hulia; Kini, Usha; Lees, Melissa M.; Meenakshi, Girish; Mewasingh, Leena; Pagnamenta, Alistair T.; Peluso, Silvio; Mey, Antje; Rice, Gregory M.; Rosenfeld, Jill A.; Taylor, Jenny C.; Troester, Matthew M.; Stanley, Christine M.; Ville, Dorothee; Walkiewicz, Magdalena; Falace, Antonio; Fassio, Anna; Lemke, Johannes R.; Biskup, Saskia; Tardif, Jessica; Ajeawung, Norbert F.; Tolun, Aslihan; Corbett, Mark; Gecz, Jozef; Afawi, Zaid; Howell, Katherine B.; Oliver, Karen L.; Berkovic, Samuel F.; Scheffer, Ingrid E.; de Falco, Fabrizio A.; Oliver, Peter L.; Striano, Pasquale; Zara, Federico

    2016-01-01

    Objective: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. Methods: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). Results: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. Conclusions: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes. PMID:27281533

  14. Nascent bipolar outflows associated with the first hydrostatic core candidates Barnard 1b-N and 1b-S

    CERN Document Server

    Gerin, M; Fuente, A; Cernicharo, J; Commerçon, B; Marcelino, N

    2015-01-01

    In the theory of star formation, the first hydrostatic core (FHSC) phase is a critical step in which a condensed object emerges from a prestellar core. This step lasts about one thousand years, a very short time compared with the lifetime of prestellar cores, and therefore is hard to detect unambiguously. We present IRAM Plateau de Bure observations of the Barnard 1b dense molecular core, combining detections of H2CO and CH3OH spectral lines and dust continuum at 2.3" resolution (~ 500 AU). The two compact cores B1b-N and B1b-S are detected in the dust continuum at 2mm, with fluxes that agree with their spectral energy distribution. Molecular outflows associated with both cores are detected. They are inclined relative to the direction of the magnetic field, in agreement with predictions of collapse in turbulent and magnetized gas with a ratio of mass to magnetic flux somewhat higher than the critical value, \\mu ~ 2 - 7. The outflow associated with B1b-S presents sharp spatial structures, with ejection velocit...

  15. Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors from an Indonesian ascidian-derived Penicillium verruculosum.

    Science.gov (United States)

    Yamazaki, Hiroyuki; Nakayama, Wataru; Takahashi, Ohgi; Kirikoshi, Ryota; Izumikawa, Yuta; Iwasaki, Kohei; Toraiwa, Kengo; Ukai, Kazuyo; Rotinsulu, Henki; Wewengkang, Defny S; Sumilat, Deiske A; Mangindaan, Remy E P; Namikoshi, Michio

    2015-08-15

    Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data (1D and 2D NMR, HRMS, UV, CD, and IR). Compound 2 had a linear sesquiterpene moiety and was considered to be the derivative of the biosynthetic precursor for 1 and 3-5. Compounds 1, 3, and 5 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 8.4, 8.5, and 14.9 μM, respectively. Compound 2 showed 40% inhibition at 23.1 μM, while 4 was not active at 20.7 μM.

  16. Performance and Applications of L1B2 Ultrasonic Motors

    OpenAIRE

    Gal Peled; Roman Yasinov; Nir Karasikov

    2016-01-01

    Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operat...

  17. Lithostratigraphy from downhole logs in Hole AND-1B, Antarctica

    Science.gov (United States)

    Williams, Trevor; Morin, Roger H.; Jarrard, Richard D.; Jackolski, Chris L.; Henrys, Stuart A.; Niessen, Frank; Magens, Diana; Kuhn, Gerhard; Monien, Donata; Powell, Ross D.

    2012-01-01

    The ANDRILL (Antarctic Drilling Project) McMurdo Ice Shelf (MIS) project drilled 1285 m of sediment in Hole AND–1B, representing the past 12 m.y. of glacial history. Downhole geophysical logs were acquired to a depth of 1018 mbsf (meters below seafloor), and are complementary to data acquired from the core. The natural gamma radiation (NGR) and magnetic susceptibility logs are particularly useful for understanding lithological and paleoenvironmental change at ANDRILL McMurdo Ice Shelf Hole AND–1B. NGR logs cover the entire interval from the seafloor to 1018 mbsf, and magnetic susceptibility and other logs covered the open hole intervals between 692 and 1018 and 237–342 mbsf. In the upper part of AND–1B, clear alternations between low and high NGR values distinguish between diatomite (lacking minerals containing naturally radioactive K, U, and Th) and diamictite (containing K-bearing clays, K-feldspar, mica, and heavy minerals). In the lower open hole logged section, NGR and magnetic susceptibility can also distinguish claystones (rich in K-bearing clay minerals, relatively low in magnetite) and diamictites (relatively high in magnetite). Sandstones can be distinguished by their high resistivity values in AND–1B. On the basis of these three downhole logs, diamictite, claystones, and sandstones can be predicted correctly for 74% of the 692–1018 mbsf interval. The logs were then used to predict facies for the 6% of this interval that was unrecovered by coring. Given the understanding of the physical property characteristics of different facies, it is also possible to identify subtle changes in lithology from the physical properties and help refine parts of the lithostratigraphy, for example, the varying terrigenous content of diatomites and the transitions from subice diamictite to open-water diatomite.

  18. Pharmacophore modeling for protein tyrosine phosphatase 1B inhibitors.

    Science.gov (United States)

    Bharatham, Kavitha; Bharatham, Nagakumar; Lee, Keun Woo

    2007-05-01

    A three dimensional chemical feature based pharmacophore model was developed for the inhibitors of protein tyrosine phosphatase 1B (PTP1B) using the CATALYST software, which would provide useful knowledge for performing virtual screening to identify new inhibitors targeted toward type II diabetes and obesity. A dataset of 27 inhibitors, with diverse structural properties, and activities ranging from 0.026 to 600 microM, was selected as a training set. Hypol, the most reliable quantitative four featured pharmacophore hypothesis, was generated from a training set composed of compounds with two H-bond acceptors, one hydrophobic aromatic and one ring aromatic features. It has a correlation coefficient, RMSD and cost difference (null cost-total cost) of 0.946, 0.840 and 65.731, respectively. The best hypothesis (Hypol) was validated using four different methods. Firstly, a cross validation was performed by randomizing the data using the Cat-Scramble technique. The results confirmed that the pharmacophore models generated from the training set were valid. Secondly, a test set of 281 molecules was scored, with a correlation of 0.882 obtained between the experimental and predicted activities. Hypol performed well in correctly discriminating the active and inactive molecules. Thirdly, the model was investigated by mapping on two PTP1B inhibitors identified by different pharmaceutical companies. The Hypol model correctly predicted these compounds as being highly active. Finally, docking simulations were performed on few compounds to substantiate the role of the pharmacophore features at the binding site of the protein by analyzing their binding conformations. These multiple validation approaches provided confidence in the utility of this pharmacophore model as a 3D query for virtual screening to retrieve new chemical entities showing potential as potent PTP1B inhibitors.

  19. Zinc ions modulate protein tyrosine phosphatase 1B activity.

    Science.gov (United States)

    Bellomo, Elisa; Massarotti, Alberto; Hogstrand, Christer; Maret, Wolfgang

    2014-07-01

    Protein tyrosine phosphatases (PTPs) are key enzymes in cellular regulation. The 107 human PTPs are regulated by redox signalling, phosphorylation, dimerisation, and proteolysis. Recent findings of very strong inhibition of some PTPs by zinc ions at concentrations relevant in a cellular environment suggest yet another mechanism of regulation. One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes. The development of novel assay conditions to investigate zinc inhibition of PTP1B provides estimates of about 5.6 nM affinity for inhibitory zinc(II) ions. Analysis of three PTP1B 3D structures (PDB id: 2CM2, 3I80 and 1A5Y) identified putative zinc binding sites and supports the kinetic studies in suggesting an inhibitory zinc only in the closed and cysteinyl-phosphate intermediate forms of the enzyme. These observations gain significance with regard to recent findings of regulatory roles of zinc ions released from the endoplasmic reticulum.

  20. Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL-positive leukemia cells to the ABL kinase inhibitor STI571.

    Science.gov (United States)

    Koyama, Noriko; Koschmieder, Steffen; Tyagi, Sandhya; Portero-Robles, Ignacio; Chromic, Jörg; Myloch, Silke; Nürnberger, Heike; Rossmanith, Tanja; Hofmann, Wolf-Karsten; Hoelzer, Dieter; Ottmann, Oliver Gerhard

    2006-04-01

    Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of BCR-ABL-mediated transformation in vitro and in vivo. To investigate whether PTP1B modulates the biological effects of the abl kinase inhibitor STI571 in BCR-ABL-positive cells, we transfected Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia cell-derived K562 cells with either wild-type PTP1B (K562/PTP1B), a substrate-trapping dominant-negative mutant PTP1B (K562/D181A), or empty vector (K562/mock). Cells were cultured with or without STI571 and analyzed for its effects on proliferation, differentiation, and apoptosis. In both K562/mock and K562/PTP1B cells, 0.25 to 1 mumol/L STI571 induced dose-dependent growth arrest and apoptosis, as measured by a decrease of cell proliferation and an increase of Annexin V-positive cells and/or of cells in the sub-G(1) apoptotic phase. Western blot analysis showed increased protein levels of activated caspase-3 and caspase-8 and induction of poly(ADP-ribose) polymerase cleavage. Low concentrations of STI571 promoted erythroid differentiation of these cells. Conversely, K562/D181A cells displayed significantly lower PTP1B-specific tyrosine phosphatase activity and were significantly less sensitive to STI571-induced growth arrest, apoptosis, and erythroid differentiation. Pharmacologic inhibition of PTP1B activity in wild-type K562 cells, using bis(N,N-dimethylhydroxamido)hydroxooxovanadate, attenuated STI571-induced apoptosis. Lastly, comparison of the STI571-sensitive Ph+ acute lymphoblastic leukemia cell line SupB15 with a STI571-resistant subline revealed significantly decreased PTP1B activity and enhanced BCR-ABL phosphorylation in the STI571-resistant SupB15 cells. In conclusion, functional PTP1B is involved in STI571-induced growth and cell cycle arrest, apoptosis, and differentiation, and attenuation of PTP1B function may contribute to resistance towards STI571.

  1. Trisodium scandium bis(orthoborate

    Directory of Open Access Journals (Sweden)

    Kunpeng Wang

    2012-05-01

    Full Text Available Single crystals of trisodium scandium bis(orthoborate, Na3Sc(BO32, have been obtained by spontaneous crystallization from an Na2O–Sc2O3–B2O3 melt. The crystal structure features a three-dimensional framework composed of planar [BO3]3− groups and distorted ScO6 octahedra with Na atoms in the cavities. The Sc atom occupies a special position (Wyckoff position 2b, site symmetry -1 and of the two Na atoms, one occupies a special position (Wyckoff position 2c, site symmetry -1.

  2. Novel bis-arylalkylamines as myeloperoxidase inhibitors

    DEFF Research Database (Denmark)

    Aldib, Iyas; Gelbcke, Michel; Soubhye, Jalal;

    2016-01-01

    Human myeloperoxidase (MPO) plays an important role in innate immunity but also aggravates tissue damage by oxidation of biomolecules at sites of inflammation. As a result from a recent high-throughput virtual screening approach for MPO inhibitors, bis-2,2'-[(dihydro-1,3(2H,4H) pyrimidinediyl)bis...

  3. Bis(1,3-dithiole) Compounds

    DEFF Research Database (Denmark)

    Andersen, Jan Rud; Engler, E. M.; Green, D. C.;

    1977-01-01

    There is described the preparation of bis-1,3-dithiole compounds (I) which are key synthetic precursors for the preparation of new polymeric metal bis(dithiolene) (i.e., II) and tetrathiafulvalene compounds (i.e., III): (Image Omitted)...

  4. Flexible Photodetectors Based on 1D Inorganic Nanostructures

    Science.gov (United States)

    Lou, Zheng

    2015-01-01

    Flexible photodetectors with excellent flexibility, high mechanical stability and good detectivity, have attracted great research interest in recent years. 1D inorganic nanostructures provide a number of opportunities and capabilities for use in flexible photodetectors as they have unique geometry, good transparency, outstanding mechanical flexibility, and excellent electronic/optoelectronic properties. This article offers a comprehensive review of several types of flexible photodetectors based on 1D nanostructures from the past ten years, including flexible ultraviolet, visible, and infrared photodetectors. High‐performance organic‐inorganic hybrid photodetectors, as well as devices with 1D nanowire (NW) arrays, are also reviewed. Finally, new concepts of flexible photodetectors including piezophototronic, stretchable and self‐powered photodetectors are examined to showcase the future research in this exciting field. PMID:27774404

  5. 1D nanocrystals with precisely controlled dimensions, compositions, and architectures.

    Science.gov (United States)

    Pang, Xinchang; He, Yanjie; Jung, Jaehan; Lin, Zhiqun

    2016-09-16

    The ability to synthesize a diverse spectrum of one-dimensional (1D) nanocrystals presents an enticing prospect for exploring nanoscale size- and shape-dependent properties. Here we report a general strategy to craft a variety of plain nanorods, core-shell nanorods, and nanotubes with precisely controlled dimensions and compositions by capitalizing on functional bottlebrush-like block copolymers with well-defined structures and narrow molecular weight distributions as nanoreactors. These cylindrical unimolecular nanoreactors enable a high degree of control over the size, shape, architecture, surface chemistry, and properties of 1D nanocrystals. We demonstrate the synthesis of metallic, ferroelectric, upconversion, semiconducting, and thermoelectric 1D nanocrystals, among others, as well as combinations thereof.

  6. Quantum electrodynamics with 1D arti cial atoms

    DEFF Research Database (Denmark)

    Javadi, Alisa

    A 1D atom, a single quantum emitter coupled to a single optical mode, exhibits rich quantum electrodynamic (QED) e_ects and is thought to be the key ingredient for many applications in quantuminformation processing. Single quantum dots (QD) in photonic-crystal waveguides (PCW) constitute a robust...... platform for realizing a 1D atom, and are the subject of theoretical and experimental investigations in this thesis. We use _nite element method in 3D to calculate the local density of states (LDOS) in photonic-crystal membranes. The detailed spatial maps show strong inhibition of LDOS in the bandgap...... atom. One of the signatures and functions of a 1D atom is the nonlinear optical response at the single-photon level. A PCW chip is designed to experimentally study the transmission spectrum of an embedded QD. The transmission spectrum is shown to be modi_ed by 30% around the resonance of the QD...

  7. 1D nanocrystals with precisely controlled dimensions, compositions, and architectures

    Science.gov (United States)

    Pang, Xinchang; He, Yanjie; Jung, Jaehan; Lin, Zhiqun

    2016-09-01

    The ability to synthesize a diverse spectrum of one-dimensional (1D) nanocrystals presents an enticing prospect for exploring nanoscale size- and shape-dependent properties. Here we report a general strategy to craft a variety of plain nanorods, core-shell nanorods, and nanotubes with precisely controlled dimensions and compositions by capitalizing on functional bottlebrush-like block copolymers with well-defined structures and narrow molecular weight distributions as nanoreactors. These cylindrical unimolecular nanoreactors enable a high degree of control over the size, shape, architecture, surface chemistry, and properties of 1D nanocrystals. We demonstrate the synthesis of metallic, ferroelectric, upconversion, semiconducting, and thermoelectric 1D nanocrystals, among others, as well as combinations thereof.

  8. Quantum electrodynamics with 1D arti cial atoms

    DEFF Research Database (Denmark)

    Javadi, Alisa

    atom. One of the signatures and functions of a 1D atom is the nonlinear optical response at the single-photon level. A PCW chip is designed to experimentally study the transmission spectrum of an embedded QD. The transmission spectrum is shown to be modi_ed by 30% around the resonance of the QD......A 1D atom, a single quantum emitter coupled to a single optical mode, exhibits rich quantum electrodynamic (QED) e_ects and is thought to be the key ingredient for many applications in quantuminformation processing. Single quantum dots (QD) in photonic-crystal waveguides (PCW) constitute a robust...... platform for realizing a 1D atom, and are the subject of theoretical and experimental investigations in this thesis. We use _nite element method in 3D to calculate the local density of states (LDOS) in photonic-crystal membranes. The detailed spatial maps show strong inhibition of LDOS in the bandgap...

  9. A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro

    DEFF Research Database (Denmark)

    Echwald, Søren M; Riis, Helle Bach; Vestergaard, Henrik

    2002-01-01

    In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes...

  10. New 5-deoxyflavonoids and their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) activity

    DEFF Research Database (Denmark)

    Nguyen, Phi Hung; Dao, Trong Tuan; Kim, Jayeon;

    2011-01-01

    , MS, CD, 1D- and 2D-NMR) and physicochemical analyses. All isolates exhibited moderate inhibitory effects on the enzyme assay with IC₅₀ values ranging from 14.9 ± 1.6 to 98.1 ± 11.3 μM. Compounds with prenyl and methoxy groups in the B ring (1, 2, 4, 8, and 13) possessed strong activity (IC(50) 14...

  11. μ-Carbonato-bis-(bis-{2-[(diethyl-amino)-meth-yl]phen-yl}bis-muth(III)).

    Science.gov (United States)

    Soran, Albert P; Nema, Mihai G; Breunig, Hans J; Silvestru, Cristian

    2011-01-12

    The mol-ecular structure of the title compound, [Bi(2)(C(11)H(16)N)(4)(CO(3))], consists of a symmetrically bridging carbonato group which binds two [2-Et(2)NCH(2)C(6)H(4)](2)Bi units that are crystallographically related via a twofold rotation axis bis-ecting the carbonate group. The two Bi atoms and two of the C atoms directly bonded to bis-muth are quasi-planar [deviations of 0.323 (1) and 0.330 (9)Å for the Bi and C atoms, respectively] with the carbonate group. The remaining two ligands are in a trans arrangement relative to the quasi-planar (CBi)(2)CO(3) system. The metal atom is strongly coordinated by the N atom of one pendant arm [Bi-N = 2.739 (6) Å], almost trans to the O atom, while the N atom of the other pendant arm exhibits a weaker intra-molecular inter-action [Bi⋯N = 3.659 (7) Å] almost trans to a C atom. If both these intra-molecular N→Bi inter-actions per metal atom are considered, the overall coordination geometry at bis-muth becomes distorted square-pyramidal [(C,N)(2)BiO cores] and the compound can be described as a hypervalent 12-Bi-5 species. Additional quite short intra-molecular Bi⋯O inter-actions are also present [3.796 (8)-4.020 (9) Å]. Inter-molecular associations through weak η(6)⋯Bi inter-actions [Bi⋯centroid of benzene ring = 3.659 (1) Å] lead to a ribbon-like supra-molecular association.

  12. Diffusion and particle mobility in 1D system

    Energy Technology Data Exchange (ETDEWEB)

    Borman, V.D. [Moscow Engineering Physics Institute (State University), Kashirskoe shosse, 31, 115409 Moscow (Russian Federation); Johansson, B. [Condensed Matter Theory Group, Department of Physics, Box 530, Uppsala University, S-75121 Uppsala (Sweden); Applied Materials Physics, Department of Materials and Engineering, Royal Institute of Technology (KTH), S-10044 Stockholm (Sweden); Skorodumova, N.V. [Condensed Matter Theory Group, Department of Physics, Box 530, Uppsala University, S-75121 Uppsala (Sweden); Tronin, I.V. [Moscow Engineering Physics Institute (State University), Kashirskoe shosse, 31, 115409 Moscow (Russian Federation)]. E-mail: ivt@rbcmail.ru; Tronin, V.N. [Moscow Engineering Physics Institute (State University), Kashirskoe shosse, 31, 115409 Moscow (Russian Federation); Troyan, V.I. [Moscow Engineering Physics Institute (State University), Kashirskoe shosse, 31, 115409 Moscow (Russian Federation)

    2006-12-04

    The transport properties of one-dimensional (1D) systems have been studied theoretically. Contradictory experimental results on molecular transport in quasi-1D systems, such as zeolite structures, when both diffusion transport acceleration and the existence of the diffusion mode with lower particle mobility (single-file diffusion ({approx}t{sup 1/2})) have been reported, are consolidated in a consistent model. Transition from the single-file diffusion mode to an Einstein-like diffusion {approx}t with diffusion coefficient increasing with the density has been predicted to occur at large observation times.

  13. GIS-BASED 1-D DIFFUSIVE WAVE OVERLAND FLOW MODEL

    Energy Technology Data Exchange (ETDEWEB)

    KALYANAPU, ALFRED [Los Alamos National Laboratory; MCPHERSON, TIMOTHY N. [Los Alamos National Laboratory; BURIAN, STEVEN J. [NON LANL

    2007-01-17

    This paper presents a GIS-based 1-d distributed overland flow model and summarizes an application to simulate a flood event. The model estimates infiltration using the Green-Ampt approach and routes excess rainfall using the 1-d diffusive wave approximation. The model was designed to use readily available topographic, soils, and land use/land cover data and rainfall predictions from a meteorological model. An assessment of model performance was performed for a small catchment and a large watershed, both in urban environments. Simulated runoff hydrographs were compared to observations for a selected set of validation events. Results confirmed the model provides reasonable predictions in a short period of time.

  14. Cytochrome P1B1 (CYP1B1) polymorphisms and ovarian cancer risk: a meta-analysis.

    Science.gov (United States)

    Gajjar, Ketan; Owens, Gemma; Sperrin, Matthew; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-12-16

    CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of the MEDLINE bibliographic database for the period up to April 2012 identified five relevant studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to

  15. Cytochrome P1B1 (CYP1B1) polymorphisms and cancer risk: a meta-analysis of 52 studies.

    Science.gov (United States)

    Li, Cuiping; Long, Bingshuang; Qin, Xianjing; Li, Weixiong; Zhou, Yang

    2015-01-02

    CYP1B1 plays a critical role in the oxidative metabolism of a variety of exogenous compounds, including carcinogenic compounds, which may be activated during metabolism. There are only a few studies that have examined the association between the two polymorphisms and cancer, and that these studies have been inconclusive. Hence, the aim of the present meta-analysis was to evaluate the relationship between polymorphisms in CYP1B1 G119T and A453G and cancer risk. We performed a detailed search using the PubMed and EMBASE libraries to obtain all relevant published reports on the relationship between the G119T and A453G polymorphisms in CYP1B1 and cancer risk. Combined odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by Stata version 11.2. We conducted stratified analyses based on cancer types, ethnicity, source of controls, and quality assessments. We also made assessments of heterogeneity tests, sensitivity analyses, and publication bias. There were a total of 25 articles with 15,376 cases and 18,382 controls concerning CYP1B1 G119T and 40 articles with 27,983 cases and 35,839 controls concerning A453G polymorphisms. Regarding G119T, the combined results indicate that the variant genotypes were significantly associated with a slightly increased cancer risk in comparison to the homozygote (TT versus GG: p=0.006, OR=1.231, 95% CI: 1.061-1.428), especially for breast cancer and prostate cancer. Moreover, significantly increased associations with cancer risk were demonstrated in Asians in all genetic models. The combined results indicated no association of A453G with cancer risk; however, an association was observed specifically for prostate cancer. This meta-analysis suggests that the CYP1B1 G119T polymorphism may confer to genetic susceptibility to cancer in Asians, especially to breast cancer and prostate cancer. The A453G polymorphism was found to modify the risk of prostate cancer.

  16. Syntheses and characterization of two novel 1D Pb(II) Halide supramolecular polymers possessing incomplete Cubane subunit directed by -conjugated Dication templates

    Indian Academy of Sciences (India)

    Chengjie Ma; Mei Liu; Wenli Zhang; Haijuan Du; Yao Li; Chaohai Wang; Yunyin Niu

    2015-07-01

    Two novel cation-templated complexes, {(1, 4-PMBP)[Pb4I10]·DMF} n(1) {(DBBP)2[Pb5I8Br6]} n(2), (1,4-PMBP·2Br =1,1”-[1,4-phenylene-bis(methylene)]bis-4,4’-bipyridinium dibromide; DBBP·2Br = N, N’-dibenzyl- 4, 4’-bipyridinium dibromide) have been synthesized via the self-assembly reaction in solution. X-ray crystallography showed that compounds 1 and 2 can be regarded as 1D iodoplumbate examples which contain incomplete cubane subunit directed by -conjugated dication templates. It is the H-bonds and electrostatic interactions between the organic counter cations and inorganic moieties that contribute the crystal packing. These compounds have been further characterized by IR spectroscopy, UV-Vis spectra, elemental analysis and thermostability properties.

  17. 2-Methyl-1-(phenylsulfonylnaphtho[2,1-b]furan

    Directory of Open Access Journals (Sweden)

    Uk Lee

    2008-04-01

    Full Text Available The title compound, C19H14O3S, was prepared by the oxidation of 2-methyl-1-(phenylsulfanylnaphtho[2,1-b]furan with 3-chloroperoxybenzoic acid. The phenyl ring makes a dihedral angle of 87.13 (4° with the plane of the naphthofuran fragment. The crystal structure is stabilized by π–π interactions between the furan and benzene rings of neighbouring molecules [centroid–centroid distance = 3.850 (2 Å] and weak C—H...π interactions. In addition, there are also intramolecular C—H...O interactions.

  18. Expression of MAP1B protein and its phosphorylated form MAP1B-P in the CNS of a continuously growing fish, the rainbow trout.

    Science.gov (United States)

    Alfei, Laura; Soares, Sylvia; Alunni, Alessandro; Ravaille-Veron, Michèle; Von Boxberg, Ysander; Nothias, Fatiha

    2004-05-29

    Microtubule-associated protein-1B (MAP1B), and particularly its phosphorylated isoform MAP1B-P, play an important role in axonal outgrowth during development of the mammalian nervous system and have also been shown to be associated with axonal plasticity in the adult. Here, we used antibodies and mRNA probes directed against mammalian MAP1B to extend our analysis to fish species, trout (Oncorhynchus mykiss), at different stages of development. The specificity of the cross-reaction of our anti-total-MAP1B/MAP1B-P antibodies was confirmed by Western blotting. Trout MAP1B-like proteins exhibited about the same apparent molecular weight (320 kDa) as rat-MAP1B. Immunohistochemistry and in situ hybridization analysis performed on hindbrain and spinal cord revealed the presence of MAP1B in neurons and some glial subpopulations. Primary sensory neurons and motoneurons maintain high levels of MAP1B expression from early stages throughout adulthood, as has been shown for mammals. Unlike mammals, however, MAP1B and axon-specific MAP1B-P continue to be strongly expressed by hindbrain neurons projecting into spinal cord, with the important exception of Mauthner cells. MAP1B/MAP1B-P immunostaining were also detected elsewhere within the brain, including axons of the retino-tectal projection. This obvious difference between adult fish and mammals is likely to reflect the capacity of fish for continued growth and regeneration. Our results suggest that MAP1B/MAP1B-P expression is generally maintained in neurons known to regenerate after axotomy. The regenerative potential of the adult nervous system may in fact depend on continued expression of neuron-intrinsic growth related proteins, a feature of MAP1B that appears phylogenetically conserved.

  19. (Acetonitrile[bis(2-pyridylmethylamine]bis(perchloratocopper(II

    Directory of Open Access Journals (Sweden)

    Ray J. Butcher

    2008-01-01

    Full Text Available In the title compound, [Cu(ClO42(C12H13N3(C2H3N], the CuII atom is six-coordinate in a Jahn–Teller distorted octahedral geometry, with coordination by the tridentate chelating ligand, an acetonitrile molecule, and two axial perchlorate anions. The tridentate ligand bis(2-pyridylmethylamine chelates meridionally and equatorially while an acetonitrile molecule is coordinated at the fourth equatorial site. The two perchlorate anions are disordered with site occupancy factors of 0.72/0.28. The amine H is involved in intramolecular hydrogen bonding to the perchlorate O atoms and there are extensive but weak intermolecular C—H...O interactions.

  20. On the D1-D5 conformal field theory

    Science.gov (United States)

    Dijkgraaf, Robbert

    2000-03-01

    I give a review of some aspects of the D1-D5 conformal field theory that is dual to string theory on AdS 3 . Particular attention is paid to the gravitational interpretation of the elliptic genus as a sum over 3-manifolds.

  1. Nonclassical Particle Transport in the 1-D Diffusive Limit

    CERN Document Server

    Vasques, Richard; Krycki, Kai

    2016-01-01

    This paper provides numerical results that demonstrate the validity of the nonclassical diffusion approximation to the nonclassical transport equation in certain 1-D diffusive systems. This result provides a more solid foundation in which to improve this theory for relevant nuclear applications.

  2. Quantitative 1D saturation profiles on chalk by NMR

    DEFF Research Database (Denmark)

    Olsen, Dan; Topp, Simon; Stensgaard, Anders;

    1996-01-01

    Quantitative one-dimensional saturation profiles showing the distribution of water and oil in chalk core samples are calculated from NMR measurements utilizing a 1D CSI spectroscopy pulse sequence. Saturation profiles may be acquired under conditions of fluid flow through the sample. Results reveal...

  3. Ultracold spherical horizons in gauged N=1, d=4 supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Meessen, Patrick, E-mail: meessenpatrick@uniovi.e [Department of Physics, University of Oviedo, Avda. Calvo Sotelo s/n, E-33007 Oviedo (Spain); Ortin, Tomas, E-mail: Tomas.Ortin@cern.c [Instituto de Fisica Teorica UAM/CSIC, Facultad de Ciencias C-XVI, C.U. Cantoblanco, E-28049 Madrid (Spain)

    2010-10-04

    We show that the near-horizon limit of ultracold magnetic Reissner-Nordstroem-De Sitter black holes, whose geometry is the direct product of 2-dimensional Minkowski spacetime and a 2-sphere, preserves half of the supersymmetries of minimal R-gauged N=1, d=4 supergravity.

  4. Active damping of the 1D rocking mode

    NARCIS (Netherlands)

    Babakhani, B.; de Vries, Theodorus J.A.

    Active damping of a rotational vibration mode in the linear guidance of a precision machine in a one dimensional (1D) setting is considered in this paper. This so-called rocking mode presents itself in machines having linear actuation. The limitation this vibration mode imposes on the machine

  5. Energy harvesting and storage in 1D devices

    Science.gov (United States)

    Sun, Hao; Zhang, Ye; Zhang, Jing; Sun, Xuemei; Peng, Huisheng

    2017-06-01

    Power systems and electronic devices that are bulky and rigid are not practical for use in wearable applications that require flexibility and breathability. To address this, a range of 1D energy harvesting and storage devices have been fabricated that show promise for such applications compared with their 2D and 3D counterparts. These 1D devices are based on fibres that are flexible and can accommodate deformation, for example, by twisting and stretching. The fibres can be woven into textiles and fabrics that breathe freely or can be integrated into different materials that fit the curved surface of the human body. In this Review, the development of fibre-based energy harvesting and storage devices is presented, focusing on dye-sensitized solar cells, lithium-ion batteries, supercapacitors and their integrated devices. An emphasis is placed on the interface between the active materials and the electrodes or electrolyte in the 1D devices. The differing properties of these interfaces compared with those in 2D and 3D devices are derived from the curved surface and long charge transport path in 1D electrodes.

  6. Simulation of Organic Solar Cells Using AMPS-1D Program

    Directory of Open Access Journals (Sweden)

    Samah G. Babiker

    2012-03-01

    Full Text Available The analysis of microelectronic and photonic structure in one dimension program [AMPS-1D] program has been successfully used to study inorganic solar cells. In this work the program has been used to optimize the performance of the organic solar cells. The cells considered consist of poly(2-methoxy-5-(3,7- dimethyloctyloxy-1,4-phenylenevinylene [MDMO-PPV

  7. Suppression of spin-orbit effects in 1D system

    OpenAIRE

    Entin, M. V.; Magarill, L. I.

    2004-01-01

    We report the absence of spin effects such as spin-galvanic effect, spin polarization and spin current under static electric field and inter-spin-subband absorption in 1D system with spin-orbit interaction of arbitrary form. It was also shown that the accounting for the direct interaction of electron spin with magnetic field violates this statement.

  8. Inverse parameter identification for a branching 1D arterial network

    CSIR Research Space (South Africa)

    Bogaers, Alfred EJ

    2012-07-01

    Full Text Available In this paper we investigate the invertability of a branching 1D arterial blood flow network. We limit our investigation to a single bifurcating vessel, where the material properties, unloaded areas and variables characterizing the input and output...

  9. Active damping of the 1D rocking mode

    NARCIS (Netherlands)

    Babakhani, Bayan; Vries, de Theo

    2010-01-01

    Active damping of a rotational vibration mode in the linear guidance of a precision machine in a one dimensional (1D) setting is considered in this paper. This so-called rocking mode presents itself in machines having linear actuation. The limitation this vibration mode imposes on the machine precis

  10. Berberine inhibits PTP1B activity and mimics insulin action.

    Science.gov (United States)

    Chen, Chunhua; Zhang, Yuebo; Huang, Cheng

    2010-07-02

    Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.

  11. Relative photometry of HAT-P-1b occultations

    CERN Document Server

    Béky, Bence; Gilliland, Ronald L; Bakos, Gáspár Á; Winn, Joshua N; Noyes, Robert W; Sasselov, Dimitar D

    2013-01-01

    We present HST STIS observations of two occultations of the transiting exoplanet HAT-P-1b. By measuring the planet to star flux ratio near opposition, we constrain the geometric albedo of the planet, which is strongly linked to its atmospheric temperature gradient. An advantage of HAT-P-1 as a target is its binary companion ADS 16402 A, which provides an excellent photometric reference, simplifying the usual steps in removing instrumental artifacts from HST time-series photometry. We find that without this reference star, we would need to detrend the lightcurve with the time of the exposures as well as the first three powers of HST orbital phase, and this would introduce a strong bias in the results for the albedo. However, with this reference star, we only need to detrend the data with the time of the exposures to achieve the same per-point scatter, therefore we can avoid most of the bias associated with detrending. Our final result is a 2 sigma upper limit of 0.64 for the geometric albedo of HAT-P-1b betwee...

  12. The Response of Marine Biota to OAE 1b

    Science.gov (United States)

    Herrle, J. O.

    2006-12-01

    The latest Aptian to earliest Albian is characterized by the first appearance of a distinctly modern phytoplankton community accompanied by a cold episode during a generally extreme greenhouse climate. Massive burial of organic matter caused the formation of the black shale `Niveaus' Jacob, Kilian, Paquier and Leenhardt in the Vocontian Basin (SE France). This interval is reported as the Oceanic Anoxic Event 1b (OAE1b) following the definition of Leckie et al. (2002). Lasting about four million years, OAE1b facilitates analysis of rapid climate change in a greenhouse world, and crucial for understanding climate change. During latest Aptian angiosperms and diatoms became abundant in the terrestrial and marine environments (Gersonde & Haywood 1990; Heimhofer et al. 2005). Planktic foraminifera experienced their greatest turnover rates since their first appearance, accompanied by a decrease in test size and changes of the ultrastructures of their shells (Leckie et al. 2002). Calcareous nannoplankton show a major change characterized by the influx of the boreal cool water indicator Repagulum parvidentatum into the Tethyan Realm (Herrle & Mutterlose 2003). Moreover, ammonite faunas became more cosmopolitan at the expense of Tethyan taxa during this period. Both the influx of boreal nannoplankton taxa and the trend to more cosmopolitian ammonite assemblages in the Tethyan Realm was probably favored by a long-term sea level rise accompanied by a global cooling during the late Aptian to early Albian interval. Most dramatic changes of the marine carbonate system are reflected by the stepwise decrease of nannoconids and carbonate platform drowning accompanied by a positive carbon isotope excursion which is similar to the biocalcification crisis associated with the early Aptian OAE1a (Erba 1994, Weissert et al., 1998). The massive change in the global carbon cycle is probably linked to a major change in global marine productivity from a calcareous system (nannoconids

  13. Monochromator development at 4W1B beamline of BSRF

    Science.gov (United States)

    Xie, Yaning; Yan, Y.; Hu, T. D.; Liu, T.; Xian, D. C.

    2001-07-01

    The 4W1B is a X-ray monochromator beamline for XAFS at BSRF. During the upgrading phase, we have redesigned the monochromator to improve the performance of the beamline. It is a goniometer based, fixed exit double crystal monochromator. A mechanical linkage is employed to adjust the distance between the surfaces of the two crystals as the Bragg angle is changed to keep the outgoing beam direction constant. The whole mechanism is driven by only one stepping motor. The testing result shows that over the scanning range of 5-30°, the shift of outgoing beam position is less then 70 μm in the vertical direction. The basic principle, the mechanical realization, and the error analysis are discussed in detail. The performance and the testing results are also presented in this paper.

  14. Monochromator development at 4W1B beamiline of BSRF

    Institute of Scientific and Technical Information of China (English)

    YaningXie; Y.Yan; T.D.Hu; T.Liu; D.C.Xian

    2001-01-01

    The 4W1B is a X-ary monochromator beamline for XAFS at BSRF.During the upgrading phase,we have redsigned the monochromator to improve the performnce of beamline.It is a goniometer based,fixed exit double crystal monochromator.A mechanical linkage is employed to adjust the distance between the surfaces of the two crystals as the Bragg angle is changed to keep the outgoing beam direction constant.The whole mechanism is driven by only one stepping motor.The testing result shows that over the scanning range of 5-30°,the shift of outgoing beam position is less then 70μm in the vertical direction.The basic principle,the mechanical realization,and the error analysis are discussed in detail.The performance and the testing results are also presented in this paper.2001 Elsevier Science B.V.All rights reserved.

  15. Performance and Applications of L1B2 Ultrasonic Motors

    Directory of Open Access Journals (Sweden)

    Gal Peled

    2016-06-01

    Full Text Available Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operational robustness. This paper reviews the design of high precision motion solutions based on L1B2 ultrasonic motors—from the basic motor structure to the complete motion solution architecture, including motor drive and control, material considerations and performance envelope. The performance is demonstrated, via constructed motion stages, to exhibit fast move and settle, a repeatability window of tens of nanometers, lifetime into the tens of millions of operational cycles, and compatibility with clean room and aerospace environments. Example stages and modules for semiconductor, aerospace, electro-optical and biomedical applications are presented. The described semiconductor and aerospace solutions are powered by Nanomotion HR type motors, driven by a sine wave up to 80 V/mm rms, having a driving frequency of 39.6 kHz, providing a maximum force up to 4 N per driving element (at 5 W power consumption per element and a maximum linear velocity above 300 mm/s. The described electro-optical modules are powered by small Nanomotion Edge motors driven by voltages up to 11 V AC, providing stall forces up to 0.35 N (power consumption up to 0.75 W and maximum linear velocity above 200 mm/s.

  16. Synthesis and Crystal Structure of the Intermediate Bis-9-fluorenylmethylphenyl Silane

    Institute of Scientific and Technical Information of China (English)

    罗悔; 马怀柱; 苏庆德; 刘青山

    2003-01-01

    The title compound bis-9-fluorenylmethylphenyl silane (C33H26Si, Mr = 450.63) was synthesized and its structure has been synthesized and determined by X-ray analysis. The crystal is of triclinic, space group Pī with a = 9.478(1), b = 10.0956(1), c = 13.0243(2)(A°),α= 92.668(2),β= 90.809(2),γ= 99.348(2)°,λ= 0.71073(A°),μ(MoKα)= 0.115 mm-1, V = 1288.1(2)(A°)3, Z = 2, Dc = 1.219 g/cm3 and F(000) = 476. The structure was refined to R = 0.0437 and wR(F2) = 0.0963 for 3346 observed reflections with I>2σ(I). X-ray diffraction analysis reveals that the title compound is bis-9-fluorenylmethylphenyl silane.

  17. Pharmacological evidence that 5-HT1D activation induces renal vasodilation by NO pathway in rats.

    Science.gov (United States)

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-06-01

    5-HT is a powerful vasoconstrictor substance in renal vasculature (mainly by 5-HT₂ activation). Nevertheless, 5-HT is notable for its dual cardiovascular effects, producing both vasodilator and vasoconstrictor actions. This study aimed to investigate whether, behind the predominant serotonergic vasoconstrictor action, THE 5-HT system may exert renal vasodilator actions, and, if so, characterize the 5-HT receptors and possible indirect pathways. Renal perfusion pressure (PP), systemic blood pressure (SBP) and heart rate (HR) measurement in in situ autoperfused rat kidney was determined in phenylephrine infused rats. Intra arterial (i.a.) bolus administration of 5-HT (0.00000125-0.1 μg/kg) decreased renal PP in the presence of a phenylephrine continuous infusion (phenylephrine-infusion group), without modifying SBP or HR. These vasodilator responses were potentiated by 5-HT₂ antagonism (ritanserin, 1 mg/kg i.v.), whereas the responses were abolished by 5-HT₁ /₇ antagonist (methiothepin, 100 μg/kg i.v.) or 5-HT1D antagonist (LY310762, 1 mg/kg i.v.). The i.a. administration (0.00000125 to 0.1 μg/kg) of 5-CT or L-694,247 (5-HT1D agonist) mimicked 5-HT vasodilator effect, while other agonists (1-PBG, α-methyl-5-HT, AS-19 (5-HT₇), 8-OH-DPAT (5-HT1A) or CGS-12066B (5-HT1B)) did not alter baseline haemodynamic variables. L-694,247 vasodilation was abolished by i.v. bolus of antagonists LY310762 (5-HT1D, 1 mg/kg) or L-NAME (nitric oxide, 10 mg/kg), but not by i.v. bolus of indomethacin (cyclooxygenase, 2 mg/kg) or glibenclamide (ATP-dependent K(+) channel, 20 mg/kg). These outcomes suggest that 5-HT1D activation produces a vasodilator effect in the in situ autoperfused kidney of phenylephrine-infusion rats mediated by the NO pathway.

  18. 1D Josephson quantum interference grids: diffraction patterns and dynamics

    Science.gov (United States)

    Lucci, M.; Badoni, D.; Corato, V.; Merlo, V.; Ottaviani, I.; Salina, G.; Cirillo, M.; Ustinov, A. V.; Winkler, D.

    2016-02-01

    We investigate the magnetic response of transmission lines with embedded Josephson junctions and thus generating a 1D underdamped array. The measured multi-junction interference patterns are compared with the theoretical predictions for Josephson supercurrent modulations when an external magnetic field couples both to the inter-junction loops and to the junctions themselves. The results provide a striking example of the analogy between Josephson phase modulation and 1D optical diffraction grid. The Fiske resonances in the current-voltage characteristics with voltage spacing {Φ0}≤ft(\\frac{{\\bar{c}}}{2L}\\right) , where L is the total physical length of the array, {Φ0} the magnetic flux quantum and \\bar{c} the speed of light in the transmission line, demonstrate that the discrete line supports stable dynamic patterns generated by the ac Josephson effect interacting with the cavity modes of the line.

  19. D1-D5-P microstates at the cap

    CERN Document Server

    Giusto, Stefano; Mathur, Samir D; Turton, David

    2012-01-01

    The geometries describing D1-D5-P bound states in string theory have three regions: flat asymptotics, an anti-de Sitter throat, and a 'cap' region at the bottom of the throat. We identify the CFT description of a known class of supersymmetric D1-D5-P microstate geometries which describe degrees of freedom in the cap region. The class includes both regular solutions and solutions with conical defects, and generalizes configurations with known CFT descriptions: a parameter related to spectral flow in the CFT is generalized from integer to fractional values. We provide strong evidence for this identification by comparing the massless scalar excitation spectrum between gravity and CFT and finding exact agreement.

  20. New D1-D5-P geometries from string amplitudes

    CERN Document Server

    Giusto, Stefano; Turton, David

    2011-01-01

    We derive the long range supergravity fields sourced by a D1-D5-P bound state from disk amplitudes for massless closed string emission. We suggest that since the parameter controlling the string perturbation expansion for this calculation decreases with distance from the bound state, the resulting asymptotic fields are valid even in the regime of parameters in which there is a classical black hole solution with the same charges. The supergravity fields differ from the black hole solution by multipole moments and are more general than those contained within known classes of solutions in the literature, whilst still preserving four supersymmetries. Our results support the conjecture that the black hole solution should be interpreted as a coarse-grained description rather than an exact description of the gravitational field sourced by D1-D5-P bound states in this regime of parameters.

  1. Developing 1D nanostructure arrays for future nanophotonics

    Directory of Open Access Journals (Sweden)

    Cooke DG

    2006-01-01

    Full Text Available AbstractThere is intense and growing interest in one-dimensional (1-D nanostructures from the perspective of their synthesis and unique properties, especially with respect to their excellent optical response and an ability to form heterostructures. This review discusses alternative approaches to preparation and organization of such structures, and their potential properties. In particular, molecular-scale printing is highlighted as a method for creating organized pre-cursor structure for locating nanowires, as well as vapor–liquid–solid (VLS templated growth using nano-channel alumina (NCA, and deposition of 1-D structures with glancing angle deposition (GLAD. As regards novel optical properties, we discuss as an example, finite size photonic crystal cavity structures formed from such nanostructure arrays possessing highQand small mode volume, and being ideal for developing future nanolasers.

  2. Iron-based 1D nanostructures by electrospinning process.

    Science.gov (United States)

    Eid, Cynthia; Brioude, Arnaud; Salles, Vincent; Plenet, Jean-Claude; Asmar, Roy; Monteil, Yves; Khoury, Randa; Khoury, Antonio; Miele, Philippe

    2010-03-26

    Iron-based 1D nanostructures have been successfully prepared using an electrospinning technique and varying the pyrolysis atmospheres. Hematite (Fe(2)O(3)) nanotubes and polycrystalline Fe(3)C nanofibers were obtained by simple air or mixed gas (H(2), Ar) annealing treatments. Using the air annealing treatment, a high control of the morphology as well as of the wall thickness of the nanotubes was demonstrated with a direct influence of the starting polymer concentration. When mixed gases (H(2) and Ar) were used for the annealing treatments, for the first time polycrystalline Fe(3)C nanofibers composed of carbon graphitic planes were obtained, ensuring Fe(3)C nanoparticle stability and nanofiber cohesion. The morphology and structural properties of all these iron-based 1D nanostructures were fully characterized by SEM, TEM, XRD and Raman spectroscopy.

  3. Phase diagram of a bulk 1d lattice Coulomb gas

    Science.gov (United States)

    Démery, V.; Monsarrat, R.; Dean, D. S.; Podgornik, R.

    2016-01-01

    The exact solution, via transfer matrix, of the simple one-dimensional lattice Coulomb gas (1d LCG) model can reproduce peculiar features of ionic liquid capacitors, such as overscreening, layering, and camel- and bell-shaped capacitance curves. Using the same transfer matrix method, we now compute the bulk properties of the 1d LCG in the constant voltage ensemble. We unveil a phase diagram with rich structure exhibiting low-density disordered and high-density ordered phases, separated by a first-order phase transition at low temperature; the solid state at full packing can be ordered or not, depending on the temperature. This phase diagram, which is strikingly similar to its three-dimensional counterpart, also sheds light on the behaviour of the confined system.

  4. Synthesis of mangiferin derivates and study their potent PTP1B inhibitory activity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Protein tyrosine phosphatase 1B (PTP1B) has received considerable attention from the drug industry as a potential treatment fordiabetes mellitus. Mangiferin has been reported to possess significant antidiabetic activity. Based on the previous study, eight new mangiferin derivates were synthesized and evaluated for their PTP1B inhibitory activity. Some of them displayed good inhibitory activity on PTP1B.

  5. Interferon β-1b-neutralizing antibodies 5 years after clinically isolated syndrome

    DEFF Research Database (Denmark)

    Hartung, H-P; Freedman, M S; Polman, C H

    2011-01-01

    To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b).......To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b)....

  6. Data of evolutionary structure change: 1B7QA-2G4QA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7QA-2G4QA 1B7Q 2G4Q A A KVFERCELARTLKRLGMDGYRGISLALWMCLAKWESGYN...GRCELAAAMKRHGLDNYRGYSLGNWVCAAKFESNFNTQATNRNTD-GSTDYGILQINSRWWCNDGRTPGSRNLCNIPCSALLSSDITASVNCAKKIVSDGNGMNAWVAWRNRCKGTDVQA... A 2G4QA NRNTD-GSTDY 1B7Q A 1B7QA

  7. Ultrahigh-Q nanocavity with 1D photonic gap.

    Science.gov (United States)

    Notomi, M; Kuramochi, E; Taniyama, H

    2008-07-21

    Recently, various wavelength-sized cavities with theoretical Q values of approximately 10(8) have been reported, however, they all employ 2D or 3D photonic band gaps to realize strong light confinement. Here we numerically demonstrate that ultrahigh-Q (2.0x10(8)) and wavelength-sized (V(eff) approximately 1.4(lambda/n)3) cavities can be achieved by employing only 1D periodicity.

  8. Polaron in a quasi 1D cylindrical quantum wire

    Directory of Open Access Journals (Sweden)

    I.Nsangou

    2005-01-01

    Full Text Available Polaron states in a quasi 1D cylindrical quantum wire with a parabolic confinement potential are investigated applying the Feynman variational principle. The effect of the wire radius on the polaron ground state energy level, the mass and the Fröhlich electron-phonon-coupling constant are obtained for the case of a quasi 1D cylindrical quantum wire. The effect of anisotropy of the structure on the polaron ground state energy level and the mass are also investigated. It is observed that as the wire radius tends to zero, the polaron mass and energy diverge logarithmically. The polaron mass and energy differ from the canonical strong-coupling behavior by the Fröhlich electron-phonon coupling constant and the radius of the quasi 1D cylindrical quantum wire that are expressed through a logarithmic function. Moreover, it is observed that the polaron energy and mass for strong coupling for the case of the quasi 1D cylindrical quantum wire are greater than those for bulk crystals. It is also observed that the anisotropy of the structure considerably affects both the polaron ground state energy level and the mass. It is found that as the radius of the cylindrical wire reduces, the regimes of the weak and intermediate coupling polaron shorten while the region of the strong coupling polaron broadens and extends into those of the weak and intermediate ones. Analytic expressions for the polaron ground state energy level and mass are derived for the case of strong coupling polarons.

  9. Supported plasma-made 1D heterostructures: perspectives and applications

    Energy Technology Data Exchange (ETDEWEB)

    Borras, Ana; Macias-Montero, Manuel; Romero-Gomez, Pablo; Gonzalez-Elipe, Agustin R, E-mail: anaisabel.borras@icmse.csic.es [Materials Science Institute of Seville (CSIC-Universidad Sevilla), C/Americo Vespucio 49 41092, Sevilla (Spain)

    2011-05-04

    Plasma-related methods have been widely used in the fabrication of carbon nanotubes and nanofibres (NFs) and semiconducting inorganic nanowires (NWs). A natural progression of the research in the field of 1D nanostructures is the synthesis of multicomponent NWs and NFs. In this paper we review the state of the art of the fabrication by plasma methods of 1D heterostructures including applications and perspectives. Furthermore, recent developments on the use of metal seeds (Ag, Au, Pt) to obtain metal-oxide nanostructures are also extensively described. Results are shown for various metal substrates, either metal foils or supported nanoparticles/thin films of the metal where the effects of the size, surface coverage, percolation degree and thickness of the metal seeds have been systematically evaluated. The possibilities of the process are illustrated by the preparation of nanostructured films and supported NFs of different metal-oxides (Ag, Au and SiO{sub 2}, TiO{sub 2}, ZnO). Particularly, in the case of silver, the application of an oxygen plasma treatment prior to the deposition of the oxide was critical for efficiently controlling the growth of the 1D heterostructures. A phenomenological model is proposed to account for the thin-film nanostructuring and fibre formation by considering basic phenomena such as stress relaxation, inhomogeneities in the plasma sheath electrical field and the local disturbance of the oxide growth.

  10. Enhancing Solar Cell Efficiencies through 1-D Nanostructures

    Directory of Open Access Journals (Sweden)

    Yu Kehan

    2008-01-01

    Full Text Available Abstract The current global energy problem can be attributed to insufficient fossil fuel supplies and excessive greenhouse gas emissions resulting from increasing fossil fuel consumption. The huge demand for clean energy potentially can be met by solar-to-electricity conversions. The large-scale use of solar energy is not occurring due to the high cost and inadequate efficiencies of existing solar cells. Nanostructured materials have offered new opportunities to design more efficient solar cells, particularly one-dimensional (1-D nanomaterials for enhancing solar cell efficiencies. These 1-D nanostructures, including nanotubes, nanowires, and nanorods, offer significant opportunities to improve efficiencies of solar cells by facilitating photon absorption, electron transport, and electron collection; however, tremendous challenges must be conquered before the large-scale commercialization of such cells. This review specifically focuses on the use of 1-D nanostructures for enhancing solar cell efficiencies. Other nanostructured solar cells or solar cells based on bulk materials are not covered in this review. Major topics addressed include dye-sensitized solar cells, quantum-dot-sensitized solar cells, and p-n junction solar cells.

  11. The stability of 1-D soliton in transverse direction

    Science.gov (United States)

    Verma, Deepa; Bera, Ratan Kumar; Das, Amita; Kaw, Predhiman

    2016-12-01

    The complete characterization of the exact 1-D solitary wave solutions (both stationary and propagating) for light plasma coupled system have been studied extensively in the parameter space of light frequency and the group speed [Poornakala et al., Phys. Plasmas 9(5), 1820 (2002)]. It has been shown in 1-D that solutions with single light wave peak and paired structures are stable and hence long lived. However, solutions having multiple peaks of light wave are unstable due to Raman scattering instability [Saxena et al., Phys. Plasmas 14, 072307 (2007)]. Here, we have shown with the help of 2-D fluid simulation that single peak and paired solutions too get destabilized by the transverse filamentation instability. The numerical growth rates obtained from simulations is seen to compare well with the analytical values. It is also shown that multiple peaks solitons first undergo the regular 1-D forward Raman scattering instability. Subsequently, they undergo a distinct second phase of destabilization through transverse filamentation instability. This is evident from the structure as well as the plot of the perturbed energy which shows a second phase of growth after saturating initially. The growth rate of the filamentation instability being comparatively slower than the forward Raman instability this phase comes quite late and is clearly distinguishable.

  12. Development of 1D Liner Compression Code for IDL

    Science.gov (United States)

    Shimazu, Akihisa; Slough, John; Pancotti, Anthony

    2015-11-01

    A 1D liner compression code is developed to model liner implosion dynamics in the Inductively Driven Liner Experiment (IDL) where FRC plasmoid is compressed via inductively-driven metal liners. The driver circuit, magnetic field, joule heating, and liner dynamics calculations are performed at each time step in sequence to couple these effects in the code. To obtain more realistic magnetic field results for a given drive coil geometry, 2D and 3D effects are incorporated into the 1D field calculation through use of correction factor table lookup approach. Commercial low-frequency electromagnetic fields solver, ANSYS Maxwell 3D, is used to solve the magnetic field profile for static liner condition at various liner radius in order to derive correction factors for the 1D field calculation in the code. The liner dynamics results from the code is verified to be in good agreement with the results from commercial explicit dynamics solver, ANSYS Explicit Dynamics, and previous liner experiment. The developed code is used to optimize the capacitor bank and driver coil design for better energy transfer and coupling. FRC gain calculations are also performed using the liner compression data from the code for the conceptual design of the reactor sized system for fusion energy gains.

  13. Homogenization of 1D and 2D magnetoelastic lattices

    Directory of Open Access Journals (Sweden)

    Schaeffer Marshall

    2015-01-01

    Full Text Available This paper investigates the equivalent in-plane mechanical properties of one dimensional (1D and two dimensional (2D, periodic magneto-elastic lattices. A lumped parameter model describes the lattices using magnetic dipole moments in combination with axial and torsional springs. The homogenization procedure is applied to systems linearized about stable configurations, which are identified by minimizing potential energy. Simple algebraic expressions are derived for the properties of 1D structures. Results for 1D lattices show that a variety of stiffness changes are possible through reconfiguration, and that magnetization can either stiffen or soften a structure. Results for 2D hexagonal and re-entrant lattices show that both reconfigurations and magnetization have drastic effects on the mechanical properties of lattice structures. Lattices can be stiffened or softened and the Poisson’s ratio can be tuned. Furthermore for certain hexagonal lattices the sign of Poisson’s ratio can change by varying the lattice magnetization. In some cases presented, analytical and numerically estimated equivalent properties are validated through numerical simulations that also illustrate the unique characteristics of the investigated configurations.

  14. Proteasomal degradation of human CYP1B1: effect of the Asn453Ser polymorphism on the post-translational regulation of CYP1B1 expression.

    Science.gov (United States)

    Bandiera, Silvio; Weidlich, Simone; Harth, Volker; Broede, Peter; Ko, Yun; Friedberg, Thomas

    2005-02-01

    Allelic variations in CYP1B1 are reported to modulate the incidence of several types of cancer. To provide a mechanistic basis for this association, we investigated the impact of nonsilent allelic changes on the intracellular levels and post-translational regulation of CYP1B1 protein. When transiently expressed in COS-1 cells, either in the presence or absence of recombinant cytochrome P450 reductase, the cellular level of the CYP1B1.4 allelic variant (containing a Ser at the amino acid position 453; Ser453) was 2-fold lower compared with the other four allelic CYP1B1 proteins (containing Asn453), as analyzed by both immunoblotting and ethoxyresorufin O-deethylase activity. This difference was caused by post-translational regulation; as in the presence of cycloheximide, the rate of degradation of immunodetectable and enzymatically active CYP1B1.4 was distinctly faster than that of CYP1B1.1. Pulse-chase analysis revealed that the half-life of CYP1B1.4 was a mere 1.6 h compared with 4.8 h for CYP1B1.1. The presence of the proteasome inhibitor MG132 [N-benzoyloxycarbonyl (Z)-Leu-Leuleucinal] increased the stability not only of immunodetectable CYP1B1, but also--unexpectedly given the size of the proteasome access channel--increased the stability of enzymatically active CYP1B1. The data presented herein also demonstrate that CYP1B1 is targeted for its polymorphism-dependent degradation by polyubiquitination but not phosphorylation. Our results importantly provide a mechanism to explain the recently reported lower incidence of endometrial cancer in individuals carrying the CYP1B1*4 compared with the CYP1B1*1 haplo-type. In addition, the mechanistic paradigms revealed herein may explain the strong overexpression of CYP1B1 in tumors compared with nondiseased tissues.

  15. Protein tyrosine phosphatase 1B (PTP1B)-inhibiting constituents from the leaves of Syzygium polyanthum.

    Science.gov (United States)

    Saifudin, Azis; Tanaka, Ken; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2012-08-01

    A methanol extract of the leaves of Syzygium polyanthum (Wight) Walp. afforded four new acylbenzene derivatives (1-4) together with seven known compounds (5-11). The structures of 1-11 were elucidated by extensive spectroscopic methods and comparison with the literature data. The new compounds 1-3 and a known compound, campest-4-en-3-one (10), exhibited a significant protein tyrosine phosphatase 1B inhibitory activity with IC₅₀ values of 13.1 ± 0.1, 5.77 ± 0.15, 4.01 ± 0.26, and 10.4 ± 0.5 µM, respectively. The inhibitory potency of the new compounds 2 and 3 was comparable to that of a positive control RK-682 (IC₅₀, 5.51 ± 0.04 µM).

  16. Bis[1,3-bis(2-cyanophenyltriazenido]mercury(II

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Rofouei

    2009-10-01

    Full Text Available In the title compound, [Hg(C14H8N52], the central atom is four-coordinated by two bidentate 1,3-bis(2-cyanophenyltriazenide ligands in a distorted square-planar geometry. The asymmteric unit is composed of one ligand molecule and one HgII ion, which is disordered over two sites, one lying on an inversion center and the other on a general position with site-occupancy factors of 0.2378 (7 and 0.3811 (7, respectively. The monomeric molecules of the complex are linked into pairs through non-classical C—H...N hydrogen bonds. The resulting dimeric units are assembled by translation along the crystallographic c axis into chains linked through secondary π–π interactions [centroid–centroid distances = 3.685 (2 and 3.574 (2 Å], as well as C—H...π stacking interactions, resulting in a two-dimensional architecture.

  17. 云南美登木共生放线菌菌株1B1产生的一个新的angucycline抗生素%New angucycline antibiotic produced by Streptomyces sp.1B1,a commensal microbe of Maytenus hookeri Loes

    Institute of Scientific and Technical Information of China (English)

    鲁春华; 沈月毛

    2003-01-01

    A compound from the fermentation extracts of the commensal microbe(Streptomyces sp.1B1)of Maytenus hookeri was elucidated as a new angucycline antibiotic on the basis of 1D-NMR,2D-NMR and HREIMS techniques.%从云南美登木共生放线菌菌株1B1的发酵提取物中分离得到了一个新的angucycline抗生素,并通过其谱学特征鉴定了化合物1的化学结构.

  18. Unusual Transformation from a Solvent-Stabilized 1D Coordination Polymer to a Metal-Organic Framework (MOF)-Like Cross-Linked 3D Coordination Polymer.

    Science.gov (United States)

    Lee, Seung-Chul; Choi, Eun-Young; Lee, Sang-Beom; Kim, Sang-Wook; Kwon, O-Pil

    2015-10-26

    An unusual 1D-to-3D transformation of a coordination polymer based on organic linkers containing highly polar push-pull π-conjugated side chains is reported. The coordination polymers are synthesized from zinc nitrate and an organic linker, namely, 2,5-bis{4-[1-(4-nitrophenyl)pyrrolidin-2-yl]butoxy}terephthalic acid, which possesses highly polar (4-nitrophenyl)pyrrolidine groups, with high dipole moments of about 7 D. The coordination polymers exhibit an unusual transformation from a soluble, solvent-stabilized 1D coordination polymer into an insoluble, metal-organic framework (MOF)-like 3D coordination polymer. The coordination polymer exhibits good film-forming ability, and the MOF-like films are insoluble in conventional organic solvents.

  19. Tensor network simulation of QED on infinite lattices: Learning from (1 +1 ) d , and prospects for (2 +1 ) d

    Science.gov (United States)

    Zapp, Kai; Orús, Román

    2017-06-01

    The simulation of lattice gauge theories with tensor network (TN) methods is becoming increasingly fruitful. The vision is that such methods will, eventually, be used to simulate theories in (3 +1 ) dimensions in regimes difficult for other methods. So far, however, TN methods have mostly simulated lattice gauge theories in (1 +1 ) dimensions. The aim of this paper is to explore the simulation of quantum electrodynamics (QED) on infinite lattices with TNs, i.e., fermionic matter fields coupled to a U (1 ) gauge field, directly in the thermodynamic limit. With this idea in mind we first consider a gauge-invariant infinite density matrix renormalization group simulation of the Schwinger model—i.e., QED in (1 +1 ) d . After giving a precise description of the numerical method, we benchmark our simulations by computing the subtracted chiral condensate in the continuum, in good agreement with other approaches. Our simulations of the Schwinger model allow us to build intuition about how a simulation should proceed in (2 +1 ) dimensions. Based on this, we propose a variational ansatz using infinite projected entangled pair states (PEPS) to describe the ground state of (2 +1 ) d QED. The ansatz includes U (1 ) gauge symmetry at the level of the tensors, as well as fermionic (matter) and bosonic (gauge) degrees of freedom both at the physical and virtual levels. We argue that all the necessary ingredients for the simulation of (2 +1 ) d QED are, a priori, already in place, paving the way for future upcoming results.

  20. Coupling of Nod1D and HOTCHANNEL: static case; Acoplamiento de Nod1D y HOTCHANNEL: caso estatico

    Energy Technology Data Exchange (ETDEWEB)

    Gomez T, A.M. [IPN-ESFM, 07738 Mexico D.F. (Mexico); Ovando C, R. [IIE-Gcia. de Energia Nuclear, Cuernavaca, Morelos (Mexico)]. e-mail: rovando@iie.org.mx

    2003-07-01

    In this work the joining of the programs Nod1D and HOTCHANNEL, developed in the National Polytechnic Institute (IPN) and in the Electrical Research Institute (IIE) respectively is described. The first one allows to study the neutronic of a nuclear reactor and the second one allows to carry out the analysis of hot channel of a Boiling Water Reactor (BWR). Nod1 D is a program that it solves by nodal methods type finite element those diffusion equations in multigroup, and it is the static part of Nod Kin that it solves the diffusion equation in their time dependent part. For another side HOTCHANNEL is based on a mathematical model constituted by four conservation equations (two of mass conservation, one of motion quantity and one of energy), which are solved applying one discretization in implicit finite differences. Both programs have been verified in independent form using diverse test problems. In this work the modifications that were necessary to carry out to both for obtaining a coupled program that it provides the axial distribution of the neutron flux, the power, the burnup and the void fraction, among others parameters as much as neutronic as thermal hydraulics are described. Those are also mentioned limitations, advantages and disadvantages of the final product to which has been designated Nod1 D-HotChn. Diverse results for the Cycle 1 of the Laguna Verde Unit 1 reactor of the Nucleo electric central comparing them with those obtained directly with the CoreMasterPresto code are provided. (Author)

  1. Transit timing analysis of CoRoT-1b

    CERN Document Server

    Csizmadia, Sz; Barge, P; Agol, E; Aigrain, S; Alonso, R; Almenara, J M; Bonomo, A S; Borde, P; Bouchy, F; Cabrera, J; Deeg, H J; De la Reza, R; Deleuil, M; Dvorak, R; Erikson, A; Guenther, E W; Fridlund, M; Gondoin, P; Guillot, T; Hatzes, A; Jorda, L; Lammer, H; Lázaro, C; Leger, A; Llebaria, A; Magain, P; Moutou, C; Ollivier, M; Paetzold, M; Queloz, D; Rauer, H; Rouan, D; Schneider, J; Wuchterl, G; Gandolfi, D

    2009-01-01

    CoRoT, the pioneer space-based transit search, steadily provides thousands of high-precision light curves with continuous time sampling over periods of up to 5 months. The transits of a planet perturbed by an additional object are not strictly periodic. By studying the transit timing variations (TTVs), additional objects can be detected in the system. A transit timing analysis of CoRoT-1b is carried out to constrain the existence of additional planets in the system. We used data obtained by an improved version of the CoRoT data pipeline (version 2.0). Individual transits were fitted to determine the mid-transit times, and we analyzed the derived $O-C$ diagram. N-body integrations were used to place limits on secondary planets. No periodic timing variations with a period shorter than the observational window (55 days) are found. The presence of an Earth-mass Trojan is not likely. A planet of mass greater than $\\sim 1$ Earth mass can be ruled out by the present data if the object is in a 2:1 (exterior) mean mot...

  2. A Photometric Survey of Ori OB1b

    Science.gov (United States)

    Merritt, Allison T.; Sherry, W.

    2011-01-01

    Several mechanisms have been suggested to describe the formation of sub-stellar mass objects (SSMOs), specifically brown dwarfs. Each proposed mechanism predicts a unique spatial distribution of the brown dwarfs relative to the O and B stars of the association. We have 9 square degrees of optical (VRI) data and 7 square degrees of NIR (JHK) data of Orion OB1b. The purpose of the survey is to obtain the photometric data that will allow us to determine the spatial distribution of brown dwarfs in this region and constrain the various formation theories. We present an overview of the survey, with an emphasis on the NIR data, as well as color-magnitude diagrams. This research was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program and the Department of Defense ASSURE program through Scientific Program Order No. 13 (AST-0754223) of the Cooperative Agreement No. AST-0132798 between the Association of Universities for Research in Astronomy (AURA) and the NSF.

  3. Genetic variants in MTNR1B affecting insulin secretion.

    Science.gov (United States)

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto; Häring, Hans-Ulrich; Fritsche, Andreas

    2010-09-01

    The incidence of type 2 diabetes mellitus has markedly increased worldwide over the past decades. Pancreatic beta-cell dysfunction as well as central and peripheral insulin resistance appears to be elementary features in the pathophysiology of type 2 diabetes mellitus. Major environmental conditions predisposing to the development of type 2 diabetes are excessive food intake and sedentary life-style on the background of a genetic predisposition. Recent genome-wide association studies identified several novel type 2 diabetes risk genes, with impaired pancreatic beta-cell function as the underlying mechanism of increased diabetes risk in the majority of genes. Many of the novel type 2 diabetes risk genes, including MTNR1B which encodes one of the two known human melatonin receptors, were unexpected at first glance. However, previous animal as well as human studies already pointed to a significant impact of the melatonin system on the regulation of glucose homeostasis, in addition to its well known role in modulation of sleep and circadian rhythms. This brief review aims to give an overview of how alterations in the melatonin system could contribute to an increased diabetes risk, paying special attention to the role of melatonin receptors in pancreatic beta-cell function.

  4. The secondary eclipse of CoRoT-1b

    CERN Document Server

    Alonso, R; Aigrain, S; Auvergne, M; Baglin, A; Barbieri, M; Barge, P; Bonomo, A S; Borde, P; Bouchy, F; Chaintreuil, S; De la Reza, R; Deeg, H J; Deleuil, M; Dvorak, R; Erikson, A; Fridlund, M; Fialho, F; Gondoin, P; Guillot, T; Hatzes, A; Jorda, L; Lammer, H; Léger, A; Llebaria, A; Magain, P; Mazeh, T; Moutou, C; Ollivier, M; Patzold, M; Pont, F; Queloz, D; Rauer, H; Rouan, D; Schneider, J; Wuchterl, G

    2009-01-01

    The transiting planet CoRoT-1b is thought to belong to the pM-class of planets, in which the thermal emission dominates in the optical wavelengths. We present a detection of its secondary eclipse in the CoRoT white channel data, whose response function goes from ~400 to ~1000 nm. We used two different filtering approaches, and several methods to evaluate the significance of a detection of the secondary eclipse. We detect a secondary eclipse centered within 20 min at the expected times for a circular orbit, with a depth of 0.016+/-0.006%. The center of the eclipse is translated in a 1-sigma upper limit to the planet's eccentricity of ecosomega<0.014. Under the assumption of a zero Bond Albedo and blackbody emission from the planet, it corresponds to a T_{CoRoT}=2330 +120-140 K. We provide the equilibrium temperatures of the planet as a function of the amount of reflected light. If the planet is in thermal equilibrium with the incident flux from the star, our results imply an inefficient transport mechanism ...

  5. BGK electron solitary waves: 1D and 3D

    Directory of Open Access Journals (Sweden)

    L.-J. Chen

    2002-01-01

    Full Text Available This paper presents new results for 1D BGK electron solitary wave (phase-space electron hole solutions and, based on the new results, extends the solutions to include the 3D electrical interaction (E ~ 1/r 2 of charged particles. Our approach for extending to 3D is to solve the nonlinear 3D Poisson and 1D Vlasov equations based on a key feature of 1D electron hole (EH solutions; the positive core of an EH is screened by electrons trapped inside the potential energy trough. This feature has not been considered in previous studies. We illustrate this key feature using an analytical model and argue that the feature is independent of any specific model. We then construct azimuthally symmetric EH solutions under conditions where electrons are highly field-aligned and ions form a uniform background along the magnetic field. Our results indicate that, for a single humped electric potential, the parallel cut of the perpendicular component of the electric field (E⊥ is unipolar and that of the parallel component (E|| bipolar, reproducing the multi-dimensional features of the solitary waves observed by the FAST satellite. Our analytical solutions presented in this article capture the 3D electric interaction and the observed features of (E|| and E⊥. The solutions predict a dependence of the parallel width-amplitude relation on the perpendicular size of EHs. This dependence can be used in conjunction with experimental data to yield an estimate of the typical perpendicular size of observed EHs; this provides important information on the perpendicular span of the source region as well as on how much electrostatic energy is transported by the solitary waves.

  6. Briefwechsel uber die Partikel "bis" (An Exchange of Letters about the Particle "bis").

    Science.gov (United States)

    Ludwig, Horst; Holschuh, Albrecht

    1990-01-01

    A discussion, in the form of an animated letter exchange, argues that, contrary to most current grammatical descriptions, the German particle "bis" should not be viewed as a preposition governing the accusative case. Rather, it is demonstrated that "bis" most often occurs as a proclitic adverb. (16 references) (JTC)

  7. Briefwechsel uber die Partikel "bis" (An Exchange of Letters about the Particle "bis").

    Science.gov (United States)

    Ludwig, Horst; Holschuh, Albrecht

    1990-01-01

    A discussion, in the form of an animated letter exchange, argues that, contrary to most current grammatical descriptions, the German particle "bis" should not be viewed as a preposition governing the accusative case. Rather, it is demonstrated that "bis" most often occurs as a proclitic adverb. (16 references) (JTC)

  8. Automatic simulation of 1D and 2D chaotic oscillators

    Energy Technology Data Exchange (ETDEWEB)

    Tlelo-Cuautle, E; Munoz-Pacheco, J-M [Department of Electronics, INAOE, Luis Enrique Erro No. 1, Tonantzintla, Puebla, 72840 MEXICO (Mexico)], E-mail: e.tlelo@ieee.org, E-mail: mpacheco@inaoep.mx

    2008-02-15

    A new method is introduced for automatic simulation of three kinds of chaotic oscillators: Chua's circuit, generalized Chua's circuit and chaotic oscillator implemented with saturated functions. The former generates the double-scroll, and the others 1D n-scroll attractors. The third chaotic oscillator is modified to generate 2D n-scrolls attractors. The oscillators are modelled by applying state variables and piecewise-linear approximation. Basically, the method computes the eigenvalues of the oscillators to begin time simulation and to make control of step-size automatically.

  9. Main: 1D6R [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D6R 大豆 Soybean Glycine max (L.) Merrill Bowman-Birk Type Proteinase Inhibitor Precursor Glycine Ma...x Molecule: Trypsinogen; Chain: A; Fragment: Cationic Precursor; Molecule: Bowman-Birk Prote...inase Inhibitor Precursor; Chain: I Hydrolase 3.4.21.4 (Bowman-Birk Proteinase Inhibitor Precursor) J.Koepke...r Crystal Structure Of Cancer Chemopreventive Bowman-Birk Inhibitor In Ternary Complex With Bovine Trypsin A... 477 2000 Protease Inhibitor, Serine Protease, Bowman-Birk Inhibitor SWS:TRY1_BOV

  10. Nonlocal order parameters for the 1D Hubbard model.

    Science.gov (United States)

    Montorsi, Arianna; Roncaglia, Marco

    2012-12-07

    We characterize the Mott-insulator and Luther-Emery phases of the 1D Hubbard model through correlators that measure the parity of spin and charge strings along the chain. These nonlocal quantities order in the corresponding gapped phases and vanish at the critical point U(c)=0, thus configuring as hidden order parameters. The Mott insulator consists of bound doublon-holon pairs, which in the Luther-Emery phase turn into electron pairs with opposite spins, both unbinding at U(c). The behavior of the parity correlators is captured by an effective free spinless fermion model.

  11. 1D superconductivity in porous Nb ultrathin films

    Energy Technology Data Exchange (ETDEWEB)

    Trezza, M., E-mail: trezza@sa.infn.it [CNR-SPIN Salerno and Dipartimento di Fisica, ' E. R. Caianiello' , Universita degli Studi di Salerno, Via Ponte don Melillo, Fisciano I-84084 (Italy); Prischepa, S.L. [State University of Informatics and RadioElectronics, P. Brovka Street 6, Minsk 220013 (Belarus); Cirillo, C.; Attanasio, C. [CNR-SPIN Salerno and Dipartimento di Fisica, ' E. R. Caianiello' , Universita degli Studi di Salerno, Via Ponte don Melillo, Fisciano I-84084 (Italy)

    2012-09-15

    We report on the measurements of the transport properties of superconducting Nb ultrathin bridges grown by UHV magnetron sputtering on porous Si substrates. The films are about 10 nm thick and inherit from the substrate a structure made of holes with diameter of 10 nm and interpore spacing in the range 20-40 nm. Due to their reduced dimensions, they are sensitive to thermal fluctuations typical of 1D superconductors and exhibit a nonzero resistance below the superconducting transition temperature, T{sub c}. Clear hysteresis and finite jumps in the I-V curves are also observed.

  12. ESO science data product standard for 1D spectral products

    Science.gov (United States)

    Micol, Alberto; Arnaboldi, Magda; Delmotte, Nausicaa A. R.; Mascetti, Laura; Retzlaff, Joerg

    2016-07-01

    The ESO Phase 3 process allows the upload, validation, storage, and publication of reduced data through the ESO Science Archive Facility. Since its introduction, 2 million data products have been archived and published; 80% of them are one-dimensional extracted and calibrated spectra. Central to Phase3 is the ESO science data product standard that defines metadata and data format of any product. This contribution describes the ESO data standard for 1d-spectra, its adoption by the reduction pipelines of selected instrument modes for in-house generation of reduced spectra, the enhanced archive legacy value. Archive usage statistics are provided.

  13. Restrained Dark $U(1)_d$ at Low Energies

    CERN Document Server

    Correia, F C

    2016-01-01

    We investigate a spontaneously broken $U(1)_d$ gauge symmetry with a muon-specific dark Higgs. Our first goal is to verify how the presence of a new dark Higgs, $\\phi$, and a dark gauge boson, $V$, can simultaneously face the anomalies from the muon magnetic moment and the proton charge radius. Secondly, by assuming that $V$ must decay to an electron-positron pair, we explore the corresponding parameter space determined with the low energy constraints coming from $ K \\to \\mu X$, electron $(g-2)_e$, $K \\to \\mu \

  14. Breakdown of 1D water wires inside Charged Carbon Nanotubes

    CERN Document Server

    Pant, Shashank

    2016-01-01

    Using Molecular Dynamics approach we investigated the structure, dynamics of water confined inside pristine and charged 6,6 carbon nanotubes (CNTs). This study reports the breakdown of 1D water wires and the emergence of triangular faced water on incorporating charges in 6,6 CNTs. Incorporation of charges results in high potential barriers to the flipping of water molecules due to the formation of a large number of hydrogen bonds. The PMF analyses show the presence of ~2 kcal/mol barrier for the movement of water inside pristine CNT and almost negligible barrier in charged CNTs.

  15. Pregnancy and pregnancy outcome in hepatitis C type 1b.

    LENUS (Irish Health Repository)

    Jabeen, T

    2012-02-03

    A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

  16. Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity.

    Science.gov (United States)

    Nguyen, Phi-Hung; Yang, Jun-Li; Uddin, Mohammad N; Park, So-Lim; Lim, Seong-Il; Jung, Da-Woon; Williams, Darren R; Oh, Won-Keun

    2013-11-22

    As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

  17. Modeling atrazine transport in soil columns with HYDRUS-1D

    Directory of Open Access Journals (Sweden)

    John Leju CELESTINO LADU

    2011-09-01

    Full Text Available Both physical and chemical processes affect the fate and transport of herbicides. It is useful to simulate these processes with computer programs to predict solute movement. Simulations were run with HYDRUS-1D to identify the sorption and degradation parameters of atrazine through calibration from the breakthrough curves (BTCs. Data from undisturbed and disturbed soil column experiments were compared and analyzed using the dual-porosity model. The study results show that the values of dispersivity are slightly lower in disturbed columns, suggesting that the more heterogeneous the structure is, the higher the dispersivity. Sorption parameters also show slight variability, which is attributed to the differences in soil properties, experimental conditions and methods, or other ecological factors. For both of the columns, the degradation rates were similar. Potassium bromide was used as a conservative non-reactive tracer to characterize the water movement in columns. Atrazine BTCs exhibited significant tailing and asymmetry, indicating non-equilibrium sorption during solute transport. The dual-porosity model was verified to best fit the BTCs of the column experiments. Greater or lesser concentration of atrazine spreading to the bottom of the columns indicated risk of groundwater contamination. Overall, HYDRUS-1D successfully simulated the atrazine transport in soil columns.

  18. Study of 1D Strange Charmed Meson Family Using HQET

    Directory of Open Access Journals (Sweden)

    Pallavi Gupta

    2016-01-01

    Full Text Available Recently LHCb predicted spin 1 and spin 3 states Ds1⁎(2860 and Ds3⁎(2860 which are studied through their strong decays and are assigned to fit the 13D1 and 13D3 states in the charm spectroscopy. In this paper, using the heavy quark effective theory, we state that assigning Ds1⁎(2860 as the mixing of 13D1-23S1 states is rather a better justification to its observed experimental values than a pure state. We study its decay modes variation with hadronic coupling constant gxh and the mixing angle θ. We appoint spin 3 state Ds3⁎(2860 as the missing 1D  3-JP state and also study its decay channel behavior with coupling constant gyh. To appreciate the above results, we check the variation of decay modes for their spin partners states, that is, 1D2 and 1D2′, with their masses and strong coupling constant, that is, gxh and gyh. Our calculation using HQET approach gives mixing angle of the 13D1-23S1 state for Ds1⁎(2860 to lie in the range (-1.6 radians ≤θ≤-1.2 radians. Our calculation for coupling constant values gives gxh to lie within value range of 0.17–0.20 and gyh to be 0.40. We expect from experiments to observe this mixing angle to verify our results.

  19. A Framework for Low-Communication 1-D FFT

    Directory of Open Access Journals (Sweden)

    Ping Tak Peter Tang

    2013-01-01

    Full Text Available In high-performance computing on distributed-memory systems, communication often represents a significant part of the overall execution time. The relative cost of communication will certainly continue to rise as compute-density growth follows the current technology and industry trends. Design of lower-communication alternatives to fundamental computational algorithms has become an important field of research. For distributed 1-D FFT, communication cost has hitherto remained high as all industry-standard implementations perform three all-to-all internode data exchanges (also called global transposes. These communication steps indeed dominate execution time. In this paper, we present a mathematical framework from which many single-all-to-all and easy-to-implement 1-D FFT algorithms can be derived. For large-scale problems, our implementation can be twice as fast as leading FFT libraries on state-of-the-art computer clusters. Moreover, our framework allows tradeoff between accuracy and performance, further boosting performance if reduced accuracy is acceptable.

  20. Tunability and Sensing Properties of Plasmonic/1D Photonic Crystal.

    Science.gov (United States)

    Shaban, Mohamed; Ahmed, Ashour M; Abdel-Rahman, Ehab; Hamdy, Hany

    2017-02-08

    Gold/one-dimensional photonic crystal (Au/1D-PC) is fabricated and applied for sensitive sensing of glucose and different chemical molecules of various refractive indices. The Au layer thickness is optimized to produce surface plasmon resonance (SPR) at the right edge of the photonic band gap (PBG). As the Au deposition time increased to 60 sec, the PBG width is increased from 46 to 86 nm in correlation with the behavior of the SPR. The selectivity of the optimized Au/1D-PC sensor is tested upon the increase of the environmental refractive index of the detected molecules. The resonance wavelength and the PBG edges increased linearly and the transmitted intensity increased nonlinearly as the environment refractive index increased. The SPR splits to two modes during the detection of chloroform molecules based on the localized capacitive coupling of Au particles. Also, this structure shows high sensitivity at different glucose concentrations. The PBG and SPR are shifted to longer wavelengths, and PBG width is decreased linearly with a rate of 16.04 Å/(μg/mm(3)) as the glucose concentration increased. The proposed structure merits; operation at room temperature, compact size, and easy fabrication; suggest that the proposed structure can be efficiently used for the biomedical and chemical application.

  1. Entanglement and Nonlocality in Infinite 1D Systems

    Science.gov (United States)

    Wang, Zizhu; Singh, Sukhwinder; Navascués, Miguel

    2017-06-01

    We consider the problem of detecting entanglement and nonlocality in one-dimensional (1D) infinite, translation-invariant (TI) systems when just near-neighbor information is available. This issue is deeper than one might think a priori, since, as we show, there exist instances of local separable states (classical boxes) which admit only entangled (nonclassical) TI extensions. We provide a simple characterization of the set of local states of multiseparable TI spin chains and construct a family of linear witnesses which can detect entanglement in infinite TI states from the nearest-neighbor reduced density matrix. Similarly, we prove that the set of classical TI boxes forms a polytope and devise a general procedure to generate all Bell inequalities which characterize it. Using an algorithm based on matrix product states, we show how some of them can be violated by distant parties conducting identical measurements on an infinite TI quantum state. All our results can be easily adapted to detect entanglement and nonlocality in large (finite, not TI) 1D condensed matter systems.

  2. Error analysis of subaperture processing in 1-D ultrasound arrays.

    Science.gov (United States)

    Zhao, Kang-Qiao; Bjåstad, Tore Gruner; Kristoffersen, Kjell

    2015-04-01

    To simplify the medical ultrasound system and reduce the cost, several techniques have been proposed to reduce the interconnections between the ultrasound probe and the back-end console. Among them, subaperture processing (SAP) is the most straightforward approach and is widely used in commercial products. This paper reviews the most important error sources of SAP, such as static focusing, delay quantization, linear delay profile, and coarse apodization, and the impacts introduced by these errors are shown. We propose to use main lobe coherence loss as a simple classification of the quality of the beam profile for a given design. This figure-ofmerit (FoM) is evaluated by simulations with a 1-D ultrasound subaperture array setup. The analytical expressions and the coherence loss can work as a quick guideline in subaperture design by equalizing the merit degradations from different error sources, as well as minimizing the average or maximum loss over ranges. For the evaluated 1-D array example, a good balance between errors and cost was achieved using a subaperture size of 5 elements, focus at 40 mm range, and a delay quantization step corresponding to a phase of π/4.

  3. Tunability and Sensing Properties of Plasmonic/1D Photonic Crystal

    Science.gov (United States)

    Shaban, Mohamed; Ahmed, Ashour M.; Abdel-Rahman, Ehab; Hamdy, Hany

    2017-01-01

    Gold/one-dimensional photonic crystal (Au/1D-PC) is fabricated and applied for sensitive sensing of glucose and different chemical molecules of various refractive indices. The Au layer thickness is optimized to produce surface plasmon resonance (SPR) at the right edge of the photonic band gap (PBG). As the Au deposition time increased to 60 sec, the PBG width is increased from 46 to 86 nm in correlation with the behavior of the SPR. The selectivity of the optimized Au/1D-PC sensor is tested upon the increase of the environmental refractive index of the detected molecules. The resonance wavelength and the PBG edges increased linearly and the transmitted intensity increased nonlinearly as the environment refractive index increased. The SPR splits to two modes during the detection of chloroform molecules based on the localized capacitive coupling of Au particles. Also, this structure shows high sensitivity at different glucose concentrations. The PBG and SPR are shifted to longer wavelengths, and PBG width is decreased linearly with a rate of 16.04 Å/(μg/mm3) as the glucose concentration increased. The proposed structure merits; operation at room temperature, compact size, and easy fabrication; suggest that the proposed structure can be efficiently used for the biomedical and chemical application. PMID:28176799

  4. Lack of XAGE-1b and NY-ESO-1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients.

    Science.gov (United States)

    Mori, Mariko; Funakoshi, Takeru; Kameyama, Kaori; Kawakami, Yutaka; Sato, Eiichi; Nakayama, Eiichi; Amagai, Masayuki; Tanese, Keiji

    2017-06-01

    The cancer-testis antigens (CTA) are a large family of tumor-associated antigens expressed by a variety of cancer cells and primitive germ cells of the adult testis and placenta. These tumor-restricted expressing patterns suggest that CTA would be ideal targets for tumor-specific immunotherapy. XAGE-1 is a CTA that was originally identified by computer-based screening, and four transcription variants, XAGE-1a, -1b, -1c and -1d, have been characterized to date. Although the presence of XAGE-1 transcripts has been reported in various cancers, the expression of XAGE-1b in melanoma has not been fully characterized. In this study, we performed immunohistochemical staining of XAGE-1b together with NY-ESO-1, a well-known CTA, in 113 melanoma samples obtained from 84 patients and evaluated their expression in tumor cells. The effects of expression on tumor progression and patient prognosis were analyzed. Both XAGE-1b and NY-ESO-1 were expressed at high levels in lymph node metastasis and skin metastasis samples compared with the primary site (P ESO-1). In a subgroup analysis of 22 patients with stage III lymph node metastasis, overall survival was significantly higher in the XAGE-1b and NY-ESO-1 double-negative group than in the other groups (P ESO-1 expression could have a positive influence on clinical outcome in patients with melanoma. © 2017 Japanese Dermatological Association.

  5. Transformation of 1-D Chiral-chained Titanium Phosphate to 2-D Layer Structure Through a 1-D Zigzag Chain

    Institute of Scientific and Technical Information of China (English)

    CHEN Chao; YANG Yu-lin; LI Wei-sheng; LIU Yun-ling; YI Zhuo; GUO Yang-hong; PANG Wen-qin

    2005-01-01

    The transformation of titanium phosphate from 1-D chiral- chain(JTP-A) to 2-D layer(TP-J1) has been carefully investigated. Through a hydrolysis-condensation self-assembly pathway, the crystals of TP-J1 can be obtained from the JTP-A phase under hydrothermal conditions. An intermediate material with zigzag chain during the transformation was observed by XRD characterization. A hypothesis of the transformation mechanism is also described in this article. It is noteworthy that ethylenediamine plays an important role in the transformation.

  6. The N-terminal region of organic anion transporting polypeptide 1B3 (OATP1B3) plays an essential role in regulating its plasma membrane trafficking.

    Science.gov (United States)

    Chun, Se-Eun; Thakkar, Nilay; Oh, Yunseok; Park, Ji Eun; Han, Songhee; Ryoo, Gongmi; Hahn, Hyunggu; Maeng, Sang Hyun; Lim, Young-Ran; Han, Byung Woo; Lee, Wooin

    2017-05-01

    Organic anion transporting polypeptide 1B3 (OATP1B3) is a major influx transporter mediating the hepatic uptake of various endogenous substrates as well as clinically important drugs such as statins and anticancer drugs. However, molecular mechanisms controlling the membrane trafficking of OATP1B3 have been largely unknown. Several reports recently indicated the presence of a distinct, cancer-type OATP1B3 variant lacking the N-terminal 28 amino acids compared to OATP1B3 expressed in non-malignant hepatocytes. Interestingly, the cancer-type OATP1B3 variant is located predominantly in the cytoplasm, implicating the involvement of the N-terminal region of OATP1B3 in its membrane trafficking. In the current study, we set out to experimentally validate the importance of the N-terminal region of OATP1B3 and to identify responsible sequence motif(s) in that region. A number of truncation or point mutants of OATP1B3 were transiently expressed in HEK293T, HCT-8 or MDCK II cells and their expression in cytoplasmic and surface membrane fractions were analyzed by immunoblotting. Our results indicated that the N-terminal sequence of OATP1B3, in particular, at the amino acid positions between 12 and 28, may be indispensable in its membrane trafficking. Moreover, our results using a fusion construct indicated that the first 50 amino acids of OATP1B3 are sufficient for its membrane localization. The importance of the N-terminal region in membranous localization was shared among the other OATP1B subfamily members, OATP1B1 and rat Oatp1b2. Our efforts to identify the responsible amino acid(s) or structure motif(s) in the N-terminal region did not pinpoint individual amino acids or motifs with putative secondary structures. Our current findings however demonstrate that the N-terminal region is important for the membrane localization of the OATP1B subfamily members and should facilitate future investigations of the mechanisms involved in the regulation and membrane trafficking of

  7. Nostocyclopeptide-M1: a potent, nontoxic inhibitor of the hepatocyte drug transporters OATP1B3 and OATP1B1.

    Science.gov (United States)

    Herfindal, Lars; Myhren, Lene; Kleppe, Rune; Krakstad, Camilla; Selheim, Frode; Jokela, Jouni; Sivonen, Kaarina; Døskeland, Stein O

    2011-04-01

    We have isolated a novel cyanobacterial cyclic peptide (nostocyclopeptide M1; Ncp-M1) that blocks the hepatotoxic action of microcystin (MC) and nodularin (Nod). We show here that Ncp-M1 is nontoxic to primary hepatocytes in long-term culture. Ncp-M1 does not affect any known intracellular targets or pathways involved in MC action, like protein phosphatases, CaM-KII, or ROS-dependent cell death effectors. In support of this conclusion Ncp-M1 had no protective effect when microinjected into cells. Rather, the antitoxin effect was solely due to blocked hepatocyte uptake of MC and Nod. The hepatic uptake of MC and Nod is mainly via the closely related organic anion transporters OATP1B1 and OATP1B3, which also mediate hepatic transport of endogenous metabolites and hormones as well as drugs. OATP1B3 is also expressed in some aggressive cancers, where it confers apoptosis resistance. We show that Ncp-M1 inhibits transport through OATP1B3 and OATP1B1 expressed in HEK293 cells. The Ncp-M1 molecule has several nonproteinogenic amino acids and an imino bond, which hamper its synthesis. Moreover, a cyclic all L-amino acid heptapeptide analogue of Ncp-M1 also inhibits the OATP1B1/1B3 transporters, and with higher OATP1B3 preference than Ncp-M1 itself. The nontoxic Ncp-M1 and its synthetic cyclic peptide analogues thus provide new tools to probe the role of OATB1B1/1B3 mediated drug and metabolite transport in liver and cancer cells. They can also serve as scaffolds to design new, exopeptidase resistant OATP1B3-specific modulators.

  8. Isolation of modulators of the liver-specific organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae).

    Science.gov (United States)

    Roth, Megan; Araya, Juan J; Timmermann, Barbara N; Hagenbuch, Bruno

    2011-11-01

    Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are liver-specific transporters that mediate the uptake of a broad range of drugs into hepatocytes, including statins, antibiotics, and many anticancer drugs. Compounds that alter transport by one or both of these OATPs could potentially be used to target drugs to hepatocytes or improve the bioavailability of drugs that are cleared by the liver. In this study, we applied a bioassay-guided isolation approach to identify such compounds from the organic extract of Rollinia emarginata Schlecht (Annonaceae). Fractions of the plant extract were screened for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates estradiol-17β-glucuronide and estrone-3-sulfate. We isolated three compounds, ursolic acid, oleanolic acid, and 8-trans-p-coumaroyloxy-α-terpineol, which inhibited estradiol-17β-glucuronide uptake by OATP1B1 but not OATP1B3. In addition, a rare compound, quercetin 3-O-α-l-arabinopyranosyl(1→2) α-L-rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1 was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17β-glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated 4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent affinity for estrone-3-sulfate was increased (decreased K(m)), whereas the maximal rate of transport (V(max)) was significantly reduced. These results demonstrate a mechanism through which the hepatic uptake of drug OATP substrates could be stimulated.

  9. Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior.

    Science.gov (United States)

    Hodgson, Robert A; Mullins, Deborra; Lu, Sherry X; Guzzi, Mario; Zhang, Xiaoping; Bleickardt, Carina J; Scott, Jack D; Miller, Michael W; Stamford, Andrew W; Parker, Eric M; Varty, Geoffrey B

    2014-05-05

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to affective disorders such as anxiety and depression. Dampening HPA activity has, therefore, been considered as a possible means of treating affective disorders. Given the important role of vasopressin in modulating the HPA axis, one strategy has focused on inhibiting activity of the vasopressin 1b (V1b) receptor. In animals, V1b receptor antagonists reduce plasma stress hormone levels and have been shown to have an anxiolytic-like effect. Recently, V1B-30N was identified as a highly potent V1b receptor antagonist with selectivity over other vasopressin receptors, which is evaluated here in rodent models of anxiety-like and depression-like behaviors. V1B-30N (1-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in rat pups without producing any sedative effects in the animals. Similarly, V1B-30N (3-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in guinea pig pups. In a conflict assay, conditioned lick suppression, V1B-30N (3-30mg/kg, IP) increased punished licking. To assess antidepressive-like properties, V1B-30N (1-30mg/kg) was tested in the mouse and rat forced-swim tests but was found to be inactive. These results are consistent with previous findings with other V1b antagonists, which suggest that acute pharmacological antagonism of the V1b receptor has anxiolytic-like but not antidepressant-like properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Neutron powder diffraction study on Mg sup 1 sup 1 B sub 2 synthesized by different procedures

    CERN Document Server

    Oikawa, K; Arai, M; Mochiku, T; Takeya, H; Furuyama, M; Kamisawa, S; Kadowaki, K

    2002-01-01

    The crystal structure of a new superconducting material, MgB sub 2 , was studied by high-resolution neutron powder diffraction as a function of temperature from 8K to 305K. Two samples of Mg sup 1 sup 1 B sub 2 were measured; one was synthesized for 2d at 1050degC, and the other one was done for 1d at 1100degC. All of the diffraction data were precisely refined by the Rietveld method, and we confirmed that there was no clear anomaly on the temperature dependence of the lattice constants around T sub c for both samples. The difference in sample synthesis procedures affects the profile shapes of the 001 reflections, whereas the hh0 lines are almost the same.

  11. Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

    Directory of Open Access Journals (Sweden)

    Mandana Ghisari

    2013-06-01

    Full Text Available Background. The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs such as polychlorinated biphenyls (PCBs and organochlorine pesticides (OCPs, and an elucidation of gene–environment interactions in relation to health risks is needed. Objectives. The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943, CYP1B1 Leu432Val (rs1056836 and catechol-O-methyltransferase COMT Val158Met (rs4680 in Greenlandic Inuit (n=254 and Europeans (n=262 and explore the possible relation between the genotypes and serum levels of POPs. Results. The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153 and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl-ethylene (p,p′-DDE levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Conclusion. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

  12. Data of evolutionary structure change: 1B5XA-1GHLA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5XA-1GHLA 1B5X 1GHL A A -KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGY...NTRATNYNAGDRSTDYGIFQINSRYWCNDGKTPGAVNACHLACSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRDVRQYVQGCGV GK...ID> A 1GHLA TNRNT-DGS

  13. Data of evolutionary structure change: 1DTGA-1B7ZA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B7ZA 1DTG 1B7Z A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...VAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFV...> 0 1DTG A 1DTGAA 1DTGA LFSSP-HGKDL 1DTGA HMKSVIPSDGPSV

  14. Data of evolutionary structure change: 1DTGA-1B0LA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B0LA 1DTG 1B0L A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...GYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGD...ignment> 0 1DTG A 1DTGA...> 1 1DTG A 1DTGA 1DTG A 1DTGA

  15. Data of evolutionary structure change: 1B06A-2GDSB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B06A-2GDSB 1B06 2GDS A B VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGYVNGANSLLDRL-EKLIKGD...NLQIMTVENH-FMNHIAELPVILIVDEFEHAYYLQYKNKRGDYLNAWWNVVNWDDAEKRLQKYLNK -----KHSLPDLPYDYGALEPHINAQIM...QLHHSKNHAAYVNNLNVTEEKYQEALAKGD-------VTAQIALQPALKFNGGGHINHSIFWTNLSP--NGGGEPKGELLE...264 2GDS B 2GD...el> 1 2GDS

  16. Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration

    Science.gov (United States)

    Xu, Jin; Cui, Jiaxi; Del Campo, Aranzazu; Shin, Chong Hyun

    2016-01-01

    The liver and pancreas originate from overlapping embryonic regions, and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b) signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b), which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling. fhl1b depletion compromised liver specification and enhanced induction of pancreatic cells from endodermal progenitors. Conversely, overexpression of fhl1b favored liver specification and inhibited induction of pancreatic cells. By single-cell lineage tracing, we showed that fhl1b depletion led lateral endodermal cells, destined to become liver cells, to become pancreatic cells. Reversely, when fhl1b was overexpressed, medially located endodermal cells, fated to differentiate into pancreatic and intestinal cells, contributed to the liver by directly or indirectly modulating the discrete levels of pdx1 expression in endodermal progenitors. Moreover, loss of fhl1b increased the regenerative capacity of β-cells by increasing pdx1 and neurod expression in the hepatopancreatic ductal system. Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in β-cell regeneration. PMID:26845333

  17. 20 CFR 655.705 - What Federal agencies are involved in the H-1B and H-1B1 programs, and what are the...

    Science.gov (United States)

    2010-04-01

    ... Employers Seeking To Employ Nonimmigrants on H-1b Visas in Specialty Occupations and as Fashion Models, and Requirements for Employers Seeking To Employ Nonimmigrants on H-1b1 and E-3 Visas in Specialty Occupations... petition, whether the occupation named in the labor condition application is a specialty occupation or...

  18. Four and a Half LIM Domains 1b (Fhl1b Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    2016-02-01

    Full Text Available The liver and pancreas originate from overlapping embryonic regions, and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b, which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling. fhl1b depletion compromised liver specification and enhanced induction of pancreatic cells from endodermal progenitors. Conversely, overexpression of fhl1b favored liver specification and inhibited induction of pancreatic cells. By single-cell lineage tracing, we showed that fhl1b depletion led lateral endodermal cells, destined to become liver cells, to become pancreatic cells. Reversely, when fhl1b was overexpressed, medially located endodermal cells, fated to differentiate into pancreatic and intestinal cells, contributed to the liver by directly or indirectly modulating the discrete levels of pdx1 expression in endodermal progenitors. Moreover, loss of fhl1b increased the regenerative capacity of β-cells by increasing pdx1 and neurod expression in the hepatopancreatic ductal system. Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in β-cell regeneration.

  19. Involvement of α1B-adrenoceptors in the anti-immobility effect of imipramine in the tail suspension test.

    Science.gov (United States)

    Ribeiro, Carlos Alberto S; Pupo, André S

    2015-03-05

    Imipramine is a tricyclic antidepressant inhibitor of norepinephrine and serotonin neuronal reuptake. The roles of specific α1-adrenoceptor subtypes that might be targeted by the increased synaptic levels of noradrenaline induced by imipramine are not well understood. This study investigates the α1-adrenoceptor subtypes involved in the anti-immobility effect of imipramine in the mouse tail suspension test. The anti-immobility effect of imipramine (32mg/kg, i.p.) was significantly antagonised by the non-subtype-selective α1-adrenoceptor antagonist prazosin (0.5 and 1.0mg/kg, i.p.). Neither the selective α1A-adrenoceptor antagonist 5-methyl-3-[3-[3-[4-[2-(2,2,2,-trifluroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H,3H)-pyrimidinedione (RS-100329, 0.5 and 1.0mg/kg) nor the selective α1D-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride, (BMY-7378, up to 1.0mg/kg, i.p.) affected the anti-immobility effect of imipramine. However, the anti-immobility effect of imipramine was significantly antagonised by the selective α1B-adrenoceptor antagonist (2S)-4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-2-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperazinecarboxylate (L-765,314). In addition, mice treated only with RS-100329 or BMY-7378, but not with L-765,314, showed reduced immobility times in comparison to mice treated with vehicle. These results indicate that the selective antagonism of α1A- and α1D-adrenoceptors results in antidepressant-like effects and that the α1B-subtype is the main target for the increased levels of noradrenaline caused by imipramine.

  20. Phenomenological predictions of 3+1d anisotropic hydrodynamics

    CERN Document Server

    Nopoush, Mohammad; Ryblewski, Radoslaw

    2016-01-01

    We make phenomenological predictions for particle spectra and elliptic flow in heavy-ion collisions using 3+1d anisotropic hydrodynamics (aHydro) including the effects of both shear and bulk viscosities. The dynamical equations necessary are derived by taking moments of the Boltzmann equation allowing for three distinct (diagonal) momentum-space anisotropy parameters. The formulation is based on relaxation-time approximation for the collisional kernel and a lattice-QCD-based equation of state. Evolving the system to late times, we calculate particle production using THERMINATOR 2, modified to account for an ellipsoidal distribution function. We obtain particle spectra for different particle species such as pions, kaons, and protons, and elliptic flow $v_2$ as a function of centrality, transverse momentum, and rapidity. In our model, we have four free parameters, i.e. freeze-out temperature, initial central energy density, initial momentum-space anisotropies, and shear viscosity to entropy density ratio. Using...

  1. Effective theory of Black Holes in the 1/D expansion

    CERN Document Server

    Emparan, Roberto; Suzuki, Ryotaku; Tanabe, Kentaro; Tanaka, Takahiro

    2015-01-01

    The gravitational field of a black hole is strongly localized near its horizon when the number of dimensions D is very large. In this limit, we can effectively replace the black hole with a surface in a background geometry (eg Minkowski or Anti-deSitter space). The Einstein equations determine the effective equations that this 'black hole surface' (or membrane) must satisfy. We obtain them up to next-to-leading order in 1/D for static black holes of the Einstein-(A)dS theory. To leading order, and also to next order in Minkowski backgrounds, the equations of the effective theory are the same as soap-film equations, possibly up to a redshift factor. In particular, the Schwarzschild black hole is recovered as a spherical soap bubble. Less trivially, we find solutions for 'black droplets', ie black holes localized at the boundary of AdS, and for non-uniform black strings.

  2. Effective theory of black holes in the 1/D expansion

    Science.gov (United States)

    Emparan, Roberto; Shiromizu, Tetsuya; Suzuki, Ryotaku; Tanabe, Kentaro; Tanaka, Takahiro

    2015-06-01

    The gravitational field of a black hole is strongly localized near its horizon when the number of dimensions D is very large. In this limit, we can effectively replace the black hole with a surface in a background geometry (e.g. Minkowski or Anti-deSitter space). The Einstein equations determine the effective equations that this `black hole surface' (or membrane) must satisfy. We obtain them up to next-to-leading order in 1/ D for static black holes of the Einstein-(A)dS theory. To leading order, and also to next order in Minkowski backgrounds, the equations of the effective theory are the same as soap-film equations, possibly up to a redshift factor. In particular, the Schwarzschild black hole is recovered as a spherical soap bubble. Less trivially, we find solutions for `black droplets', i.e. black holes localized at the boundary of AdS, and for non-uniform black strings.

  3. Identification of a T1D Susceptibility Gene

    Directory of Open Access Journals (Sweden)

    Grant Morahan

    2001-01-01

    Full Text Available It is not known what causes type 1 diabetes (T1D, which affects over 1 million people in the U.S. alone. Each year, 30,000 young people in the U.S. develop this disease and depend on insulin injections thereafter. Because of the huge cost to the individual, the family, and to society in increased health care costs, it is important to find what makes these people susceptible. The disease process itself is clear: the individual’s immune system — T lymphocytes in particular — attack and destroy the body’s insulin-producing cells. But how and why this autoimmune process starts or proceeds unregulated is still not known.

  4. Microlens Masses from 1-D Parallaxes and Heliocentric Proper Motions

    CERN Document Server

    Gould, Andrew

    2014-01-01

    One-dimensional (1-D) microlens parallaxes can be combined with heliocentric lens-source relative proper motion measurements to derive the lens mass and distance, as suggested by Ghosh et al. (2004). Here I present the first mathematical anlysis of this procedure, which I show can be represented as a quadratic equation. Hence, it is formally subject to a two-fold degeneracy. I show that this degeneracy can be broken in many cases using the relatively crude 2-D parallax information that is often available for microlensing events. I also develop an explicit formula for the region of parameter space where it is more difficult to break this degeneracy. Although no mass/distance measurements have yet been made using this technique, it is likely to become quite common over the next decade.

  5. 1D-transport properties of single superconducting lead nanowires

    DEFF Research Database (Denmark)

    Michotte, S.; Mátéfi-Tempfli, Stefan; Piraux, L.

    2003-01-01

    We report on the transport properties of single superconducting lead nanowires grown by an electrodeposition technique, embedded in a nanoporous track-etched polymer membrane. The nanowires are granular, have uniform diameter of ̃40 nm and a very large aspect ratio (̃500). The diameter of the nan......We report on the transport properties of single superconducting lead nanowires grown by an electrodeposition technique, embedded in a nanoporous track-etched polymer membrane. The nanowires are granular, have uniform diameter of ̃40 nm and a very large aspect ratio (̃500). The diameter...... of the nanowire is small enough to ensure a 1D superconducting regime in a wide temperature range below T. The non-zero resistance in the superconducting state and its variation caused by fluctuations of the superconducting order parameter were measured versus temperature, magnetic field, and applied DC current...

  6. 1-D array of perforated diode neutron detectors

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, Walter J. [Kansas State University, Mechanical and Nuclear Engineering Department, Manhattan, KS 66506 (United States)], E-mail: wjm4444@ksu.edu; Bellinger, Steven L.; Unruh, Troy C.; Henderson, Chris M.; Ugorowski, Phil; Morris-Lee, Bryce [Kansas State University, Mechanical and Nuclear Engineering Department, Manhattan, KS 66506 (United States); Taylor, Russell D. [Electronics Design Laboratory, Kansas State University, Manhattan, KS 66506 (United States); McGregor, Douglas S. [Kansas State University, Mechanical and Nuclear Engineering Department, Manhattan, KS 66506 (United States)], E-mail: mcgregor@ksu.edu

    2009-06-01

    Performance of a 4 cm long 64-pixel perforated diode neutron detector array is compared with an identical array of thin-film coated diodes. The perforated neutron detector design has been adapted to a 1-D pixel array capable of 120 {mu}m spatial resolution and counting efficiency greater than 12%. Deep vertical trenches filled with {sup 6}LiF provide outstanding improvement in efficiency over thin-film coated diode designs limited to only 4.5%. This work marks the final step towards the construction of a much larger array consisting of 1024 pixels spanning 10 cm. The larger detector array will be constructed with a sub-array of 64-pixel sensors, and will be used for small-angle neutron scattering experiments at the Spallation Neutron Source of Oak Ridge National Laboratory.

  7. Coherent thermal conductance of 1-D photonic crystals

    Energy Technology Data Exchange (ETDEWEB)

    Tschikin, Maria [Institut für Physik, Carl von Ossietzky Universität, D-26111 Oldenburg (Germany); Ben-Abdallah, Philippe [Laboratoire Charles Fabry, UMR 8501, Institut d' Optique, CNRS, Université Paris-Sud, 2, Avenue Augustin Fresnel, RD128, 91127 Palaiseau Cedex (France); Biehs, Svend-Age, E-mail: biehs@theorie.physik.uni-oldenburg.de [Institut für Physik, Carl von Ossietzky Universität, D-26111 Oldenburg (Germany)

    2012-10-01

    We present an exact calculation of coherent thermal conductance in 1-D multilayer photonic crystals using the S-matrix method. In particular, we study the thermal conductance in a bilayer structure of Si/vacuum or Al{sub 2}O{sub 3}/vacuum slabs by means of the exact radiative heat flux expression. Based on the results obtained for the Al{sub 2}O{sub 3}/vacuum structure we show by comparison with previous works that the material losses and (localized) surface modes supported by the inner layers play a fundamental role and cannot be omitted in the definition of thermal conductance. Our results could have significant implications in the conception of efficient thermal barriers.

  8. Data of evolutionary structure change: 1D6QA-2G4QA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D6QA-2G4QA 1D6Q 2G4Q A A KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...GRCELAAAMKRHGLDNYRGYSLGNWVCAAKFESNFNTQATNRNTD-GSTDYGILQINSRWWCNDGRTPGSRNLCNIPCSALLSSDITASVNCAKKIVSDGNGMNAWVAWRNRCKGTDVQA...bID> A 2G4QA NRNTD-GS...> 1D6Q A 1D6QA

  9. XENON ANESTHESIA IN CHILDREN: BIS-MONITORING

    Directory of Open Access Journals (Sweden)

    V. G. Bagaev

    2013-01-01

    Full Text Available We conducted 60 low-flow xenon anesthesias in children of 1-18 years of age. We measured the sedation level using bispectral (BIS index and clinically on the stage of induction, xenon anesthesia maintenance and during recovery. The trial showed that, according to the clinical and BIS-monitoring data, sevoflurane inhalational induction in children of 1-5 years of age and propofol intravenous induction in children of 6-18 years of age provides children with the required sedation level. BIS index objectively reflects intensity of the sedative component of an anesthesia both in the junior and the senior age groups on the stages of xenon anesthesia maintenance and during recovery.

  10. Data of evolutionary structure change: 1CG8A-2DN1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available equence>FSGFE-----ACNEQ ure> ----- HH> B 2DN1B FGDLSTPDAVMGNPK re>G HHHH HH...ence>VNLQA-FTPVT >HH - HHH> 2DN1 B 2DN1B HHFGKEFTPPV ...>HHHGGG HHH> ATOM 1931 CA HIS B 116 17.758 39.

  11. File list: Oth.ALL.10.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.10.HNF1B.AllCell hg19 TFs and others HNF1B All cell types SRX359840,SRX7020...21,SRX825396,SRX702024,SRX702022 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.10.HNF1B.AllCell.bed ...

  12. File list: Oth.ALL.05.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.HNF1B.AllCell hg19 TFs and others HNF1B All cell types SRX359840,SRX7020...21,SRX702022,SRX825396,SRX702024,SRX702023 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.05.HNF1B.AllCell.bed ...

  13. File list: Oth.PSC.20.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.20.HNF1B.AllCell hg19 TFs and others HNF1B Pluripotent stem cell SRX702021,...SRX702024,SRX702022 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.PSC.20.HNF1B.AllCell.bed ...

  14. 18 CFR 1b.17 - Appearance and practice before the Commission.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Appearance and practice before the Commission. 1b.17 Section 1b.17 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.17...

  15. 18 CFR 1b.15 - Non-compliance with compulsory processes.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Non-compliance with compulsory processes. 1b.15 Section 1b.15 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.15 Non-compliance...

  16. Interference of kallikrein 1b26 (klk1b26 translation by microRNA specifically expressed in female mouse submandibular glands: an additional mechanism for sexual dimorphism of klk1b26 protein in the glands

    Directory of Open Access Journals (Sweden)

    Kurihara Kinji

    2011-11-01

    Full Text Available Abstract Background Mouse kallikrein 1b26 (klk1b26 protein is more abundant in male submandibular glands (SMGs than in female ones. This sexual dimorphism has been thought to be due to increased mRNA synthesis stimulated by androgen. However, the klk1b26 protein level in female SMG is far less than that expected from the mRNA level, suggesting an additional mechanism for down-regulation of klk1b26 expression in female SMGs. Methods We examined the effects of small non-coding RNAs in mouse SMGs on in vitro translation of klk1b26 using a reticulocyte lysate system and reverse transcription (RT-PCR for klk1b26 mRNA. Statistical analyses were performed with a computer package (Microsoft Excel. Results The microRNA (miRNA preparation from female SMGs, but not male SMGs, interfered with the in vitro translation of the klk1b26 protein and inhibited the RT-PCR for klk1b26 mRNA with forward primers targeting its 5'-terminal region (between the 15th and 40th nucleotide from the 5'-terminal. The miRNA preparation from castrated mouse SMGs showed the inhibitory effect on the klk1b26 translation, but that from a 5α-dihydrotestosterone-treated female mouse SMGs did not. Synthetic miRNAs (miR-325 and miR-1497a, which have partial complementarity with klk1b26 mRNA at its 5'-terminal region (15th to 40th nucleotide position from the 5'-terminal, also interfered with the in vitro klk1b26 translation. When the female miRNA preparation was incubated with a 30-nucleotide-long single-strand oligoDNA (named [15th-44th]ssDNA, whose sequence corresponded to the 15th to 44th position from the 5'-terminal of klk1b26 mRNA prior to the addition into the in vitro translation system, the inhibitory effect of the miRNA preparation on klk1b26 translation disappeared, while [15th-44th]ssDNA itself had no effect on the translation. Preincubation of the miRNA preparation with another single-strand DNA ([169th-198th]ssDNA, whose sequence corresponded with 169th to 198th position

  17. [(Dimethylaminomethyl]dimethylazanium bis(trifluoromethanesulfonylamide

    Directory of Open Access Journals (Sweden)

    Michael Hummel

    2016-10-01

    Full Text Available The title molecular salt, C5H15N2+·C2F6NO4S2−, was obtained by a proton transfer reaction between bis(trifluoromethanesulfonylamine and bis(dimethylaminomethane. In the crystal, the ions are linked by N—H...O=S hydrogen bonds, and these units are linked by C—H...O hydrogen bonds, forming sheets parallel to the bc plane. The crystal was refined as a non-merohedral twin with a BASF factor of 0.316 (1.

  18. PCl5 as a mild and efficient catalyst for the synthesis of bis(indolylmethanes and di-bis(indolylmethanes

    Directory of Open Access Journals (Sweden)

    Alireza Hasaninejad

    2008-12-01

    Full Text Available Phosphorus pentachloride (PCl5 can efficiently catalyze the condensation of indoles with aldehydes as well as ketones at room temperature to afford bis(indolylmethanes and di-bis(indolylmethanes in high yields and short reaction times.

  19. Bis-naphthalimides self-assembly organogel formation and application in detection of p-phenylenediamine.

    Science.gov (United States)

    Cao, Xinhua; Zhao, Na; Gao, Aiping; Lv, Haiting; Jia, Yuling; Wu, Renmiao; Wu, Yongquan

    2017-01-01

    Two new gelators containing bis-naphthalimides group were designed and synthesized. The gelator 1b could form gels in DMF and mixed solvent of DMSO/H2O (10/1, v/v). The self-assembly processes of 1b in two kinds of solvents were detailedly investigated by UV-vis, fluorescence, infrared spectroscopy, field emission scanning electron microscope (FE-SEM), X-ray diffraction and contact angle experiments. The experiment results showed the hydrogen bonding was the main force for the gel formation. The gel 1b formed in mixed solvent of DMSO/H2O (10/1, v/v) possessed of the ability of distinguishing of o-phenylenediamine, m-phenylenediamine and p-phenylenediamine. At the same time, the gelator 1b could selectively and sensitively detect p-phenylenediamine in solution with the detection limit of 8.961×10(-8)ML(-1). The detection experiment was also confirmed by DFT theoretical calculations. This research would expand the supramolecular self-assembly materials application in sensor field and offer a new detection method for organic amines.

  20. A novel role for protein tyrosine phosphatase 1B as a positive regulator of neuroinflammation

    OpenAIRE

    Song, Gyun Jee; Jung, Myungsu; Kim, Jong-Heon; Park, Hana; RAHMAN, MD. HABIBUR; Zhang, Sheng; Zhang, Zhong-Yin; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Suk, Kyoungho

    2016-01-01

    Background Protein tyrosine phosphatase 1B (PTP1B) is a member of the non-transmembrane phosphotyrosine phosphatase family. Recently, PTP1B has been proposed to be a novel target of anti-cancer and anti-diabetic drugs. However, the role of PTP1B in the central nervous system is not clearly understood. Therefore, in this study, we sought to define PTP1B’s role in brain inflammation. Methods PTP1B messenger RNA (mRNA) and protein expression levels were examined in mouse brain and microglial cel...

  1. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  2. Assembling carbon fiber-graphene-carbon fiber hetero-structures into 1D-2D-1D junction fillers and patterned structures for improved microwave absorption

    Science.gov (United States)

    Li, Huimin; Liu, Lin; Li, Hai-Bing; Song, Wei-Li; Bian, Xing-Ming; Zhao, Quan-Liang; Chen, Mingji; Yuan, Xujin; Chen, Haosen; Fang, Daining

    2017-04-01

    Since carbon-based structures of various dimensions, including one-dimensional (1D) carbon nanotubes, two-dimensional (2D) graphene and three-dimensional (3D) carbon foams, have attracted significant attention as microwave absorption fillers, we present an exceptional hetero-junction filler with a 1D-2D-1D feature, achieved by manipulating 2D graphene into 1D carbon fibers in the fiber-extruding process under the electric field. The as-fabricated 1D-2D-1D structural fillers exhibited much-improved dielectric properties and promoted microwave absorption performance in their composites, which is linked to the establishment of enhanced polarization capability, the generation of increased electric loss pathway and the creation of more favorable electromagnetic energy consumption conditions. The results suggest that employing 2D graphene in the 1D-2D-1D nanostructures played the critical role in tuning the electromagnetic response ability, because of its intrinsic electric advantages and dimensional features. To broaden the effective absorption bandwidth, periodic pattern-absorbing structures were designed, which showed combined absorption advantages for various thicknesses. Our strategy for fabricating 1D-2D-1D structural fillers illuminates a universal approach for manipulating dimensions and structures in the nanotechnology.

  3. Expression of Catalytic Domain of Protein Tyrosine Phosphatase 1B and Preparation of Its Polyclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This study focuses on the expression of human protein tyrosine phosphatase 1B(PTP1B) catalytic domain (△PTP1B) and preparation of polyclonal antibody against △PTP1B. △PTP1B gene was PCR amplified with the cDNA of human PTP1B as the template, and cloned into the pT7 expression vector. The recombinant pT7-△PTP1B was expressed in E. coli Rosetta( DE3 ) host cells and purified. The antiserum was prepared by immunizing rabbit with purified recombinant △PTP1B. The polyclonal antibody against △PTP1B was purified by PVDF immobilized antigen affinity chromatography. △PTP1B was correctly cloned, expressed, and purified as confirmed by PCR, DNA sequence ratio) and 0. 1 ng, respectively. This study provides an important basis for further studying the biological function of PTP1B and its relationship with human diseases.

  4. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

    Cytochrome P450 (CYP) 1B1 is involved in the metabolic activation of various procarcinogens, and some CYP1B1 genetic variants alter CYP1B1-dependent procarcinogen metabolism. Cynomolgus and rhesus macaques are frequently used in toxicity tests due to their evolutionary closeness to humans. In this study, we attempted to identify CYP1B1 genetic variants in 13 cynomolgus and 4 rhesus macaques. A total of 17 genetic variants were identified, including 8 non-synonymous genetic variants, indicating that, similar to humans, CYP1B1 is polymorphic in macaques. These CYP1B1 genetic variants could be the basis for understanding potential inter-animal differences in macaque CYP1B1-dependent metabolism of promutagens.

  5. Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: Three novel mutations in CYP1B1

    OpenAIRE

    Hilal, Latifa; Boutayeb, Soraya; Serrou, Aziza; Refass-Buret, Loubna; Shisseh, Hafsa; Bencherifa, Fatiha; El Mzibri, Mohammed; Benazzouz, Bouchra; Berraho, Amina

    2010-01-01

    Purpose To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. Methods This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negati...

  6. CYP1B1 mRNA inducibility due to benzo(a)pyrene is modified by the CYP1B1 L432V gene polymorphism.

    Science.gov (United States)

    Helmig, Simone; Wenzel, Sibylle; Maxeiner, Hagen; Schneider, Joachim

    2014-07-01

    Benzo(a)pyrene (BaP), a primary component of tobacco smoke, is activated by cytochrome P450 1B1 (CYP1B1). Smokers homozygous for the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism have shown increased CYP1B1 expression, compared to smokers homozygous for the G-allele *3/*3. Since no difference has been shown in CYP1B1 expression between both genotypes in non-smokers, we assumed that the genetic impact is produced in combination with an exogenous induction (e.g. BaP). To confirm this theory and to quantify the effect, we induced human leucocytes with increasing BaP concentrations and determined CYP1B1 mRNA expression with real-time polymerase chain reaction (PCR). We incubated human leucocytes from 27 healthy donors with BaP concentrations ranging from 2.5 to 250 µM. We identified the CYP1B1 genotypes by melting curve analysis and assessed relative CYP1B1 mRNA expression using real-time PCR. Expression was related to β-2-microglobulin with the 2(-ΔΔCT) method. Inducibility of CYP1B1 mRNA by BaP was higher in leucocytes carrying the CYP1B1*1/*1 genotype than in leucocytes carrying the CYP1B1*3/*3 genotype (P = 0.012). We revealed significant differences, with BaP concentrations of 2.5 µM (P = 0.0094), 5 µM (P = 0.027), 10 µM (P = 0.0006), 25 µM (P = 0.0007) and 50 µM (P = 0.017). Homozygous carriers of the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism show a higher response to environmental factors, such as carcinogenic BaP, than homozygous carriers of the G-allele *3/*3.

  7. Protein tyrosine phosphatase PTP1B is involved in hippocampal synapse formation and learning.

    Directory of Open Access Journals (Sweden)

    Federico Fuentes

    Full Text Available ER-bound PTP1B is expressed in hippocampal neurons, and accumulates among neurite contacts. PTP1B dephosphorylates ß-catenin in N-cadherin complexes ensuring cell-cell adhesion. Here we show that endogenous PTP1B, as well as expressed GFP-PTP1B, are present in dendritic spines of hippocampal neurons in culture. GFP-PTP1B overexpression does not affect filopodial density or length. In contrast, impairment of PTP1B function or genetic PTP1B-deficiency leads to increased filopodia-like dendritic spines and a reduction in mushroom-like spines, while spine density is unaffected. These morphological alterations are accompanied by a disorganization of pre- and post-synapses, as judged by decreased clustering of synapsin-1 and PSD-95, and suggest a dynamic synaptic phenotype. Notably, levels of ß-catenin-Tyr-654 phosphorylation increased ∼5-fold in the hippocampus of adult PTP1B(-/- (KO mice compared to wild type (WT mice and this was accompanied by a reduction in the amount of ß-catenin associated with N-cadherin. To determine whether PTP1B-deficiency alters learning and memory, we generated mice lacking PTP1B in the hippocampus and cortex (PTP1B(fl/fl-Emx1-Cre. PTP1B(fl/fl-Emx1-Cre mice displayed improved performance in the Barnes maze (decreased time to find and enter target hole, utilized a more efficient strategy (cued, and had better recall compared to WT controls. Our results implicate PTP1B in structural plasticity within the hippocampus, likely through modulation of N-cadherin function by ensuring dephosphorylation of ß-catenin on Tyr-654. Disruption of hippocampal PTP1B function or expression leads to elongation of dendritic filopodia and improved learning and memory, demonstrating an exciting novel role for this phosphatase.

  8. GFI1B controls its own expression binding to multiple sites.

    Science.gov (United States)

    Anguita, Eduardo; Villegas, Ana; Iborra, Francisco; Hernández, Aurora

    2010-01-01

    Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines. To investigate GFI1B regulation, we searched for multispecies conserved non-coding elements between GFI1B and neighboring genes. We used a formaldehyde-assisted isolation of regulatory elements (FAIRE) assay and DNase1 hypersensitivity to assess the chromatin conformation of these sites. Next, we analyzed transcription factor binding and histone modifications at the GFI1B locus including the conserved non-coding elements by a chromatin immunoprecipitation assay. Finally, we studied the interaction of the GFI1B promoter and the conserved non-coding elements with the chromatin conformation capture technique and used immunofluorescence to evaluate GFI1B levels in individual cells. We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors. Conclusions Our findings indicate that GFI1B regulatory elements behave as activators and repressors. Different protein levels within a cell population suggest that cells must activate and repress GFI1B continuously to control its final level. These data are consistent with a model of GFI1B regulation in which GFI1B binds to its own promoter and to the conserved non-coding elements as its levels rise. This would attract repressor complexes that progressively down-regulate the gene. GFI1B expression would decrease until a stage at which the activating complexes predominate and

  9. Dynamic decoupling in the presence of 1D random walk

    Science.gov (United States)

    Chakrabarti, Arnab; Chakraborty, Ipsita; Bhattacharyya, Rangeet

    2016-05-01

    In the recent past, many dynamic decoupling sequences have been proposed for the suppression of decoherence of spins connected to thermal baths of various natures. Dynamic decoupling schemes for suppressing decoherence due to Gaussian diffusion have also been developed. In this work, we study the relative performances of dynamic decoupling schemes in the presence of a non-stationary Gaussian noise such as a 1D random walk. Frequency domain analysis is not suitable to determine the performances of various dynamic decoupling schemes in suppressing decoherence due to such a process. Thus, in this work, we follow a time domain calculation to arrive at the following conclusions: in the presence of such a noise, we show that (i) the traditional Carr-Purcell-Meiboom-Gill (CPMG) sequence outperforms Uhrig’s dynamic decoupling scheme, (ii) CPMG remains the optimal sequence for suppression of decoherence due to random walk in the presence of an external field gradient. Later, the theoretical predictions are experimentally verified by using nuclear magnetic resonance spectroscopy on spin 1/2 particles diffusing in a liquid medium.

  10. 1-D Modeling of Massive Particle Injection (MPI) in Tokamaks

    Science.gov (United States)

    Wu, W.; Parks, P. B.; Izzo, V. A.

    2008-11-01

    A 1-D Fast Current Quench (FCQ) model is developed to study current evolution and runaway electron suppression under massive density increase. The model consists of coupled toroidal electric field and energy equations, and it is solved numerically for DIII-D and ITER operating conditions. Simulation results suggest that fast shutdown by D2 liquid jet/pellet injection is in principle achievable for the desired plasma cooling time (˜15 ms for DIII-D and ˜50 ms for ITER) under ˜150x or higher densification. The current density and pressure profile are practically unaltered during the initial phase of jet propagation when dilution cooling dominates. With subsequent radiation cooling, the densified discharge enters the strongly collisional regime where Pfirsch-Schluter thermal diffusion can inhibit current contraction on the magnetic axis. Often the 1/1 kink instability, addressed by Kadomtsev's magnetic reconnection model, can be prevented. Our results are compared with NIMROD simulations in which the plasma is suddenly densified by ˜100x and experiences instantaneous dilution cooling, allowing for use of actual (lower) Lundquist numbers.

  11. An implicit solver for 1D arterial network models.

    Science.gov (United States)

    Carson, Jason; Van Loon, Raoul

    2017-07-01

    In this study, the 1D blood flow equations are solved using a newly proposed enhanced trapezoidal rule method (ETM), which is an extension to the simplified trapezoidal rule method. At vessel junctions, the conservation of mass and conservation of total pressure are held as system constraints using Lagrange multipliers that can be physically interpreted as external flow rates. The ETM scheme is compared with published arterial network benchmark problems and a dam break problem. Strengths of the ETM scheme include being simple to implement, intuitive connection to lumped parameter models, and no restrictive stability criteria such as the Courant-Friedrichs-Lewy (CFL) number. The ETM scheme does not require the use of characteristics at vessel junctions, or for inlet and outlet boundary conditions. The ETM forms an implicit system of equations, which requires only one global solve per time step for pressure, followed by flow rate update on the elemental system of equations; thus, no iterations are required per time step. Consistent results are found for all benchmark cases, and for a 56-vessel arterial network problem, it gives very satisfactory solutions at a spatial and time discretization that results in a maximum CFL of 3, taking 4.44 seconds per cardiac cycle. By increasing the time step and element size to produce a maximum CFL number of 15, the method takes only 0.39 second per cardiac cycle with only a small compromise on accuracy. Copyright © 2016 John Wiley & Sons, Ltd.

  12. 1-D Numerical Analysis of RBCC Engine Performance

    Science.gov (United States)

    Han, Samuel S.

    1998-01-01

    An RBCC engine combines air breathing and rocket engines into a single engine to increase the specific impulse over an entire flight trajectory. Considerable research pertaining to RBCC propulsion was performed during the 1960's and these engines were revisited recently as a candidate propulsion system for either a single-stage-to-orbit (SSTO) or two-stage-to-orbit (TSTO) launch vehicle. There are a variety of RBCC configurations that had been evaluated and new designs are currently under development. However, the basic configuration of all RBCC systems is built around the ejector scramjet engine originally developed for the hypersonic airplane. In this configuration, a rocket engine plays as an ejector in the air-augmented initial acceleration mode, as a fuel injector in scramjet mode and the rocket in all rocket mode for orbital insertion. Computational fluid dynamics (CFD) is a useful tool for the analysis of complex transport processes in various components in RBCC propulsion systems. The objective of the present research was to develop a transient 1-D numerical model that could be used to predict flow behavior throughout a generic RBCC engine following a flight path.

  13. Towards a consistent picture for quasi-1D organic superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Doiron-Leyraud, N. [Departement de physique and RQMP, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1 (Canada); Auban-Senzier, P. [Laboratoire de Physique des Solides, UMR 8502, CNRS - Univ. Paris-Sud, Bat. 510, 91405 Orsay (France); Rene de Cotret, S. [Departement de physique and RQMP, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1 (Canada); Bechgaard, K. [Department of Chemistry, H.C. Orsted Institute, Copenhagen (Denmark); Jerome, D., E-mail: jerome@lps.u-psud.f [Laboratoire de Physique des Solides, UMR 8502, CNRS - Univ. Paris-Sud, Bat. 510, 91405 Orsay (France); Canadian Institute for Advanced Research, Toronto, Ontario, M5G 1Z8 (Canada); Taillefer, L. [Departement de physique and RQMP, Universite de Sherbrooke, Sherbrooke, Quebec, J1K 2R1 (Canada); Canadian Institute for Advanced Research, Toronto, Ontario, M5G 1Z8 (Canada)

    2010-06-01

    The electrical resistivity of the quasi-1D organic superconductor (TMTSF){sub 2}PF{sub 6} was recently measured at low temperature from the critical pressure needed to suppress the spin-density-wave state up to a pressure where superconductivity has almost disappeared. This data revealed a direct correlation between the onset of superconductivity at T{sub c} and the strength of a non-Fermi-liquid linear term in the normal-state resistivity, going as {rho}(T)={rho}{sub 0}+AT+BT{sup 2} at low temperature, so that A{yields}0 as T{sub c{yields}}0. Here we show that the contribution of low-frequency antiferromagnetic fluctuations to the spin-lattice relaxation rate is also correlated with this non-Fermi-liquid term AT in the resistivity. These correlations suggest that anomalous scattering and pairing have a common origin, both rooted in the low-frequency antiferromagnetic fluctuations measured by NMR. A similar situation may also prevail in the recently discovered iron-pnictide superconductors.

  14. Sulfur chemistry: 1D modeling in massive dense cores

    CERN Document Server

    Wakelam, V; Herpin, F

    2011-01-01

    The main sulfur-bearing molecules OCS, H2S, SO, SO2, and CS have been observed in four high mass dense cores (W43-MM1, IRAS 18264, IRAS 05358, and IRAS 18162). Our goal is to put some constraints on the relative evolutionary stage of these sources by comparing these observations with time-dependent chemical modeling. We used the chemical model Nahoon, which computes the gas-phase chemistry and gas-grain interactions of depletion and evaporation. Mixing of the different chemical compositions shells in a 1D structure through protostellar envelope has been included since observed lines suggest nonthermal supersonic broadening. Observed radial profiles of the temperature and density are used to compute the chemistry as a function of time. With our model, we underproduce CS by several orders of magnitude compared to the other S-bearing molecules, which seems to contradict observations, although some uncertainties in the CS abundance observed at high temperature remain. The OCS/SO2, SO/SO2, and H2S/SO2 abundance ra...

  15. Cavitation Influence in 1D Part-load Vortex Models

    Science.gov (United States)

    Dörfler, P. K.

    2016-11-01

    Residual swirl in the draft tube of Francis turbines may cause annoying low- frequency pulsation of pressure and power output, in particular during part-load operation. A 1D analytical model for these dynamic phenomena would enable simulation by some conventional method for computing hydraulic transients. The proper structure of such a model has implications for the prediction of prototype behaviour based on laboratory tests. The source of excitation as well as the dynamic transmission behaviour of the draft tube flow may both be described either by lumped or distributed parameters. The distributed version contains more information and, due to limited possibilities of identification, some data must be estimated. The distributed cavitation compliance is an example for this dilemma. In recent publications, the customary assumption of a constant wave speed has produced dubious results. The paper presents a more realistic model for distributed compressibility. The measured influence of the Thoma number is applied with the local cavitation factor. This concept is less sensitive to modelling errors and explains both the Thoma and Froude number influence. The possible effect of the normally unknown non-condensable gas content in the vortex cavity is shortly commented. Its measurement in future tests is recommended. It is also recommended to check the available analytical vortex models for possible dispersion effects.

  16. Nonclassical Particle Transport in 1-D Random Periodic Media

    CERN Document Server

    Vasques, Richard; Slaybaugh, Rachel N

    2016-01-01

    We investigate the accuracy of the recently proposed nonclassical transport equation. This equation contains an extra independent variable compared to the classical transport equation (the path-length $s$), and models particle transport taking place in homogenized random media in which a particle's distance-to-collision is not exponentially distributed. To solve the nonclassical equation one needs to know the $s$-dependent ensemble-averaged total cross section, $\\Sigma_t(\\mu,s)$, or its corresponding path-length distribution function, $p(\\mu,s)$. We consider a 1-D spatially periodic system consisting of alternating solid and void layers, randomly placed in the $x$-axis. We obtain an analytical expression for $p(\\mu,s)$ and use this result to compute the corresponding $\\Sigma_t(\\mu,s)$. Then, we proceed to numerically solve the nonclassical equation for different test problems in rod geometry; that is, particles can move only in the directions $\\mu=\\pm 1$. To assess the accuracy of these solutions, we produce ...

  17. Modeling of 1D Anomalous Diffusion in Fractured Nanoporous Media

    Directory of Open Access Journals (Sweden)

    Albinali Ali

    2016-07-01

    Full Text Available Fractured nanoporous reservoirs include multi-scale and discontinuous fractures coupled with a complex nanoporous matrix. Such systems cannot be described by the conventional dual-porosity (or multi-porosity idealizations due to the presence of different flow mechanisms at multiple scales. More detailed modeling approaches, such as Discrete Fracture Network (DFN models, similarly suffer from the extensive data requirements dictated by the intricacy of the flow scales, which eventually deter the utility of these models. This paper discusses the utility and construction of 1D analytical and numerical anomalous diffusion models for heterogeneous, nanoporous media, which is commonly encountered in oil and gas production from tight, unconventional reservoirs with fractured horizontal wells. A fractional form of Darcy’s law, which incorporates the non-local and hereditary nature of flow, is coupled with the classical mass conservation equation to derive a fractional diffusion equation in space and time. Results show excellent agreement with established solutions under asymptotic conditions and are consistent with the physical intuitions.

  18. Electronically asymmetric bis(porphyrin) sandwich complexes

    Energy Technology Data Exchange (ETDEWEB)

    Girolami, G.S.; Gorlin, P.A.; Suslick, K.S. [Univ. of Illinois, Urbana, IL (United States)

    1994-02-16

    Bis(porphyrin)metal(IV) complexes (M(porph){sub 2}) have been extensively studies in recent years due to their structural, chemical, and spectroscopic similarity to the {open_quotes}special pair{close_quotes} found in the reaction center of photosynthetic bacteria. Strong interactions arise in the bis(porphyrin) complexes due to the short inter-porphyrin separation (< 3 {angstrom}), which results in properties not seen in mono(porphyrin) analogs. For example, the bis(porphyrin) complexes are considerably easier to oxidize than analogous mono(porphyrin) species, and the M(porph){sub 2{sup n+}} cations (n = 1,2) exhibit near-IR absorptions not found in simple mono(porphyrin)cations. As part of the authors continuing effort to understand the factors that govern the electronic structures of bis(porphyrin) supermolecules, the authors now describe the synthesis of a series of zirconium sandwich complexes. Introduction of electron-withdrawing or -donating groups on the {beta}-pyrrole position considerably affects the electronic properties of these molecules without altering their steric parameters. Thus, peripheral substitution allows modification of the inter-porphyrin {pi} interactions while keeping the inter-porphyrin separation constant. Previous studies have changed the identity of the central metal, but the electronic structure and the interplanar distance could not be varied independently.

  19. Basal and 3-methylcholanthrene-induced expression of cytochrome P450 1A, 1B and 1C genes in the Brazilian guppy, Poecilia vivipara.

    Science.gov (United States)

    Dorrington, Tarquin; Zanette, Juliano; Zacchi, Flávia L; Stegeman, John J; Bainy, Afonso C D

    2012-11-15

    In fish there are four cytochrome P450 (CYP1) subfamilies: CYP1A, CYP1B, CYP1C, and CYP1D. Here we cloned Poecilia vivipara CYP1A, with an inferred amino acid sequence 91% identical to CYP1A from the killifish Fundulus heteroclitus, another member of the Cypriniformes, and an important model in ecotoxicology. In addition, we examined the expression of CYP1A, CYP1B1, and CYP1C1 by qPCR in liver, gill, and intestine of adult P. vivipara injected with 3-methylcholanthrene (3-MC) or held in clean water (control group) for 24h. All three tissues examined showed basal expression of the three CYP1 genes. CYP1A was most strongly expressed in the liver, while CYP1B1, and CYP1C1 were most strongly expressed in the gill and intestine respectively. 3-MC induced CYP1A, CYP1B1, and CYP1C1 significantly (20-120-fold) in the three organs, consistent with the regulation of CYP1A, CYP1B1 and CYP1C1 via the aryl hydrocarbon receptor. Validation of CYP1 gene biomarkers in fish collected from a contaminated urban mangrove environment was confirmed with significant induction of CYP1A and CYP1C1 in gills (10-15-fold) and CYP1B1 in liver (23-fold), relative to fish from a control site. The responsiveness of these CYP1 genes indicates P. vivipara is suitable as a model for environmental toxicology studies and environmental assessment in Brazil.

  20. Synthesis of 1-D ZnO nanorods and polypyrrole/1-D ZnO nanocomposites for photocatalysis and gas sensor applications

    Indian Academy of Sciences (India)

    PRITAM PATIL; GANESH GAIKWAD; D R PATIL; JITENDRA NAIK

    2016-06-01

    1-D ZnO nanorods and PPy/1-D ZnO nanocomposites were prepared by the surfactant-assisted precipitation and in situ polymerization method, respectively. The synthesized nanorods and nanocomposites were characterized by UV–Vis spectrophotometer, Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD) and field emission scanning electron microscope (FE-SEM), which gave the evidence of 1-D ZnO nanorods, polymerization of pyrrole monomer and strong interaction between PPy and 1-D ZnO nanorods, respectively. Photocatalytic activity of 1-D ZnO nanorods was conducted by $3^3$ level full-factorial design to evaluate the effect of three independent process variables viz., dye concentration (crystal violet), catalyst concentration (1-D ZnO nanorods) and the reaction time on the preferred response: photodegradation efficiency (%). The PPy/1-D ZnO nanocompositeswere used for the sensing of NH$_3$, LPG, CO$_2$ and H$_2$S gases, respectively, at room temperature. It was observed that PPy/1-D ZnO nanocomposites with different 1-D ZnO nanorod weight ratios (15 and 25%) had better selectivity and sensitivity towards NH3 at room temperature.

  1. Absolute rate constant determinations for the deactivation of O/1D/ by time resolved decay of O/1D/ yields O/3P/ emission

    Science.gov (United States)

    Davidson, J. A.; Sadowski, C. M.; Schiff, H. I.; Howard, C. J.; Schmeltekopf, A. L.; Jennings, D. A.; Streit, G. E.

    1976-01-01

    Absolute rate constants for the deactivation of O(1D) atoms by some atmospheric gases have been determined by observing the time-resolved emission of O(1D) at 630 nm. O(1D) atoms were produced by the dissociation of ozone via repetitive laser pulses at 266 nm. Absolute rate constants for the relaxation of O(1D) at 298 K are reported for N2, O2, CO2, O3, H2, D2, CH4, HCl, NH3, H2O, N2O, and Ne. The results obtained are compared with previous relative and absolute measurements reported in the literature.

  2. Benchmarking of a 1D Scrape-off layer code SOLF1D with SOLPS and its use in modelling long-legged divertors

    CERN Document Server

    Havlickova, E; Subba, F; Coster, D; Wischmeier, M; Fishpool, G

    2013-01-01

    A 1D code modelling SOL transport parallel to the magnetic field (SOLF1D) is benchmarked with 2D simulations of MAST-U SOL performed via the SOLPS code for two different collisionalities. Based on this comparison, SOLF1D is then used to model the effects of divertor leg stretching in 1D, in support of the planned Super-X divertor on MAST. The aim is to separate magnetic flux expansion from volumetric power losses due to recycling neutrals by stretching the divertor leg either vertically or radially.

  3. Synthesis, characterization and stereochemistry of N-acyl-r-2,c-4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes

    Science.gov (United States)

    Akila, A.; Ponnuswamy, S.; Shreevidhyaa Suressh, V.; Usha, G.

    2015-08-01

    Four new N-acyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes 3-6 have been synthesized. The structural characterization and the conformational preferences of the compounds 3-6 have been carried out using IR, 1D and 2D NMR and Mass spectral data. The NMR spectral data indicates that the N-acyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes 3-6 prefer to exist in twin-chair conformation with partial flattening at nitrogen end. To avoid A1,3-strain, the anisyl groups at C2 and C4 are forced to occupy the quasi-axial orientation. X-ray crystal structure of the N-dichloroacetyl-2,4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonane 6 also supports the similar conformation in the solid state.

  4. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wen Chen

    2016-03-01

    Full Text Available Background/Aims: Overexpression of cytosolic sulfotransferase 2B1b (SULT2B1b has been commonly found in colorectal and hepatocellular carcinoma, suggesting that SULT2B1b might act as a potential oncogenic protein. However, its clinical significance and biological role in gastric cancer progression remain largely unknown. Methods: Expressions of SULT2B1b in clinical gastric cancer (GC samples were examined using qRT-PCR and Western blot. Results: SULT2B1b was markedly overexpressed in human GC samples, and positively correlated with vessel density and associated with poor clinical features. We also demonstrated that overexpression of SULT2B1b resulted in increased tumor angiogenesis and tumor growth in mouse GC models. In addition, ablation of SULT2B1b in human GC cells lines BGC823 and MKN45 decreased the capability of the cells to recruit endothelial cells. Moreover, depletion of SULT2B1b in GC cells reduced VEGF-A expression by downregulating SP1 and AP2. Conclusion: Our results suggested that the SULT2B1b-mediated angiogenic pathway could serve as biomarkers for GC diagnosis and prognosis, and suppressing SULT2B1b-mediated angiogenic signaling might be a promising strategy for developing novel GC treatment.

  5. The Pafah1b complex interacts with the reelin receptor VLDLR.

    Directory of Open Access Journals (Sweden)

    Guangcheng Zhang

    Full Text Available Reelin is an extracellular protein that directs the organization of cortical structures of the brain through the activation of two receptors, the very low-density lipoprotein receptor (VLDLR and the apolipoprotein E receptor 2 (ApoER2, and the phosphorylation of Disabled-1 (Dab1. Lis1, the product of the Pafah1b1 gene, is a component of the brain platelet-activating factor acetylhydrolase 1b (Pafah1b complex, and binds to phosphorylated Dab1 in response to Reelin. Here we investigated the involvement of the whole Pafah1b complex in Reelin signaling and cortical layer formation and found that catalytic subunits of the Pafah1b complex, Pafah1b2 and Pafah1b3, specifically bind to the NPxYL sequence of VLDLR, but not to ApoER2. Compound Pafah1b1(+/-;Apoer2(-/- mutant mice exhibit a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization, whereas double Pafah1b1(+/-;Vldlr(-/- mutants do not. These results suggest that a cross-talk between the Pafah1b complex and Reelin occurs downstream of the VLDLR receptor.

  6. [Preparation and identification of rabbit anti-AKR1B10 polyclonal antibody].

    Science.gov (United States)

    Hu, Jian; Wang, Qingmei; Huang, Li; Zeng, Yuanqing; Hu, Zheng; Luo, Dixian

    2016-11-01

    Objective To prepare rabbit anti-aldo-keto reductase family 1 member B10 (AKR1B10) polyclonal antibody and identify its specificity. Methods AKR1B10 cDNA was amplified by reverse transcription PCR (RT-PCR) and inserted into prokaryotic expression vector pET-15b to form recombinant plasmid pET-15b-AKR1B10. The recombinant plasmid pET-15b-AKR1B10 was transformed into E.coli DH5α. Isopropylthio-β-D-galactoside (IPTG) was used to induce the expression of the recombinant protein His-tagged AKR1B10 in E.coli DH5α. The expression products from different clones of E.coli DH5α were identified by SDS-PAGE. The positive bacteria were picked out and amplified. His-Tag-AKR1B10 protein was purified from the expression product of the positive clones by His-tagged purification column. The purified recombinant protein His-Tag-AKR1B10 was used to immunize New Zealand white rabbits. Antisera were acquired after two months. Anti-AKR1B10 polyclonal antibodies were purified by antigen purification column with AKR1B10 recombinant protein. Lastly, the purified polyclonal antibodies were identified by SDS-PAGE, ELISA, Western blotting. Results The recombinant plasmid pET-15b-AKR1B10 was constructed successfully, and the recombinant protein His-Tag-AKR1B10 with high purity was acquired. The purified polyclonal antibodies were able to specifically recognize AKR1B10 protein. Conclusion The rabbit anti-AKR1B10 polyclonal antibodies is prepared successfully with high specificity.

  7. Herschel observations of B1-bS and B1-bN: two first hydrostatic core candidates in the Perseus star-forming cloud

    CERN Document Server

    Pezzuto, Stefano; Schisano, E; Strafella, F; Di Francesco, J; Sadavoy, S; André, P; Benedettini, M; Bernard, J P; di Giorgio, A M; Facchini, A; Hennemann, M; Hill, T; Könyves, V; Molinari, S; Motte, F; Nguyen-Luong, Q; Peretto, N; Pestalozzi, M; Polychroni, D; Rygl, K L J; Saraceno, P; Schneider, N; Spinoglio, L; Testi, L; Ward-Thompson, D; White, G J

    2012-01-01

    We report far-IR Herschel observations obtained between 70 $\\mu$m and 500 $\\mu$m of two star-forming dusty condensations, B1-bS and B1-bN, in the B1 region of the Perseus star-forming cloud. In the Western part of the Perseus cloud, B1-bS is the only source detected in all of the 6 PACS and SPIRE photometric bands without being visible in the Spitzer map at 24 $\\mu$m. B1-bN is clearly detected between 100 $\\mu$m and 250 $\\mu$m. We have fitted the spectral energy distributions of these sources to derive their physical properties, and find that a simple greybody model fails to reproduce the observed SEDs. At least a two-component model, consisting of a central source surrounded by a dusty envelope is required. The properties derived from the fit, however, suggest that the central source is not a Class 0 object. We then conclude that while B1-bS and B1-bN appear to be more evolved than a pre-stellar core, the best-fit models suggest that their central objects are younger than a Class 0 source. Hence, they may be...

  8. Modeling shear band interaction in 1D torsion

    Science.gov (United States)

    Partom, Yehuda; Hanina, Erez

    2017-01-01

    When two shear bands are being formed at close distance from each other they interact, and further development of one of them may be quenched down. As a result there should be a minimum distance between shear bands. In the literature there are at least three analytical models for this minimum distance. Predictions of these models do not generally agree with each other and with test results. Recently we developed a 1D numerical scheme to predict the formation of shear bands in a torsion test of a thin walled pipe. We validated our code by reproducing results of the pioneering experiments of Marchand and Duffy, and then used it to investigate the mechanics of shear localization and shear band formation. We describe our shear band code in a separate publication, and here we use it only as a tool to investigate the interaction between two neighboring shear bands during the process of their formation. We trigger the formation of shear bands by specifying two perturbations of the initial strength. We vary the perturbations in terms of their amplitude and/or their width. Usually, the stronger perturbation triggers a faster developing shear band, which then prevails and quenches the development of the other shear band. We change the distance between the two shear bands and find, that up to a certain distance one of the shear bands becomes fully developed, and the other stays only partially developed. Beyond this distance the two shear bands are both fully developed. Finally, we check the influence of certain material and loading parameters on the interaction between the two shear bands, and compare the results to predictions of the analytical models from the literature.

  9. Evidence against dopamine D1/D2 receptor heteromers

    Science.gov (United States)

    Frederick, Aliya L.; Yano, Hideaki; Trifilieff, Pierre; Vishwasrao, Harshad D.; Biezonski, Dominik; Mészáros, József; Sibley, David R.; Kellendonk, Christoph; Sonntag, Kai C.; Graham, Devon L.; Colbran, Roger J.; Stanwood, Gregg D.; Javitch, Jonathan A.

    2014-01-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

  10. Spatio-temporal stability of 1D Kerr cavity solitons

    Science.gov (United States)

    Gelens, L.; Parra-Rivas, P.; Leo, F.; Gomila, D.; Matias, Manuel A.; Coen, S.

    2014-05-01

    The Lugiato-Lefever equation (LLE) has been extensively studied since its derivation in 1987, when this meanfield model was introduced to describe nonlinear optical cavities. The LLE was originally derived to describe a ring cavity or a Fabry-Perot resonator with a transverse spatial extension and partially filled with a nonlinear medium but it has also been shown to be applicable to other types of cavities, such as fiber resonators and microresonators. Depending on the parameters used, the LLE can present a monostable or bistable input-output response curve. A large number of theoretical studies have been done in the monostable regime, but the bistable regime has remained widely unexplored. One of the reasons for this was that previous experimental setups were not able to works in such regimes of the parameter space. Nowadays the possibility of reaching such parameter regimes experimentally has renewed the interest in the LLE. In this contribution, we present an in-depth theoretical study of the different dynamical regimes that can appear in parameter space, focusing on the dynamics of localized solutions, also known as cavity solitons (CSs). We show that time-periodic oscillations of a 1D CS appear naturally in a broad region of parameter space. More than this oscillatory regime, which has been recently demonstrated experimentally,1 we theoretically report on several kinds of chaotic dynamics. We show that the existence of CSs and their dynamics is related with the spatial dynamics of the system and with the presence of a codimension-2 point known as a Fold-Hopf bifurcation point. These dynamical regimes can become accessible by using devices such as microresonators, for instance widely used for creating optical frequency combs.

  11. Restrained dark U (1 )d at low energies

    Science.gov (United States)

    Correia, Fagner C.; Fajfer, Svjetlana

    2016-12-01

    We investigate a spontaneously broken U (1 )d gauge symmetry with a muon-specific dark Higgs. Our first goal is to verify how the presence of a new dark Higgs, ϕ , and a dark gauge boson, V , can simultaneously face the anomalies from the muon magnetic moment and the proton charge radius. Second, by assuming that V must decay to an electron-positron pair, we explore the corresponding parameter space determined with the low-energy constraints coming from K →μ X , electron (g -2 )e, K →μ νμe+e-, K →μ νμμ+μ-, and τ →ντμ νμe+e-. We focus on the scenario where the V mass is below ˜2 mμ and the ϕ mass runs from few MeV to 250 MeV, with V -photon mixing of the order ˜O (10-3). Among weak process at low energies, we check the influence of the new light vector on kaon decays as well as on the scattering e+e-→μ+μ-e+e- and discuss the impact of the dark Higgs on e+e-→μ+μ-μ+μ-. Finally, we consider contributions of the V -photon mixing in the decays π0→γ e+e-, η →γ e+e-, ρ →π e+e-, K*→K e+e-, and ϕ (1020 )→η e+e-.

  12. Halogen-free bis(imidazolium)/bis(ammonium)-di[bis(salicylato)borate] ionic liquids as energy-efficient and environmentally friendly lubricant additives.

    Science.gov (United States)

    Gusain, Rashi; Gupta, Piyush; Saran, Sandeep; Khatri, Om P

    2014-09-10

    Bis(imidazolium)- and bis(ammonium)-di[bis(salicylato)borate] ionic liquids with variable alkyl chain and cyclic ring structures, were synthesized and then evaluated them as potential lubricant additives. The copper strip test results revealed noncorrosive properties of these ionic liquids. Introduction of halogen content in bis(imidazolium) ionic liquid by replacement of bis(salicylato)borate (BScB) anion with hexafluorophosphate (PF6(-)), severely corroded the copper strip. Thermogravimetric results showed that bis(imidazolium) ionic liquids exhibited higher thermal stability than bis(ammonium) ionic liquids owing to compact structure provided by imidazolium rings, higher intermolecular interactions, smaller free volume and low steric hindrance. The lubrication properties of these ionic liquids as additives to synthetic lubricant poly(ethylene) glycol (PEG 200) were evaluated for steel balls. Results showed that bis(ammonium)- and bis(imidazolium)-(BScB)2 ionic liquids as additives significantly reduced both friction coefficient and wear of PEG 200. The structure of cations, particularly the variation in substituted alkyl chain length monitored the degree of reduction in friction and wear. The excellent lubrication properties were attributed to the formation of adsorbed tribo-thin film and tribochemical product during the tribo-contact. Being halogen-, phosphorus-, and sulfur-free, these ionic liquids (a) protects contact surfaces from tribo-corrosive events, (b) reduces the friction and wear, and (c) keep environment green and clean.

  13. 1D zigzag chain and 0D monomer Cd(II)/Zn(II) compounds based on flexible phenylenediacetic ligand: Synthesis, crystal structures and fluorescent properties

    Science.gov (United States)

    Yang, Fang; Ren, Yixia; Li, Dongsheng; Fu, Feng; Qi, Guangcai; Wang, Yaoyu

    2008-12-01

    Three novel Cd(II)/Zn(II) compounds, [Cd 2(poda) 2(phen) 3(H 2O)] n· nEtOH·3 nH 2O (1), [Zn(poda) 2(bpy)(H 2O)] n(2) and [Zn(Hpoda) 2(bpy)] (3) (H 2poda = 1,2-phenylenediacetic acid, phen = 1,10-phenanthroline, bpy = 2,2'-bipyridyl), have been synthesized and characterized by IR, TG, fluorescent spectrum and single-crystal X-ray diffraction techniques. In 1, poda 2- anions link the adjacent Cd(II) centers to generate a 1D zigzag chain. Furthermore, an unprecedented four-footed "8-shaped" mixed water-ethanol (H 2O) 6(C 2H 5OH) 2 cluster connects four double chains based on 1D zigzag chain into 3D supramolecular architecture. By bis(chelate-monodentate) fashion of poda 2- ligand, compound 2 exhibits 1D zigzag chains, which forming a dense zipper-like 2D structure via strong π-π stacking interactions. Differed from 1 and 2, compound 3 has a mononuclear motif, and displays a 3D 6-connected α-Po net hydrogen-bonded topology. The structure-related solid-state fluorescence spectra of compounds 1 and 2 have been determined.

  14. Resolution-optimized NMR measurement of (1)D(CH), (1)D(CC) and (2)D(CH) residual dipolar couplings in nucleic acid bases.

    Science.gov (United States)

    Boisbouvier, Jérôme; Bryce, David L; O'neil-Cabello, Erin; Nikonowicz, Edward P; Bax, Ad

    2004-11-01

    New methods are described for accurate measurement of multiple residual dipolar couplings in nucleic acid bases. The methods use TROSY-type pulse sequences for optimizing resolution and sensitivity, and rely on the E.COSY principle to measure the relatively small two-bond (2)D(CH) couplings at high precision. Measurements are demonstrated for a 24-nt stem-loop RNA sequence, uniformly enriched in (13)C, and aligned in Pf1. The recently described pseudo-3D method is used to provide homonuclear (1)H-(1)H decoupling, which minimizes cross-correlation effects and optimizes resolution. Up to seven (1)H-(13)C and (13)C-(13)C couplings are measured for pyrimidines (U and C), including (1)D(C5H5), (1)D(C6H6), (2)D(C5H6), (2)D(C6H5), (1)D(C5C4), (1)D(C5C6), and (2)D(C4H5). For adenine, four base couplings ((1)D(C2H2), (1)D(C8H8), (1)D(C4C5), and (1)D(C5C6)) are readily measured whereas for guanine only three couplings are accessible at high relative accuracy ((1)D(C8H8), (1)D(C4C5), and (1)D(C5C6)). Only three dipolar couplings are linearly independent in planar structures such as nucleic acid bases, permitting cross validation of the data and evaluation of their accuracies. For the vast majority of dipolar couplings, the error is found to be less than +/-3% of their possible range, indicating that the measurement accuracy is not limiting when using these couplings as restraints in structure calculations. Reported isotropic values of the one- and two-bond J couplings cluster very tightly for each type of nucleotide.

  15. Src regulates membrane trafficking of the Kv3.1b channel.

    Science.gov (United States)

    Bae, Seong Han; Kim, Dong Hyun; Shin, Seok Kyo; Choi, Jin Sung; Park, Kang-Sik

    2014-01-03

    The Kv3.1 channel plays a crucial role in regulating the high-frequency firing properties of neurons. Here, we determined whether Src regulates the subcellular distributions of the Kv3.1b channel. Co-expression of active Src induced a dramatic redistribution of Kv3.1b to the endoplasmic reticulum. Furthermore, co-expression of the Kv3.1b channel with active Src induced a remarkable decrease in the pool of Kv3.1b at the cell surface. Moreover, the co-expression of active Src results in a significant decrease in the peak current densities of the Kv3.1b channel, and a substantial alteration in the voltage dependence of its steady-state inactivation. Taken together, these results indicate that Src kinase may play an important role in regulating membrane trafficking of Kv3.1b channels.

  16. Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening

    Institute of Scientific and Technical Information of China (English)

    Lei SHI; Hai-ping YU; Yue-yang ZHOU; Jun-qin DU; Qiang SHEN; Jing-ya LI; Jia LI

    2008-01-01

    Aim: The aim of the present study was to discover novel protein tyrosine phos-phatase 1B (PTP1B) inhibitors. We expressed and purified the human PTP1B catalytic domain and set up a molecular level high-throughput screening (HTS) assay to screen a set of 48 000 pure compounds. Results: HTS was finished with an averaged Z' factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein ty-rosine phosphatases, was identified. Conclusion: We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.

  17. Data of evolutionary structure change: 1D3AB-1LLDA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D3AB-1LLDA 1D3A 1LLD B A -TKVSVVGAAGTVGAAAGYNIALRDIADEVVFVDIPDKE...PNAIYMLITNPVDIATHVAQKLTGLPENQIFGSGTNLDSARLRFLIAQQTGVNVKNVHAYIAGEHGDSEVPLWESATIGGVPMSDWTPLPGHDPLDADKREEIHQEVK... 1LLD A 1LLDA...> 1 1LLD A 1LLDA

  18. Solvent-free Thia-Michael Addition Reactions Using 3-[Bis(alkylthio)methylene]pentane-2,4-diones as Efficient and Odorless Thiol Equivalents

    Institute of Scientific and Technical Information of China (English)

    LIN Chun; ZHAO Xiao-Liang; OUYANG Yan; YU Hai-Feng; DONG De-Wen

    2008-01-01

    3-[Bis(alkylthio)methylene]pentane-2,4-diones (1a and 1b) have been investigated as nonthiolic and odorless thiol equivalents for thia-Michael addition reactions under solvent-free conditions. Promoted by HCl (aq.), the cleavage of compounds 1 took place, and the in-situ generated thiols underwent facile conjugate addition to α,β-unsaturated carbonyl compounds 2 affording the corresponding β-keto sulfides 3 in high yields.

  19. Ethanol and Mesolimbic Serotonin/Dopamine Interactions via 5HT-1B Receptors

    Science.gov (United States)

    2007-03-01

    Addiction, 101 (Suppl. 1): 23-30, 2006. 16. Kranzler HR, Hernandez -Avila CA, Gelenter J,: Polymorphism of the 5-HT1B receptor gene (HTR1B): strong within...Serotonin1B receptor stimulation enhances cocaine reinforcement, J. Neurosci., 18: 10078-10089, 1998. 25. Rojas -Corrales MO, Berrocoso E, Mico JA,: Role of...it has been reported that the effective receptor antagonist concentration of SB 216641 is similar to that of WAY 100635 ( Rojas -Corrales et al

  20. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal

    DEFF Research Database (Denmark)

    Stewart, Morag H; Albert, Mareike; Sroczynska, Patrycja;

    2015-01-01

    Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias...... compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential....

  1. From discrete [Mn4] cluster to 1D complex: Two new mixed-valence manganese complexes with slow magnetization relaxation

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    A tetranuclear manganese complex [Mn4(HL)4(MeOH)4(SCN)2]·3MeOH (1) and a one-dimensional assembly of [Mn4] units, [Mn4(HL)4(MeOH)4(N(CN)2)2]·2.5MeOH (2) (H3L = 2,6-bis(hydroxymethyl)-4-methyl-phenol), have been synthesized and studied. Complexes 1 and 2 crystallize in the triclinic space group P 1and monoclinic space group P21/n, respectively. Complex 1 possesses a mixed-valence tetranuclear dicubane unit, which comprises two MnⅡ and two MnⅢ ions. Complex 2 is built from the similar tetranuclear [Mn4] units connected through two N(CN)2-anions into a 1-D chain. The temperature dependence of the magnetic susceptibilities of 1 and 2 indicates ferromagnetic interactions between the manganese ions. Frequency-dependent out-of-phase signals of alternating current magnetic susceptibilities are observed in the low temperature range for both complexes, indicating a slow magnetic relaxation.

  2. From nonfinite to finite 1D arrays of origami tiles.

    Science.gov (United States)

    Wu, Tsai Chin; Rahman, Masudur; Norton, Michael L

    2014-06-17

    average solution structures for blocks is more readily achieved using computer models than using direct imaging methods. The development of scalable 1D-origami arrays composed of uniquely addressable components is a logical, if not necessary, step in the evolution of higher order fully addressable structures. Our research into the fabrication of arrays has led us to generate a listing of several important areas of future endeavor. Of high importance is the re-enforcement of the mechanical properties of the building blocks and the organization of multiple arrays on a surface of technological importance. While addressing this short list of barriers to progress will prove challenging, coherent development along each of these lines of inquiry will accelerate the appearance of commercial scale molecular manufacturing.

  3. Kv3.1b is a novel component of CNS nodes.

    Science.gov (United States)

    Devaux, Jérôme; Alcaraz, Gisèle; Grinspan, Judith; Bennett, Vann; Joho, Rolf; Crest, Marcel; Scherer, Steven S

    2003-06-01

    We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in a subset of nodes in the spinal cord, particularly those of large myelinated axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but does not colocalize with Na+ channels in initial segments. In the PNS, few nodes are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes. 4-Aminopyridine, a K+ channel blocker, broadened the compound action potential recorded from adult rat optic nerve and spinal cord, but not from the sciatic nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts.

  4. SUMOylation of the ING1b tumor suppressor regulates gene transcription

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Guérillon, Claire; Kim, Tae-Sun;

    2014-01-01

    The INhibitor of Growth (ING) proteins are encoded as multiple isoforms in five ING genes (ING1 -5) and act as type II tumor suppressors. They are growth inhibitory when overexpressed and are frequently mislocalized or downregulated in several forms of cancer. ING1 and ING2 are stoichiometric mem......1b E195A), we further demonstrate that ING1b SUMOylation regulates the binding of ING1b to the ISG15 and DGCR8 promoters, consequently regulating ISG15 and DGCR8 transcription. These results suggest a role for ING1b SUMOylation in the regulation of gene transcription....

  5. Tobacco smoke induces CYP1B1 in the aerodigestive tract.

    Science.gov (United States)

    Port, Jeffrey L; Yamaguchi, Kentaro; Du, Baoheng; De Lorenzo, Mariana; Chang, Mindy; Heerdt, Paul M; Kopelovich, Levy; Marcus, Craig B; Altorki, Nasser K; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2004-11-01

    Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.

  6. The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Shuai Li

    Full Text Available As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B is an attractive target for therapeutic interventions in type 2 diabetes. The extremely conserved catalytic site of PTP1B renders the design of selective PTP1B inhibitors intractable. Although discovered allosteric inhibitors containing a benzofuran sulfonamide scaffold offer fascinating opportunities to overcome selectivity issues, the allosteric inhibitory mechanism of PTP1B has remained elusive. Here, molecular dynamics (MD simulations, coupled with a dynamic weighted community analysis, were performed to unveil the potential allosteric signal propagation pathway from the allosteric site to the catalytic site in PTP1B. This result revealed that the allosteric inhibitor compound-3 induces a conformational rearrangement in helix α7, disrupting the triangular interaction among helix α7, helix α3, and loop11. Helix α7 then produces a force, pulling helix α3 outward, and promotes Ser190 to interact with Tyr176. As a result, the deviation of Tyr176 abrogates the hydrophobic interactions with Trp179 and leads to the downward movement of the WPD loop, which forms an H-bond between Asp181 and Glu115. The formation of this H-bond constrains the WPD loop to its open conformation and thus inactivates PTP1B. The discovery of this allosteric mechanism provides an overall view of the regulation of PTP1B, which is an important insight for the design of potent allosteric PTP1B inhibitors.

  7. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    Science.gov (United States)

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

  8. Yersinia pestis Requires Host Rab1b for Survival in Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael G Connor

    2015-10-01

    Full Text Available Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.

  9. Plectin isoform 1b mediates mitochondrion-intermediate filament network linkage and controls organelle shape.

    Science.gov (United States)

    Winter, Lilli; Abrahamsberg, Christina; Wiche, Gerhard

    2008-06-16

    Plectin is a versatile intermediate filament (IF)-bound cytolinker protein with a variety of differentially spliced isoforms accounting for its multiple functions. One particular isoform, plectin 1b (P1b), remains associated with mitochondria after biochemical fractionation of fibroblasts and cells expressing exogenous P1b. Here, we determined that P1b is inserted into the outer mitochondrial membrane with the exon 1b-encoded N-terminal sequence serving as a mitochondrial targeting and anchoring signal. To study P1b-related mitochondrial functions, we generated mice that selectively lack this isoform but express all others. In primary fibroblasts and myoblasts derived from these mice, we observe a substantial elongation of mitochondrial networks, whereas other mitochondrial properties remain largely unaffected. Normal morphology of mitochondria could be restored by isoform-specific overexpression of P1b in P1b-deficient as well as plectin-null cells. We propose a model where P1b both forms a mitochondrial signaling platform and affects organelle shape and network formation by tethering mitochondria to IFs.

  10. Data of evolutionary structure change: 1D0GD-2RJLA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D0GD-2RJLA 1D0G 2RJL D A PQRVAAHITGTRGEKALGRKINSWESSRSGHSFLS-NLH...LRNGELVIHEKGFYYIYSQTYFRFQEEIKENTKNDKQMVQYIYKYTS-YPDPILLMKSARNSCWSKDAEYGLYSIYQGGIFELKENDRIFVSVTNEHLIDM-DHEASFFGAFLVG GD...KPRAHLTVVRQTPTQFPALHWEHEL--GLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRG--------MKPDSITVVITKVTDS...YPEPTQLLMGTKSVS-EVG-SNWFQPIYLGAMFSLQEGDKLMVNVSDISLVDYTKEDKTFFGAFLL- ...D0G D 1D0GD HSFLS-NLHLR

  11. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...... for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  12. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...... for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  13. Influence of Drug Formulation on OATP1B-Mediated Transport of Paclitaxel

    Science.gov (United States)

    Nieuweboer, Annemieke J.M.; Hu, Shuiying; Hagenbuch, Bruno; Moghaddam-Helmantel, Inge Ghobadi; Gibson, Alice A.; de Bruijn, Peter; Mathijssen, Ron H. J.; Sparreboom, Alex

    2014-01-01

    Purpose Taxane antineoplastic agents are extensively taken up into hepatocytes by OATP1B-type transporters prior to metabolism and excretion. Because the biodistributional properties imposed upon these agents by different solubilizers drive clinically-important pharmacodynamic endpoints, we tested the hypothesis that the in vitro and in vivo interaction of taxanes with OATP1B transporters is affected by the choice of drug delivery system. Experimental Design Transport of paclitaxel, docetaxel, and cabazitaxel was studied in vitro using various cell lines transfected with OATP1B1, OATP1B3, or the rodent equivalent Oatp1b2. Pharmacokinetic studies were done in wildtype and Oatp1b2-knockout mice in the presence or absence of polysorbate 80 (PS80) or Kolliphor EL (formerly Cremophor EL; CrEL). Results Paclitaxel and docetaxel, but not cabazitaxel, were transported substrates of OATP1B1, OATP1B3, and Oatp1b2, and these transport processes were strongly reduced in the presence of clinically-relevant concentrations of PS80 and CrEL. In the absence of solubilizers, deficiency of Oatp1b2 in mice was associated with a significantly decreased taxane clearance due to a liver distribution defect (P0.05). Conclusions Our findings confirm the importance of OATP1B-type transporters in the hepatic elimination of taxanes, and that this process can be inhibited by PS80 and CrEL. These results suggest that the likelihood of drug-drug interactions mediated by these transporters is strongly dependent on the selected taxane solubilizer. PMID:24755470

  14. LMX1B is part of a transcriptional complex with PSPC1 and PSF.

    Directory of Open Access Journals (Sweden)

    Elisa J Hoekstra

    Full Text Available The LIM homeodomain transcription factor Lmx1b is essential for the development of the isthmic organizer and mesodiencephalic dopaminergic neurons. The uncoupling of Pitx3 and Th expression, in the Lmx1b null mutant, suggests that Lmx1b may act as a positional activator of the mdDA domain, eventually leading to properly differentiating mdDA neurons. In this study, we aimed to elucidate how Lmx1b functions mechanistically in this developmental process, by searching for molecular interactors of Lmx1b at the protein level. Initially, affinity-purification of LMX1B-HIS overexpressed protein in MN9D dopaminergic cells followed by mass-spectrometry analysis, resulted in the identification of PSPC1 protein as a possible binding partner of LMX1B. Subsequent immunoprecipitation experiments revealed an interaction between LMX1B and PSPC1 in a larger protein complex also containing PSF. This complex was observed in vitro and in vivo, and we hypothesize that, via PSF and PSPC1, LMX1B may be part of the previously identified Nurr1 transcriptional complex wherein interaction with the co-repressor PSF and the transcription factor Pitx3 is needed to drive expression of Nurr1 target genes in specifying the dopaminergic phenotype. Furthermore, we identified GRLF1, DHX9, MYO1C, HSP70 and TMPO as potential LMX1B interactors. DHX9 and GRLF1 are highly expressed in the developing mdDA neuronal field, and GRLF1 and MYO1C have both been linked to neurite outgrowth. The identification of these proteins suggests that Lmx1b may act directly in the transcriptional activation of Nurr1 target genes and be involved in other processes like neurite outgrowth as well.

  15. Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors.

    Science.gov (United States)

    De Vas, Matias G; Kopp, Janel L; Heliot, Claire; Sander, Maike; Cereghini, Silvia; Haumaitre, Cécile

    2015-03-01

    Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3(+) endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.

  16. Synthesis, Characterization and Properties of Bis{oxo-bis[heteroaromatic carboxylatodibenzyltin(Ⅳ)]} and Crystal Structure of Bis{oxo-bis[2-furylcarboxylatodibenzyltin(Ⅳ)]}

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A series of bis{oxo-bis[heteroaromatic carboxylatodibenzyltin(Ⅳ)]} complexes {[(PhCH2)2Sn*(O2CR)]2O}2[where R=2-furyl, 2-(2-furyl)vinyl, 2-(5-tert-butyl)furyl, 2-thiophenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-indolyl, 3-indolylmethyl, 3-indolylpropyl] was synthesized by the reactions of heteroaromatic carboxylic acids with dibenzyltin(Ⅳ) oxide. All the complexes were characterized by elemental analysis, IR, and NMR spectra. The complexes were tested against two human tumour cell lines: MCF-7 and WiDr. The results show that they have higher activities in vitro. The crystal structure of bis{oxo-bis[2-furylcarboxylatodibenzyltin(Ⅳ)]}(1) was determined by X-ray diffraction. The crystal belongs to monoclinic space group P21/n, a=1.6641(2) nm, b=1.25073(18) nm, c=1.7193(3) nm, β=101.951(2)°, Z=2, R1=0.0446, wR2=0.1100. Complex 1 is of a centrosymmetric dimer structure with a four-membered central endo-cyclic Sn2O2 unit in which the bridged oxygen atoms are tri-coordinated. Each bridged oxygen atom also connects with an exo-cyclic tin atom. The tin atoms are six-coordinated and have a coordination geometry of a distorted octahedron. The exo-cyclic tin atoms are five-coordinated and have a coordination geometry of a monocapped trigonal bipyramid with a very similarly distorted mode. Four carboxylate ligands are divided into two types. The two of the four carboxylate ligands are bidentate and bridged to each pair of exo- and endo-cyclic tin atoms by using both the oxygen atoms. The other two are monodentate and bridged to each pair of exo- and endo-cyclic tin atoms but each utilizes one O atom only.

  17. [N,N-Bis(diphenylphosphinoisopropylamine]dibromidonickel(II

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available The title compound, [NiBr2(C27H27NP2], was synthesized by the reaction of NiBr2(dme (dme is 1,2-dimethoxyethane with N,N-bis(diphenylphosphinoisopropylamine in methanol/tetrahydrofuran. The nickel(II center is coordinated by two P atoms of the chelating PNP ligand, Ph2PN(iPrPPh2, and two bromide ions in a distorted square-planar geometry.

  18. A novel 1D chain of azido bridged copper(II) with a salen-type di-Schiff base ligand

    Science.gov (United States)

    Biswas, Saptarshi; Ghosh, Ashutosh

    2012-07-01

    One new complex of Cu(II), [(CuL)2Cu3(N3)6]n (1) has been synthesized by reacting the "ligand complex", [CuL] with copper acetate and sodium azide (NaN3) in methanol-water where the di-Schiff base ligand H2L = N,N‧-bis(α-methylsalicylidene)-1,3-propanediamine. The X-ray single crystal structural analysis shows that complex 1 consists of an incomplete face-sharing double cube of four Cu(II) ions with the formula of [(CuL)2Cu2(N3)2]2+ which are connected by [Cu(N3)4]2- unit to form a novel 1D chain.

  19. Synthesis of novel bis-allyloxy and hydroxypropoxy derivatives of 4, 5-diaryl thiophene-2-carboxylic acid and their biological evaluation

    Indian Academy of Sciences (India)

    T SHANMUGANATHAN; M VENUGOPAL; K PARTHASARATHY; N DHATCHANAMOORTHY; Y ARUN; A A M PRINCE

    2017-05-01

    In our earlier studies, we have shown that the introduction of amino moieties at carboxylic acid of 4,5-diarylthiophene-2-carboxylic acid significantly improved the anti-inflammatory activity of the compound against the standard drug diclofenac sodium. In the present study, we have synthesized new derivatives of 4,5- diarylthiophene-2-carboxylic acid by modifying the hydroxyl group of the phenyl ring and carboxylic acid group of the thiophene ring.Aseries of novel 4,5-diarylthiophene-2-carboxylic acid derivatives containing bis-allyloxyand hydroxypropoxy with methyl or ethyl ester moieties were synthesized, characterized and subsequently evaluated for anti-inflammatory and antioxidant property. Among the novel compounds, the inhibition of bovineserum albumin denaturation assay revealed that the compound 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene- 2-carboxylic acid (15) and ethyl ester (13) having anti-inflammatory activity better than the standard drugdiclofenac sodium. The antioxidant screening showing 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylic acid (10), 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid methyl ester (11) and 4,5-bis(4-(3- hydroxypropoxy)phenyl)thiophene-2-carboxylic acid ethyl ester (13) exhibited a slightly moderate antioxidant activity than standard ascorbic acid. Molecular docking analysis was performed for the synthesized compounds with the cyclooxygenase-2 (COX-2) receptor (PDB 1D: 1PXX). Docking studies revealed that all the synthesised compounds exhibit greater binding affinity than the standard drug. Particularly, the compound ethyl 4,5-bis(4- (allyloxy)phenyl)thiophene-2-carboxylate (8) and allyl 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylate (9) having high free energy binding of −10.40 and −10.48 Kcal/mol, respectively.

  20. Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis

    NARCIS (Netherlands)

    Sticova, E.; Lodererova, A.; Steeg, E. van de; Frankova, S.; Kollar, M.; Lanska, V.; Kotalova, R.; Dedic, T.; Schinkel, A.H.; Jirsa, M.

    2015-01-01

    Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to cor

  1. Data of evolutionary structure change: 1B38A-1WBSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B38A-1WBSA 1B38 1WBS A A -----------------MENFQKVEKIGEGTYGVVYKAR... ALA CA 254 ILE CA 274 1WBS A 1WBSA VKKLSRPFQSIIHA PRO CA 313 ASN CA 408 ILE CA 432 1WBS... A 1WBSA RELRLLKHMKHENV

  2. Jarid1b targets genes regulating development and is involved in neural differentiation

    DEFF Research Database (Denmark)

    Schmitz, Sandra U; Albert, Mareike; Malatesta, Martina

    2011-01-01

    -renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly...

  3. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Science.gov (United States)

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  4. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Márcia Faria

    2016-01-01

    Full Text Available RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs and 33 follicular thyroid adenomas (FTAs. RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01 and poorer clinical outcome (P = 0.01 suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

  5. Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel

    NARCIS (Netherlands)

    A.J.M. de Graan (Anne-Joy); C.S. Lancaster (Cynthia); A. Obaidat (Amanda); B. Hagenbuch (Bruno); L. Elens (Laure); L.E. Friberg (Lena); P. de Bruijn (Peter); S. Hu (Shuiying); A.A. Gibson; G.H. Bruun (G.); T.J. Corydon (T.); T.S. Mikkelsen; A.L. Walker (Aisha); G. Du (Guoqing); W.J. Loos (Walter); R.H.N. van Schaik (Ron); S.D. Baker (Sharyn); A.H.J. Mathijssen (Ron); A. Sparreboom (Alex)

    2012-01-01

    textabstractPurpose: Docetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inhe

  6. Data of evolutionary structure change: 1B3JA-1TVBA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B3JA-1TVBA 1B3J 1TVB A A EPHSLRYNLTVLSWDGSVQSGFLTEVHLDGQPFLRCDRQ... 297 1TVB A 1TVBA...ine> LYS CA 187 1TVB A 1TVBA...bID> A 1TVBA RYLENGKE...pdbID>1TVB A 1TVBA VQHEGLPKPLTL

  7. PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.

    Science.gov (United States)

    Krishnan, Navasona; Krishnan, Keerthi; Connors, Christopher R; Choy, Meng S; Page, Rebecca; Peti, Wolfgang; Van Aelst, Linda; Shea, Stephen D; Tonks, Nicholas K

    2015-08-01

    The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.

  8. Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. (Univ. of California, San Francisco, CA (United States)); Brooks, D.G.; Ravetch, J.V. (Sloan-Kettering Institute, New York, NY (United States)); Trofatter, J.A. (Massachusetts General Hospital, Boston, MA (United States))

    1993-11-15

    The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

  9. Data of evolutionary structure change: 1DTGA-1B1XA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B1XA 1DTG 1B1X A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...VVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKD...ndex>0 1DTG A 1DTGA A 1DTGA CQLCP-----GCGCS 2 1DTG A 1DTGA

  10. Tumor-specific expression of cytochrome P450 CYP1B1.

    Science.gov (United States)

    Murray, G I; Taylor, M C; McFadyen, M C; McKay, J A; Greenlee, W F; Burke, M D; Melvin, W T

    1997-07-15

    Cytochrome P450 CYP1B1 is a recently cloned dioxin-inducible form of the cytochrome P450 family of xenobiotic metabolizing enzymes. An antibody raised against a peptide specific for CYP1B1 was found to recognize CYP1B1 expressed in human lymphoblastoid cells but not to recognize other forms of cytochrome P450, particularly CYP1A1 and CYP1A2. Using this antibody, the cellular distribution and localization of CYP1B1 were investigated by immunohistochemistry in a range of malignant tumors and corresponding normal tissues. CYP1B1 was found to be expressed at a high frequency in a wide range of human cancers of different histogenetic types, including cancers of the breast, colon, lung, esophagus, skin, lymph node, brain, and testis. There was no detectable immunostaining for CYP1B1 in normal tissues. These results provide the basis for the development of novel methods of cancer diagnosis based on the identification of CYP1B1 in tumor cells and the development of anticancer drugs that are selectively activated in tumors by CYP1B1.

  11. Pterocarpans with inhibitory effects on protein tyrosine phosphatase 1B from Erythrina lysistemon Hutch

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Nguyen, Phi Hung; Thuong, Phuong Thien

    2009-01-01

    ',5':3,4]-2'',2''-dimethyldihydropyrano[6'',5'':9,10]pterocarpan (1), furano[5',4':3,4]-9-hydroxy-10-prenylpterocarpan (2), and 8-formyl-3,9-dihydroxy-4,10-diprenylpterocarpan (3), based on spectroscopic analyses. All the isolates, with the exception of 3, 6, and 11, strongly inhibited protein tyrosine phosphatase 1B (PTP1B) activity...

  12. The Phosphate Exporter xpr1b Is Required for Differentiation of Tissue-Resident Macrophages

    Directory of Open Access Journals (Sweden)

    Ana M. Meireles

    2014-09-01

    Full Text Available Phosphate concentration is tightly regulated at the cellular and organismal levels. The first metazoan phosphate exporter, XPR1, was recently identified, but its in vivo function remains unknown. In a genetic screen, we identified a mutation in a zebrafish ortholog of human XPR1, xpr1b. xpr1b mutants lack microglia, the specialized macrophages that reside in the brain, and also displayed an osteopetrotic phenotype characteristic of defects in osteoclast function. Transgenic expression studies indicated that xpr1b acts autonomously in developing macrophages. xpr1b mutants display no gross developmental defects that may arise from phosphate imbalance. We constructed a targeted mutation of xpr1a, a duplicate of xpr1b in the zebrafish genome, to determine whether Xpr1a and Xpr1b have redundant functions. Single mutants for xpr1a were viable, and double mutants for xpr1b;xpr1a were similar to xpr1b single mutants. Our genetic analysis reveals a specific role for the phosphate exporter Xpr1 in the differentiation of tissue macrophages.

  13. CYP1B1 and myocilin gene mutations in Egyptian patients with ...

    African Journals Online (AJOL)

    Mahmoud R. Fassad

    2016-08-09

    Aug 9, 2016 ... in CYP1B1 gene (G61E, R368H) and one mutation in MYOC gene (Gln48His) using polymerase .... IOP between the 2 eyes [11], or if successive examination under ... coding region of MYOC gene encompassing Gln48His muta- tion was ..... CYP1B1 involvement in the molecular basis of primary congenital.

  14. Data of evolutionary structure change: 1B9HA-2FNIA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9HA-2FNIA 1B9H 2FNI A A -KAPEFPAWPQYDDAERNGLVRALEQGQWWRMGGDEVNS...------------QLFNTAPLKSAEDFYHAEISLPCHA-NLNLESVQNIAHSVLKTFESFKI - HHHHHHHHHHHH HHHHHHHHHHH EEEEE ... 2FNI A 2FNIA 2FNI A 2FNIA MLKKDFFEGEV 2FNI A 2FNIA KQLTQ--GKR

  15. Data of evolutionary structure change: 1B9IA-2FNIA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9IA-2FNIA 1B9I 2FNI A A KAPEFPAWPQYDDAERNGLVRALEQGQWWRMGGDEVNSF...------QLYQQLFNTAPLKSAEDFYHAEISLPCH-ANLNLESVQNIAHSVLKTFESFKI HHHHHHHHHHHH HHHHHHHHHHHH EEEEE HH...ryChain> 2FNI A 2FNIA HIS CA 209 2FNI A 2FNIA...n14> 2FNI A 2FNIA

  16. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism

    Science.gov (United States)

    Interleukin 1b (IL1B or IL-1ß), is a key modulator of the immune response which exerts its functions mainly via interleukin 6 (IL6) regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susc...

  17. Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor

    Institute of Scientific and Technical Information of China (English)

    Gui-xia LIU; Jin-zhi TAN; Chun-ying NIU; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Kai-xian CHEN; Hua-liang JIANG

    2006-01-01

    Aim: To investigate the dynamic properties of protein-tyrosine phosphatase (PTP)1B and reveal the structural factors responsible for the high inhibitory potency and selectivity of the inhibitor SNA for PTP1B. Methods: We performed molecular dynamics (MD) simulations using a long time-scale for both PTP1B and PTP1B complexed with the inhibitor SNA, the most potent and selective PTP1B inhibitor reported to date. The trajectories were analyzed by using principal component analysis. Results: Trajectory analyses showed that upon binding the ligand, the flexibility of the entire PTP1B molecule decreases. The most notable change is the movement of the WPD-loop. Our simulation results also indicated that electrostatic interactions contribute more to PTP1B-SNA complex conformation than the van der Waals interactions, and that Lys41, Arg47, and Asp48 play important roles in determining the conformation of the inhibitor SNA and in the potency and selectivity of the inhibitor. Of these, Arg47 contributed most. These results were in agreement with previous experimental results. Conclusion: The information presented here suggests that potent and selective PTP1B inhibitors can be designed by targeting the surface residues, for example the region containing Lys41,Arg47, and Asp48, instead of the second phosphate binding site (besides the active phosphate binding site).

  18. Data of evolutionary structure change: 1AIBB-2AY1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AIBB-2AY1B 1AIB 2AY1 B B MFENITAAPADPILGLADLFRADERPGKINLGIGVYKDE...HHH HHHHHHHH EEEE EEEEEGG HHHHHHHHHHHHH 0 1AIB... B 1AIBB DFSFI--...e>ALA CA 413 THR CA 475 LEU CA 494 1AIB... B 1AIBB GSALINDKRARTA <

  19. Data of evolutionary structure change: 1B9OA-1IOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9OA-1IOTA 1B9O 1IOT A A KQFTKCELSQLLKDI--DGYGGIALPELICTMFHTSGYD...dbChain>A 1IOTA ALKRHGLDNYRG 5.116000175476074 15.197999954223633 tion> 0.9950000047683716 -0.796999990940094 tion> 2.0168049335479736 4.099109172821045 1IOT A 1IOTA <

  20. Data of evolutionary structure change: 1B4WD-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WD-2NOTA 1B4W 2NOT D A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK...line> 2NOT A 2NOTA...z>13.574999809265137 tion> -0.8450000286102295 -0....0000074505806 -0.44600000977516174 -0.09099999815225601 -0.8899999856948853 1 2NOT A 2NOTA

  1. Data of evolutionary structure change: 1B4WC-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WC-2NOTA 1B4W 2NOT C A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK...03 2NOT A 2NOTA...y> -17.684999465942383 tion> -0.7129999995231628 -0.03400000184774399 -0.04600000008940697 0.9980000257492065 ...el> 1 2NOT A 2NOTA

  2. Data of evolutionary structure change: 1B4WB-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WB-2NOTA 1B4W 2NOT B A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK... 2NOT A 2NOTA... 28.97100067138672 tion> 0.8460000157356262 0.4...550000190734863 0.531000018119812 -0.7149999737739563 -0.45399999618530273 ti...el> 1 2NOT A 2NOTA

  3. Data of evolutionary structure change: 1B4WA-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WA-2NOTA 1B4W 2NOT A A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK... 2NOT A 2NOTA....69599914550781 tion> 0.7179999947547913 0.4429999...042915344 -0.19200000166893005 0.8669999837875366 0.46000000834465027 tion> 1 2NOT A 2NOTA

  4. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Science.gov (United States)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  5. Tissue-specific alternative splicing and expression of ATP1B2 gene ...

    African Journals Online (AJOL)

    Tissue-specific alternative splicing and expression of ATP1B2 gene. ... It also balances metabolism and body temperature. ... In the study, ATP1B2-AS2 showed that many of the amino acid residues were in an unfavorable energy environment.

  6. High fat diet deviates PtC-specific B1 B cell phagocytosis in obese mice.

    Science.gov (United States)

    Vo, Hung; Chiu, Joanna; Allaimo, Danielle; Mao, Changchuin; Wang, Yaqi; Gong, Yuefei; Ow, Hooisweng; Porter, Tyrone; Zhong, Xuemei

    2014-12-01

    Phagocytosis had been attributed predominantly to "professional" phagocytes such as macrophages, which play critical roles in adipose tissue inflammation. However, recently, macrophage-like phagocytic activity has been reported in B1 B lymphocytes. Intrigued by the long-established correlation between high fat diet (HFD)-induced obesity and immune dysfunction, we investigated how HFD affects B1 B cell phagocytosis. A significant number of B1 B cells recognize phosphatidylcholine (PtC), a common phospholipid component of cell membrane. We report here that unlike macrophages, B1 B cells have a unique PtC-specific phagocytic function. In the presence of both PtC-coated and non-PtC control fluorescent nano-particles, B1 B cells from healthy lean mice selectively engulfed PtC-coated beads, whereas B1 B cells from HFD-fed obese mice non-discriminately phagocytosed both PtC-coated and control beads. Morphologically, B1 B cells from obese mice resembled macrophages, displaying enlarged cytosol and engulfed more beads. Our study suggests for the first time that HFD can affect B1 B cell phagocytosis, substantiating the link of HFD-induced obesity and immune deviation.

  7. Data of evolutionary structure change: 1B1GA-1CLMA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1GA-1CLMA 1B1G 1CLM A A KSPEELKGIFEKYAAK-EGDPNQLSKEELKLLLQTEFPS...-- LTEEQIAEFKEAFALFDKDGDGTITTKELGTVMRSL-----GQNPTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFK...SN CA 464 1CLM A 1CLMA...dbChain> 1CLMA LQDMINEVDADGN HHHHHH 2 1CLM A 1CLMA

  8. Data of evolutionary structure change: 1B1ZA-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZA-2NTSA 1B1Z 2NTS A A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTN--------------GPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...ine> 2NTS A 2NTSA 2NTS A 2NTS.../line> PHE CA 274 2NTS A 2NTS

  9. Data of evolutionary structure change: 1B1ZC-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZC-2NTSA 1B1Z 2NTS C A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTNG--------------PSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...e>THR CA 392 2NTS A 2NTS...CA 343 LYS CA 296 2NTS A 2NTS...208 PHE CA 276 THR CA 304 2NTS

  10. Data of evolutionary structure change: 1B1ZD-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZD-2NTSA 1B1Z 2NTS D A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...R CA 395 2NTS A 2NTS... LYS CA 294 2NTS A 2NTS...e>PHE CA 282 THR CA 304 2NTS

  11. Data of evolutionary structure change: 1B1ZB-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZB-2NTSA 1B1Z 2NTS B A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...4 2NTS A 2NTSA 2NTS A 2NTSAPHE CA 283 2NTS A 2NTS

  12. A key role for PTP1B in dendritic cell maturation, migration, and T cell activation.

    Science.gov (United States)

    Martin-Granados, Cristina; Prescott, Alan R; Le Sommer, Samantha; Klaska, Izabela P; Yu, Tian; Muckersie, Elizabeth; Giuraniuc, Claudiu V; Grant, Louise; Delibegovic, Mirela; Forrester, John V

    2015-12-01

    Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid cell-specific PTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

  13. Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Jin, Tiantian; Yu, Haibo; Huang, Xu-Feng

    2016-02-11

    Protein Tyrosine Phosphatase 1B (PTP1B) has been recognized as a promising therapeutic target for treating obesity, diabetes, and certain cancers for over a decade. Previous drug design has focused on inhibitors targeting the active site of PTP1B. However, this has not been successful because the active site is positively charged and conserved among the protein tyrosine phosphatases. Therefore, it is important to develop PTP1B inhibitors with alternative inhibitory strategies. Using computational studies including molecular docking, molecular dynamics simulations, and binding free energy calculations, we found that lupane triterpenes selectively inhibited PTP1B by targeting its more hydrophobic and less conserved allosteric site. These findings were verified using two enzymatic assays. Furthermore, the cell culture studies showed that lupeol and betulinic acid inhibited the PTP1B activity stimulated by TNFα in neurons. Our study indicates that lupane triterpenes are selective PTP1B allosteric inhibitors with significant potential for treating those diseases with elevated PTP1B activity.

  14. 18 CFR 2.1b - Availability in contested cases of information acquired by staff investigation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Availability in contested cases of information acquired by staff investigation. 2.1b Section 2.1b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES GENERAL...

  15. 18 CFR 1b.13 - Powers of persons conducting formal investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Powers of persons conducting formal investigations. 1b.13 Section 1b.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS §...

  16. Data of evolutionary structure change: 1B7QA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7QA-2G4NF 1B7Q 2G4N A F KVFERCELARTLKRLGMDGYRGISLALWMCLAKWESGYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF VQNND...tation> 1.5742559432983398 3.2563140392303467 EVI...D> 1 2G4N F 2G4NF

  17. Data of evolutionary structure change: 1B5XA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5XA-2G4NF 1B5X 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...G HHHH -GGGG -- EVID>EVID> 0 2G4N F 2G4NF ELKDL...242798 2.054610013961792 4.014041900634766 ...EVID> 1 2G4N F 2G4NF

  18. Data of evolutionary structure change: 1B7OA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7OA-2G4NF 1B7O 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESQYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF IVQNN...on> 0.7017530202865601 1.3242100477218628 EVID> 1 2G4N F 2G4NF <

  19. Data of evolutionary structure change: 1B06A-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B06A-1UNFX 1B06 1UNF A X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...EEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH EVID> ...n> 1UNF X 1UNFX AVNP...127516031265259 5.276762008666992 EVID>...99 TRP CA 383 ASP CA 305 ASP CA 355 1UNF

  20. Data of evolutionary structure change: 1B5WA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5WA-2G4NF 1B5W 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...G HHHH -GGGG -- EVID>EVID> 0 2G4N F 2G4NF ELKDL...18 2.079693078994751 4.073005199432373 EVID>...EVID> 1 2G4N F 2G4NF

  1. Data of evolutionary structure change: 1B7NA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7NA-2G4NF 1B7N 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWLSGYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF IVQNN...n> 0.6914700269699097 1.3510249853134155 EVID> 1 2G4N F 2G4NF

  2. Data of evolutionary structure change: 1B06D-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available EVID>EVID> 2 1UNF X 1UNF...1B06D-1UNFX 1B06 1UNF D X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...HHHHHHHHHHHHH EEEEEEEEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH ... 1UNF X 1UNFX 3.1296169757843018 5.294285774230957

  3. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics

    NARCIS (Netherlands)

    Groves, M R; Yao, Z J; Roller, P P; Burke, T R; Barford, D

    1998-01-01

    Protein tyrosine phosphatases regulate diverse cellular processes and represent important targets for therapeutic intervention in a number of diseases. The crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with small molecule inhibitors based upon two classes of phosphotyrosin

  4. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes

    DEFF Research Database (Denmark)

    Schubert, J.; Siekierska, A.; Langlois, M.

    2014-01-01

    Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encodi...

  5. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  6. Chemical segregation in the young protostars Barnard 1b-N and S. Evidence of pseudo-disk rotation in Barnard 1b-S

    Science.gov (United States)

    Fuente, A.; Gerin, M.; Pety, J.; Commerçon, B.; Agúndez, M.; Cernicharo, J.; Marcelino, N.; Roueff, E.; Lis, D. C.; Wootten, H. A.

    2017-10-01

    The extremely young Class 0 object B1b-S and the first hydrostatic core (FSHC) candidate, B1b-N, provide a unique opportunity to study the chemical changes produced in the elusive transition from the prestellar core to the protostellar phase. We present 40″ × 70″ images of Barnard 1b in the 13CO 1 → 0, C18O 1 → 0, NH2D 11,1a→ 10,1s, and SO 32→ 21 lines obtained with the NOEMA interferometer. The observed chemical segregation allows us to unveil the physical structure of this young protostellar system down to scales of 500 au. The two protostellar objects are embedded in an elongated condensation, with a velocity gradient of 0.2-0.4 m s-1 au-1 in the east-west direction, reminiscent of an axial collapse. The NH2D data reveal cold and dense pseudo-disks (R 500 - 1000 au) around each protostar. Moreover, we observe evidence of pseudo-disk rotation around B1b-S. We do not see any signature of the bipolar outflows associated with B1b-N and B1b-S, which were previously detected in H2CO and CH3OH, in any of the imaged species. The non-detection of SO constrains the SO/CH3OH abundance ratio in the high-velocity gas. Based on observations carried out with the IRAM Northern Extended Millimeter Array (NOEMA). IRAM is supported by INSU/ CNRS (France), MPG (Germany), and IGN (Spain).The reduced datacube is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/606/L3

  7. Radical bonding: structure and stability of bis(phenalenyl) complexes of divalent metals from across the periodic table.

    Science.gov (United States)

    Craciun, Smaranda; Donald, Kelling J

    2009-07-06

    We examine the bonding possibilities of the bis(phenalenyl) MP(2) sandwich complexes of the divalent metals M = Be, Mg, Ca, Sr, Ba, Zn, Cd, and Hg, at the B3LYP level of theory. The outcome is an extraordinarily diverse class of low symmetry bis(phenalenyl)metal complexes in which bonding preferences and binding enthalpies differ dramatically. The lowest energy group 2 metal MP(2) complexes include an intriguing eta(1),eta(3) BeP(2) structure, and bent eta(6),eta(6) systems for M = Ca, Sr, and Ba. The group 12 bis(phenalenyl) complexes are thermodynamically unstable eta(1),eta(1) slip-sandwich structures. To better understand changes in the structural preferences going from the (eta(6),eta(6)) group 2 to the (eta(1),eta(1)) group 12 complexes, we explored the bonding in the bis(phenalenyl) complexes of transition metals with stable +2 oxidations states between Ca and Zn in period 4. The computed binding enthalpies are large and negative for nearly all of the minimum energy bis(phenalenyl) complexes of the group 2 and the transition metals; they are tiny for MgP(2), and are quite positive for the group 12 systems. The structural preferences and stability of the complexes is a subtle negotiation of several influences: the (un)availability of (n - 1)d and np, orbitals for bonding, the cost of the rehybridization at carbon sites in the phenalenyl rings in preparation for bonding to the metals, and the (P---P) interaction between the phenalenyl radicals.

  8. Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition.

    Directory of Open Access Journals (Sweden)

    Wenjun Ni

    Full Text Available BACKGROUND: Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent. CONCLUSIONS/SIGNIFICANCE: Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO

  9. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolylpyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Directory of Open Access Journals (Sweden)

    Gerhard Kelter

    2013-03-01

    Full Text Available 2,5-bis(3′-Indolylpyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  10. Synthesis and antiproliferative activity of 2,5-bis(3'-indolyl)pyrroles, analogues of the marine alkaloid nortopsentin.

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-03-01

    2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  11. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-01-01

    2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes. PMID:23455514

  12. Inhibition of protein tyrosine phosphatase 1B by lignans from Myristica fragrans.

    Science.gov (United States)

    Yang, Senugmi; Na, Min Kyun; Jang, Jun Pil; Kim, Kyung Ah; Kim, Bo Yeon; Sung, Nak Ju; Oh, Won Keun; Ahn, Jong Seog

    2006-08-01

    Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.

  13. Palatal insufficiency as isolated sign of GQ1b antibody syndrome.

    Science.gov (United States)

    Verhelst, Helene; Maes, Michaela; Deblaere, Karel; Van Coster, Rudy

    2011-04-01

    Antiganglioside GQ1b antibodies mediate a continuum of disorders with overlapping features, fostering the concept of anti-GQ1b antibody syndrome. We present a patient whose palatal insufficiency was the only clinical sign of postinfectious GQ1b antibody syndrome. Cerebral magnetic resonance imaging confirmed involvement of the glossopharyngeal nerve and vagus nerve bilaterally, revealing gadolinium enhancement of both nerves bilaterally and thickening of the left nervus vagus. Magnetic resonance imaging may help in diagnosing postinfectious GQ1b antibody syndrome, especially at early stages and in monosymptomatic patients. Early diagnosis may lead to early therapy, resulting in a milder disease course by preventing further deterioration leading to the ataxia and ophthalmoplegia usually observed in patients with postinfectious GQ1b antibody syndrome.

  14. Goniodysgenesis variability and activity of CYP1B1 genotypes in primary congenital glaucoma

    Science.gov (United States)

    de Hoz, Rosa; Rojas, Blanca; Ramírez, Ana I.; Triviño, Alberto; Aroca-Aguilar, José-Daniel; García-Feijoo, Julián; Escribano, Julio

    2017-01-01

    Mutations in the CYP1B1 gene are currently the main known genetic cause of primary congenital glaucoma (PCG), a leading cause of blindness in children. Here, we analyze for the first time the CYP1B1 genotype activity and the microscopic and clinical phenotypes in human PCG. Surgical pieces from trabeculectomy from patients with PCG (n = 5) and sclerocorneal rims (n = 3) from cadaver donors were processed for transmission electron microscopy. Patients were classified into three groups depending on goniodysgenesis severity, which was influenced by CYP1B1 enzymatic activity. The main histological changes observed in the outflow pathway of patients with PCG and mutations in CYP1B1 were: i) underdeveloped collector channels and the Schlemm’s canal; ii) abnormal insertion of the ciliary muscle; iii) death of the trabecular endothelial cells. Our findings could be useful in improving treatment strategy of PCG associated with CYP1B1 mutations. PMID:28448622

  15. JARID1B is a luminal lineage-driving oncogene in breast cancer.

    Science.gov (United States)

    Yamamoto, Shoji; Wu, Zhenhua; Russnes, Hege G; Takagi, Shinji; Peluffo, Guillermo; Vaske, Charles; Zhao, Xi; Moen Vollan, Hans Kristian; Maruyama, Reo; Ekram, Muhammad B; Sun, Hanfei; Kim, Jee Hyun; Carver, Kristopher; Zucca, Mattia; Feng, Jianxing; Almendro, Vanessa; Bessarabova, Marina; Rueda, Oscar M; Nikolsky, Yuri; Caldas, Carlos; Liu, X Shirley; Polyak, Kornelia

    2014-06-16

    Recurrent mutations in histone-modifying enzymes imply key roles in tumorigenesis, yet their functional relevance is largely unknown. Here, we show that JARID1B, encoding a histone H3 lysine 4 (H3K4) demethylase, is frequently amplified and overexpressed in luminal breast tumors and a somatic mutation in a basal-like breast cancer results in the gain of unique chromatin binding and luminal expression and splicing patterns. Downregulation of JARID1B in luminal cells induces basal genes expression and growth arrest, which is rescued by TGFβ pathway inhibitors. Integrated JARID1B chromatin binding, H3K4 methylation, and expression profiles suggest a key function for JARID1B in luminal cell-specific expression programs. High luminal JARID1B activity is associated with poor outcome in patients with hormone receptor-positive breast tumors.

  16. Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta.

    Science.gov (United States)

    Na, Minkyun; Kim, Bo Yeon; Osada, Hiroyuki; Ahn, Jong Seog

    2009-08-01

    Protein tyrosine phosphatase 1B (PTP1B) appears to be an attractive target for the development of new drugs for type 2 diabetes and obesity. In our preliminary test, a MeOH extract of the stem barks of Sorbus commixta Hedl. (Rosaceae) showed strong PTP1B inhibitory activity. Bioassay-guided fractionation of the MeOH extract resulted in the isolation of two lupane-type triterpenes, lupenone (1) and lupeol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 13.7 +/- 2.1 and 5.6 +/- 0.9 microM, respectively. Kinetic studies revealed that both the compounds 1 and 2 are non-competitive inhibitors of PTP1B that decrease V(max) values with no effect on K(m) values.

  17. Water molecule network and active site flexibility of apo protein tyrosine phosphatase 1B

    DEFF Research Database (Denmark)

    Pedersen, A.K.; Peters, Günther H.J.; Møller, K.B.;

    2004-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including...... the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 Angstrom apo PTP1B structure has been obtained, showing four highly coordinated water molecules in the active...... of PTP1B and form a novel basis for structure-based inhibitor design....

  18. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling

    DEFF Research Database (Denmark)

    Lund, I K; Hansen, J A; Andersen, H S

    2005-01-01

    Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators...... of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice. The present study was undertaken to investigate the mechanism by which...... PTP1B mediates the cessation of the leptin signal transduction. Leptin-induced activation of a STAT3 responsive reporter was dose-dependently inhibited by co-transfection with PTP1B. No inhibition was observed when a catalytically inactive mutant of PTP1B was used or when other PTPs were co...

  19. [Structure and function of heavy metal transporter P(1B)-ATPase in plant: a review].

    Science.gov (United States)

    Zhang, Yuxiu; Zhang, Yuanya; Sun, Tao; Chai, Tuanyao

    2010-06-01

    The regulation of the heavy-metal accumulation in vivo for plant survival is very complex. The metal cation transporter plays key roles in the metabolic process. P(1B)-ATPases are the only subgroup of P-ATPases that contribute to heavy metal homeostasis presented in most organisms. Arabidopsis thaliana contains eight genes encoding P(1B)-ATPases. The current reports show that the functions of P(1B)-ATPases are involved in maintaining metal homeostasis, transporting and detoxification in plants. P(1B)-ATPases not only mediated metal ion mobilization and uptake in roots, but also contribute to the metal transport, storage and tolerance in shoots, especially in heavy metal hyperaccumulators. In this paper, we reviewed and discussed the evolution, classification, structure and function of P(1B)-ATPases in plants. HMAs-transgenic manipulation could be a feasible approach for phytoremediation and mineral nutrition fortification.

  20. Cytochrome P450 CYP1B1 activity in renal cell carcinoma.

    Science.gov (United States)

    McFadyen, M C E; Melvin, W T; Murray, G I

    2004-08-31

    Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10 nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n=11). Measurable levels of active P450R were determined in all normal (n=11) and tumour samples (n=26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention.

  1. Hereditary and histologic characteristics of the CF1/b cac mouse cataract model.

    Science.gov (United States)

    Kondo, Tomohiro; Nagai, Hiroaki; Kawashima, Takamune; Taniguchi, Yusuke; Koyabu, Nozomu; Takeshita, Ai; Kusakabe, Ken-Takeshi; Okada, Toshiya

    2014-10-01

    A substrain of mice originating from the CF1 strain (an outbred colony) reared at Osaka Prefecture University (CF1/b cac mice) develops cataracts beginning at 14 d old. Affected mice were fully viable and fertile and had developed cataracts by 22 d of age. The incidence of cataracts did not differ between male and female mice. Histologically, 14-wk-old CF1/b cac mice showed vacuolated lens epithelial cells, swollen lens fibers, many pyknotic nuclei, and vacuolation of the lens cortex. To elucidate the mode of inheritance, we analyzed heterozygous mutants hybrids generated from CF1/b cac and wildtype BALB/c mice and the offspring of the backcrossed heterozygous mutants. None of the heterozygous mutants was affected, but the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. The initial genomewide screen of 20 affected backcrossed offspring (CF1/b cac × [CF1/b cac × BALB/c]) indicated that the mutant gene resides on chromosome 16. For further mapping, we used affected progeny of CF1/b cac × (CF1/b cac × MSM/Ms) mice. We concluded that the cataracts in CF1/b cac mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 16 between D16Mit5 and D16Mit92 and between D16Mit92 and D16Mit201. The mapping of the mutant gene of the CF1/b cac mice to mouse chromosome 16 provides the positional information necessary to identify the candidate gene responsible for the CF1/b cac phenotype.

  2. Perioperative cerebral ischaemia in cardiac surgery and BIS.

    Science.gov (United States)

    Villacorta, J; Kerbaul, F; Collart, F; Guidon, C; Bonnet, M; Guillen, J C; Gouin, F

    2005-08-01

    A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.

  3. Comparisons Between Tridentate Bis(benzazoles-pyridine and Bis(benzazolestriazine Ligands: a Theoretical Study

    Directory of Open Access Journals (Sweden)

    Mihaiela Andoni

    2015-12-01

    Full Text Available Twelve bis(benzazole structures with potential ligand character were investigated by means of computational chemistry. Global and local reactivity descriptors within DFT (Density Functional Theory theory (Fukui functions, chemical potential, hardness, electrophilicity index have been computed at B3LYP/6-31G(d,p level of theory. NICS(0 (Nucleus Independent Chemical Shift index computations were employed for the evaluation of the local aromatic character of each heterocyclic moiety. Best results have been reported for the bis(benzimidazole derivatives. Copper and zinc complexes of the investigated tridentate ligands have been proposed.

  4. Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

    Science.gov (United States)

    Kang, Gaeun; Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jin; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jong-Keun

    2014-06-01

    It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results

  5. Intramolecular Electron Transfer in Bis(tetraalkyl Hydrazine) and Bis(hydrazyl) Radical Cations.

    Science.gov (United States)

    Chang, Hao

    A series of multicyclic bis(hydrazine) and bis(diazenium) compounds connected by relatively rigid hydrocarbon frameworks were prepared for the study of intramolecular electron transfer. The thermodynamics of electron removal of these compounds was investigated by cyclic voltammetry. The difference between the first and second oxidation potentials for the 4 sigma-bonded species was found to be larger for the bis(hydrazyl) radical systems than for the bis(hydrazines) by ca. 0.2 V (4.6 kcal/mol). This indicates a greater degree of interaction between the two nitrogen moieties for the hydrazyl systems, which is consistent with a greater degree of electronic coupling (H _{rm AB}) in these systems. The ESR spectra of the 4 sigma -bonded bis(hydrazine) radical cations indicate localized radical cations, which corresponds to slow intramolecular electron transfer on the ESR timescale. Conversely, the ESR spectra of the corresponding bis(hydrazyl) radical cation systems show nitrogen hyperfine splittings of a(4N) of ca. 4.5 G. This indicates that intramolecular electron transfer between the two nitrogen moieties is fast on the ESR timescale; the rate of exchange, k_ {rm ex} was estimated to be well above 1.9 times 10^8 s^{-1}. The contrast in exchange rates is consistent with the large geometry change upon oxidation which is characteristic of hydrazines. The hydrazyls undergo a smaller geometry change upon oxidation, and thus are expected to exhibit smaller inner-sphere reorganization energies. The optical spectra of these radical species was investigated in hopes of observing absorption bands corresponding to intramolecular electron transfer, as predicted by Hush theory. A broad absorption band was observed in the near IR region for the saturated bis(hydrazyl) radical cation system at 1060 nm (9420 cm^{-1} ) in acetonitrile at room temperature, and was accompanied by a narrower band at 1430 nm (6993 cm^ {-1}). The width of this band was estimated to be 545 nm (6496 cm^{-1

  6. Imidazo[2,1-b]benzothiazoles. II. Synthesis and antiinflammatory activity of some imidazo[2,1-b]benzothiazoles.

    Science.gov (United States)

    El-Shorbagi, A N; Sakai, S; el-Gendy, M A; Omar, N; Farag, H H

    1989-11-01

    3-[2-[p-(Un)substituted phenyl]imidazo [2,1-b]benzothiazol-3- yl]propionic acid derivatives (2a--e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (1a--e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a--e produced methyl esters (3a--e). Upon the interaction of 3a with m-chloroperbenzoic acid, the S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3- yl]formaldehyde derivatives (6a--e). Derivatives 6a--e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol- 3-yl]propionate esters (7a--e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a--e showed weak or no activity in the carrageein-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.

  7. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency

    DEFF Research Database (Denmark)

    Sim, J. C. H.; White, S. M.; Fitzpatrick, E.

    2014-01-01

    or nonsense mutations in all of them. Conclusions: This study broadens the spectrum of ARID1B associated phenotypes by describing a distinctive phenotype including plantar fat pads but lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris syndrome. We present the first direct...

  8. Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 in human skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Pehmøller, Christian; Kristensen, Jonas Møller

    2014-01-01

    We investigated the phosphorylation signatures of two Rab GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers...... in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK was regulating phosphorylation...... of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between...

  9. Zerumbone modulates CD1d expression and lipid antigen presentation pathway in breast cancer cells.

    Science.gov (United States)

    Shyanti, Ritis K; Sehrawat, Anuradha; Singh, Shivendra V; Mishra, J P N; Singh, Rana P

    2017-10-01

    Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro. The growth inhibitory effect of ZER against breast cancer cells was augmented by treatment with anti-CD1d mAb. This effect was mediated by G1-phase cell cycle arrest and apoptosis induction coupled with an increase in mitochondrial membrane depolarization. CD1d expression and cell proliferation were inhibited by both CD1d siRNA and ZER. The α-galactosylceramide, a ligand for CD1d, showed increased CD1d expression as well as cell proliferation which was opposite to the effects of ZER. This study shows that, CD1d overexpression is associated with the progressive stages of breast cancer and ZER could be an adjuvant to potentiate cancer immunotherapy. Copyright © 2017. Published by Elsevier Ltd.

  10. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  11. Synthesis and Thermal Rearrangement of Tetramethyldisilane-bridged Bis(cyclopentadienyl) Diiron Complexes with Bis(phosphine)Substitution

    Institute of Scientific and Technical Information of China (English)

    孙秀丽; 王佰全; 等

    2003-01-01

    Photolysis of [Me2SiSiMe2)[C5H4Fe(CO2)]2with a series of bis(phosphine)ligands Ph2P(CH2)n PPh2(n=1-4) leads to the formation of the corresponding diiron complexes with intramolecular and intermolecular bis(phosphine) substitution.When these complexes were heated in refluxing xylene.only in the complexes with intermolecular bis(phosphine )substitution the thermal rearrangement reaction occurred.

  12. 21 CFR 73.3100 - 1,4-Bis[(2-hydroxyethyl)amino]-9,10-anthracenedione bis(2-propenoic)ester copolymers.

    Science.gov (United States)

    2010-04-01

    ...)ester copolymers. 73.3100 Section 73.3100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... § 73.3100 1,4-Bis -9,10-anthracenedione bis(2-propenoic)ester copolymers. (a) Identity. The color additives are 1,4-bis -9,10-anthracenedione bis(2-propenoic)ester (CAS Reg. No. 109561-07-1)...

  13. Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors.

    Science.gov (United States)

    Bobade, Vijeta; Bodhankar, Subhash L; Aswar, Urmila; Vishwaraman, Mohan; Thakurdesai, Prasad

    2015-04-01

    The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.

  14. Long-term impact of interferon beta-1b in patients with CIS

    DEFF Research Database (Denmark)

    Edan, G; Kappos, L; Montalbán, X

    2014-01-01

    . Cognitive outcomes remained higher in the early treated patients. EDSS remained low over time with a median of 1.5 in both arms. CONCLUSIONS: These 8-year results provide further evidence supporting early initiation of treatment with IFNB1b in patients with a first event suggestive of MS.......OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...... 468 patients, 284 (60.7%; IFNB1b: 178 (61.0% of the original arm), placebo: 106 (60.2% of original arm)) were enrolled in the extension study. 94.2% of patients were receiving IFNB1b. Patients originally randomised to IFNB1b had a reduced risk of developing CDMS by 32.2% over the 8-year observation...

  15. Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Damiano Paolicelli

    2009-07-01

    Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

  16. Expression and localization of aquaporin 1b during oocyte development in the Japanese eel (Anguilla japonica

    Directory of Open Access Journals (Sweden)

    Matsubara Hajime

    2011-05-01

    Full Text Available Abstract To elucidate the molecular mechanisms underling hydration during oocyte maturation, we characterized the structure of Japanese eel (Anguilla japonica novel-water selective aquaporin 1 (AQP1b that thought to be involved in oocyte hydration. The aqp1b cDNA encodes a 263 amino acid protein that includes the six potential transmembrane domains and two Asn-Pro-Ala motifs. Reverse transcription-polymerase chain reaction showed transcription of Japanese eel aqp1b in ovary and testis but not in the other tissues. In situ hybridization studies with the eel aqp1b cRNA probe revealed intense eel aqp1b signal in the oocytes at the perinucleolus stage and the signals became faint during the process of oocyte development. Light microscopic immunocytochemical analysis of ovary revealed that the Japanese eel AQP1b was expressed in the cytoplasm around the yolk globules which were located in the peripheral region of oocytes during the primary yolk globule stage; thereafter, the immunoreactivity was observed throughout the cytoplasm of oocyte as vitellogenesis progressed. The immunoreactivity became localized around the large membrane-limited yolk masses which were formed by the fusion of yolk globules during the oocyte maturation phase. These results together indicate that AQP1b, which is synthesized in the oocyte during the process of oocyte growth, is essential for mediating water uptake into eel oocytes.

  17. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    Science.gov (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie

    2015-09-01

    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality. © 2015 The Institute of Psychology, Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  18. Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter activity.

    Science.gov (United States)

    Guo, Cheng-Xian; Deng, Sheng; Yin, Ji-Ye; Liu, Zhao-Qian; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important transporter in the organic anion transporting polypeptide family. OATP1B1 plays an important role in the hepatic uptake of many endogenous compounds and xenobiotics, including many clinical drugs. At present, the combinational usage of Chinese traditional herbal medicines and conventional chemical pharmaceuticals may affect the activity of enzymes and transporters activity and cause absorption of their substrates and metabolic changes. In this study, we aimed to investigate the effect of schisandrin A, schisandrin B and tanshinone IIA, which were extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in vitro models for OATP1B1 activity studies. A combination of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time RT-PCR, and transporter activity analysis were employed. We found that schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p Schisandrin A of 1 μM and 10 μM and schisandrin B of 10 μM significantly increased the uptake of [3H] estrone-3-sulfate (p schisandrin A and B induced OATP1B1 expression and increased its transporter activity in HepG2 cells.

  19. Essential roles for Pot1b in HSC self-renewal and survival.

    Science.gov (United States)

    Wang, Yang; Shen, Mei-Feng; Chang, Sandy

    2011-12-01

    Maintenance of mammalian telomeres requires both the enzyme telomerase and shelterin, which protect telomeres from inappropriately activating DNA damage response checkpoints. Dyskeratosis congenita is an inherited BM failure syndrome disorder because of defects in telomere maintenance. We have previously shown that deletion of the shelterin component Pot1b in the setting of telomerase haploinsufficiency results in rapid telomere shortening and fatal BM failure in mice, eliciting phenotypes that strongly resemble human syskeratosis congenita. However, it was unclear why BM failure occurred in the setting of Pot1b deletion. In this study, we show that Pot1b plays an essential role in HSC survival. Deletion of Pot1b results in increased apoptosis, leading to severe depletion of the HSC reserve. BM from Pot1b(Δ/Δ) mice cannot compete with BM from wild-type mice to provide multilineage reconstitution, indicating that there is an intrinsic requirement for Pot1b the maintenance of HSC function in vivo. Elimination of the p53-dependent apoptotic function increased HSC survival and significantly extended the lifespan of Pot1b-null mice deficient in telomerase function. Our results document for the first time the essential role of a component of the shelterin complex in the maintenance of HSC and progenitor cell survival.

  20. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  1. Ibuprofen Inhibits Colitis-Induced Overexpression of TumorRelated Rac1b

    Directory of Open Access Journals (Sweden)

    Paulo Matos

    2013-01-01

    Full Text Available The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene, which are sufficient for initiation of hyperplastic growth but not for tumor progression. A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival. Here, we provide evidence for increased expression of Rac1b in patients with inflamed human colonic mucosa as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the nonsteroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumor cells through a cyclooxygenase inhibition–independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely, inflammation, can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors or with inflammatory colon syndromes.

  2. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  3. Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling.

    Science.gov (United States)

    Wu, Chia-Lun; Buszard, Bree; Teng, Chun-Hung; Chen, Wei-Lin; Warr, Coral G; Tiganis, Tony; Meng, Tzu-Ching

    2011-10-01

    PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

  4. Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women.

    Science.gov (United States)

    Gaudet, Mia M; Chanock, Stephen; Lissowska, Jolanta; Berndt, Sonja I; Yang, Xiaohong Rose; Peplonska, Beata; Brinton, Louise A; Welch, Robert; Yeager, Meredith; Bardin-Mikolajczak, Alicja; Sherman, Mark E; Sutter, Thomas R; Garcia-Closas, Montserrat

    2006-08-01

    Four single nucleotide polymorphisms (SNPs) in CYP1B1 (Ex2 + 143 C > G, Ex2 + 356 G > T, Ex3 + 251 G > C, Ex3 + 315 A > G) cause amino acid changes (R48G, A119S, L432V and N453S, respectively) and are associated with increased formation of catechol estrogens; however, epidemiologic evidence only weakly supports an association between these variants and breast cancer risk. Because genetic variability conferring increased susceptibility could exist beyond these putative functional variants, we comprehensively examined the common genetic variability within CYP1B1. A total of eight haplotype-tagging (ht)SNPs (including Ex3 + 315 A > G), in addition to two putatively functional SNPs (Ex2 + 143 C > G and Ex3 + 251 G > C), were selected and genotyped in a large case-control study of Polish women (1995 cases and 2296 controls). Haplotypes were estimated using the expectation-maximization algorithm, and overall differences in the haplotype distribution between cases and controls were assessed using a global score test. We also evaluated levels of tumor CYP1B1 protein expression in a subset of 841 cases by immunohistochemistry, and their association with genetic variants. In the Polish population, we observed two linkage disequilibrium (LD)-defined blocks. Neither haplotypes (global P-value of 0.99 and 0.67 for each block of LD, respectively), nor individual SNPs (including three putatively functional SNPs) were associated with breast cancer risk. CYP1B1 was expressed in most tumor tissues (98%), and the level of expression was not related to the studied genetic variants. We found little evidence for modification of the estimated effect of haplotypes or individual SNPs by age, family history of breast cancer, or tumor hormone receptor status. The present study provides strong evidence against the existence of a substantial overall association between common genetic variation in CYP1B1 and breast cancer risk.

  5. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors.

    Science.gov (United States)

    Murray, Katherine C; Stephens, Marilee J; Rank, Michelle; D'Amico, Jessica; Gorassini, Monica A; Bennett, David J

    2011-08-01

    Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT(1B) or 5-HT(1F) receptor agonists, including zolmitriptan (5-HT(1B/1D/1F)) and LY344864 (5-HT(1F)), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC(50)) and potency (-log EC(50)). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT(1B) and 5-HT(1F) receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT(1B) receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT(1B) agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT(1B) receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at -73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT(1B/1F) agonists, such as zolmitriptan, can restore inhibition

  6. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuo

    Full Text Available Protein-tyrosine phosphatase 1B (PTP1B is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A and sumoylation-resistant (K/R PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR and insulin receptor substrate 1 (IRS1 tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

  7. Association between CYP1B1 Gene Polymorphisms and Risk Factors and Susceptibility to Laryngeal Cancer

    OpenAIRE

    Yu, Peng-Ju; Chen, Wei-Guan; Feng, Quan-Lin; Chen, Wei; Jiang, Man-Jie; Li, Ze-Qing

    2015-01-01

    Background The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. Material/Methods In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with ...

  8. Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons

    Science.gov (United States)

    Sherf, Orna; Nashelsky Zolotov, Limor; Liser, Keren; Tilleman, Hadas; Jovanovic, Vukasin M.; Zega, Ksenija; Jukic, Marin M.; Brodski, Claude

    2015-01-01

    Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson’s disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA neurons in vivo. Here we report on our investigation of Lmx1b as downstream target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2 under the control of the En1 promoter (En1+/Otx2) showed increased Otx2 expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased expression of Otx2 and impairments in several aspects of mdDA neuronal formation. To study the functional interaction between Otx2 and Lmx1b, we generated compound mutants in which Otx2 expression was restored in mice lacking Lmx1b (En1+/Otx2;Lmx1b-/-). In these animals Otx2 was not sufficient to rescue any of the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/- embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced but subsequently lost in the mdDA precursor domain and the mid-hindbrain organizer in a specific, spatio-temporal manner. In summary, we demonstrate that Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are essential for mid-hindbrain organizer function and the formation of mdDA neurons. PMID:26444681

  9. Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons.

    Directory of Open Access Journals (Sweden)

    Orna Sherf

    Full Text Available Studying the development of mesodiencephalic dopaminergic (mdDA neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson's disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA neurons in vivo. Here we report on our investigation of Lmx1b as downstream target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2 under the control of the En1 promoter (En1+/Otx2 showed increased Otx2 expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased expression of Otx2 and impairments in several aspects of mdDA neuronal formation. To study the functional interaction between Otx2 and Lmx1b, we generated compound mutants in which Otx2 expression was restored in mice lacking Lmx1b (En1+/Otx2;Lmx1b-/-. In these animals Otx2 was not sufficient to rescue any of the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/- embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced but subsequently lost in the mdDA precursor domain and the mid-hindbrain organizer in a specific, spatio-temporal manner. In summary, we demonstrate that Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are essential for mid-hindbrain organizer function and the formation of mdDA neurons.

  10. CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark

    DEFF Research Database (Denmark)

    Grønskov, Karen; Redó-Riveiro, Alba; Sandfeld, Lisbeth;

    2016-01-01

    Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing...... mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma....

  11. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of oatp1b1s

    NARCIS (Netherlands)

    Steeg, E. van de; Greupink, R.; Schreurs, M.; Nooijen, I.H.G.; Verhoeck, K.C.M.; Hanemaaijer, R.; Ripken, D.; Monshouwer, M.; Vlaming, M.L.H.; DeGroot, J.; Verwei, M.; Russel, F.G.M.; Huisman, M.T.; Wortelboer, H.M.

    2013-01-01

    Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with o

  12. Poly[bis[μ-1,4-bis(imidazol-1-ylmethylbenzene]dichloridocadmium(II

    Directory of Open Access Journals (Sweden)

    Xinliang Hu

    2008-07-01

    Full Text Available The title compound, [CdCl2(C14H14N42]n, has a slightly distorted octahedral coordination geometry, formed by four N atoms from 1,4-bis(imidazol-1-ylmethylbenzene ligands and two Cl atoms, giving a two-dimensional network. The Cd atom lies on a centre of inversion.

  13. Bis[N,N-bis(2-hydroxyethyldithiocarbamato-κ2S,S′]copper(II

    Directory of Open Access Journals (Sweden)

    Jun Fan

    2009-12-01

    Full Text Available In the title compound, [Cu(C5H10NO2S22], the CuII cation is chelated by two bis(2-hydroxyethyldithiocarbamate anions with a distorted square-planar coordination geometry. Intermolecular O—H...O hydrogen bonding is observed between the terminal hydroxy groups in the crystal structure.

  14. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice....... In conclusion, TBC1D1 plays a role in regulation of glucose metabolism in skeletal muscle. Moreover, functional TBC1D1 is required for AICAR- or contraction-induced metabolic responses, implicating a role in energy-sensing signals....

  15. Expression of CD1d protein in human testis showing normal and abnormal spermatogenesis.

    Science.gov (United States)

    Adly, Mohamed A; Abdelwahed Hussein, Mahmoud-Rezk

    2011-05-01

    CD1d is a member of CD1 family of transmembrane glycoproteins, which represent antigen-presenting molecules. Immunofluorescent staining methods were utilized to examine expression pattern of CD1d in human testicular specimens. In testis showing normal spermatogenesis, a strong CD1d cytoplasmic expression was seen the Sertoli cells, spermatogonia, and Leydig cells. A moderate expression was observed in the spermatocytes. In testes showing maturation arrest, CD1d expression was strong in the Sertoli cells and weak in spermatogonia and spermatocytes compared to testis with normal spermatogenesis. In Sertoli cell only syndrome, CD1d expression was strong in the Sertoli and Leydig cells. This preliminary study displayed testicular infertility-related changes in CD1d expression. The ultrastructural changes associated with with normal and abnormal spermatogenesis are open for further investigations.

  16. Synthesis and Structure of Bis-(o-vanillin)di-pyridine Nickel(Ⅱ)-pyridine Dihydrate

    Institute of Scientific and Technical Information of China (English)

    孙命; 王瑾玲; 段月琴; 缪方明; 翁林红; 冷雪冰

    2001-01-01

    The structure of the complex bis-(o-vanillin)di-pyridine nickel(Ⅱ)([ Ni X-ray analysis.The crystal data are as follows: Monoclinic,P21/n,a=12.273(1),b=17.4700.674mm-1,F(000)=1328,final R=0.0428,Rw=0.1228 for 4528 observable reflections with I≥2σ(Ⅰ).The Nickel(Ⅱ)atom in the complex has a slightly distorted octahedral coordination geometr y and is six-coordinated by four O atoms from two O-Vanillin ligands and two N atoms from two pyridines.In the crystal,the Ni(Ⅱ)-complex and water molecules are linked through a network of hydrogen bonds.

  17. α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

    Directory of Open Access Journals (Sweden)

    Takao Hirai

    2015-11-01

    Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

  18. TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features

    OpenAIRE

    Balestrini, S; Milh, M.; Castiglioni, C.; Lüthy, K.; Finelli, M. J.; Verstreken, P.; Cardon, A; Stražišar, B. G.; Holder, J. L.; Lesca, G; Mancardi, M. M.; Poulat, A. L.; Repetto, G. M.; Banka, S.; Bilo, L.

    2016-01-01

    Objective: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. Methods: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). Results: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients...

  19. Examination of 1D Solar Cell Model Limitations Using 3D SPICE Modeling: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, W. E.; Olson, J. M.; Geisz, J. F.; Friedman, D. J.

    2012-06-01

    To examine the limitations of one-dimensional (1D) solar cell modeling, 3D SPICE-based modeling is used to examine in detail the validity of the 1D assumptions as a function of sheet resistance for a model cell. The internal voltages and current densities produced by this modeling give additional insight into the differences between the 1D and 3D models.

  20. Synthesis of a Bis(thiophenolate)pyridine Ligand and Its Titanium, Zirconium, and Tantalum Complexes

    KAUST Repository

    Lenton, Taylor N.

    2012-11-12

    A precursor to a new tridentate LX 2 type ligand, bis(thiophenol)pyridine ((SNS)H 2 = (2-C 6H 4SH) 2-2,6-C 5H 3N), was prepared. Bis(thiophenolate)pyridine complexes of Ti, Zr, and Ta having dialkylamido coligands were synthesized and structurally characterized. The zirconium complex (SNS)Zr(NMe 2) 2 (4) displays C 2 symmetry in the solid state, unlike a related bis(phenolate)pyridine compound, C s-symmetric (ONO)Ti(NMe 2) 2. This change is likely the result of strain about the sulfur atom in the six-membered chelate with longer metal-sulfur and carbon-sulfur bonds. Solid-state structures of tantalum complexes (SNS)Ta(NMe 2) 3 (5) and (SNS)TaCl(NEt 2) 2 (6) also display pronounced C 2 twisting of the SNS ligand. 1D and 2D NMR experiments show that 5 is fluxional, with rotation about the Ta-N(amide) bonds occurring on the NMR time scale that interchange the equatorial amide methyl groups (ΔG ‡ 393 = 25.0(3) kcal/mol). The fluxional behavior of 6 in solution was also studied by variable-temperature 1H NMR. Observation of separate signals for the diastereotopic protons of the methylene unit of the diethylamide indicates that the complex remains locked on the NMR time scale in one diastereomeric conformation at temperatures below -50 °C, fast rotation about the equatorial amide Ta-N bonds occurs at higher temperature (ΔG ‡ 393 = 13.4(3) kcal/mol), and exchange of diastereomeric methylene protons occurs via inversion at Ta that interconverts antipodes (ΔG ‡ 393 ≈ 14(1) kcal/mol). © 2012 American Chemical Society.

  1. The Planar Sandwich and Other 1D Planar Heat Flow Test Problems in ExactPack

    Energy Technology Data Exchange (ETDEWEB)

    Singleton, Jr., Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-01-24

    This report documents the implementation of several related 1D heat flow problems in the verification package ExactPack [1]. In particular, the planar sandwich class defined in Ref. [2], as well as the classes PlanarSandwichHot, PlanarSandwichHalf, and other generalizations of the planar sandwich problem, are defined and documented here. A rather general treatment of 1D heat flow is presented, whose main results have been implemented in the class Rod1D. All planar sandwich classes are derived from the parent class Rod1D.

  2. Tunable Design of Structural Colors Produced by Pseudo-1D Photonic Crystals of Graphene Oxide.

    Science.gov (United States)

    Tong, Liping; Qi, Wei; Wang, Mengfan; Huang, Renliang; Su, Rongxin; He, Zhimin

    2016-07-01

    It is broadly observed that graphene oxide (GO) films appear transparent with a thickness of about several nanometers, whereas they appear dark brown or almost black with thickness of more than 1 μm. The basic color mechanism of GO film on a sub-micrometer scale, however, is not well understood. This study reports on GO pseudo-1D photonic crystals (p1D-PhCs) exhibiting tunable structural colors in the visible wavelength range owing to its 1D Bragg nanostructures. Striking structural colors of GO p1D-PhCs could be tuned by simply changing either the volume or concentration of the aqueous GO dispersion during vacuum filtration. Moreover, the quantitative relationship between thickness and reflection wavelength of GO p1D-PhCs has been revealed, thereby providing a theoretical basis to rationally design structural colors of GO p1D-PhCs. The spectral response of GO p1D-PhCs to humidity is also obtained clearly showing the wavelength shift of GO p1D-PhCs at differently relative humidity values and thus encouraging the integration of structural color printing and the humidity-responsive property of GO p1D-PhCs to develop a visible and fast-responsive anti-counterfeiting label. The results pave the way for a variety of potential applications of GO in optics, structural color printing, sensing, and anti-counterfeiting.

  3. The role of microtubule-associated protein 1B in axonal growth and neuronal migration in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Maoguang Yang; Xiaoyu Yang; Minfei Wu; Peng Xia; Chunxin Wang; Peng Yan; Qi Gao; Jian Liu; Haitao Wang; Xingwei Duan

    2012-01-01

    In this review, we discuss the role of microtubule-associated protein 1B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAP1B in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.

  4. GLAS/ICESat L1B Global Waveform-based Range Corrections Data V033

    Data.gov (United States)

    National Aeronautics and Space Administration — The level 1B waveform parameterization data will contain waveform-based range corrections and surface characteristics at the full 40 per second resolution. Data...

  5. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V004

    Data.gov (United States)

    National Aeronautics and Space Administration — Level 1B pixel group transmission profiles for a single solar event (Suggested Usage: Vertical transmission profiles for input into an inversion algorithm)

  6. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V003

    Data.gov (United States)

    National Aeronautics and Space Administration — Level 1B pixel group transmission profiles for a single solar event (Suggested Usage: Vertical transmission profiles for input into an inversion algorithm)

  7. Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

    Institute of Scientific and Technical Information of China (English)

    MingXU; Ying-huaGUAN; NingXU; Zhang-yiLIANG; Shu-yiWang; YaoSONG; Chi-deHAN; Xin-shengZHAO; You-yiZHANG

    2005-01-01

    AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell 3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

  8. Detection of the urban heat island in Beijing using HJ-1B satellite imagery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Satellite images are used extensively in studying the urban heat island(UHI) phenomenon.We evaluated the suitability of thermal infrared(TIR) data from the HJ-1B satellite for detecting UHI using a case study in Beijing.Two modified algorithms for retrieving the land surface temperature(LST) from HJ-1B data were tested.The results were compared with LST images derived from a Landsat TM thermal band and the MODIS LST output.The spatial pattern of UHI generated using HJ-1B data matched well with that produced using TM and MODIS data.Of the two algorithms,the mono-window algorithm performed better but further tests are necessary.With more frequent coverage than TM and higher spatial resolution than MODIS,the HJ-1B TIR data present a unique opportunity to study thermal environments in cities in China and neighboring countries.

  9. TES/Aura L1B Spectra Special Observation Low Resolution V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  10. TES/Aura L1B Spectra Special Observation Low Resolution V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  11. TES/Aura L1B Spectra Special Observation Low Resolution V005

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  12. Data of evolutionary structure change: 1B0FA-1O37A [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available -GYDPV >EEE - > ATOM 556 CA ARG ...ntryIDChain>1O37A KSIVHPSYNSN >EEEEE ...> 1B0FA LGRNR-GIASV > - ...KSSGTSYPDV > > ATOM 1849 CA THR ...tryIDChain> AHCYK----SGIQV >GGG ---- EEE>

  13. The new powder diffractometer D1B of the Institut Laue Langevin

    Science.gov (United States)

    Puente Orench, I.; Clergeau, J. F.; Martínez, S.; Olmos, M.; Fabelo, O.; Campo, J.

    2014-11-01

    D1B is a medium resolution high flux powder diffractometer located at the Institut Laue Langevin, ILL. D1B a suitable instrument for studying a large variety of polycrystalline materials. D1B runs since 1998 as a CRG (collaborating research group) instrument, being exploited by the CNRS (Centre National de la Recherche Scientifique, France) and CSIC (Consejo Superior de Investigaciones Cientificas, Spain). In 2008 the Spanish CRG started an updating program which included a new detector and a radial oscillating collimator (ROC). The detector, which has a sensitive height of 100mm, covers an angular range of 128°. Its 1280 gold wires provide a neutron detection point every 0.1°. The ROC is made of 198 gadolinium- based absorbing collimation blades, regular placed every 0.67°. Here the present characteristics of D1B are reviewed and the different experimental performances will be presented.

  14. Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in vitro.

    Directory of Open Access Journals (Sweden)

    Kwan T Chow

    Full Text Available Growth factor independence genes (Gfi1 and Gfi1b repress recombination activating genes (Rag transcription in developing B lymphocytes. Because all blood lineages originate from hematopoietic stem cells (HSCs and different lineage progenitors have been shown to share transcription factor networks prior to cell fate commitment, we hypothesized that GFI family proteins may also play a role in repressing Rag transcription or a global lymphoid transcriptional program in other blood lineages. We tested the level of Rag transcription in various blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag expression in plasmacytoid dendritic cells (pDCs. Using microarray analysis, we observed that Gfi1 and Gfi1b do not regulate a lymphoid or pDC-specific transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag regulation in a non-B lineage cell type.

  15. MISR Level 1B1 Local Mode Radiance Data V002

    Data.gov (United States)

    National Aeronautics and Space Administration — This is the Local Mode Level 1B1 Product containing the DNs radiometrically scaled to radiances with no geometric resampling (Suggested Usage: The MISR Instrument...

  16. TES/Aura L1B Spectra Special Observation High Resolution V004

    Data.gov (United States)

    National Aeronautics and Space Administration — A L1B High Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for a Special Observation &...

  17. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic

    2010-03-01

    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

  18. Bis-perfluoroalkylation of aromatic compounds with sodium perfluoroalkanesulfinates

    Institute of Scientific and Technical Information of China (English)

    LIU, Jin-Tao(刘金涛); LU, He-Jun(吕贺军)

    2000-01-01

    Bis-perfluoroalkylation of aromatic compounds such as dimethoxybenzenes (2,4,6), anisole (8), pyridine (10) and quinoline (13) was accomplished by reaction with excess sodium perfluoroalkanesulfinates, RFSO2Na (1), in the presence of Mn(OAc)3·2H2O under mild conditions. The reaction provides a facile method for the synthesis of bis-perfluoroalkylated aromatic compounds.

  19. Accelerated optical holographic recording using bis-DNO

    DEFF Research Database (Denmark)

    Rasmussen, Palle H.; Ramanujam, P.S.; Hvilsted, Søren

    1999-01-01

    The design, synthesis and optical holographic recording properties of bis-DNO are reported. Bis-DNO is composed of two identical azobenzene oligoornithine segments (DNO) connected via a dipeptide linker. The two segments were assembled in a parallel fashion at the two amino groups of the dipeptide...

  20. Convenient Synthesis of Bis(oxazoline) Dicarboxylate Derivatives

    Institute of Scientific and Technical Information of China (English)

    Bin FU; Da Ming DU; Qing XIA

    2004-01-01

    The synthesis of bis(oxazoline) dicarboxylate derivatives was investigated.Diethyl-aminosulfur trifluoride(DAST)was used as a convenient cyclization reagent in the synthesis of bis(oxazoline)dicarboxylate derivatives,which can not be obtained by the general method using MsCl and Et3N as dehydrating cyclization reagent.

  1. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    OpenAIRE

    Trubicka Joanna; Grabowska-Kłujszo Ewa; Suchy Janina; Masojć Bartłomiej; Serrano-Fernandez Pablo; Kurzawski Grzegorz; Cybulski Cezary; Górski Bohdan; Huzarski Tomasz; Byrski Tomasz; Gronwald Jacek; Złowocka Elżbieta; Kładny Józef; Banaszkiewicz Zbigniew; Wiśniowski Rafał

    2010-01-01

    Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be ...

  2. Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10.

    Science.gov (United States)

    Cousido-Siah, Alexandra; Ruiz, Francesc X; Crespo, Isidro; Porté, Sergio; Mitschler, André; Parés, Xavier; Podjarny, Alberto; Farrés, Jaume

    2015-06-05

    Aldose reductase (AR, AKR1B1) and AKR1B10 are enzymes implicated in important pathologies (diabetes and cancer) and therefore they have been proposed as suitable targets for drug development. Sulindac is the metabolic precursor of the potent non-steroidal anti-inflammatory drug (NSAID) sulindac sulfide, which suppresses prostaglandin production by inhibition of cyclooxygenases (COX). In addition, sulindac has been found to be one of the NSAIDs with higher antitumoral activity, presumably through COX inhibition. However, sulindac anticancer activity could be partially mediated through COX-independent mechanisms, including the participation of AR and AKR1B10. Previously, it had been shown that sulindac and sulindac sulfone were good AR inhibitors and the structure of the ternary complex with NADP(+) and sulindac was described (PDB ID 3U2C). In this work, we determined the three-dimensional structure of AKR1B10 with sulindac and established structure-activity relationships (SAR) of sulindac and their derivatives with AR and AKR1B10. The difference in the IC50 values for sulindac between AR (0.36 μM) and AKR1B10 (2.7 μM) might be explained by the different positioning and stacking interaction given by Phe122/Phe123, and by the presence of two buried and ordered water molecules in AKR1B10 but not in AR. Moreover, SAR analysis shows that the substitution of the sulfinyl group is structurally allowed in sulindac derivatives. Hence, sulindac and its derivatives emerge as lead compounds for the design of more potent and selective AR and AKR1B10 inhibitors.

  3. Contribution of Organic Anion-Transporting Polypeptides 1A/1B to Doxorubicin Uptake and Clearance.

    Science.gov (United States)

    Lee, Hannah H; Leake, Brenda F; Kim, Richard B; Ho, Richard H

    2017-01-01

    The organic anion-transporting polypeptides represent an important family of drug uptake transporters that mediate the cellular uptake of a broad range of substrates including numerous drugs. Doxorubicin is a highly efficacious and well-established anthracycline chemotherapeutic agent commonly used in the treatment of a wide range of cancers. Although doxorubicin is a known substrate for efflux transporters such as P-glycoprotein (P-gp; MDR1, ABCB1), significantly less is known regarding its interactions with drug uptake transporters. Here, we investigated the role of organic anion transporting polypeptide (OATP) transporters to the disposition of doxorubicin. A recombinant vaccinia-based method for expressing uptake transporters in HeLa cells revealed that OATP1A2, but not OATP1B1 or OATP1B3, and the rat ortholog Oatp1a4 were capable of significant doxorubicin uptake. Interestingly, transwell assays using Madin-Darby canine kidney II cell line cells stably expressing specific uptake and/or efflux transporters revealed that OATP1B1, OATP1B3, and OATP1A2, either alone or in combination with MDR1, significantly transported doxorubicin. An assessment of polymorphisms in SLCO1A2 revealed that four variants were associated with significantly impaired doxorubicin transport in vitro. In vivo doxorubicin disposition studies revealed that doxorubicin plasma area under the curve was significantly higher (1.7-fold) in Slco1a/1b(-/-) versus wild-type mice. The liver-to-plasma ratio of doxorubicin was significantly decreased (2.3-fold) in Slco1a/1b2(-/-) mice and clearance was reduced by 40% compared with wild-type mice, suggesting Oatp1b transporters are important for doxorubicin hepatic uptake. In conclusion, we demonstrate important roles for OATP1A/1B in transporter-mediated uptake and disposition of doxorubicin. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.

    2010-04-01

    This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution.

  5. Integrative bioinformatics links HNF1B with clear cell carcinoma and tumor-associated thrombosis.

    Directory of Open Access Journals (Sweden)

    Justin Cuff

    Full Text Available Clear cell carcinoma (CCC is a histologically distinct carcinoma subtype that arises in several organ systems and is marked by cytoplasmic clearing, attributed to abundant intracellular glycogen. Previously, transcription factor hepatocyte nuclear factor 1-beta (HNF1B was identified as a biomarker of ovarian CCC. Here, we set out to explore more broadly the relation between HNF1B and carcinomas with clear cell histology. HNF1B expression, evaluated by immunohistochemistry, was significantly associated with clear cell histology across diverse gynecologic and renal carcinomas (P<0.001, as was hypomethylation of the HNF1B promoter (P<0.001. From microarray analysis, an empirically-derived HNF1B signature was significantly enriched for computationally-predicted targets (with HNF1 binding sites (P<0.03, as well as genes associated with glycogen metabolism, including glucose-6-phophatase, and strikingly the blood clotting cascade, including fibrinogen, prothrombin and factor XIII. Enrichment of the clotting cascade was also evident in microarray data from ovarian CCC versus other histotypes (P<0.01, and HNF1B-associated prothrombin expression was verified by immunohistochemistry (P = 0.015. Finally, among gynecologic carcinomas with cytoplasmic clearing, HNF1B immunostaining was linked to a 3.0-fold increased risk of clinically-significant venous thrombosis (P = 0.043, and with a 2.3-fold increased risk (P = 0.011 in a combined gynecologic and renal carcinoma cohort. Our results define HNF1B as a broad marker of clear cell phenotype, and support a mechanistic link to glycogen accumulation and thrombosis, possibly reflecting (for gynecologic CCC derivation from secretory endometrium. Our findings also implicate a novel mechanism of tumor-associated thrombosis (a major cause of cancer mortality, based on the direct production of clotting factors by cancer cells.

  6. Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

    Science.gov (United States)

    2010-08-01

    cells via identifying the functional domain(s). Body 1) AKR1B10 silencing inhibits breast cancer cells BT-20 growth in culture and...Laboratory of Chemical Biology, Guangdong Province, Tsinghua University Graduate School at Shenzhen , Guangdong 518055 and 6School of Medicine, Tsinghua...breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Taken

  7. Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.

    Science.gov (United States)

    Eriksson, T M; Alvarsson, A; Stan, T L; Zhang, X; Hascup, K N; Hascup, E R; Kehr, J; Gerhardt, G A; Warner-Schmidt, J; Arango-Lievano, M; Kaplitt, M G; Ogren, S O; Greengard, P; Svenningsson, P

    2013-10-01

    Cognitive impairments are common in depression and involve dysfunctional serotonin neurotransmission. The 5-HT1B receptor (5-HT(1B)R) regulates serotonin transmission, via presynaptic receptors, but can also affect transmitter release at heterosynaptic sites. This study aimed at investigating the roles of the 5-HT(1B)R, and its adapter protein p11, in emotional memory and object recognition memory processes by the use of p11 knockout (p11KO) mice, a genetic model for aspects of depression-related states. 5-HT(1B)R agonist treatment induced an impairing effect on emotional memory in wild type (WT) mice. In comparison, p11KO mice displayed reduced long-term emotional memory performance. Unexpectedly, 5-HT(1B)R agonist stimulation enhanced memory in p11KO mice, and this atypical switch was reversed after hippocampal adeno-associated virus mediated gene transfer of p11. Notably, 5-HT(1B)R stimulation increased glutamatergic neurotransmission in the hippocampus in p11KO mice, but not in WT mice, as measured by both pre- and postsynaptic criteria. Magnetic resonance spectroscopy demonstrated global hippocampal reductions of inhibitory GABA, which may contribute to the memory enhancement and potentiation of pre- and post-synaptic measures of glutamate transmission by a 5-HT(1B)R agonist in p11KO mice. It is concluded that the level of hippocampal p11 determines the directionality of 5-HT(1B)R action on emotional memory processing and modulates hippocampal functionality. These results emphasize the importance of using relevant disease models when evaluating the role of serotonin neurotransmission in cognitive deficits related to psychiatric disorders.

  8. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis

    Directory of Open Access Journals (Sweden)

    Tyler J. Broering

    2015-07-01

    Full Text Available Meiosis is precisely regulated by the factors involved in DNA damage response in somatic cells. Among them, phosphorylation of H2AX on Serine 139 (γH2AX is an essential signal for the silencing of unsynapsed sex chromosomes during male meiosis. However, it remains unknown how adjacent H2AX phosphorylation on Tyrosine 142 (pTyr142 is regulated in meiosis. Here we investigate the meiotic functions of BAZ1B (WSTF, the only known Tyr142 kinase in somatic cells, using mice possessing a conditional deletion of BAZ1B. Although BAZ1B deletion causes ectopic γH2AX signals on synapsed autosomes during the early pachytene stage, BAZ1B is dispensable for fertility and critical events during spermatogenesis. BAZ1B deletion does not alter events on unsynapsed axes and pericentric heterochromatin formation. Furthermore, BAZ1B is dispensable for localization of the ATP-dependent chromatin remodeling protein SMARCA5 (SNF2h during spermatogenesis despite the complex formation between BAZ1B and SMARCA5, known as the WICH complex, in somatic cells. Notably, pTyr142 is regulated independently of BAZ1B and is dephosphorylated on the sex chromosomes during meiosis in contrast with the presence of adjacent γH2AX. Dephosphorylation of pTyr142 is regulated by MDC1, a binding partner of γH2AX. These results reveal the distinct regulation of two adjacent phosphorylation sites of H2AX during meiosis, and suggest that another kinase mediates Tyr142 phosphorylation.

  9. Unit 1b: A General Approach to the Teaching of Architecture

    DEFF Research Database (Denmark)

    Toft, Anne Elisabeth

    2011-01-01

    The chapter presents the overall academic aims of the teaching at Unit 1b and how these were implemented in the curriculum for 2009/2010. The section includes considerations about learning targets, method, discourse, pedagogy and didactics.......The chapter presents the overall academic aims of the teaching at Unit 1b and how these were implemented in the curriculum for 2009/2010. The section includes considerations about learning targets, method, discourse, pedagogy and didactics....

  10. Pea Albumin 1 Subunit b (PA1b), a Promising Bioinsecticide of Plant Origin.

    OpenAIRE

    Corinne Royer; Vanessa Eyraud; Lamis Karaki; Frédéric Gressent; Pedro Da Silva

    2011-01-01

    International audience; PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand man...

  11. Synthesis and Crystal Structure of a 1-D Coordination Polymer {[Cu(NIT4py)2(ip)]·6H2O}n

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-Ping; GAO Dong-Zhao; LIAO Dai-Zheng; JIANG Zong-Hui; YAN Shi-Ping; LI Li-Cun

    2006-01-01

    A new complex {[Cu(NIT4py)2(ip)]·6H2O}n (NIT4py=2-(4'-pyridinyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and ip = isophthalate dianion) has been synthesized and structurally characterized by X-ray diffraction. It crystallizes in orthorhombic, space group Cmcm with a = 25.161(3), b =10.045(1), c = 15.450(2)(A), C32H48N6O14Cu, Mr = 804.30, V = 3904.8(8)(A)3, Z = 4, Dc = 1.368 g/cm3,μ(MoKα) = 0.630 mm-1, F(000) = 1692, the final R = 0.0326 and wR = 0.0787 for 1843 independent reflections with Rint = 0.0372. Each Cu(II) ion is four-coordinated by two carboxylate oxygen atoms and two pyridyl-N atoms from NIT4py radicals to furnish a rhombus geometry. The central Cu(II) ion is located at an inversion center and a crystallographic two-fold axis. Each isophthalate dianion binds two Cu(II) ions in bis-monodentate mode, leading to a 1-D chain, and these 1-D chains are further linked into a 2-D network via hydrogen-bonding interactions.

  12. Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1.

    Science.gov (United States)

    Gilder, Andrew S; Chen, Yong-Bin; Jackson, Ramon J; Jiang, Jin; Maher, Joseph F

    2013-10-25

    The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Bassan, Merav; Liu, Hongguang; Madsen, Kenneth L

    2008-01-01

    with the PDZ domain protein PICK1, which plays a critical role in regulating the expression of glutamate receptors at excitatory synapses. A yeast two-hybrid screen of a neuronal library using the carboxyl tail of GLT1b yielded clones expressing PICK1. The GLT1b C-terminal peptide bound to PICK1 with high...... affinity (K(i) = 6.5 +/- 0.4 microM) in an in vitro fluorescence polarization assay. We also tested peptides based on other variants of GLT1 and other glutamate transporters. GLT1b co-immunoprecipitated with PICK1 from rat brain lysates and COS7 cell lysates derived from cells transfected with plasmids...... expressing PICK1 and GLT1b. In addition, expression of GLT1b in COS7 cells changed the distribution of PICK1, bringing it to the surface. GLT1b and PICK1 co-localized with each other and with synaptic markers in hippocampal neurons in culture. Phorbol ester, an activator of protein kinase C (PKC), a known...

  14. Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish.

    Science.gov (United States)

    Yin, Wu; Hu, Bing

    2014-01-01

    Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development.

  15. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer.

    Science.gov (United States)

    McFadyen, M C; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; Haites, N E; Parkin, D; Murray, G I

    2001-07-20

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P = 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary.

  16. A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery

    Directory of Open Access Journals (Sweden)

    Xiangsheng Kong

    2009-02-01

    Full Text Available The HJ-1B satellite, which was launched on September 6, 2008, is one of the small ones placed in the constellation for disaster prediction and monitoring. HJ-1B imagery was simulated in this paper, which contains fires of various sizes and temperatures in a wide range of terrestrial biomes and climates, including RED, NIR, MIR and TIR channels. Based on the MODIS version 4 contextual algorithm and the characteristics of HJ-1B sensor, a contextual fire detection algorithm was proposed and tested using simulated HJ-1B data. It was evaluated by the probability of fire detection and false alarm as functions of fire temperature and fire area. Results indicate that when the simulated fire area is larger than 45 m2 and the simulated fire temperature is larger than 800 K, the algorithm has a higher probability of detection. But if the simulated fire area is smaller than 10 m2, only when the simulated fire temperature is larger than 900 K, may the fire be detected. For fire areas about 100 m2, the proposed algorithm has a higher detection probability than that of the MODIS product. Finally, the omission and commission error were evaluated which are important factors to affect the performance of this algorithm. It has been demonstrated that HJ-1B satellite data are much sensitive to smaller and cooler fires than MODIS or AVHRR data and the improved capabilities of HJ-1B data will offer a fine opportunity for the fire detection.

  17. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Zhi, Ying; Gao, Li-Xin; Jin, Yi; Tang, Chun-Lan; Li, Jing-Ya; Li, Jia; Long, Ya-Qiu

    2014-07-15

    Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  18. Expression of the novel gene NM23-H1B in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    LI Wen; LIU Yan; JIN Zhi-Jun; FENG You-ji; XU Ling-ling

    2005-01-01

    Objective:To study the expression of the human novel gene NM23-H1B in ovarian cancer. Methods: Totally 24 samples from patients with epithelial ovarian tumor at different clinical stages and 4 from normal ovaries were examined for NM23-H1B mRNA expression by RT-PCR and Northern blot. Results: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of expression in ovarian tumor was higher than that of normal ovary. The results of Northern blot showed that NM23-H1B was overexpressed in ovarian cancer while lowexpressed in normal ovary or low malignant potential (LMP). The level of expression at early stage cancer(stageⅠand Ⅱ) was higher than those in advanced cancer(stage Ⅲ and Ⅳ). In early stage carcinoma, the expression level was involved in the differentiation of tumor cell, and well-differentiated cancer expressed NM23-H1B mRNA in comparatively higher level. Conclusion: The novel gene NM23-N1B is closely correlated with the ovarian cancer.

  19. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1.

    Directory of Open Access Journals (Sweden)

    Rita Fragoso

    Full Text Available Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL. mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

  20. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy

    Science.gov (United States)

    Rivera Franco, Monica M.; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G.; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients’ responses were graded according to the Miller–Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded. PMID:27840578

  1. Identification of a hemerythrin-like domain in a P1B-type transport ATPase†

    Science.gov (United States)

    Traverso, Matthew E.; Subramanian, Poorna; Davydov, Roman; Hoffman, Brian M.; Stemmler, Timothy L.; Rosenzweig, Amy C.

    2010-01-01

    The P1B-type ATPases couple the energy of ATP hydrolysis to metal ion translocation across cell membranes. Important for prokaryotic metal resistance and essential metal distribution in eukaryotes, P1B-ATPases are divided into subclasses on the basis of their metal substrate specificities. Sequence analysis of putative P1B-5-ATPases, for which the substrate has not been identified, led to the discovery of a C-terminal soluble domain homologous to hemerythrin (Hr) proteins and domains. The Hr domain from the Acidothermus cellulolyticus P1B-5-ATPase was cloned, expressed, and purified (P1B-5-Hr). P1B-5-Hr binds two iron ions per monomer and adopts a predominantly helical fold. Optical absorption features of the iron-loaded and azide-treated protein are consistent with features observed for other Hr proteins. Autooxidation to the met form is very rapid, as reported for other prokaryotic Hr domains. The presence of a diiron center was confirmed by electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) data. The occurrence of a Hr-like domain in a P-type ATPase is unprecedented and suggests new regulatory mechanisms as well as an expanded function for Hr proteins in biology. PMID:20672819

  2. Cadmium coordination polymers based on flexible bis(imidazole) ligands: A rare example for doublet of doublet cadmium polyhedron arrangements

    Science.gov (United States)

    Babu, Chatla Naga; Suresh, Paladugu; Sampath, Natarajan; Prabusankar, Ganesan

    2014-10-01

    Two one-dimensional (1D) coordination polymers, [{LCd(O2NO)2(DMF)2}2{(LCd(O2NO)2(DMF))(DMF)}2]n (1) and [L‧Cd(O2NO)(ONO2)(DMF)2]n (2), having an aryl chromophoric unit and a flexible bis(imidazole) tail, 9,10-bis{(benzimidazol)methyl}anthracene (L) and 1,4-bis{(imidazol)methyl}benzene (L‧), with various coordination modes have been obtained. Molecule 1 represents the first structurally characterized one dimensional coordination polymer consisting of both hepta- and octa-coordinated cadmium centers. In 1, two distorted pentagonal bipyramidal Cd(II) centers and two distorted triangular dodecahedral Cd(II) centers are alternately arranged via bridging bidentate N,N-chelating ligand, L. Whereas, a distorted pentagonal bipyramidal Cd(II) center is formed in 2 where the sterically less crowded L‧ serves as a bridging bidentate N,N-chelating ligand. Furthermore, 1 and 2 have been characterized by elemental analysis, FT-IR, 1H NMR, UV-vis and fluorescent techniques.

  3. Three 3D hybrid networks based on octamolybdates and different Cu I/Cu II-bis(triazole) motifs

    Science.gov (United States)

    Zhang, Chun-Jing; Pang, Hai-Jun; Tang, Qun; Wang, Hui-Yuan; Chen, Ya-Guang

    2010-12-01

    Three 3D compounds based on octamolybdate clusters and various Cu I/Cu II-bis(triazole) motifs, [Cu I2btb][ β-Mo 8O 26] 0.5 ( 1), [Cu I2btpe][ β-Mo 8O 26] 0.5 ( 2), and [Cu II(btpe) 2][ β-Mo 8O 26] 0.5 ( 3) [btb=1,4-bis(1,2,4-triazol-1-yl)butane, btpe=1,5-bis(1,2,4-triazol-1-yl)pentane], were isolated via tuning flexible ligand spacer length and metal coordination preferences. In 1, the copper(I)-btb motif is a one-dimensional (1D) chain which is further linked by hexadentate β-[Mo 8O 26] 4- clusters via coordinating to Cu I cations giving a 3D structure. In 2, the copper(I)-btpe motif exhibits a "stairs"-like [Cu I2btpe] 2+ sheet, and the tetradentate β-[Mo 8O 26] 4- clusters interact with two neighboring [Cu I2btpe] 2+ sheets constructing a 3D framework. In 3, the copper(II)-btpe motif possesses a novel (2D→3D) interdigitated structure, which is further connected by the tetradentate β-[Mo 8O 26] 4- clusters forming a 3D framework. The thermal stability and luminescent properties of 1- 3 are investigated in the solid state.

  4. A bis-calixarene from olefin metathesis

    Directory of Open Access Journals (Sweden)

    Shimelis T. Hailu

    2012-06-01

    Full Text Available A ring-closing olefin metathesis reaction of tetrakis(allyloxycalix[4]arene gave the bis calixarene, (15E,40E,60E-65,74-bis(prop-2-en-1-yloxy-13,18,38,43,58,63-hexaoxadodecacyclo[28.26.8.720,36.111,45.151,55.05,57.07,12.019,24.026,64.032,37.044,49.168,72]tetraheptaconta-1,3,5(57,7,9,11,15,19(24,20,22,26,28,30(64,32,34,36,40,44(49,45,47,51,53,55(65,60,68,70,72(74-heptacosaene, C74H68O8. It is a cage formed from two calix[4]arene units joined by butenyl groups at three of the O atoms on the narrow rim. The fourth O atom on each calixarene unit is joined with an allyl group. Each of the calix[4]arene units has a flattened cone conformation in which the allyloxy-substituted aryl group and the opposite aryl group are close together and almost parallel [dihedral angle between planes = 1.09 (11°], and the other two aryl groups are splayed outward [dihedral angle between planes = 79.53 (11°]. No guest molecule (e.g. solvent was observed within the cage. The alkene C atoms of one of the links between the calixarene moieties are disordered over two orientations with occupancies of 0.533 (9 and 0.467 (9.

  5. Mapping of the serotonin 5-HT{sub 1D{alpha}} autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region

    Energy Technology Data Exchange (ETDEWEB)

    Ozaki, N.; Lappalainen, J.; Linnoila, M. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1995-04-24

    Serotonin (5-HT){sub ID} receptors are 5-HT release-regulating autoreceptors in the human brain. Abnormalities in brain 5-HT function have been hypothesized in the pathophysiology of various psychiatric disorders, including obsessive-compulsive disorder, autism, mood disorders, eating disorders, impulsive violent behavior, and alcoholism. Thus, mutations occurring in 5-HT autoreceptors may cause or increase the vulnerability to any of these conditions. 5-HT{sub 1D{alpha}} and 5-HT{sub 1D{Beta}} subtypes have been previously localized to chromosomes 1p36.3-p34.3 and 6q13, respectively, using rodent-human hybrids and in situ localization. In this communication, we report the detection of a 5-HT{sub 1D{alpha}} receptor gene polymorphism by single strand conformation polymorphism (SSCP) analysis of the coding sequence. The polymorphism was used for fine scale linkage mapping of 5-HT{sub 1D{alpha}} on chromosome 1. This polymorphism should also be useful for linkage studies in populations and in families. Our analysis also demonstrates that functionally significant coding sequence variants of the 5-HT{sub 1D{alpha}} are probably not abundant either among alcoholics or in the general population. 14 refs., 1 fig., 1 tab.

  6. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

    Science.gov (United States)

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

    2015-01-01

    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

  7. Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells.

    Science.gov (United States)

    Takumi, Shota; Ikema, Satoshi; Hanyu, Tamami; Shima, Yusuke; Kurimoto, Takashi; Shiozaki, Kazuhiro; Sugiyama, Yasumasa; Park, Ho-Dong; Ando, Seiichi; Furukawa, Tatsuhiko; Komatsu, Masaharu

    2015-03-01

    Microcystin-LR, which is an inhibitor of serine/threonine protein phosphatase (PP)1 and PP2A, induces liver injury by its selective uptake system into the hepatocyte. It is also thought that microcystin-LR induces reactive oxygen species (ROS). We tried to establish the chemical prevention of microcystin-LR poisoning. We investigated the effect of grapefruit flavanone glycoside naringin on cytotoxicity of microcystin-LR using human hepatocyte uptake transporter OATP1B3-expressing HEK293-OATP1B3 cells. We found cytotoxicity of microcystin-LR was attenuated by naringin in a dose dependent manner. The inhibition magnitude of total cellular serine/threonine protein phosphatase activity induced by microcystin-LR was suppressed by naringin. In addition, uptake of microcystin-LR into HEK293-OATP1B3 cells was inhibited by naringin. Furthermore, microcystin-LR induced phosphorylation of p53 was inhibited by naringin. Regardless of the difference in the exposure pattern of pre-processing and post-processing of naringin, the toxicity of microcystin-LR was comparable. These results suggested that naringin is promising remedy as well as preventive medicine for liver damage with microcystin-LR. In addition, involvement of ROS production after exposure to the sublethal concentrations of microcystin-LR in the onset of cytotoxicity was negligible. Therefore, inhibition of microcystin-LR uptake and the pathway other than ROS production would be involved in the effect of naringin on the attenuation of microcystin-LR toxicity.

  8. Analysis of CYP1B1 in pediatric and adult glaucoma and other ocular phenotypes

    Science.gov (United States)

    Reis, Linda M.; Tyler, Rebecca C.; Weh, Eric; Hendee, Kathryn E.; Kariminejad, Ariana; Abdul-Rahman, Omar; Ben-Omran, Tawfeg; Manning, Melanie A.; McCarty, Catherine A.; Kitchner, Terrie E.; Costakos, Deborah

    2016-01-01

    Purpose The CYP1B1 gene encodes an enzyme that is a member of the cytochrome P450 superfamily. Mutations in CYP1B1 have been mainly reported in recessive pediatric ocular phenotypes, such as primary congenital glaucoma (PCG) and congenital glaucoma with anterior segment dysgenesis (CG with ASD), with some likely pathogenic variants also identified in families affected with adult-onset primary open angle glaucoma (POAG). Methods We examined CYP1B1 in 158 pediatric patients affected with PCG (eight), CG with ASD (22), CG with other developmental ocular disorders (11), juvenile glaucoma with or without additional ocular anomalies (26), and ASD or other developmental ocular conditions without glaucoma (91); in addition, a large cohort of adult patients with POAG (193) and POAG-negative controls (288) was examined. Results Recessive pathogenic variants in CYP1B1 were identified in two PCG pedigrees, three cases with CG and ASD, and two families with CG and other ocular defects, such as sclerocornea in one patient and microphthalmia in another individual; neither sclerocornea nor microphthalmia has been previously associated with CYP1B1. Most of the identified causative mutations are new occurrences of previously reported pathogenic alleles with two novel variants identified: a c.1325delC, p.(Pro442Glnfs*15) frameshift allele in a family with PCG and a c.157G>A, p.(Gly53Ser) variant identified in a proband with CG, Peters anomaly, and microphthalmia. Analysis of the family history in the CYP1B1-positive families revealed POAG in confirmed or presumed heterozygous relatives in one family with PCG and two families with ASD/CG; POAG was associated with the c.1064_1076del, p.(Arg355Hisfs*69) allele in two of these pedigrees. Screening of an unrelated POAG cohort identified the same c.1064_1076del heterozygous allele in one individual with sporadic POAG but not in age- and ethnicity-matched POAG-negative individuals. Overall, there was no significant enrichment for mutant

  9. Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis.

    Science.gov (United States)

    Economopoulos, Konstantinos P; Sergentanis, Theodoros N

    2010-07-01

    Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896-1.097) for heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984 (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.

  10. A rational route to SCM materials based on a 1-D cobalt selenocyanato coordination polymer.

    Science.gov (United States)

    Boeckmann, Jan; Näther, Christian

    2011-07-07

    Thermal annealing of a discrete complex with terminal SeCN anions and monodentate coligands enforces the formation of a 1D cobalt selenocyanato coordination polymer that shows slow relaxation of the magnetization. Therefore, this approach offers a rational route to 1D materials that might show single chain magnetic behaviour.

  11. Data of evolutionary structure change: 1D07A-2PSEA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D07A-2PSEA 1D07 2PSE A A ---------GA----KPFGEKKFIEIKGRRMAYIDEGTG...MPI-EWADFPEQDRDLFQAFRSQAGEELVLQDNVFVEQVLPGLILRPLSEAEMAAYREPFLAAGEARRPTLSWPRQIPIAGT-PADVVAIARDYAGWLSESP-IPKLF...entryChain> 2PSE A 2PSEA VAL CA 328 2PSE A 2PSEA...dbChain> 2PSEA LRASDDLPKLF HH EEE

  12. Quasiperiodicity and 2D topology in 1D charge-ordered materials

    NARCIS (Netherlands)

    Flicker, F.; van Wezel, J.

    2015-01-01

    The mathematical description of 1D quasicrystals has recently been linked to that of 2D quantum Hall states. The topological classification of 1D quasicrystals and the corresponding interpretation of their observed charge transport have been widely discussed. We demonstrate the equivalence of both 1

  13. Data of evolutionary structure change: 1D7EA-1OTAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D7EA-1OTAA 1D7E 1OTA A A ---VAFGSEDIENTLAKMDDGQLDGLAFGAIQLDGDGNI...ne>VAL CA 559 PHE CA 524 1OTA A 1OTAA KKALSGDSYWVF E EE...9981689453 7.820000171661377 tion> 0.8790000081062...1399 0.36500000953674316 -0.3330000042915344 -0.25200000405311584 -0.9089999794960022

  14. Molecular cloning, sequence analysis and pharmacological properties of the porcine 5-HT(1D) receptor.

    NARCIS (Netherlands)

    P.L. Bhalla (Pankaj); H.S. Sharma (Hari); T. Wurch (Thierry); P.J. Pauwels (Petrus); P.R. Saxena (Pramod Ranjan)

    2000-01-01

    textabstractA cDNA encoding the full-length 5-HT(1D) receptor derived from porcine cerebral cortex was amplified, cloned and sequenced, using guinea-pig 5-HT(1D) receptor coding sequence oligonucleotide primers in reverse transcription-polymerase chain reaction (RT - PC

  15. Data of evolutionary structure change: 1D5IL-2GJJA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1D5IL-2GJJA 1D5I 2GJJ L A -DIKMTQSPSSMYASLGERVTITCKASQDIN------SY... 219 ALA CA 310 SER CA 336 2GJJ A 2GJJA PEVVKTGASVK 5.283660888671875 1 2GJJ... A 2GJJA RLEIK----RGEVQ

  16. Data of evolutionary structure change: 1D5NC-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available msd> 1.0891029834747314 EVID> 1 1UNF...1D5NC-1UNFX 1D5N 1UNF C X ----SYTLPSLPYAYDALEPHFDKQTMEIHHTKHHQTYV...NNANAALESL----PEFANLPVEELITKLDQLPADKKTVL---------RNNAGGHANHSLFWKGLKKGT--TLQGDLKAAIERDFGSVDNFKAEFEKAAASRFGSGW...HH EVID> 0 TRP CA 380 1UNF X 1UNF

  17. Data of evolutionary structure change: 1D5ND-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1.0915240049362183 EVID> 1 1UNF...1D5ND-1UNFX 1D5N 1UNF D X ----SYTLPSLPYAYDALEPHFDKQTMEIHHTKHHQTYV...NNANAALESL----PEFANLPVEELITKLDQLPADKKTVL---------RNNAGGHANHSLFWKGLKKGTT--LQGDLKAAIERDFGSVDNFKAEFEKAAASRFGSGW...H EVID> 0 TRP CA 379 1UNF X 1UNF

  18. High-resolution imaging of brain 5-HT{sub 1B} receptors in the rhesus monkey using [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Nabulsi, Nabeel; Huang Yiyun; Weinzimmer, David; Ropchan, Jim; Frost, James J. [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States); McCarthy, Timothy [Pfizer Global R and D, Groton, CT 06340 (United States); Carson, Richard E.; Ding Yushin [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States)

    2010-02-15

    The serotonin 5-HT{sub 1B} receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [{sup 11}C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT{sub 1B} receptor. [{sup 11}C]P943 was synthesized via N-methylation of the precursor with [{sup 11}C]methyl iodide or [{sup 11}C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8{+-}3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP{sub ND}) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT{sub 1B} receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP{sub ND} values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT{sub 1B}/5-HT{sub 1D} antagonist, resulted in reduction of BP{sub ND} values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [{sup 11}C]P943 for 5-HT{sub 1B} receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT{sub 1B} receptor system in humans.

  19. Analysis of the interaction proteins of PIH1D1%与PIH1D1相互作用的蛋白分析

    Institute of Scientific and Technical Information of China (English)

    章元; 张业

    2016-01-01

    目的 分析细胞中与PIH1D1相互作用的蛋白.方法 构建稳定表达FLAG-HA双标签标记的PIH1D1蛋白的HEK293T细胞株,利用FLAG-HA串联亲和纯化(TAP)双标签纯化实验,对目的条带进行质谱分析.结果 成功构建稳定表达FLAG-HA双标签标记的PIH1D1细胞株.通过质谱分析得到了PIH1D1相互作用的蛋白数据,包括细胞质内RNA PolⅡ组装复合物成员RPAP3、UXT、PFD2和PFD6等,凋亡复合物成员MONAD/WDR92等,钙调蛋白信号通路中的PIP和CALM1以及代谢通路中的PKM和LCN1等.结论 PIH1D1与细胞中RPAP3、UXT、PFD2、PFD6、MONAD/WDR92、PIP、CALM1、PKM和LCN1等相互作用,提示PIH1D1可能参与细胞中RNApol Ⅱ组装、细胞凋亡、钙调蛋白通路等多种生理过程.

  20. Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris.

    Science.gov (United States)

    Nurul Islam, Md; Jung, Hyun Ah; Sohn, Hee Sook; Kim, Hye Mi; Choi, Jae Sue

    2013-05-01

    As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop