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Sample records for 1b bis 1d

  1. 5-HT(1B) and 5-HT(1D) receptors in the human trigeminal ganglion

    Hou, M; Kanje, M; Longmore, J; Tajti, J; Uddman, R; Edvinsson, L

    5-Hydroxytryptamine (5-HT) is implicated in migraine and agonist directed against 5-HT(1B) and 5-HT(1D) receptors are commonly used as effective therapies. The antimigraine mechanisms involve the inhibition of intracranial sensory neuropeptide release. In order to determine which 5-HT(1) receptor...... expressed in the human trigeminal ganglion and they are mainly localized in medium-sized cells and they seem to colocalize with CGRP, SP and NOS....

  2. PROGESTERONE REDUCES THE EFFECT OF THE SEROTONIN 1B/1D RECEPTOR ANTAGONIST, GR 127935, ON LORDOSIS BEHAVIOR

    Uphouse, Lynda; Hiegel, Cindy; Guptarak, Jutatip; Maswood, Navin

    2008-01-01

    Ovariectomized rats were hormonally primed with 10 μg estradiol benzoate or with estradiol benzoate plus 500 μg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT1B/1D receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1′-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females ...

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

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

    2002-01-01

    1. Organ culture has been shown to upregulate both endothelin (ET) and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The purpose of the present study was to investigate the involvement of protein kinases, especially protein kinases C (PKC) and A (PKA) in this process...

  4. Microiontophoretic application of serotonin (5HT)1B/1D agonists inhibits trigeminal cell firing in the cat.

    Storer, R J; Goadsby, P J

    1997-12-01

    Migraine is a common and debilitating condition. Its treatment has received considerable attention in recent times with the introduction into clinical use of the 5HT1B/1D agonist sumatriptan. It is known from human studies that the intracranial blood vessels and dura mater are important pain-producing structures since mechanical or electrical stimulation of these vessels, such as the superior sagittal sinus, causes pain. We have developed a model of craniovascular pain by stimulating the superior sagittal sinus and monitoring trigeminal neuronal activity using electrophysiological techniques. Cats were anaesthetized with alpha-chloralose (60 mg/kg, intraperitoneally), paralysed (gallamine 6 mg/kg, intravenously) and ventilated. The superior sagittal sinus was accessed and isolated for electrical stimulation by a mid-line circular craniotomy. The region of the dorsal surface of C2 spinal cord was exposed by a laminectomy and an electrode placed for recording evoked activity from sinus stimulation and spontaneous activity of the same cells. The electrode was a custom-made seven barrel glass microelectrode with the central barrel containing a tungsten recording wire. Signals were amplified and monitored on-line using a custom-written sampling program. Cells were recorded that were activated by electrical stimulation of the sinus and were also spontaneously activated. Cells fired with latencies consistent with A delta and C fibres, generally firing three or four times per stimulus (0.3 Hz, 250 microseconds duration, 100 V) delivered to the sinus. Both evoked and spontaneous firing could be inhibited by iontophoresis of ergometrine (9/10 cells), sumatriptan (2/3 cells) and zolmitriptan (9/15 cells) but not by saline (3/10 cells). These data are the first demonstration of inhibition of second order trigeminal neurons by direct local application of 5HT1B/1D agonists. Although intravenous administration of these compounds has demonstrated inhibition of sinus evoked firing

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

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

    2015-01-01

    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. PMID:26019234

  6. Characterization of 5-HT receptors mediating constriction of porcine carotid arteriovenous anastomoses; involvement of 5-HT1B/1D and novel receptors

    De Vries, Peter; Villalón, Carlos M; Heiligers, Jan P C; Saxena, Pramod R

    1998-01-01

    It was previously shown that porcine cranial arteriovenous anastomoses (AVAs) constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydroergotamine, as well as sumatriptan and that sumatriptan acts exclusively via 5-HT1B/1D receptors. The present study was devoted to establish the contribution of 5-HT1B/1D receptors in the constriction of AVAs elicited by 5-HT (in presence of 0.5 mg kg−1 ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs.Intracarotid infusion of 5-HT (2 μg k...

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

    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

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

    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

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

    Gurbuz, Nilgun; Ashour, Ahmed A; Alpay, S Neslihan; Ozpolat, Bulent

    2014-01-01

    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, and valuable new

  10. Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test.

    Vidal-Cantú, Guadalupe C; Jiménez-Hernández, Mildred; Rocha-González, Héctor I; Villalón, Carlos M; Granados-Soto, Vinicio; Muñoz-Islas, Enriqueta

    2016-06-15

    Sumatriptan, dihydroergotamine and methysergide inhibit 1% formalin-induced nociception by activation of peripheral 5-HT1B/1D receptors. This study set out to investigate the pharmacological profile of the antinociception produced by intrathecal and intraplantar administration of ergotamine (a 5-HT1B/1D and 5-HT5A/5B receptor agonist) and valerenic acid (a partial agonist at 5-HT5A receptors). Intraplantar injection of 1% formalin in the right hind paw resulted in spontaneous flinching behavior of the injected hindpaw of female Wistar rats. Intrathecal ergotamine (15nmol) or valerenic acid (1 nmol) blocked in a dose dependent manner formalin-induced nociception. The antinociception by intrathecal ergotamine (15nmol) or valerenic acid (1nmol) was partly or completely blocked by intrathecal administration of the antagonists: (i) methiothepin (non-selective 5-HT5A/5B; 0.01-0.1nmol); (ii) SB-699551 (selective 5-HT5A; up to 10nmol); (iii) anti-5-HT5A antibody; (iv) SB-224289 (selective 5-HT1B; 0.1-1nmol); or (v) BRL-15572 (selective 5-HT1D; 0.1-1nmol). Likewise, antinociception by intraplantar ergotamine (15nmol) and valerenic acid (10nmol) was: (i) partially blocked by methiothepin (1nmol), SB-699551 (10nmol) or SB-224289 (1nmol); and (ii) abolished by BRL-15572 (1nmol). The above doses of antagonists (which did not affect per se the formalin-induced nociception) were high enough to completely block their respective receptors. Our results suggest that ergotamine and valerenic acid produce antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites. This provides new evidence for understanding the modulation of nociceptive pathways in inflammatory pain. PMID:27068146

  11. Legal problems of electricity quotas according to paragraph 7 Abs. 1b bis 1d AtGesetz

    On April 27, 2002, the 'Act of the Planned Termination of the Use of Nuclear Power for Industrial Electricity Generation - Atomic Energy Act' entered into force. It was preceded, among other things, by the 'Agreement between the Federal Government and the Power Utilities of June 14, 2000' in which the Red-Gree federal government and the operators of nuclear power plants had agreed on a timetable of termination and on the conditions of nuclear power plant operation for the residual plant operating life. One major part of that Agreement, which later was incorporated also in the Atomic Energy Act, are provisions about flexibiling the residual periods of operation of existing nuclear power plants. The arguments underlying the act on opting out of the use of nuclear power cite, as a key reason for the possibility to transfer electricity quotas, the constitutional principle of protection of bona fide acts. The transfer possibility opened up in the law is to 'allow the best possible residual periods of operation in the light of both plant operation and the national economy' to be agreed upon for each individual nuclear power plant. In principle, the Atomic Energy Act provides for any transfer of electricity quotas from one German nuclear power plant to another. An approval procedure is required for transfer from younger to older plants. Transfers from older to younger plants can be arranged without any approval. The report covers the basic legal principles and consequences, the details of the approval procedure, and the transfer of the electricity quotas attributed to the Muelheim-Kaerlich nuclear power plant. (orig./GL)

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

    Gupta, S.; Villalon, C.M.

    2010-01-01

    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-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...

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

    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. PMID:23325368

  14. 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

    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.

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

    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. PMID:15944648

  16. Influence of β-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol

    Goldberg, Michael R; Sciberras, David; De Smet, Marina; Lowry, Richard; Tomasko, Lisa; Lee, Yih; Olah, Timothy V; Zhao, Jamie; Vyas, Kamlesh P; Halpin, Rita; Kari, Prasad H; James (deceased), Ian

    2001-01-01

    Aims Patients with migraine may receive the 5-HT1B/1D agonist, rizatriptan (5 or 10 mg), to control acute attacks. Patients with frequent attacks may also receive propranolol or other β-adrenoceptor antagonists for migraine prophylaxis. The present studies investigated the potential for pharmacokinetic or pharmacodynamic interaction between β-adrenoceptor blockers and rizatriptan. Methods Four double-blind, placebo-controlled, randomized crossover investigations were performed in a total of 51 healthy subjects. A single 10 mg dose of rizatriptan was administered after 7 days' administration of propranolol (60 and 120 mg twice daily), nadolol (80 mg twice daily), metoprolol (100 mg twice daily) or placebo. Rizatriptan pharmacokinetics were assessed. In vitro incubations of rizatriptan and sumatriptan with various β-adrenoceptor blockers were performed in human S9 fraction. Production of the indole-acetic acid-MAO-A metabolite of each triptan was measured. Results Administration of rizatriptan during propranolol treatment (120 mg twice daily for 7.5 days) increased the AUC(0,∞) for rizatriptan by approximately 67% and the Cmax by approximately 75%. A reduction in the dose of propranolol (60 mg twice daily) and/or the incorporation of a delay (1 or 2 h) between propranolol and rizatriptan administration did not produce a statistically significant change in the effect of propranolol on rizatriptan pharmacokinetics. Administration of rizatriptan together with nadolol (80 mg twice daily) or metoprolol (100 mg twice daily) for 7 days did not significantly alter the pharmacokinetics of rizatriptan. No untoward adverse experiences attributable to the pharmacokinetic interaction between propranolol and rizatriptan were observed, and no subjects developed serious clinical, laboratory, or other significant adverse experiences during coadministration of rizatriptan with any of the β-adrenoceptor blockers. In vitro incubations showed that propranolol, but not other

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

    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

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

    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.

  19. Solutions of the reflection equation for face and vertex models associated with A$_{n}^{(1}$),B$_{n}^{(1}$),C. sub(n)$^{(1}$), D$_{n}^{(1}$) and A$_{n}^{(2}$)

    Batchelor, M T; Kuniba, A; Zhou, Y K

    1996-01-01

    We present new diagonal solutions of the reflection equation for elliptic solutions of the star-triangle relation. The models considered are related to the affine Lie algebras A_n^{(1)},B_n^{(1)}, C_n^{(1)},D_n^{(1)} and A_n^{(2)}. We recover all known diagonal solutions associated with these algebras and find how these solutions are related in the elliptic regime. Furthermore, new solutions of the reflection equation follow for the associated vertex models in the trigonometric limit.

  20. Spin crossover and solvate effects in 1D Fe{sup II} chain compounds containig Bis(dipyridylamine)-linked triazine ligands.

    Ross, , T. M.; Moubaraki, B.; Turner, D. R.; Halder, G. J.; Chastanet, G.; Neville, S. M.; Cashion, J. D.; Letard, J. F.; Batten, S. R.; Murray, K. S. (X-Ray Science Division); (Monash Univ.); (Univ. de Bordeaux)

    2011-03-01

    A series of 1D polymeric FeII spin crossover (SCO) compounds of type trans-[FeII(NCX)2(L)] Solvent has been synthesised {l_brace}L = DPPyT = 1-[4,6-bis(dipyridin-2-ylamino)-1,3,5-triazin-2-yl]pyridin-4(1H)-one for 1-4{r_brace}; NCX = NCS- for 1 and 2, NCSe- for 3 and 4; Solvent = 2.5CH2Cl2 for 1, 2CHCl3 {center_dot} 0.5CH3OH for 2 and 4, CH2Cl2 for 3; L = DPT (6-phenoxy-N2,N2,N4,N4-tetra-2-pyridinyl-1,3,5-triazine-2,4-diamine) for 5; NCX = NCS- for 5; Solvent = 2CH3OH {center_dot} H2O for 5; L = DQT {l_brace}4-[4,6-bis(dipyridin-2-ylamino)-1,3,5-triazin-2-yloxy]phenol{r_brace} for 6-8; NCX- = NCS- for 6; Solvent = 2CH2Cl2 for 6; NCX- = NCSe- for 7; Solvent = CH2Cl2 {center_dot} CH2ClCH2Cl for 7; NCX- = NCSe- for 8; Solvent = 1.5CH2Cl2 {center_dot} 0.5CH3OH for 8. Two mononuclear complexes, trans-[FeII(NCS)2(DPT)2] {center_dot} 2CH3OH (9) and trans-[FeII(NCSe)2(DPT)2] {center_dot} 2CH3OH (10), contained the L ligand in a terminal bidentate coordination mode. As well as variations made in the NCX- ligands, variations were also made in substituent groups on the s-triazine 'core' of L to investigate their intermolecular/supramolecular role in crystal packing and, thus, their influence on SCO properties. All the complexes crystallised as solvates, and the influence of the latter on the magnetism and spin transitions was explored. A wide range of physical methods was employed, as a function of temperature, viz. crystallography, PXRD (synchrotron), susceptibilities, LIESST and Moessbauer effect, in order to probe magnetostructural correlations in these 1D families. New examples of half-crossovers, with ordered -LS-HS-LS-HS- intrachain states existing below T1/2, have been observed and comparisons made to related one- or two-step systems. All the observed transitions are gradual and non-hysteretic, and brief comments are made in relation to recent theoretical models for cooperativity, developed elsewhere.

  1. Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats.

    Villamil-Hernández, Ma Trinidad; Alcántara-Vázquez, Oscar; Sánchez-López, Araceli; Gutiérrez-Lara, Erika J; Centurión, David

    2014-10-01

    The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats: (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 μg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 μg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 μg/kg) and rauwolscine (α2-adrenoceptor; 300 μg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 μg/kg) or raclopride (D2-like; 300 and 1000 μg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats. PMID:24975101

  2. Effect of peptides corresponding to extracellular domains of serotonin 1B/1D receptors and melanocortin 3 and 4 receptors on hormonal regulation of adenylate cyclase in rat brain.

    Shpakova, E A; Derkach, K V; Shpakov, A O

    2014-03-01

    The ligand-recognizing part of G protein-coupled receptors consists of their extracellular loops and N-terminal domain. Identification of these sites is essential for receptor mapping and for the development and testing of new hormone system regulators. The peptides corresponding by their structure to extracellular loop 2 of serotonin 1B/1D receptor (peptide 1), extracellular loop 3 of melanocortin 3 receptor (peptide 2), and N-terminal domain of melanocortin 4 (peptide 3) were synthesized by the solid-phase method. In synaptosomal membranes isolated from rat brain, peptide 1 (10(-5)-10(-4) M) attenuated the effects of 5-nonyloxytryptamine (selective agonist of serotonin 1B/1D receptor) and to a lesser extent serotonin and 5-methoxy-N,N-dimethyltryptamine acting on all the subtypes of serotonin receptor 1. Peptide 2 (10(-5)-10(-4) M) significantly reduced the adenylate cyclase-stimulating effect of γ-melanocyte-stimulating hormone (agonist of melanocortin receptor 3), but had no effect on the adenylate cyclase effect of THIQ (agonist melanocortin receptor 4). Peptide 3 reduced the adenylate cyclase-stimulating effects of THIQ and α-melanocyte-stimulating hormone (non-selective agonist of melanocortin receptors 3 and 4), but did not modulate the effect of γ-melanocyte-stimulating hormone. The effect of peptide 3 was weaker: it was observed at peptide 3 concentration of 10(-4) M. Peptides 1-3 did no change the adenylate cyclase-modulating effects of hormones acting through non-homologous receptors. Thus, the synthesized peptides specifically inhibited the regulatory effects of hormones acting through homologous receptors. This suggests that the corresponding extracellular domains are involved in ligand recognition and binding and determine functional activity of the receptor. PMID:24770752

  3. 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

    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.

  4. Crystalline Complexes of 2,2'-Bis(9-hydroxy-9-fluorenyl)biphenyl Host with Oligofunctional and Conjugate Functional Group Guests

    Weber, Edwin

    2007-01-01

    Abstract Four crystalline inclusion compounds of the 2,2'-bis(9-hydroxy-9-fluorenyl)biphenyl host 1, containing diethylene glycol (1:1) (1a), bis(2-aminoethyl)amine (1:1) (1b), methacrylic acid (1:1) (1c) and 2-cyclopenten-1-one (1:2) (1d), have been studied by X-ray diffraction analysis from single crystals. Departure from the expectation, the multifunctional and conjugate functional guest molecules, potentially being able to offer multiple H donor-/acceptorships or other modes of...

  5. Interferon Beta-1b Injection

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting (course ... and problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications ...

  6. Interferon Gamma-1b Injection

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

  7. BIS 245 Course Tutorial / tutorialrank

    welcome1351

    2015-01-01

    BIS 245 Week 1 Lab 1 Introduction to MS Visio and MS Access For more course tutorials visit www.tutorialrank.com Tutorial Purchased: 2 Times, Rating: A   A. Lab # : BSBA BIS 245A-1 B. Lab 1 of 7 : Introduction to MS Visio and MS Access C. Lab Overview--Scenario/Summary TCOs: 1. Given a business situation in which managers require information from a database, determine, analyze and classify that information so that reports can be designed to meet the requ...

  8. Contractile 5-HT1B receptors in human cerebral arteries

    Nilsson, T; Longmore, J; Shaw, D;

    1999-01-01

    immunocytochemistry with antibodies selective for human 5-HT1B and human 5-HT1D receptors and also studied the contractile effects of a range of 5-HT receptor agonists and antagonists in HCA. 2 Immunocytochemistry of cerebral arteries showed dense 5-HT1B receptor immunoreactivity (but no 5-HT1D receptor......1 The cerebrovascular receptor(s) that mediates 5-hydroxytryptamine (5-HT)-induced vasoconstriction in human cerebral arteries (HCA)has proven difficult to characterize, yet these are essential in migraine. We have examined 5-HT receptor subtype distribution in cerebral blood vessels by...... immunoreactivity) within the smooth muscle wall of the HCA. The endothelial cell layer was well preserved and weak 5-HT1B receptor immunoreactivity was present. 3 Pharmacological experiments on HCA with intact endothelium showed that 5-carboxamidotryptamine was significantly more potent than alpha-methyl-5-HT, 2...

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

    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.

  10. 1D Nano materials 2012

    We witnessed an initial hyped period and enthusiasm on carbon nano tubes in the 1990s later went through a significant expansion into nano tubes of other materials (metal di chalcogenides, boron nitride, etc.) as well as various nano wires and nano rods. While much of the hype might have gone, the research on one-dimensional (1D) nano materials has matured as one of the most active research areas within the nano science and nano technology community, flourishing with ample, exciting, and new research opportunities. Just like any other research frontier, researchers working in the 1D nano materials field are constantly striving to develop new fundamental science as well as potential applications. It remains a common belief that versatility and tunability of 1D nano materials would challenge many new rising tasks coming from our resource and energy demanding modern society. The traditional semiconductor industry has produced so many devices and systems from transistors, sensors, lasers, and LEDs to more sophisticated solar panels, which are now part of our daily lives. By down sizing the core components or parts to 1D form, one might wonder how fundamentally the dimensionality and morphology would impact the device performance, this is, as always, requiring us to fully understand the structure-property relationship in 1D nano materials. It may be equally crucial in connecting discovery-driven fundamental science to market-driven technology industry concerning potentially relevant findings derived from these novel materials. The importance of a platform that allows active researchers in this field to present their new development in a timely and efficient manner is therefore self-evident. Following the success of two early special issues devoted to 1D nano materials, this is the third one in a row organized by the same group of guest editors, attesting that such a platform has been well received by the readers

  11. Main: 1B37 [RPSD[Archive

    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 ...

  12. Introduction to BIS statistics

    Bank for International Settlements

    2015-01-01

    The BIS has expanded its statistics by publishing additional data, revamping their dissemination and strengthening their policy orientation. This special feature, prepared by members of the BIS Monetary and Economic Department, briefly describes each BIS data set and explains how the statistics can be used for analysis.

  13. Identification of RAPD Marker for Chromosome 1D of Common Wheat

    Imtiaz Ahmad Khan

    2010-04-01

    Full Text Available Development of genetically compensating nullisomic-tetrasomic and ditelosomic lines of commonwheat (Triticum aestivum L. have been widely used to construct high density genetic maps of homoeologouswheat chromosomes. During present research, easier, cheaper and quicker procedure of Polymerase ChainReaction (PCR was used to map Randomly Amplified Polymorphic DNA primers on chromosome 1D ofcommon wheat. Genomic DNA was isolated from two genetic stocks of wheat cultivar Chinese Spring viz;NT-1D1B and NT-2A2B. PCR were conducted using RAPD primers GLC-07 and GLC-11. RAPD primerGLC-11 amplified a polymorphic allele of approximately 500 bp, which was present in NT-2A2B (used aspositive control but was absent in NT-1D1B indicating that the locus is present on chromosome 1D of commonwheat. Hence this marker (GLC-11 can reliably be used to keep track of chromosome 1D of hexaploid wheat.

  14. 18 CFR 1b.19 - Submissions.

    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..., which may consist of a statement of fact, argument, and/or memorandum of law, with such...

  15. Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries

    Edvinsson, Lars; Uddman, Erik; Wackenfors, Angelica; Davenport, Anthony; Longmore, Jenny; Malmsjö, Malin

    2005-01-01

    Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine...

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

    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.

  17. Gene profiling of growth factor independence 1B gene (Gfi-1B) in leukemic cells.

    Koldehoff, Michael; Zakrzewski, Johannes L; Klein-Hitpass, Ludger; Beelen, Dietrich W; Elmaagacli, Ahmet H

    2008-01-01

    To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, the naturally Gfi-1B overexpressing cell line K562 was cultured in the presence of Gfi-1B target-specific small interfering RNA (siRNA). SiRNA treatment significantly knocked down Gfi-1B expression with an efficiency of nearly 90%. Analysis of the siRNA silencing protocol by colony-forming units ensured that it was not cytotoxic. Samples from Gfi-1B overexpressing cells and cells with knocked-down Gfi-1B were analyzed by oligonucleotide microarray technology and based upon rigorous statistical analysis of the data; relevant genes were chosen for confirmation by reserve transcriptase-polymerase chain reaction, including MYC/MYCBP and CDKN1A. Interestingly, transcripts within components of the signalling cascade of immune cells (PLD1, LAMP1, HSP90, IL6ST), of the tyrosine kinase pathway (TPR, RAC3) and of the transcription factors (RAC3, CEP290, JEM-1, ATR, MYC, SMC3, RARA, RBBP6) were found to be differentially expressed in Gfi-1B overexpressing cells compared to controls. Individual genes such as ZDHHC17, DMXL1, ZNF292 were found to be upregulated in Gfi-1B overexpressing cells. In addition, down-regulated transcripts showed cell signaling transcripts for several chemokine gene members including GNAL, CXCL5, GNL3L, GPR65, TMEM30, BCL11B and transcription factors (GTF2H3, ATXN3). In conclusion, several essential cell signalling factors, as well as transcriptional and post-translational regulation genes were differentially expressed in cells that overexpressed Gfi-1B compared to control cells with knocked-down Gfi-1B. Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations. PMID:18224412

  18. Bis-spirolabdane Diterpenoids from Leonotis nepetaefolia

    Li, Jun; Fronczek, Frank R.; Ferreira, Daneel; Burandt, Charles L.; Setola, Vincent; Roth, Bryan L.; Zjawiony, Jordan K.

    2012-01-01

    Ten new bis-spirolabdane diterpenoids, leonepetaefolins A–E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11–18) as well as two known flavonoids apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of 1D-and 2D-NMR experiments including 1H, 13C, DEPT, 1H-1H COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture ...

  19. 2000 Johnston Site 1B-P

    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...

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

    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). PMID:24815008

  1. Substituierte Erdalkalimetall-bis(pentolide) und –bis(trialkylzinkate)

    Gückel, Christian

    2001-01-01

    Im Gegensatz zu den Alkalimetall-pentoliden erweckt das Gebiet der Erdalkalimetallbis( pentolide) erst seit einigen Jahren das Interesse einiger Arbeitsgruppen. Westerhausen et al. konnten vor einigen Jahren bei der Umsetzung von Diphenylbutadiin mit Calcium- und Strontium-bis[bis(trimethylsilyl)phosphanid] die Bildung von Erdalkalimetall-bis(phospholid) nachweisen. Ein alternativer Weg nutzt die Metallierung von 1-Chlor-substituierten Pentolen durch Erdalkalimetalle zu Nutze. ...

  2. Social exploration of 1D games

    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 intere...... 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....

  3. Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex.

    Martial, J; de Montigny, C; Cecyre, D; Quirion, R

    1991-01-01

    The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- ...

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

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

    2015-02-01

    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. PMID:25529606

  5. Main: 1B5Q [RPSD[Archive

    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 ...

  6. YORP torques with 1D thermal model

    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.

  7. Mutation of Oryza sativa CORONATINE INSENSITIVE 1b (OsCOI1b) delays leaf senescence

    Sang-Hwa Lee; Yasuhito Sakuraba; Taeyoung Lee; Kyu-Won Kim; Gynheung An; Han Yong Lee; Nam-Chon Paek

    2015-01-01

    Jasmonic acid (JA) functions in plant development, including senescence and immunity. Arabidopsis thaliana CORONATINE INSENSITIVE 1 encodes a JA receptor and functions in the JA‐responsive signaling pathway. The Arabidopsis genome harbors a single COI gene, but the rice (Oryza sativa) genome harbors three COI homologs, OsCOI1a, OsCOI1b, and OsCOI2. Thus, it remains unclear whether each OsCOI has distinct, additive, synergistic, or redundant func-tions in development. Here, we use the oscoi1b‐1 knockout mutants to show that OsCOI1b mainly affects leaf senescence under senescence‐promoting conditions. oscoi1b‐1 mutants stayed green during dark‐induced and natural senescence, with substantial retention of chlorophylls and photosyn-thetic capacity. Furthermore, several senescence‐associated genes were downregulated in oscoi1b‐1 mutants, including homologs of Arabidopsis thaliana ETHYLENE INSENSITIVE 3 and ORESARA 1, important regulators of leaf senescence. These results suggest that crosstalk between JA signaling and ethylene signaling affects leaf senescence. The Arabidopsis coi1‐1 plants containing 35S:OsCOI1a or 35S:OsCOI1b rescued the delayed leaf senescence during dark incubation, sug-gesting that both OsCOI1a and OsCOI1b are required for promoting leaf senescence in rice. oscoi1b‐1 mutants showed significant decreases in spikelet fertility and grain weight, leading to severe reduction of grain yield, indicating that OsCOI1‐mediated JA signaling affects spikelet fertility and grain filling.

  8. 1D ferrimagnetism in homometallic chains

    Coronado Miralles, Eugenio; Gómez García, Carlos José; Borrás Almenar, Juan José

    1990-01-01

    The magnetic properties of the cobalt zigzag chain Co(bpy)(NCS)2 (bpy=2,2′‐bipyridine) are discussed on the basis of an Ising‐chain model that takes into account alternating Landé factors. It is emphasized, for the first time, that a homometallic chain containing only one type of site can give rise to a 1D ferrimagneticlike behavior. ,

  9. Analysis list: ARID1B [Chip-atlas[Archive

    Full Text Available ARID1B Liver + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/ARID1B.1.tsv http://dbar...chive.biosciencedbc.jp/kyushu-u/hg19/target/ARID1B.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/AR...ID1B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/ARID1B.Liver.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Liver.gml ...

  10. Expression of the Aldo-Keto Reductases AKR1B1 and AKR1B10 in Human Cancers.

    BrianLaffin

    2012-06-01

    Full Text Available The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-keto reductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com. Using this database, we found that expression of of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

  11. 1-D EQUILIBRIUM DISCRETE DIFFUSION MONTE CARLO

    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.

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

    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.

  13. Effect of three bis-pyridyl-bis-amide ligands with various spacers on the structural diversity of new multifunctional cobalt(II) coordination polymers

    Lin, Hong-Yan [Department of Chemistry, Bohai University, Jinzhou 121000 (China); Lu, Huizhe [Department of Applied Chemistry, China Agricultural University, Beijing, 100193 (China); Le, Mao; Luan, Jian [Department of Chemistry, Bohai University, Jinzhou 121000 (China); Wang, Xiu-Li, E-mail: wangxiuli@bhu.edu.cn [Department of Chemistry, Bohai University, Jinzhou 121000 (China); Liu, Guocheng; Zhang, Juwen [Department of Chemistry, Bohai University, Jinzhou 121000 (China)

    2015-03-15

    Three new cobalt(II) coordination polymers [Co{sub 2}(1,4-NDC){sub 2}(3-bpye)(H{sub 2}O)] (1), [Co(1,4-NDC)(3-bpfp)(H{sub 2}O)] (2) and [Co(1,4-NDC)(3-bpcb)] (3) [3-bpye=N,N′-bis(3-pyridinecarboxamide)-1,2-ethane, 3-bpfp=bis(3-pyridylformyl)piperazine, 3-bpcb=N,N′-bis(3-pyridinecarboxamide)-1,4-benzene, and 1,4-H{sub 2}NDC=1,4-naphthalenedicarboxylic acid] have been hydrothermally synthesized. The structures of complexes 1–3 have been determined by X-ray single crystal diffraction analyses and further characterized by infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology constructed from 3D [Co{sub 2}(1,4-NDC){sub 2}(H{sub 2}O)]{sub n} framework and bidentate 3-bpye ligands. Complex 2 shows 1D “cage+cage”-like chain formed by 1D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} ribbon chains and [Co{sub 2}(3-bpfp){sub 2}] loops, which are further linked by hydrogen bonding interactions to form a 3D supramolecular network. Complex 3 displays a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology based on 2D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} layers and bidentate 3-bpcb bridging ligands. The influences of different bis-pyridyl-bis-amide ligands with various spacers on the structures of title complexes are studied. Moreover, the fluorescent properties, electrochemical behaviors and magnetic properties of complexes 1–3 have been investigated. - Graphical abstract: Three multifunctional cobalt(II) complexes constructed from three bis-pyridyl-bis-amide and 1,4-naphthalenedicarboxylic acid have been hydrothermally synthesized and characterized. The fluorescent, electrochemical and magnetic properties of 1–3 have been investigated. - Highlights: • Three multifunctional cobalt(II) complexes based on various bis-pyridyl-bis-amide ligands. • Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8

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

    Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2013-01-01

    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....... 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...

  15. IL1B induced Smad 7 negatively regulates gastrin expression.

    Dipanjana Datta De

    Full Text Available BACKGROUND: Helicobacter pylori elicited IL1B is one of the various modulators responsible for perturbation of acid secretion in gut. We have earlier reported that IL1B activated NFkB downregulates gastrin, a major modulator of acid secretion. However, we hypothesized that regulation of gastrin by IL1B would depend on the cell's ability to integrate inputs from multiple signaling pathways to generate appropriate biological response. PRINCIPAL FINDING: In this study, we report that IL1B induces Smad 7 expression by about 4.5 fold in gastric carcinoma cell line, AGS. Smad 7 resulted in transcriptional repression of gastrin promoter by about 6.5 fold when co-transfected with Smad 7 expression vector and gastrin-promoter luciferase in AGS cells. IL1B inhibited phosphorylation of Smad 3 and subsequently interfered with nuclear translocation of the positive Smad complex, thus occluding it off the gastrin promoter. IL1B promoter polymorphisms (-511T/-31C IL1B are known to be associated with H. pylori associated gastro-duodenal ulcer. We observed that IL1B expressed from -31T promoter driven IL1B cDNA elicited 3.5 fold more Smad 7 than that expressed from the IL1B-31C variant in AGS cells. This differential activation of Smad 7 by IL1B promoter variants translated into differential downregulation of gastrin expression. We further analyzed Smad 7, NFkB, IL1B and gastrin expression in antral gut biopsy samples of patients with H. pylori associated duodenal ulcer and normal individuals. We observed that individuals with duodenal ulcer had significantly lower levels of IL1B, Smad 7, NFkB and corresponding higher level of gastrin expression. CONCLUSION: Pro-inflammatory cytokine IL1B repress gastrin expression by activating Smad 7 and subsequent inhibition of nuclear localization of Smad 3/4 complex. Polymorphic promoter variants of IL1B gene can modulate the IL1B expression which resulted in differential activation Smad 7 and consequent repression of

  16. Aldo keto reductases 1B in endocrinology and metabolism

    AntoineMartinez

    2012-08-01

    Full Text Available The aldose reductase (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 aldose reductase function in non-diabetic condition remains unresolved. Aldose reductase-like enzymes (AKR1B10, Akr1b7 and Akr1b8 are highly related isoforms often co-expressed with bona fide aldose reductase, 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 aldose reductase shows ubiquitous expression, aldose reductase-like proteins exhibit tissue-specific patterns of expression. We focused on 3 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

  17. 18 CFR 1b.20 - Request for confidential treatment.

    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....S.C. 1905, or is otherwise exempt by law from public disclosure. In such case, the person...

  18. Manganese- and Lanthanide-Based 1D Chiral Coordination Polymers as an Enantioselective Catalyst for Sulfoxidation.

    Yadav, Munendra; Bhunia, Asamanjoy; Jana, Salil K; Roesky, Peter W

    2016-03-21

    The chiral 1D-coordination polymers (CP) {[Ln2(MnLCl)2(NO3)2(dmf)6(H2O)2]·xH2O}n [Ln = Pr (1), Nd (2), Sm (3), and Gd (4)] were synthesized by the reaction of N,N'-bis(4-carboxysalicylidene)cyclohexanediamine (H4L) with [MnCl2·4(H2O)] and [Ln(NO3)3·x(H2O)] in the presence of dmf/pyridine at 90 °C. The polymers consist of manganese-salen-based moieties having carboxylate linkers connected to rare earth atoms in a 1D-chain structure. The polymers are very easily accessible. A one-step synthesis for the ligand and a second step for the preparation of the 1D coordination polymers starting from commercially available material are needed. The solid state structures of 1-4 were established by single-crystal X-ray diffraction. Compounds 1-4 were investigated as heterogeneous catalysts for the sulfoxidation reaction of various alkyl and aryl sulfides. The influence of various solvents and oxidizing agents on the catalytic reaction was examined. It was found that the catalysts were active for more than one reaction cycle without significant loss of activity. For phenylsulfide with 1 mol % of the catalyst 4, a maximum conversion 100% and a chemoselectivity 88% were observed. PMID:26923559

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

    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.

  20. Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana.

    Shah, Muhammad Raza; Ishtiaq; Hizbullah, Syed Muhammad; Habtemariam, Solomon; Zarrelli, Armando; Muhammad, Akhtar; Collina, Simona; Khan, Inamulllah

    2016-08-01

    Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 µM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds. PMID:26118418

  1. TES/Aura L1B Spectra Nadir V004

    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 &...

  2. TES/Aura L1B Spectra Limb V002

    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 &...

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

    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/Nr1d2....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d2.Liver.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  4. Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide

    Jeong HU

    2015-01-01

    Full Text Available Hyeon-Uk Jeong,1 Mihwa Kwon,2 Yongnam Lee,3 Ji Seok Yoo,3 Dae Hee Shin,3 Im-Sook Song,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea; 3Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea Abstract: We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1, OAT3, organic anion transporting polypeptide 1B1 (OATP1B1, OATP1B3, organic cation transporter 1 (OCT1, OCT2, P-glycoprotein (P-gp, and breast cancer resistance protein (BCRP. The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3 and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3. The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km =41.5 µM, maximum uptake rate (Vmax =46.2 pmol/minute, and intrinsic clearance (CLint =1.11 µL/minute. OATP1B1- and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 µL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µ

  5. [1,2-Bis(diphenylphosphinoethane]{2-[bis(diphenylphosphinomethylamino]pyridinium}fluoridohydrazidatomolybdenum(IV bis(tetrafluoridoborate

    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.

  6. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity

    He, Lan; Kim, Teayoun; Long, Qinqiang; Liu, Jian; Wang, Peiyong; Zhou, Yiqun; Ding, Yishu; Prasain, Jeevan; Wood, Philip A.; Yang, Qinglin

    2012-01-01

    Background Carnitine palmitoyltransferase 1(CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT-1 activity by specific CPT-1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby posting concerns on the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 in order to evaluate it as a safe and effective therapeutic approach. Methods and Results Heterozygous CPT1b knockout mice (CPT1b+/−) were subjected to transverse aorta constriction (TAC)-induced pressure-overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by two weeks of transverse aorta constriction (TAC), CPT1b+/− mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b+/− mice exhibited exacerbated cardiac hypertrophy and remodeling compared with that in wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b+/− than in controlled mice. Moreover, the CPT1b+/− heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocytes apoptosis. Conclusions We conclude that CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be applied in the clinical use of CPT-1 inhibitors. PMID:22932257

  7. Ferredoxin 1b (Fdx1b) Is the Essential Mitochondrial Redox Partner for Cortisol Biosynthesis in Zebrafish.

    Griffin, Aliesha; Parajes, Silvia; Weger, Meltem; Zaucker, Andreas; Taylor, Angela E; O'Neil, Donna M; Müller, Ferenc; Krone, Nils

    2016-03-01

    Mitochondrial cytochrome P450 (CYP) enzymes rely on electron transfer from the redox partner ferredoxin 1 (FDX1) for catalytic activity. Key steps in steroidogenesis require mitochondrial CYP enzymes and FDX1. Over 30 ferredoxin mutations have been explored in vitro; however, no spontaneously occurring mutations have been identified in humans leaving the impact of FDX1 on steroidogenesis in the whole organism largely unknown. Zebrafish are an important model to study human steroidogenesis, because they have similar steroid products and endocrine tissues. This study aimed to characterize the influence of ferredoxin on steroidogenic capacity in vivo by using zebrafish. Zebrafish have duplicate ferredoxin paralogs: fdx1 and fdx1b. Although fdx1 was observed throughout development and in most tissues, fdx1b was expressed after development of the zebrafish interrenal gland (counterpart to the mammalian adrenal gland). Additionally, fdx1b was restricted to adult steroidogenic tissues, such as the interrenal, gonads, and brain, suggesting that fdx1b was interacting with steroidogenic CYP enzymes. By using transcription activator-like effector nucleases, we generated fdx1b mutant zebrafish lines. Larvae with genetic disruption of fdx1b were morphologically inconspicuous. However, steroid hormone analysis by liquid chromatography tandem mass spectrometry revealed fdx1b mutants failed to synthesize glucocorticoids. Additionally, these mutants had an up-regulation of the hypothalamus-pituitary-interrenal axis and showed altered dark-light adaptation, suggesting impaired cortisol signaling. Antisense morpholino knockdown confirmed Fdx1b is required for de novo cortisol biosynthesis. In summary, by using zebrafish, we generated a ferredoxin knockout model system, which demonstrates for the first time the impact of mitochondrial redox regulation on glucocorticoid biosynthesis in vivo. PMID:26650568

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

    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.

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

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

    2003-01-01

    The vasomotor effects of triptans in the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro vessel baths. Using the arteriograph, MCAs from Sprague-Dawley rats were mounted on two glass micropipettes, pressurised to 85 mm Hg and luminally...

  10. Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and α2-adrenoceptors

    Villalón, Carlos M; De Vries, Peter; Rabelo, Gonzalo; Centurión, David; Sánchez-López, Araceli; Saxena, Pramod

    1999-01-01

    The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE) produce selective vasoconstriction in the external carotid bed of vagosympathectomized dogs anaesthetized with pentobarbital and artificially respired, but the receptors involved have not yet been completely characterized. Since the above drugs display affinity for several binding sites, including α-adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has analysed the mechanisms involved in the abov...

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

    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

  12. 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

    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...

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

    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.

  14. Oncolytic Replication of E1b-Deleted Adenoviruses

    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.

  15. 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

    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.

  16. LEUPROLIDE INHIBITS MARBLE-BURYING BEHAVIOR VIA MODULATION OF 5-HT1B RECEPTOR

    Parle Milind

    2011-04-01

    Full Text Available Obsessive compulsive disorder (OCD is characterized by intrusive thoughts followed by repetitive behaviors. Serotonin-related genes found in OCD include those required for coding of 5-HT transporter and 5-HT receptors (5-HT2A, 5-HT2B, 5-HT2C and 5-HT1B. Marble-burying behavior of mice is a well-accepted paradigm to screen anti-compulsive activity. The aim of this study was to evaluate the effect of leuprolide alone and it’s combination with sumatriptan or ondansetron on marble-burying behavior of mice. Leuprolide (100, 200 & 300 µg kg-1s.c. dose-dependently showed anti-compulsive effect, causing statistically significant inhibition of marble-burying behavior of mice. The prior treatment with 5HT1B/1D/1F agonist, sumatriptan (0.1 mg kg-1 s.c. potentiated the inhibitory effect of leuprolide (LHRH agonist on marble burying behavior of mice. Furthermore, prior treatment with 5HT3 antagonist, ondansetron (2 mg kg-1 s.c. did not affect the inhibitory effect of leuprolide (200 µg kg-1s.c. on marble burying behavior of mice.

  17. PTP1B targets the endosomal sorting machinery

    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...

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

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Right to submit... COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.18 Right to submit statements. Any person may, at any time during the course of an investigation, submit documents,...

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

    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

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

    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. PTP1B: a new therapeutic target for Rett syndrome.

    Tautz, Lutz

    2015-08-01

    Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is characterized by successive loss of acquired cognitive, social, and motor skills and development of autistic behavior. RTT affects approximately 1 in 10,000 live female births and is the second most common cause of severe mental retardation in females, after Down syndrome. Currently, there is no cure or effective therapy for RTT. Approved treatment regimens are presently limited to supportive management of specific physical and mental disabilities. In this issue, Krishnan and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated in patients with RTT and in murine models and provide strong evidence that targeting PTP1B has potential as a viable therapeutic strategy for the treatment of RTT. PMID:26214520

  2. Performance and Applications of L1B2 Ultrasonic Motors

    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...

  3. NICMOS OBSERVATIONS OF THE TRANSITING HOT JUPITER XO-1b

    We refine the physical parameters of the transiting hot Jupiter planet XO-1b and its stellar host XO-1 using Hubble Space Telescope (HST) NICMOS observations. XO-1b has a radius Rp = 1.21 ± 0.03 RJ , and XO-1 has a radius R* = 0.94 ± 0.02 Rsun, where the uncertainty in the mass of XO-1 dominates the uncertainty of Rp and R*. There are no significant differences in the XO-1 system properties between these broadband NIR observations and previous determinations based upon ground-based optical observations. We measure two transit timings from these observations with 9 s and 15 s precision. As a residual to a linear ephemeris model, there is a 2.0σ timing difference between the two HST visits that are separated by three transit events (11.8 days). These two transit timings and additional timings from the literature are sufficient to rule out the presence of an Earth mass planet orbiting in 2:1 mean motion resonance coplanar with XO-1b. We identify and correct for poorly understood 'gain-like' variations present in NICMOS time series data. This correction reduces the effective noise in time series photometry by a factor of 2 for the case of XO-1.

  4. Trisodium scandium bis(orthoborate

    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.

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

    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.

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

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

    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. PMID:25088042

  7. TBC1D24 genotype–phenotype correlation

    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

  8. 1D photonic crystal sensor integrated in a microfluidic system

    Nunes, Pedro; Mortensen, Asger; Kutter, Jörg Peter; Mogensen, Klaus Bo

    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....

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

    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...

  10. Bis(1,3-dithiole) Compounds

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

    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)...

  11. L(d1, d2,..., dt)-Number λ(Cn; d1, d2,...,dt) of Cycles

    GAO Zhen Bin; ZHANG Xiao Dong

    2009-01-01

    An L(d1,d2,...,dt)-labeling of a graph G is a function f from its vertex set V(G) to the set {0, 1,..., k} for some positive integer k such that {f(x) - f(y)| ≥ di, if the distance between vertices x and y in G is equal to i for i = 1,2,...,t. The L(d1,d2,...,dt)-number λ(G;d1,d2,... ,dt) of G is the smallest integer number k such that G has an L(d1,d2,... ,dt)labeling with max{f(x)|x ∈ V(G)} = k. In this paper, we obtain the exact values for λ(Cn; 2, 2,1) and λ(Cn; 3, 2, 1), and present lower and upper bounds for λ(Cn; 2,..., 2,1,..., 1)

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

    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.

  13. Resonant indirect exchange in 1D semiconductor nanostructures

    We consider resonant indirect exchange interaction between magnetic centers in 1D nanostructures. The magnetic centers are assumed to be coupled to the 1D conducting channel by the quantum tunneling which can be of resonant character. The indirect exchange between the centers is mediated by the free carriers of the channel. The two cases of quadratic and linear energy dispersion of the 1D free carriers are considered. The former case is attributed to conventional semiconductor (InGaAs based to be concrete) nanowires or nanowhiskers, while the latter case is associated with carbon nanotubes with magnetic adatoms. We demonstrate that whenever the energy of a bound state at the magnetic center lies within the continuum energy spectra of the delocalized carriers in the channel the indirect exchange is strongly enhanced due to effective tunnel hybridization of the bound states with the continuum. - Highlights: • A resonant indirect exchange interaction between magnetic centers mediated by a 1D conducting channel is considered. • It is shown that the indirect exchange is strongly enhanced due to resonant tunnel coupling of a magnetic bound state with the delocalized states. • The two cases of quadratic and linear energy dispersion of the 1D free carriers are considered. • Pecularities of the indirect exchange mediated by a carbon nanotube has been investigated

  14. Resonant indirect exchange in 1D semiconductor nanostructures

    Rozhansky, I.V., E-mail: rozhansky@gmail.com [Ioffe Institute, Russian Academy of Sciences, St.Petersburg 194021 (Russian Federation); Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland); St. Petersburg State Polytechnic University, St. Petersburg 195251 (Russian Federation); Krainov, I.V.; Averkiev, N.S. [Ioffe Institute, Russian Academy of Sciences, St.Petersburg 194021 (Russian Federation); Lähderanta, E. [Lappeenranta University of Technology, P.O. Box 20, FI-53851 Lappeenranta (Finland)

    2015-06-01

    We consider resonant indirect exchange interaction between magnetic centers in 1D nanostructures. The magnetic centers are assumed to be coupled to the 1D conducting channel by the quantum tunneling which can be of resonant character. The indirect exchange between the centers is mediated by the free carriers of the channel. The two cases of quadratic and linear energy dispersion of the 1D free carriers are considered. The former case is attributed to conventional semiconductor (InGaAs based to be concrete) nanowires or nanowhiskers, while the latter case is associated with carbon nanotubes with magnetic adatoms. We demonstrate that whenever the energy of a bound state at the magnetic center lies within the continuum energy spectra of the delocalized carriers in the channel the indirect exchange is strongly enhanced due to effective tunnel hybridization of the bound states with the continuum. - Highlights: • A resonant indirect exchange interaction between magnetic centers mediated by a 1D conducting channel is considered. • It is shown that the indirect exchange is strongly enhanced due to resonant tunnel coupling of a magnetic bound state with the delocalized states. • The two cases of quadratic and linear energy dispersion of the 1D free carriers are considered. • Pecularities of the indirect exchange mediated by a carbon nanotube has been investigated.

  15. Plutonium disposition study phase 1b final report

    This report provides the results of the Westinghouse activities performed as part of the Plutonium Disposition Study Phase 1b. These activities, which took place from May 16, 1993 to September 15, 1993, build upon the work completed in Phase 1a, which concluded on May 15, 1993. In Phase 1a, three Plutonium Disposal Reactor (PDR) options were developed for the disposal of excess weapons grade plutonium from returned and dismantled nuclear weapons. This report documents the results of several tasks that were performed to further knowledge in specific areas leading up to Phase 2 of the PDR Study. The Westinghouse activities for Phase 1b are summarized as follows: (1) resolved technical issues concerning reactor physics including equilibrium cycle calculations, use of gadolinium, moderator temperature coefficient, and others as documented in Section 2.0; (2) analyzed large Westinghouse commercial plants for plutonium disposal; (3) reactor safety issues including the steam line break were resolved, and are included in Section 2.0; (4) several tasks related to the PDR Fuel Cycle were examined; (5) cost and deployment options were examined to determine optimal configuration for both plutonium disposal and tritium production; (6) response to questions from DOE and National Academy of Scientists (NAS) reviewers concerning the PDR Phase 1a report are included in Appendix A

  16. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    Highlights: ► PTP1B protein showed decreased expression in 67.79% of the HCC patients. ► Low PTP1B expression predicts poor prognosis of HCC. ► Low PTP1B expression is correlated with expansion of OV6+ tumor-initiating cells. ► Down-regulation of PTP1B is associated with activation of Wnt/β-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6+ tumor-initiating cells (T-ICs) and high frequency of nuclear β-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/β-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

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

    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.

  18. Iris Feature Extraction Method Based on 1D Gabor Filter

    XU Guang-zhu; MA Yi-de; ZHANG Zai-feng

    2008-01-01

    The normalized iris image was divided into eight sub-bands, and every column of each sub-band was averaged by rows to generate eight 1D iris signals. Then the even symmetry item of 1D Gabor filter was used to describe local characteristic blocks in 1D iris signals, and the results were quantified by their polarities to generate iris codes. In order to estimate the performance of the presented method, an iris recognition platform was produced and the Hamming distance between two iris codes was computed to measure the dissimilarity of them. The experimental results in CASIA v1 0 and Bath iris image databases show that the proposed iris feature extraction algorithm has a promising potential in iris recognition.

  19. A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not associated with cerebral malaria in Thailand

    Tangpukdee Noppadon; Hananantachai Hathairad; Patarapotikul Jintana; Doi Akihiro; Naka Izumi; Ohashi Jun; Looareesuwan Sornchai; Tokunaga Katsushi

    2005-01-01

    Abstract Background IL-1β and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T. Methods To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 c...

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

    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)....

  1. Nonreciprocity of edge modes in 1D magnonic crystal

    Lisenkov, I., E-mail: ivan.lisenkov@phystech.edu [Kotelnikov Institute of Radio-engineering and Electronics of RAS, 11-7 Mokhovaya st., Moscow 125009 (Russian Federation); Department of Physics, Oakland University, 2200 N. Squirrel Rd., Rochester, MI 48309 (United States); Moscow Institute of Physics and Technology, 9 Instituskij per., Dolgoprudny, 141700, Moscow Region (Russian Federation); Kalyabin, D., E-mail: dmitry.kalyabin@phystech.edu [Kotelnikov Institute of Radio-engineering and Electronics of RAS, 11-7 Mokhovaya st., Moscow 125009 (Russian Federation); Moscow Institute of Physics and Technology, 9 Instituskij per., Dolgoprudny, 141700, Moscow Region (Russian Federation); Osokin, S. [Kotelnikov Institute of Radio-engineering and Electronics of RAS, 11-7 Mokhovaya st., Moscow 125009 (Russian Federation); Moscow Institute of Physics and Technology, 9 Instituskij per., Dolgoprudny, 141700, Moscow Region (Russian Federation); Klos, J.W.; Krawczyk, M. [Adam Mickiewicz University in Poznan, Umultowska 85, Poznan 61-614 (Poland); Nikitov, S., E-mail: nikitov@cplire.ru [Kotelnikov Institute of Radio-engineering and Electronics of RAS, 11-7 Mokhovaya st., Moscow 125009 (Russian Federation); Moscow Institute of Physics and Technology, 9 Instituskij per., Dolgoprudny, 141700, Moscow Region (Russian Federation); Saratov State University, 112 Bol' shaya Kazach' ya, Saratov 410012 (Russian Federation)

    2015-03-15

    Spin waves propagation in 1D magnonic crystals is investigated theoretically. Mathematical model based on plane wave expansion method is applied to different types of magnonic crystals, namely bi-component magnonic crystal with symmetric/asymmetric boundaries and ferromagnetic film with periodically corrugated top surface. It is shown that edge modes in magnonic crystals may exhibit nonreciprocal behaviour at much lower frequencies than in homogeneous films. - Highlights: • Magnetostatic surface spin waves in 1D magnonic crystals were studied theoretically. • Mathematical model is based on plane wave method. • Mathematical model was applied to different types of magnonic crystals. • Stop band formation and nonreciprocity were obtained.

  2. Nonreciprocity of edge modes in 1D magnonic crystal

    Spin waves propagation in 1D magnonic crystals is investigated theoretically. Mathematical model based on plane wave expansion method is applied to different types of magnonic crystals, namely bi-component magnonic crystal with symmetric/asymmetric boundaries and ferromagnetic film with periodically corrugated top surface. It is shown that edge modes in magnonic crystals may exhibit nonreciprocal behaviour at much lower frequencies than in homogeneous films. - Highlights: • Magnetostatic surface spin waves in 1D magnonic crystals were studied theoretically. • Mathematical model is based on plane wave method. • Mathematical model was applied to different types of magnonic crystals. • Stop band formation and nonreciprocity were obtained

  3. 1D antiferromagnetism in spin‐alternating bimetallic chains

    Coronado Miralles, Eugenio; Sapiña Navarro, Fernando; Drillon, M.; De Jongh, L.J.

    1990-01-01

    The magnetic and thermal properties of the ordered bimetallic chain CoNi(EDTA)⋅6H2O in the very low‐temperature range are reported. The magnetic behavior does not exhibit the characteristic features of 1D ferrimagnets, but a continuous decrease of χmT towards zero at absolute zero. This 1D antiferromagnetic behavior results from an accidental compensation between the moments located at the two sublattices. This behavior, as well as the specific‐heat results, are modeled on the basis of an Isi...

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

    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.

  5. Quantum electrodynamics with 1D arti cial atoms

    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...... photons as expected from the theory. The value of g(2)(0) is around 1.08. The results con_rm the observation of an on-chip giant optical nonlinearity and the 1D atom behavior. Another direction in this thesis has been to investigate the e_ect of Anderson localization on the electrodynamics of QDs in PCWs...

  6. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology.

    Bodaleo, Felipe J; Montenegro-Venegas, Carolina; Henríquez, Daniel R; Court, Felipe A; Gonzalez-Billault, Christian

    2016-01-01

    Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro. PMID:27425640

  7. HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms

    Hartkoorn, Ruben C; San Kwan, Wai; Shallcross, Victoria; Chaikan, Ammara; Liptrott, Neill; Egan, Deirdre; Enrique Salcedo Sora, J; James, Chloe E; Gibbons, Sara; Bray, Pat G; Back, David J; Khoo, Saye H; Owen, Andrew

    2016-01-01

    OATP1B1 and OATP1B3 are major hepatic drug transporters whilst OATP1A2 is mainly located in the brain but is also located in liver and several other organs. These transporters affect the distribution and clearance of many endo- and xenobiotics and have been reported to have functional SNPs. We have assessed the substrate specificites of these transporters for a panel of antiretrovirals and investigated the effects of SNPs within these transporters on the pharmacokinetics of lopinavir. SLCO1A2, SLCO1B1 and SLCO1B3 were cloned, verified and used to generate cRNA for use in the Xenopus laevis oocyte transport system. Using the oocyte system, antiretrovirals were tested for their substrate specificities. Plasma samples (n=349) from the Liverpool therapeutic drug monitoring registry were genotyped for SNPs in SLCO1A2, SLCO1B1 and SLCO1B3 and associations between SNPs and lopinavir plasma concentrations were analysed. Antiretroviral protease inhibitors, but not non-nucleoside reverse transcriptase inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3. Furthermore, ritonavir was not an inhibitor of OATP1B1. The 521T>C polymorphism in SLCO1B1 was significantly associated with higher lopinavir plasma concentrations. No associations were observed with functional variants of SLCO1A2 and SLCO1B3. These data add to our understanding of the factors that contribute to variability in plasma concentrations of protease inhibitors. Further studies are now required to confirm the association of SLCO1B1 521T>C with lopinavir plasma concentrations and to assess the influence of other polymorphisms in the SLCO family. PMID:20051929

  8. Performance and Applications of L1B2 Ultrasonic Motors

    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.

  9. SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 3-AMINO-11-CYANO-4-IMINO- PYRAZOLO [4, 5-E]-4H-PYRIMIDO [2, 1-B] QUINOLINE AND THEIR SUBSTUITED DERIVATIVES SYNTHESIS und antimikrobielle EVALUATION von 3-Amino-11-Cyano-4-IMINO-pyrazol [4, 5-D]-4H-pyrimido [2, 1-b] chinolin UND IHR SUBSTUITED DERIVATE

    Sambhaji P. Vartale, Nilesh K. Halikar and Yogesh D. Pawar

    2012-01-01

    Full Text Available 2-Amino-3-cyano quinoline (1 and bis (methylthio methylene malononitrile (2 were refluxed in N,N-dimethyl formamide (DMF in presence of catalytic amount of anhydrous potassium carbonate to afforded 3, 11-dicyano-4-imino-2-methylthio -4H-pyrimido [1, 2-a] quinoline (3. The latter were further reacted with different substituted hydrazino. Afforded to 3-amino-11- cyano-4-imino pyrazolo [4, 5-e]-4H-pyrimido [2, 1-b] quinoline and their 2-substuited derivatives (4a-j. All these newly synthesized compounds were characterized by elemental analysis and spectral data, and screened for their antimicrobial activities.

  10. Serotonin type-1D receptor stimulation of A-type K(+) channel decreases membrane excitability through the protein kinase A- and B-Raf-dependent p38 MAPK pathways in mouse trigeminal ganglion neurons.

    Zhao, Xianyang; Zhang, Yuan; Qin, Wenjuan; Cao, Junping; Zhang, Yi; Ni, Jianqiang; Sun, Yangang; Jiang, Xinghong; Tao, Jin

    2016-08-01

    Although recent studies have implicated serotonin 5-HT1B/D receptors in the nociceptive sensitivity of primary afferent neurons, the underlying molecular and cellular mechanisms remain unclear. In this study, we identified a novel functional role of the 5-HT1D receptor subtype in regulating A-type potassium (K(+)) currents (IA) as well as membrane excitability in small trigeminal ganglion (TG) neurons. We found that the selective activation of 5-HT1D, rather than 5-HT1B, receptors reversibly increased IA, while the sustained delayed rectifier K(+) current was unaffected. The 5-HT1D-mediated IA increase was associated with a depolarizing shift in the voltage dependence of inactivation. Blocking G-protein signaling with pertussis toxin or by intracellular application of a selective antibody raised against Gαo or Gβ abolished the 5-HT1D effect on IA. Inhibition of protein kinase A (PKA), but not of phosphatidylinositol 3-kinase or protein kinase C, abolished the 5-HT1D-mediated IA increase. Analysis of phospho-p38 (p-p38) revealed that activation of 5-HT1D, but not 5-HT1B, receptors significantly activated p38, while p-ERK and p-JNK were unaffected. The p38 MAPK inhibitor SB203580, but not its inactive analogue SB202474, and inhibition of B-Raf blocked the 5-HT1D-mediated IA response. Functionally, we observed a significantly decreased action potential firing rate induced by the 5-HT1D receptors; pretreatment with 4-aminopyridine abolished this effect. Taken together, these results suggest that the activation of 5-HT1D receptors selectively enhanced IA via the Gβγ of the Go-protein, PKA, and the sequential B-Raf-dependent p38 MAPK signaling cascade. This 5-HT1D receptor effect may contribute to neuronal hypoexcitability in small TG neurons. PMID:27156838

  11. Nonlinear ac conductivity of interacting 1d electron systems

    Rosenow, Bernd; Nattermann, Thomas

    2004-01-01

    We consider low energy charge transport in one-dimensional (1d) electron systems with short range interactions under the influence of a random potential. Combining RG and instanton methods, we calculate the nonlinear ac conductivity and discuss the crossover between the nonanalytic field dependence of the electric current at zero frequency and the linear ac conductivity at small electric fields and finite frequency.

  12. A 1D wavelet filtering for ultrasound images despeckling

    Dahdouh, Sonia; Dubois, Mathieu; Frenoux, Emmanuelle; Osorio, Angel

    2010-03-01

    Ultrasound images appearance is characterized by speckle, shadows, signal dropout and low contrast which make them really difficult to process and leads to a very poor signal to noise ratio. Therefore, for main imaging applications, a denoising step is necessary to apply successfully medical imaging algorithms on such images. However, due to speckle statistics, denoising and enhancing edges on these images without inducing additional blurring is a real challenging problem on which usual filters often fail. To deal with such problems, a large number of papers are working on B-mode images considering that the noise is purely multiplicative. Making such an assertion could be misleading, because of internal pre-processing such as log compression which are done in the ultrasound device. To address those questions, we designed a novel filtering method based on 1D Radiofrequency signal. Indeed, since B-mode images are initially composed of 1D signals and since the log compression made by ultrasound devices modifies noise statistics, we decided to filter directly the 1D Radiofrequency signal envelope before log compression and image reconstitution, in order to conserve as much information as possible. A bi-orthogonal wavelet transform is applied to the log transform of each signal and an adaptive 1D split and merge like algorithm is used to denoise wavelet coefficients. Experiments were carried out on synthetic data sets simulated with Field II simulator and results show that our filter outperforms classical speckle filtering methods like Lee, non-linear means or SRAD filters.

  13. Quantitative 1D saturation profiles on chalk by NMR

    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...

  14. Large Time existence For 1D Green-Naghdi equations

    Israwi, Samer

    2009-01-01

    We consider here the $1D $ Green-Naghdi equations that are commonly used in coastal oceanography to describe the propagation of large amplitude surface waves. We show that the solution of the Green-Naghdi equations can be constructed by a standard Picard iterative scheme so that there is no loss of regularity of the solution with respect to the initial condition.

  15. Main: 1D6R [RPSD[Archive

    Full Text Available 1D6R 大豆 Soybean Glycine max (L.) Merrill Bowman-Birk Type Proteinase Inhibitor Precursor Glyci ... Warkentin, G.Wenzl, P.Flecker Crystal Structure Of Cancer ... Chemopreventive Bowman-Birk Inhibitor In Ternary C ...

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

    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

  17. NEW FEATURES OF HYDRUS-1D, VERSION 3.0

    This paper briefly summarizes new features in version 3.0 of HYDRUS-1D, released in May 2005, as compared to version 2.1. The new features are a) new approaches to simulate preferential and nonequilibrium water flow and solute transport, b) a new hysteresis module that avoids the effects of pumpin...

  18. Optical properties of LEDs with patterned 1D photonic crystal

    Hronec, P.; Kuzma, A.; Å kriniarová, J.; Kováč, J.; Benčurová, A.; Haščík, Å.; Nemec, P.

    2015-08-01

    In this paper we focus on the application of the one-dimensional photonic crystal (1D PhC) structures on the top of Al0.295Ga0.705As/GaAs multi-quantum well light emitting diode (MQW LED). 1D PhC structures with periods of 600 nm, 700 nm, 800 nm, and 900 nm were fabricated by the E-Beam Direct Write (EBDW) Lithography. Effect of 1D PhC period on the light extraction enhancement was studied. 1D PhC LED radiation profiles were obtained from Near Surface Light Emission Images (NSLEI). Measurements showed the strongest light extraction enhancement using 800 nm period of PhC. Investigation of PhC LED radiation profiles showed strong light decoupling when light reaches PhC structure. Achieved LEE was from 22.6% for 600 nm PhC LED to 47.0% for 800 nm PhC LED. LED with PhC structure at its surface was simulated by FDTD simulation method under excitation of appropriate launch field.

  19. Scattering approach to classical quasi-1D transport

    Kogan, Eugene

    1996-01-01

    General dynamical transport of classical particles in disordered quasi-1D samples is viewed in the framework of scattering approach. Simple equation for the transfer-matrix is obtained within this unified picture. In the case of diffusive transport the solution of this equation exactly coincides with the solution of diffusion equation.

  20. Bessel Series in the Space H1(D)%H1(D)空间的Bessel级数

    木乐华

    2001-01-01

    An identity concerning the partial sums of Bessel series and power series for H1(D) functions is given.Based on it,many of precise extimates about the deviation of the partial sums of Bessel series can be obtained.%本文给出关于H1(D)空间中函数的Bessel级数的部分和用幂级数的部分和表示的一个恒等式.基于它,可以得到Bessel级数部分和偏差的诸多精确估计.

  1. A 12 GHz solid state power amplifier, phase 1B

    Bestwick, P. R.

    1986-05-01

    Attempts to develop a balanced amplifier developing 4 W power output at 12.6 GHz, with a gain of 3.5 dB are summarized. Calculation of the device large-signal conjugate match points, measurement of the points, design and tuning of single-ended amplifier, modules, and a bias insertion network are described. A Lange coupler and a termination for it are presented. The performance of the balanced amplifier, and that of a competing Fujitsu amplifier, are analyzed. The differences in device structure between the PRCL 4820 device and the Fujitsu device are assessed. The amplifier developed gives (at 1 dB gain compression) a gain of 2.4 dB and a power output of 3.2 dB. Difficulties stem from the use of the double-cell 4820 device, and of the Lange type quadrature couplers.

  2. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse

    Ji, Shaonin; You, Yun; Kerner, Janos; Hoppel, Charles L.; Schoeb, Trenton R.; Chick, Wallace S.H.; Hamm, Doug A.; Sharer, J. Daniel; Wood, Philip A.

    2008-01-01

    Carnitine palmitoyltransferase-1 (CPT-1) catalyzes the rate-limiting step of mitochondrial β-oxidation of long chain fatty acids (LCFA), the most abundant fatty acids in mammalian membranes and in energy metabolism. Human deficiency of the muscle isoform CPT-1b is poorly understood. In the current study, embryos with a homozygous knockout of Cpt-1b were lost before embryonic day 9.5 − 11.5. Also, while there were normal percentages of CPT-1b+/−pups born from both male and female CPT-1b+/− mice crossed with wild-type mates, the number of CPT-1b+/− pups from CPT-1b+/− breeding pairs was under-represented (63% of the expected number). Northern blot analysis demonstrated ∼50% Cpt-1b mRNA expression in brown adipose tissue (BAT), heart and skeletal muscles in the CPT-1b+/− male mice. Consistent with tissue-specific expression of Cpt-1b mRNA in muscle but not liver, CPT-1+/− mice had ∼60% CPT-1 activity in skeletal muscle and no change in total liver CPT-1 activity. CPT-1b+/− mice had normal fasting blood glucose concentration. Consistent with expression of CPT-1b in BAT and muscle, ∼7% CPT-1b+/− mice (n=30) developed fatal hypothermia following a 3 hr cold challenge, while none of the CPT-1b+/+ mice (n=30) did. With a prolonged cold challenge (6 hr), significantly more CPT-1b+/− mice developed fatal hypothermia (52% CPT-1b+/− mice vs. 21% CPT-1b+/+ mice), with increased frequency in females of both genotypes (67% female vs. 38% male CPT-1b+/− mice, and 33% female vs. 8% male CPT-1b+/+ mice). Therefore, lethality of homozygous CPT-1b deficiency in the mice is consistent with paucity of human cases. PMID:18023382

  3. Basel III, BIS and Global Financial Governance

    Khan, Haider

    2013-01-01

    This paper analyzes the following aspects of global financial governance: • Proposed BASEL III reforms for more stringent capital requirements and their implications for the developing world in particular. • BIS proposals for better regulation of financial derivatives, including commodities futures, by moving away from OTC transactions towards organized exchanges. The Basel reforms and the BIS proposals for regulating the derivatives markets have many positive features. However, ...

  4. Organic anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants influence the pharmacokinetics and pharmacodynamics of raloxifene

    Trdan Lušin Tina

    2012-04-01

    Full Text Available Abstract Background Raloxifene, a selective estrogen receptor modulator, exhibits quite large and unexplained interindividual variability in pharmacokinetics and pharmacodynamics. The aim of this study was to determine the role of organic-anion transporting polypeptides OATP1B1 and OATP1B3 and their genetic variants in the pharmacokinetics and pharmacodynamics of raloxifene. Methods To test the role of OATP1B1 and OATP1B3 transporters on hepatic uptake of raloxifene and its metabolites an in vitro model of Chinese Hamster Ovary cells expressing OATP1B1 or OATP1B3 was employed. The influence of OATP1B1 and OATP1B3 genetic variants on in vivo pharmacokinetics and pharmacodynamics was evaluated in 53 osteoporotic postmenopausal women treated with raloxifene. Results Our in vitro results showed that raloxifene and two of the three metabolites, raloxifene-4'-β-glucuronide (M2 and raloxifene-6,4'-diglucuronide (M3, interact with OATP1B1 and OATP1B3. Higher M3 and total raloxifene serum concentrations in patients correlated with lower serum levels of bone resorption marker, serum C-terminal telopeptide fragments of type I collagen, indicating a higher antiresorptive effect of raloxifene. Higher concentrations of M2 correlated with higher increase of lumbar spine bone mineral density supporting the raloxifene vertebral fracture specific protection effect. Finally, raloxifene, M3 and total raloxifene serum concentrations were significantly higher in patients with SLCO1B1 c.388A > G polymorphism and *1b haplotype implicating a considerable genetic effect on pharmacokinetics and pharmacodynamics of raloxifene. Conclusions These findings indicate that SLCO1B1 c.388A > G polymorphism could play an important role in pharmacokinetics and pharmacodynamics of raloxifene.

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

    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). PMID:22763740

  6. Complete Genome Sequence of Classical Swine Fever Virus Strain JSZL, Belonging to a New Subgenotype, 2.1d, Isolated in China in 2014.

    Zhang, Hongliang; Feng, Liping; Liu, Chunxiao; Chen, Jiazeng; Leng, Chaoliang; Bai, Yun; Peng, Jinmei; An, Tongqing; Cai, Xuehui; Yang, Xufu; Tian, Zhijun; Tong, Guangzhi

    2015-01-01

    The complete genome sequence of classic swine fever virus (CSFV) strain JSZL was determined in this study. JSZL was originally isolated from an immune pig farm in Jiangsu Province, China. JSZL is more closely related to subgenotype 2.1b than to 2.1a and 2.1c. Importantly, JSZL was classified into a new subgenotype, 2.1d. PMID:26294620

  7. Growth factor independence 1b (gfi1b is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

    Lothar Vassen

    Full Text Available Growth factor independence 1b (GFI1B is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b, we used conditionally deficient mice that harbor floxed Gfi1b alleles and inducible (Mx-Cre, Cre-ERT or erythroid specific (EpoR-Cre Cre expressing transgenes. In contrast to the germline knockout, EpoR-Cre mediated erythroid specific ablation of Gfi1b allows full gestation, but causes perinatal lethality with very few mice surviving to adulthood. Both the embryonic deletion of Gfi1b by EpoR-Cre and the deletion in adult mice by Mx-Cre or Cre-ERT leads to reduced numbers of erythroid precursors, perturbed and delayed erythroid maturation, anemia and extramedullary erythropoiesis. Global expression analyses showed that the Hba-x, Hbb-bh1 and Hbb-y embryonic globin genes were upregulated in Gfi1b deficient TER119+ fetal liver cells over the gestation period from day 12.5-17.5 p.c. and an increased level of Hbb-bh1 and Hbb-y embryonic globin gene expression was even maintained in adult Gfi1b deficient mice. While the expression of Bcl11a, a regulator of embryonic globin expression was not affected by Gfi1b deficiency, the expression of Gata1 was reduced and the expression of Sox6, also involved in globin switch, was almost entirely lost when Gfi1b was absent. These findings establish Gfi1b as a regulator of embryonic globin expression and embryonic and adult erythroid maturation.

  8. Identification of the GTPase-activating protein DEP domain containing 1B (DEPDC1B) as a transcriptional target of Pitx2

    Wu, Di; Zhu, Xiaoxi; Jimenez-Cowell, Kevin; Mold, Alexander J.; Sollecito, Christopher C.; Lombana, Nicholas; Jiao, Meng; Wei, Qize

    2015-01-01

    Pitx2 is a bicoid-related homeobox transcription factor implicated in regulating left-right patterning and organogenesis. However, only a limited number of Pitx2 downstream target genes have been identified and characterized. Here we demonstrate that Pitx2 is a transcriptional repressor of DEP domain containing 1B (DEPDC1B). The first intron of the human and mouse DEP domain containing 1B genes contains multiple consensus DNA-binding sites for Pitx2. Chromatin immunoprecipitation assays revea...

  9. Paresev 1-B in flight with tow cable

    1964-01-01

    The Paresev 1-B tested the concept of a paraglider, designed to enable a Gemini capsule to fly to a controlled ground landing. This would remove the need to make an ocean splashdown at the end of a spaceflight. Once the paraglider was deployed, the Gemini crew could use it to steer toward a touchdown point and to land on three retractable skids. Because the paraglider represented an unproved technology, approval was given to build a simple test vehicle to try out the concept. The paraglider research vehicle, or Paresev, was built of steel tubing, with a fabric paraglider. The Paresev was unpowered, so it had to be towed aloft either by ground vehicles or aircraft, such as a biplane or a light aircraft. The Paresev was a demanding aircraft to fly. Milt Thompson said that he found it more difficult to handle than the later lifting bodies. Due to technical and cost problems, the Gemini spacecraft never used the paraglider, and all missions made ocean splashdowns.

  10. Mirk/dyrk1B Kinase in Ovarian Cancer

    Eileen Friedman

    2013-03-01

    Full Text Available Mirk/dyrk1B kinase is expressed in about 75% of resected human ovarian cancers and in most ovarian cancer cell lines with amplification in the OVCAR3 line. Mirk (minibrain-related kinase is a member of the Minibrain/dyrk family of related serine/threonine kinases. Mirk maintains cells in a quiescent state by stabilizing the CDK inhibitor p27 and by inducing the breakdown of cyclin D isoforms. Mirk also stabilizes the DREAM complex, which maintains G0 quiescence by sequestering transcription factors needed to enter cycle. By entering a quiescent state, tumor cells can resist the nutrient deficiencies, hypoxic and acidic conditions within the tumor mass. Mirk maintains the viability of quiescent ovarian cancer cells by reducing intracellular levels of reactive oxygen species. CDKN2A-negative ovarian cancer cells treated with a Mirk kinase inhibitor escaped G0/G1 quiescence, entered cycle with high ROS levels and underwent apoptosis. The ROS scavenger N-acetyl cysteine reduced the extent of cancer cell loss. In contrast, the Mirk kinase inhibitor slightly reduced the fraction of G0 quiescent diploid epithelial cells and fibroblasts, and the majority of the cells pushed into cycle accumulated in G2 + M. Apoptotic sub-G0/G1 cells were not detected. Thus, normal cells were spared because of their expression of CDK inhibitors that blocked unregulated cycling and Mirk kinase inhibitor-treated normal diploid cells were about as viable as untreated controls.

  11. Developing 1D nanostructure arrays for future nanophotonics

    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.

  12. On the 1D Coulomb Klein-Gordon equation

    For a single particle of mass m experiencing the potential -α/vertical bar x vertical bar, the 1D Klein-Gordon equation is mathematically underdefined even when α 2 the ground-state energy E decreases through zero, and soon after that mR reaches a finite critical value below which E becomes complex, signalling a breakdown of the single-particle theory. At this critical point of the curve E(mR) the Klein-Gordon norm changes sign: the curve has a lower branch describing a bound antiparticle state, with positive energy -E, which exists for mR between the critical and some higher value where E reaches -m. Though apparently unanticipated in this context, similar scenarios are in fact familiar for strong short-range potentials (1D or 3D), and also for strong 3D Coulomb potentials with α of order unity

  13. Fuzzball solutions and D1-D5 microstates

    Skenderis, K; Skenderis, Kostas; Taylor, Marika

    2006-01-01

    We revisit the relation between fuzzball solutions and D1-D5 microstates. A consequence of the fact that the RR ground states (in the usual basis) are eigenstates of the R-charge is that only neutral operators can have non-vanishing expectation values on these states. We compute the holographic 1-point functions of the fuzzball solutions and find that charged chiral primaries have non-zero expectation values, except when the curve characterizing the solution is circular. The non-zero vevs reflect the fact that a generic curve breaks R-symmetry completely. This implies that fuzzball solutions (excepting circular ones) can only correspond to superpositions of RR states. We construct new solutions by appropriately superimposing fuzzball solutions that have vanishing vevs for all charged chiral primary operators and can therefore correspond to D1-D5 microstates.

  14. D1-D5-P microstates at the cap

    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.

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

    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)

  16. Waves in a 1D electrorheological dusty plasma lattice

    Rosenberg, M.

    2015-08-01

    The behavior of waves in a one-dimensional (1D) dusty plasma lattice where the dust interacts via Yukawa and electric dipole interactions is discussed theoretically. This study is motivated by recent reports on electrorheological dusty plasmas (e.g. Ivlev et al. 2008 Phys. Rev. Lett. 100, 095003) where the dipole interaction arises due to an external uniaxial AC electric field that distorts the Debye sphere surrounding each grain. Application to possible dusty plasma experimental parameters is discussed.

  17. Dentin dysplasia type 1d: A rare case

    Sujit Ranjan Sahoo; Sonia Aggarwal

    2014-01-01

    Dentin dysplasia is a rare hereditary disturbance of dentin formation characterized by a defective dentin development with clinically normal-appearing crowns, severe hypermobility of teeth and spontaneous dental abscesses or cysts. Radiographic analysis shows obliteration of all pulp chambers by pulp stones, short, blunted and malformed or absent roots, peri-apical radiolucencies of noncarious teeth. We present a case of dentin dysplasia type 1d in a 19-year-old boy along with the clinical, r...

  18. Blind Detection of Severely Blurred 1D Barcode

    Dridi, Noura; Delignon, Yves; Sawaya, Wadih; Septier, François

    2010-01-01

    In this paper, we present a joint blind channel estimation and symbol detection for decoding a blurred and noisy 1D barcode captured image. From an information transmission point of view, we show that the channel impulse response, the noise power and the symbols can be efficiently estimated by taking into account the signal structure such as the cyclostationary property of the hidden Markov process to estimate. Based on the Expectation-Maximisation method, we show that the new algorithm offer...

  19. A study of slow light in 1D photonic crystals

    Yudistira, D.; Hoekstra, H.J.W.M.; Hammer, M; Marpaung, D.A.I.

    2005-01-01

    Slow light (SL) states corresponding to wavelength regions near the bandgap edge of grating structure are known to show strong field enhancement. Such states may be excited efficiently by well-optimised adiabatic transitions in such structures, e.g., by slowly turning on the modulation depth. To study adiabatic excitations, a detailed research in 1D is performed to obtain insight into the relation between the device parameters and properties like enhancement and modal reflection. The results ...

  20. Theory of slow light excitation in 1D photonic crystals

    Yudistira, D.; Marpaung, D.A.I.; Handoyo, H.P.; Hoekstra, H.J.W.M.; Hammer, M; Tjia, M.O.; Iskandar, A.A.

    2004-01-01

    Slow light (SL) states corresponding to wavelength regions near the bandgap edge of grated structures are known to show strong eld enhancement. Such states may be excited efciently by well-optimised adiabatic transitions in grating structures, e.g., by slowly turning on the modulation depth. To study adiabatic excitations, a detailed investigation in 1D is performed to obtain insight into the relation between the device parameters and properties like eld enhancement and modal reection. The re...

  1. Development of 1D Liner Compression Code for IDL

    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.

  2. Coupling of Nod1D and HOTCHANNEL: static case

    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)

  3. MARG1D: One dimensional outer region matching data code

    A code MARG1D has been developed which computes outer region matching data of the one dimensional Newcomb equation. Matching data play an important role in the resistive (and non ideal) Magneto-hydrodynamic (MHD) stability analysis in a tokamak plasma. The MARG1D code computes matching data by using the boundary value method or by the eigenvalue method. Variational principles are derived for the problems to be solved and a finite element method is applied. Except for the case of marginal stability, the eigenvalue method is equivalent to the boundary value method. However, the eigenvalue method has the several advantages: it is a new method of ideal MHD stability analysis for which the marginally stable state can be identified, and it guarantees numerical stability in computing matching data close to marginal stability. We perform detailed numerical experiments for a model equation with analytical solutions and for the Newcomb equation in the m=1 mode theory. Numerical experiments show that MARG1D code gives the matching data with numerical stability and high accuracy. (author)

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

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

    2011-05-01

    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 SiO2, TiO2, 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.

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

    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 SiO2, TiO2, 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.

  6. Domain walls and instantons in N=1, d=4 supergravity

    Huebscher, M; Ortin, T

    2009-01-01

    We study the supersymmetric sources of (multi-) domain-wall and (multi-) instanton solutions of generic N=1, d=4 supergravities, that is: the worldvolume effective actions for said supersymmetric topological defects. The domain-wall solutions naturally couple to the two 3-forms recently found as part of the N=1, d=4 tensor hierarchy (i.e. they have two charges in general) and their tension is the absolute value of the superpotential section L. The introduction of sources (we study sources with finite and vanishing thickness) is equivalent to the introduction of local coupling constants and results in dramatic changes of the solutions. Our results call for a democratic reformulation of N=1,d=4 supergravity in which coupling constants are, off-shell, scalar fields. The effective actions for the instantons are always proportional to the coordinate orthogonal to the twist-free embedding of the null-geodesic (in the Wick-rotated scalar manifold) describing the instanton. We show their supersymmetry and find the as...

  7. Examining Prebiotic Chemistry Using O(^1D) Insertion Reactions

    Hays, Brian M.; Laas, Jacob C.; Weaver, Susanna L. Widicus

    2013-06-01

    Aminomethanol, methanediol, and methoxymethanol are all prebiotic molecules expected to form via photo-driven grain surface chemistry in the interstellar medium (ISM). These molecules are expected to be precursors for larger, biologically-relevant molecules in the ISM such as sugars and amino acids. These three molecules have not yet been detected in the ISM because of the lack of available rotational spectra. A high resolution (sub)millimeter spectrometer coupled to a molecular source is being used to study these molecules using O(^1D) insertion reactions. The O(^1D) chemistry is initiated using an excimer laser, and the products of the insertion reactions are adiabatically cooled using a supersonic expansion. Experimental parameters are being optimized by examination of methanol formed from O(^1D) insertion into methane. Theoretical studies of the structure and reaction energies for aminomethanol, methanediol, and methoxymethanol have been conducted to guide the laboratory studies once the methanol experiment has been optimized. The results of the calculations and initial experimental results will be presented.

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

    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.

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

    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. PMID:24224843

  10. Physiological and pharmacological functions of OATP1A/1B transporters

    Steeg, E.

    2010-01-01

    Organic Anion Transporting Polypeptide (OATP; mouse Oatp) transporters of the 1A/1B subfamilies are uptake transporters that mediate the cellular uptake of a wide range of endogenous and xenobiotic compounds. Since OATP1A/1B transporters are expressed in pharmacological important organs, like liver, kidney and small intestine, it has been hypothesized that OATP1A/1B transporters play an important role in drug disposition and elimination. By generating and utilizing novel Oatp1a/1b cluster kno...

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

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

    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)

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

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

    2016-02-01

    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

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

    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.

  15. 76 FR 62455 - Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants

    2011-10-07

    ... Employment and Training Administration Announcement of Updated Funding Availability for H-1B Technical Skills... Federal Register announcing the availability of $240 million for the H-1B Technical Skills Training Grants... available and encouraging additional applicants to apply for the H-1B Technical Skills Training...

  16. Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients

    Visser, Gepke; de Jager, Wilco; Verhagen, Liesbeth P.; Smit, G. Peter A.; Wijburg, Frits A.; Prakken, Berent J.; Coffer, Paul J.; Buitenhuis, Miranda

    2012-01-01

    Glycogen storage disease type 1b (GSD 1b) is caused by mutations in the Glucose-6-phosphate transporter and is characterized by impaired glucose homeostasis. In addition, GSD-1b is associated with chronic neutropenia resulting in recurrent infections and inflammatory bowel disease. It is unclear whe

  17. Long-term impact of interferon beta-1b in patients with CIS

    Edan, G; Kappos, L; Montalbán, X;

    2014-01-01

    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...

  18. Deletion of Protein Tyrosine Phosphatase 1B (PTP1B Enhances Endothelial Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced Endothelial Dysfunction.

    David J Herren

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B dephosphorylates receptors tyrosine kinase and acts as a molecular brake on insulin signaling pathway. Conditions of metabolic dysfunction increase PTP1B, when deletion of PTP1B protects against metabolic disorders by increasing insulin signaling. Although vascular insulin signaling contributes to the control of glucose disposal, little is known regarding the direct role of PTP1B in the control of endothelial function. We hypothesized that metabolic dysfunctions increase PTP1B expression in endothelial cells and that PTP1B deletion prevents endothelial dysfunction in situation of diminished insulin secretion. Type I diabetes (T1DM was induced in wild-type (WT and PTP1B-deficient mice (KO with streptozotocin (STZ injection. After 28 days of T1DM, KO mice exhibited a similar reduction in body weight and plasma insulin levels and a comparable increase in glycemia (WT: 384 ± 20 vs. Ko: 432 ± 29 mg/dL, cholesterol and triglycerides, as WT mice. T1DM increased PTP1B expression and impaired endothelial NO-dependent relaxation, in mouse aorta. PTP1B deletion did not affect baseline endothelial function, but preserved endothelium-dependent relaxation, in T1DM mice. NO synthase inhibition with L-NAME abolished endothelial relaxation in control and T1DM WT mice, whereas L-NAME and the cyclooxygenases inhibitor indomethacin were required to abolish endothelium relaxation in T1DM KO mice. PTP1B deletion increased COX-2 expression and PGI2 levels, in mouse aorta and plasma respectively, in T1DM mice. In parallel, simulation of diabetic conditions increased PTP1B expression and knockdown of PTP1B increased COX-2 but not COX-1 expression, in primary human aortic endothelial cells. Taken together these data indicate that deletion of PTP1B protected endothelial function by compensating the reduction in NO bioavailability by increasing COX-2-mediated release of the vasodilator prostanoid PGI2, in T1DM mice.

  19. Extended-Range Ultrarefractive 1D Photonic Crystal Prisms

    Ting, David Z.

    2007-01-01

    A proposal has been made to exploit the special wavelength-dispersive characteristics of devices of the type described in One-Dimensional Photonic Crystal Superprisms (NPO-30232) NASA Tech Briefs, Vol. 29, No. 4 (April 2005), page 10a. A photonic crystal is an optical component that has a periodic structure comprising two dielectric materials with high dielectric contrast (e.g., a semiconductor and air), with geometrical feature sizes comparable to or smaller than light wavelengths of interest. Experimental superprisms have been realized as photonic crystals having three-dimensional (3D) structures comprising regions of amorphous Si alternating with regions of SiO2, fabricated in a complex process that included sputtering. A photonic crystal of the type to be exploited according to the present proposal is said to be one-dimensional (1D) because its contrasting dielectric materials would be stacked in parallel planar layers; in other words, there would be spatial periodicity in one dimension only. The processes of designing and fabricating 1D photonic crystal superprisms would be simpler and, hence, would cost less than do those for 3D photonic crystal superprisms. As in 3D structures, 1D photonic crystals may be used in applications such as wavelength-division multiplexing. In the extended-range configuration, it is also suitable for spectrometry applications. As an engineered structure or artificially engineered material, a photonic crystal can exhibit optical properties not commonly found in natural substances. Prior research had revealed several classes of photonic crystal structures for which the propagation of electromagnetic radiation is forbidden in certain frequency ranges, denoted photonic bandgaps. It had also been found that in narrow frequency bands just outside the photonic bandgaps, the angular wavelength dispersion of electromagnetic waves propagating in photonic crystal superprisms is much stronger than is the angular wavelength dispersion obtained

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

    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.

  1. Coherent thermal conductance of 1-D photonic crystals

    Tschikin, Maria; Ben-Abdallah, Philippe; Biehs, Svend-Age

    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 Al2O3/vacuum slabs by means of the exact radiative heat flux expression. Based on the results obtained for the Al2O3/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.

  2. Spatial coherence of polaritons in a 1D channel

    Savenko, I. G., E-mail: savenko.j@mail.ru [Russian Academy of Sciences, Academic University, Research and Education Center of Nanotechnologies (Russian Federation); Iorsh, I. V. [National Research University of Information Technologies, Mechanics and Optics (Russian Federation); Kaliteevski, M. A. [Russian Academy of Sciences, Academic University, Research and Education Center of Nanotechnologies (Russian Federation); Shelykh, I. A. [University of Iceland, Science Institute (Iceland)

    2013-01-15

    We analyze time evolution of spatial coherence of a polariton ensemble in a quantum wire (1D channel) under constant uniform resonant pumping. Using the theoretical approach based on the Lindblad equation for a one-particle density matrix, which takes into account the polariton-phonon and excitonexciton interactions, we study the behavior of the first-order coherence function g{sup 1} for various pump intensities and temperatures in the range of 1-20 K. Bistability and hysteresis in the dependence of the first-order coherence function on the pump intensity is demonstrated.

  3. A Godunov method for Lagrangian hydrodynamics in 1D

    Crowley, W.P.

    1987-01-15

    For transient problems involving strong shocks, the artificial viscosity method has been the standard in numerical hydrodynamics for many years. An alternative approach was suggested by Godunov and it is gaining acceptance. We consider a Godunov method for 1D Lagrangian calculations and show that in the case of a strong shock moving through a nonuniform mesh the Godunov solution is superior to the artificial viscosity solution. For uniform mesh shock problems in spherical geometry the two methods give comparable results. 4 refs., 9 figs.

  4. 1D-transport properties of single superconducting lead nanowires

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

    2003-01-01

    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......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...

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

    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.

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

    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 \

  7. Phthalocyanine based 1D nanowires for device applications

    Saini, Rajan; Mahajan, Aman; Bedi, R. K.

    2012-06-01

    1D nanowires (NWs) of Cu (II) 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-Phthalocyanine (CuPc(OBu)8) molecule have been grown on different substrates by cost effective solution processing technique. The density of NWs is found to be strongly dependent on the concentration of solution. The possible formation mechanism of these structures is π-π interaction between phthalocyanine molecules. The improved conductivity of these NWs as compared to spin coated film indicates their potential for molecular device applications.

  8. 1-D ELECTRO-OPTIC BEAM STEERING DEVICE

    Wang, Wei-Chih; Tsui, Chi Leung

    2011-01-01

    In this paper, we present the design and fabrication of a 1D beam steering device based on planar electro-optic thermal-plastic prisms and a collimator lens array. With the elimination of moving parts, the proposed device is able to overcome the mechanical limitations of present scanning devices, such as fatigue and low operating frequency, while maintaining a small system footprint (~0.5mm×0.5mm). From experimental data, our prototype device is able to achieve a maximum deflection angle of 5...

  9. Coherent thermal conductance of 1-D photonic crystals

    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 Al2O3/vacuum slabs by means of the exact radiative heat flux expression. Based on the results obtained for the Al2O3/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.

  10. 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

    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

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

    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.

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

    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...

  13. A 1D analysis of two high order MOC methods

    The work presented here provides two different methods for evaluating angular fluxes along long characteristics. One is based off a projection of the 1D transport equation onto a complete set of Legendre polynomials, while the other uses the 1D integral transport equation to evaluate the angular flux values at specific points along each track passing through a cell. The Moment Long Characteristic (M-LC) method is shown to provide 2(P+1) spatial convergence and significant gains in accuracy with the addition of only a few spatial degrees of freedom. The M-LC method, though, is shown to be ill-conditioned at very high order and for optically thin geometries. The Point Long Characteristic (P-LC) method, while less accurate, significantly improves stability to problems with optically thin cells. The P-LC method is also more flexible, allowing for extra angular flux evaluations along a given track to give a more accurate representation of the shape along each track. This is at the expense of increasing the degrees of freedom of the system, though, and requires an increase in memory storage. This work concludes that both may be used simultaneously within the same geometry to provide the best mix of accuracy and stability possible. (authors)

  14. 1-D DCT Using Latency Efficient Floating Point Algorithms

    Viswanath Gowd A, Yedukondala Rao V, T. Shanmuganantham

    2013-04-01

    Full Text Available This paper presents the design of one-dimensional discrete cosine transform (DCT architecture for digital signal processing (DSP applications. DCT is a basic transformation for coding method which converts spatial domain to frequency domain of image. In 1-D DCT operation addition, subtraction, multiplication operations are required. These operations must be accurate, less latency. Floating point operations have dynamic range of representation, more accurate and perform millions of calculations per second. So the floating point operations are used for the above operations. In this floating point adder/subtractor is the most complex operation in a floating-point arithmetic and consists of many variable latency- and area dependent sub-operations. In floating-point addition implementations, latency is the primary performance bottleneck. So different types of floating point adder/subtractor algorithms such as LOD, LOP, Two-path are used to decrease the latency. The trade off is observed in 1-D DCT by changing different types of adders in place of summer. All architectures are designed and implemented using VHDL using Xillinx 13.1software.

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

    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.

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

    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.

  17. The Cosmological Mass Function with 1D Gravity

    Monaco, P; Monaco, Pierluigi; Murante, Giuseppe

    1999-01-01

    The cosmological mass function problem is analyzed in full detail in the case of 1D gravity, with analytical, semi-analytical and numerical techniques. The extended Press & Schechter theory is improved by detailing the relation between smoothing radius and mass of the objects. This is done by introducing in the formalism the concept of a growth curve for the objects. The predictions of the extended Press & Schechter theory are compared to large N-body simulations of flat expanding 1D universes with scale-free power spectra of primordial perturbations. The collapsed objects in the simulations are located with a clump-finding algorithm designed to find regions that have undergone orbit crossing or that are in the multi-stream regime (these are different as an effect of the finite size of the multi-stream regions). It is found that the semi-analytical mass function theory, which has no free parameters, is able to recover the properties of collapsed objects both statistically and object by object. In part...

  18. Hamming Distance and Data Compression of 1-D CA

    Raied Salman

    2013-05-01

    Full Text Available In this paper an application of von Neumann correct ion technique to the output string of some chaotic rules of 1-D Cellular Automata that are uns uitable for cryptographic pseudo random number generation due to their non uniform distribu tion of the binary elements is presented. The one dimensional (1-D Cellular Automata (CA Ru le space will be classified by the time run of Hamming Distance (HD. This has the advantage of determining the rules that have short cycle lengths and therefore deemed to be unsuitable for cryptographic pseudo random number generation. The data collected from evolution of ch aotic rules that have long cycles are subjected to the original von Neumann density corre ction scheme as well as a new generalized scheme presented in this paper and tested for stati stical testing fitness using Diehard battery of tests. Results show that significant improvement in the statistical tests are obtained when the output of a balanced chaotic rule are mutually excl usive ORed with the output of unbalanced chaotic rule that have undergone von Neumann densit y correction.

  19. 40 CFR 721.1187 - Bis(imidoethylene) benzene.

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bis(imidoethylene) benzene. 721.1187... Substances § 721.1187 Bis(imidoethylene) benzene. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance bis(imidoethylene)benzene (PMN P-93-1447) is subject to...

  20. Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice.

    Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah; Bachaalany, Santana; Griffey, Stephen; Sastre, Juan; Haj, Fawaz G

    2016-08-01

    Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein- and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein- and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-α were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein- and arginine-induced NF-κB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein- and arginine-induced acute pancreatitis. PMID:27461362

  1. Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity.

    Maples, Jill M; Brault, Jeffrey J; Witczak, Carol A; Park, Sanghee; Hubal, Monica J; Weber, Todd M; Houmard, Joseph A; Shewchuk, Brian M

    2015-08-15

    The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

  2. The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-1B (GB-10) as 1B-carriers for boron neutron capture therapy

    Purpose: To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting 1B-carriers for boron neutron capture therapy. Methods and Materials: A free mercaptoundecahydrododecaborate-1B (BSH) or decahydrodecaborate-1B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and 1B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these 1B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors. Results: Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of 1B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing 1B-carriers were significantly greater than BSH-containing 1B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes. Conclusions: In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising 1B-carriers

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

    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.

  4. High-resolution imaging of brain 5-HT1B receptors in the rhesus monkey using [11C]P943

    The serotonin 5-HT1B 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, [11C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT1B receptor. [11C]P943 was synthesized via N-methylation of the precursor with [11C]methyl iodide or [11C]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 (BPND) 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-HT1B receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BPND values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT1B/5-HT1D antagonist, resulted in reduction of BPND 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 [11C]P943 for 5-HT1B receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT1B receptor system in humans.

  5. Cobalt(II) complexes with bis(N-imidazolyl/benzimidazolyl) pyridazine: Structures, photoluminescent and photocatalytic properties

    Li, Jin-Ping; Fan, Jian-Zhong; Wang, Duo-Zhi

    2016-07-01

    Six new CoII complexes [Co(L1)4(OH)2] (1), {[Co(L1)(H2O)4]·2ClO4}∞ (2), {[Co(L1)(H2O)4]·SiF6}∞ (3), {[Co(L1)3]·2ClO4}∞ (4), [Co(L2)Cl2]∞ (5) and {[Co(L2)2]·SiF6}∞ (6) [L1=3,6-bis(N-imidazolyl) pyridazine, L2=3,6-bis (N-benzimidazolyl) pyridazine] have been synthesized and characterized by elemental analysis, IR spectra and single crystal X-ray diffraction. Complex 1 has a mononuclear structure, while complexes 2 and 3 have 1-D chain structures. Considering the CoII centers were linked by the L1 ligands, the 3-D framework of complex 4 can be rationalized to be a {4^12.6^3} 6-c topological net with the stoichiometry uninodal net. 5 reveals a coordination 1-D zigzag chain structure consisting of a neutral chain [Co(L2)Cl2]n with the CoII centers. Complex 6 has a rhombohedral grid with a (4, 4) topology. The TGA property, fluorescent property and photocatalytic activity of complexes 1-6 have been investigated and discussed.

  6. Simplified 1D modelling of the HGA test

    Document available in extended abstract form only. The HGA test is located in the Mont Terri Rock Laboratory (Switzerland). It consists of a horizontal borehole of 1.00 m of diameter and 13.00 m of length excavated in the ultra-low permeable Opalinus clay. During the tunnel drilling, the Opalinus clay near the tunnel wall was damaged, giving rise to an EDZ (Excavation Damaged Zone) around the tunnel. A steel liner was placed along the 6.00 m close to the tunnel mouth in order to guarantee the stability. The last 4.00 m at the tunnel end were backfilled with gravel. Along the remaining 3.00 m, an inflatable rubber packer of 1.00 m in diameter, was installed and inflated, thereby compressing the EDZ that was created during the tunnel excavation. The test section was filled with de-aired water and care was taken in order to eliminate the air from this tunnel section. Subsequently, a series of water and gas injection tests were carried out with varying mega-packer pressure, whereby water or gas was injected into the test section and, due to the very low permeability of the intact Opalinus clay, forced to flow back along the EDZ. In order to model the water and gas flow through the EDZ, we have followed a two-track approach. On the one hand, a 2D axisymmetric numerical model using code-bright has been made. On the other hand, a 1D analytical-numerical model has been developed and implemented in an Excel spreadsheet, whereby the field equations defined on a 1D geometrical domain are numerically solved using the finite element method. The 1D model has been used in order to calibrate the 2D axisymmetric model. Both the Opalinus clay and the EDZ will be considered to be porous media, with an incompressible solid phase (clay), an incompressible liquid phase (water and air) and a gas phase (water and air). The properties of the liquid phase will be assumed to be independent of the concentration of dissolved air and the gas phase will be assumed to be a mixture of dry air and

  7. Münchner Theatergeschichte 1600 bis 2000

    Hemler, Stefan; Zuber, Barbara

    2009-01-01

    Tagungsbericht: Münchner Theatergeschichte 1600 bis 2000 Veranstalter: Kulturreferat der Landeshauptstadt München; Institut für Theaterwissenschaft; Institut für Bayerische Geschichte an der Ludwig-Maximilians-Universität München Datum, Ort: 12.05.2000-14.05.2000, München

  8. Axion string dynamics I: 2+1D

    Fleury, Leesa M.; Moore, Guy D.

    2016-05-01

    If the axion exists and if the initial axion field value is uncorrelated at causally disconnected points, then it should be possible to predict the efficiency of cosmological axion production, relating the axionic dark matter density to the axion mass. The main obstacle to making this prediction is correctly treating the axion string cores. We develop a new algorithm for treating the axionic string cores correctly in 2+1 dimensions. When the axionic string cores are given their full physical string tension, axion production is about twice as efficient as in previous simulations. We argue that the string network in 2+1 dimensions should behave very differently than in 3+1 dimensions, so this result cannot be simply carried over to the physical case. We outline how to extend our method to 3+1D axion string dynamics.

  9. Axion String Dynamics I: 2+1D

    Fleury, Leesa M

    2016-01-01

    If the axion exists and if the initial axion field value is uncorrelated at causally disconnected points, then it should be possible to predict the efficiency of cosmological axion production, relating the axionic dark matter density to the axion mass. The main obstacle to making this prediction is correctly treating the axion string cores. We develop a new algorithm for treating the axionic string cores correctly in 2+1 dimensions. When the axionic string cores are given their full physical string tension, axion production is about twice as efficient as in previous simulations. We argue that the string network in 2+1 dimensions should behave very differently than in 3+1 dimensions, so this result cannot be simply carried over to the physical case. We outline how to extend our method to 3+1D axion string dynamics.

  10. Slug modeling with 1D two-fluid model

    Simulations of condensation-induced water hammer with one-dimensional two-fluid model requires explicit modeling of slug formation, slug propagation, and in some cases slug decay. Stratified flow correlations that are more or less well known in 1D two-fluid models, are crucial for accurate description of the initial phase of the slug formation and slug propagation. Slug formation means transition to other flow regime that requires different set of correlations. To use such two-fluid model for condensation induced water hammer simulations, a single slug must be explicitly recognized and captured. In the present work two cases of condensation-induced water hammer simulations performed with WAHA code, are described and discussed: injection of cold liquid into horizontal pipe filled with steam and injection of hot steam into horizontal pipe partially filled with cold liquid. (author)

  11. 1D PIC simulation of relativistic Buneman instability

    Buneman instability in the relativistic regime has been studied using a 1D electrostatic particle-in-cell code. In the non-relativistic case, Hirose et al. (Plasma Phys. 20, 481(1978)) has shown that breakdown of linear growth (saturation) occurs when |E|2/16πW0 ∼ ζomax, where W0 is the initial beam kinetic energy density and ζomax is maximum growth rate of the instability. In the weakly relativistic case, it has been confirmed using PIC simulation that scaling of saturation of Buneman instability follows a similar behavior as the non-relativistic case, whereas in the strongly relativistic case our simulation results show significant deviation from Hirose's results. In the strongly relativistic case, growth rate reduces due to relativistic corrections; so saturation occurs at a lower value compared to the non-relativistic/weakly relativistic case. (author)

  12. Assessment of the 2D/1D implementation in MPACT

    The 2D/1D method is used in the MPACT code to obtain 3D solutions of the Boltzmann transport equation for practical reactor geometries. The OECD C5G7 transport benchmark problem is used first to assess the accuracy of the method with a fixed set of cross-sections. The VERA Core Physics Progression Problems are then used to compare the accuracy of the transport solver using a 56-group library based on ENDFB-VII.0. Single assembly PWR designs are simulated, and the eigenvalue and pin powers are compared to continuous-energy Monte Carlo results. A 3x3 assembly cluster with a control rod inserted into the center assembly is then compared to Monte Carlo to assess the ability of MPACT to predict a control rod worth curve. Finally, MPACT is used to simulate the initial critical states of a full 3D initial core of a PWR at zero power conditions. (author)

  13. 1-D Molecular Chains of Thiophene on Ge(100)

    Jeon, Seok Min; Jung, Soon Jung; Kim, Hyeong-Do; Lim, Do Kyung; Lee, Hangil; Kim, Sehun

    2007-01-01

    The adsorption geometry of thiophene on Ge(100) have been studied by high-resolution core-level photoemission spectroscopy (HRPES) using synchrotron radiation and scanning tunneling microscopy (STM). From the analysis of the Ge 3d, S 2p, and C 1s core-level photoemission spectra, we found three different adsorption geometries, which were assigned to a dative bonding feature, a [4+2] cycloaddition reaction product, and a desulfurization reaction product. Furthermore, we investigated that the ratio of the components induced by three adsorption geometries changed depending on the molecular coverage and the annealing temperature. At low coverage, the kinetically favorable dative bonding features favorably form 1-D molecular chains. Increasing the molecular coverage, the energetically more stable [4+2] cycloaddition reaction products are additionally created.

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

    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.

  15. Detection of genes regulated by Lmx1b during limb dorsalization.

    Feenstra, Jennifer M; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E; Eppey, Richard J; Oberg, Kerby C

    2012-05-01

    Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. PMID:22417325

  16. Ganglioside GQ1b induces dopamine release through the activation of Pyk2.

    Zhang, Zhao; Chu, Shi-Feng; Mou, Zheng; Gao, Yan; Wang, Zhen-Zhen; Wei, Gui-Ning; Chen, Nai-Hong

    2016-03-01

    Growing evidence indicates that GQ1b, one of the gangliosides members, contributes to synaptic transmission and synapse formation. Previous studies have shown that GQ1b could enhance depolarization induced neurotransmitter release, while the role of GQ1b in asynchronous release is still largely unknown. Here in our result, we found low concentration of GQ1b, but not GT1b or GD1b (which were generated from GQ1b by plasma membrane-associated sialidases), evoked asynchronous dopamine (DA) release from both clonal rat pheochromocytoma PC12 cells and rat striatal slices significantly. The release peaked at 2min after GQ1b exposure, and lasted for more than 6min. This effect was caused by the enhancement of intracellular Ca(2+) and the activation of Pyk2. Inhibition of Pyk2 by PF-431396 (a dual inhibitor of Pyk2 and FAK) or Pyk2 siRNA abolished DA release induced by GQ1b. Moreover, Pyk2 Y402, but not other tyrosine site, was phosphorylated at the peaking time. The mutant of Pyk2 Y402 (Pyk2-Y402F) was built to confirm the essential role of Y402 activation. Further studies revealed that activated Pyk2 stimulated ERK1/2 and p-38, while only the ERK1/2 activation was indispensable for GQ1b induced DA release, which interacted with Synapsin I directly and led to its phosphorylation, then depolymerization of F-actin, thus contributed to DA release. In conclusion, low concentration of GQ1b is able to enhance asynchronous DA release through Pyk2/ERK/Synapsin I/actin pathway. Our findings provide new insights into the role of GQ1b in neuronal communication, and implicate the potential application of GQ1b in neurological disorders. PMID:26704905

  17. A 1-D morphodynamic model of postglacial valley incision

    Tunnicliffe, Jon F.; Church, Michael

    2015-11-01

    Chilliwack River is typical of many Cordilleran valley river systems that have undergone dramatic Holocene degradation of valley fills that built up over the course of Pleistocene glaciation. Downstream controls on base level, mainly blockage of valleys by glaciers, led to aggradation of significant glaciofluvial and glaciolacustrine valley fills and fan deposits, subsequently incised by fluvial action. Models of such large-scale, long-term degradation present a number of important challenges since the evolution of model parameters, such as the rate of bedload transport and grain size characteristics, are governed by the nature of the deposit. Sediment sampling in the Chilliwack Valley reveals a complex sequence of very coarse to fine textural modes. We present a 1-D numerical morphodynamic model for the river-floodplain system tailored to conditions in the valley. The model is adapted to dynamically adjust channel width to optimize sediment transporting capacity and to integrate relict valley fill material as the channel incises through valley deposits. Sensitivity to model parameters is studied using four principal criteria: profile concavity, rate of downstream grain size fining, bed surface sand content, and the timescale to equilibrium. Model results indicate that rates of abrasion and coarsening of the grain size distributions exert the strongest controls on all of the interrelated model performance criteria. While there are a number of difficulties in satisfying all model criteria simultaneously, results indicate that 1-D models of valley bottom sedimentary systems can provide a suitable framework for integrating results from sediment budget studies and chronologies of sediment evacuation established from dating.

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

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

    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........ Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b...

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

    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.

  1. In vivo and in vitro CYP1B mRNA expression in channel catfish.

    Willett, Kristine L; Ganesan, Shobana; Patel, Monali; Metzger, Christine; Quiniou, Sylvie; Waldbieser, Geoff; Scheffler, Brian

    2006-07-01

    Our goal was to study the induction of CYP1B mRNA expression in channel catfish (Ictalurus punctatus). CYP1B belongs to the cytochrome P450 superfamily of genes, is involved in the oxidation of endogenous and exogenous compounds, and could potentially be a useful biomarker in fish for exposure to AhR ligands. The full-length catfish CYP1B cDNA is 2417 nt to the polyA tail and encodes a putative protein of 536 amino acids. It has 67% amino acid similarity to carp and zebrafish CYP1B and 68% similarity to carp CYP1B2. Male channel catfish were collected from three Mississippi Delta sites: Lake Roebuck, Itta Bena; Bee Lake, Thornton; and Sunflower River, Indianola. Total RNA was isolated from wild-caught catfish gill, blood, gonad and liver tissues. Quantitative real-time reverse transcriptase PCR was used to determine relative induction of CYP1B in wild catfish compared to laboratory control and BaP-exposed catfish (20mg/kg i.p. after 4 days). BaP exposure significantly induced CYP1B message in blood, gonad, and liver of laboratory catfish. In these same tissues of wild catfish from sites with relatively low sediment contaminants, CYP1B message was not statistically increased relative to laboratory control catfish. CYP1B transcript abundance was higher in gills compared to other tissues in both laboratory and wild catfish. When primary cultured gill cells were treated with increasing concentrations of BaP, TCDD, and PCBs 77, 126 and 169, CYP1B mRNA was induced more than 10-fold while PCB153 and 4,4'DDT did not cause significant CYP1B induction. Our results suggest that catfish CYP1B is induced by the classic AhR ligands. PMID:16697458

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

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

    2015-01-01

    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 developme...

  3. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

    Yun Zhao; Zhuqi Tang; Aiguo Shen; Tao Tao; Chunhua Wan; Xiaohui Zhu; Jieru Huang; Wanlu Zhang; Nana Xia; Suxin Wang; Shiwei Cui; Dongmei Zhang

    2015-01-01

    Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201...

  4. Water molecule network and active site flexibility of apo protein tyrosine phosphatase 1B

    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...

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

    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.

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

    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....... 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.......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, encoding...... syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) 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...

  7. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse

    Ji, Shaonin; You, Yun; Kerner, Janos; Hoppel, Charles L.; Schoeb, Trenton R.; Chick, Wallace S H; Hamm, Doug A.; Sharer, J. Daniel; Wood, Philip A.

    2007-01-01

    Carnitine palmitoyltransferase-1 (CPT-1) catalyzes the rate-limiting step of mitochondrial β-oxidation of long chain fatty acids (LCFA), the most abundant fatty acids in mammalian membranes and in energy metabolism. Human deficiency of the muscle isoform CPT-1b is poorly understood. In the current study, embryos with a homozygous knockout of Cpt-1b were lost before embryonic day 9.5 − 11.5. Also, while there were normal percentages of CPT-1b+/−pups born from both male and female CPT-1b+/− mic...

  8. The ING1b tumor suppressor facilitates nucleotide excision repair by promoting chromatin accessibility to XPA

    ING1b is the most studied ING family protein and perhaps the most ubiquitously and abundantly expressed. This protein is involved in the regulation of various biological functions ranging from senescence, cell cycle arrest, apoptosis, to DNA repair. ING1b is upregulated by UV irradiation and enhances the removal of bulky nucleic acid photoproducts. In this study, we provide evidence that ING1b mediates nucleotide excision repair by facilitating the access to damaged nucleosomal DNA. We demonstrate that ING1b is not recruited to UV-induced DNA lesions but enhances nucleotide excision repair only in XPC-proficient cells, implying an essential role in early steps of the 'access, repair, restore' model. We also find that ING1b alters histone acetylation dynamics upon exposure to UV radiation and induces chromatin relaxation in microccocal nuclease digestion assay, revealing that ING1b may allow better access to nucleotide excision repair machinery. More importantly, ING1b associates with chromatin in a UV-inducible manner and facilitates DNA access to nucleotide excision repair factor XPA. Furthermore, depletion of the endogenous ING1b results to the sensitization of cells at S-phase to UV irradiation. Taken together, these observations establish a role of ING1b acting as a chromatin accessibility factor for DNA damage recognition proteins upon genotoxic injury

  9. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy.

    Vlaskamp, Danique R M; Rump, Patrick; Callenbach, Petra M C; Vos, Yvonne J; Sikkema-Raddatz, Birgit; van Ravenswaaij-Arts, Conny M A; Brouwer, Oebele F

    2016-05-01

    We describe an 18-year-old male patient with myoclonic astatic epilepsy (MAE), moderate to severe intellectual disability, behavioural problems, several dysmorphisms and a 1.2-Mb de novo deletion on chromosome 16p11.2. This deletion results in haploinsufficiency of STX1B and other genes. Recently, variants in the STX1B gene have been associated with a wide spectrum of fever-related epilepsies ranging from single febrile seizures to severe epileptic encephalopathies. Two previously reported patients with a STX1B missense variant or deletion were diagnosed with MAE. Our observation of a STX1B deletion in a third patient with MAE therefore supports that STX1B gene variants or deletions can be involved in the aetiology of MAE. Furthermore, STX1B encodes for syntaxin-1B, of which interaction with the protein encoded by the STXBP1 gene is essential for the regulation of the synaptic transmission of neurotransmitters. STXBP1 gene variants have been identified in patients with many different types of epilepsy, including Dravet syndrome and epileptic encephalopathies, suggesting STX1B plays a similar role. We recommend that analysis of STX1B should be considered in the diagnostic work-up of individuals with MAE. PMID:26818399

  10. 3D/1D Analysis of ICRF Antennas

    Maggiora, Riccardo; Lancellotti, Vito; Vecchi, Giuseppe

    2003-10-01

    An innovative tool has been realized for the 3D/1D simulation of Ion Cyclotron Radio Frequency (ICRF), i.e. accounting for antennas in a realistic 3D geometry and with an accurate 1D plasma model. The approach to the problem is based on an integral-equation formulation for the self-consistent evaluation of the current distribution on the conductors. The environment has been subdivided in two coupled region: the plasma region and the vacuum region. The two problems are linked by means of a magnetic current (electric field) distribution on the aperture between the two regions. In the vacuum region all the calculations are executed in the spatial domain while in the plasma region an extraction in the spectral domain of some integrals is employed that permits to significantly reduce the integration support and to obtain a high numerical efficiency leading to the practical possibility of using a large number of sub-domain (rectangular or triangular) basis functions on each solid conductor of the system. The plasma enters the formalism of the plasma region via a surface impedance matrix; for this reason any plasma model can be used; at present the FELICE code has been adopted, that affords density and temperature profiles, and FLR effects. The source term directly models the TEM mode of the coax feeding the antenna and the current in the coax is determined self-consistently, giving the input impedance/admittance of the antenna itself. Calculation of field distributions (both magnetic and electric), useful for sheath considerations, is included. This tool has been implemented in a suite, called TOPICA, that is modular and applicable to ICRF antenna structures of arbitrary shape. This new simulation tool can assist during the detailed design phase and for this reason can be considered a "Virtual Prototyping Laboratory" (VPL). The TOPICA suite has been tested against assessed codes and against measurements and data of mock-ups and existing antennas. The VPL is being used in

  11. 78 FR 5210 - Open Government Initiative: Implementation of the iCERT Labor Certification Registry for the H-1B...

    2013-01-24

    ... Certification Registry for the H-1B, H-1B1, E-3, H-2A, H-2B and Permanent Labor Certification Employment-Based... to the general public appropriately redacted copies of H-1B, H-1B1, E-3, H-2A, H-2B and permanent... a labor certification or, in the case of an H-1B, H-1B1, or E-3 visa, a labor condition...

  12. Graphs on uniform points in [0,1]d

    Appel, Martin J. B.; Russo, Ralph P.; Yang, King J.

    1995-06-01

    Statistical problems in pattern or structure recognition for a random multidimensional point set may be addressed by variations on the random graph model of Erdos and Renyui. The imposition of graph structure with a variable edge criterion on a large random point set allows a search for signature quantities or behavior under the given distributional hypothesis. The work is motivated by the question of how to make statistical inferences from sensed mine field data. This article describes recent results obtained in the following special cases. On independent random points U1,...,Un distributed uniformly on [0,1]d, a random graph Gn(x) is constructed in which two distinct such points are joined by an edge if the l(infinity )-distance between them is at most some prescribed value 0 graph are described. Almost-sure asymptotic rates of convergence/divergence are obtained for various quantities, including the maximum and minimum vertex degree of the random graph, its clique number, chromatic number, and independence number, as the number n of points becomes large and the edge distance x is allowed to vary with n. The connectivity distance cn, the smallest x such that Gn(x) is connected, and the largest nearest neighbor link dn, the smallest x such that Gn(x) has no vertices of degree zero, are asymptotic in ratio, as n becomes large, for d >= 2.

  13. 1D dynamic beam modulation: methods to counteract inertia effects

    Dynamic modulation can be affected by inaccuracies when the required acceleration is larger than the highest allowed by the mechanical characteristics of the whole apparatus. In this study, inertia effects have been investigated with regard to the single absorber 1D modulation, analysing primarily how the acceleration performed by the modulating system affects the realization of 'single absorber' fluence profiles and the type of correction which could be devised. The observed percentage deviations from desired modulation at the lowest fluence coordinate of single minimum fluence profiles, when no correction is applied, were almost negligible for 'easy' modulations of the incident fluence (i.e. slow gradients); deviations became increasingly relevant as the moving absorber executed steeper gradients (a 17.6% higher dose being delivered in the minimum position when a 0.2 modulation is required). By applying the proposed corrections, the single absorber performances were improved to a satisfactory level, with a maximum deviation from desired modulation in the minima within 1.6%. (author)

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

    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 ...

  15. The molecular spin filter constructed from 1D organic chain

    We proposed a molecular spin filter, which is constructed from the 1D metallic organic chain (Fen+1(C6H4)n). The spin-polarized transport properties of the molecular spin filter are explored by combining density functional theory with nonequilibrium Green's function formalism. Theoretical results reveal that Fen+1(C6H4)n molecular chain exhibits robust spin filtering effect, and only the spin-down electrons can transmit through the molecular chain. At the given bias voltage window [−1 eV,1 eV], the calculated spin filter efficiency is close to 100% in the case of n≥3. We find that the effect of spin polarization origin from both Fen+1 and (C6H4)n. In addition, negative difference resistance behavior appears in Fen+1(C6H4)n molecular chain. The results can help us understand the spin transport properties of organic molecular chain. - Highlights: • Theoretical results reveal that Fen+1(C6H4)n molecular chain exhibits robust spin filtering effect. • The effect of spin polarization origin from both of Fen+1 and (C6H4)n. • Negative difference resistance behavior appears in Fen+1(C6H4)n molecular chain

  16. NACA Aircraft on Lakebed - D-558-2, X-1B, and X-1E

    1955-01-01

    of increased capacity, and a thinner high-speed wing. The X-1E was used to obtain in-flight data at twice the speed of sound, with particular emphasis placed on investigating the improvements achieved with the high-speed wing. These wings, made by Stanley Aircraft, were only 3-3/8-inches thick at the root and had 343 gauges installed in them to measure structural loads and aerodynamic heating. The X-1E used its rocket engine to power it up to a speed of 1,471 miles per hour (Mach 2.24) and to an altitude of 73,000 feet. Like the X-1 it was air-launched. The X-1 aircraft were almost 31 feet long and had a wingspan of 28 feet. The X-1 was built of conventional aluminum stressed-skin construction to extremely high structural standards. The X-1E was also 31 feet long but had a wingspan of only 22 feet, 10 inches. It was powered by a Reaction Motors, Inc., XLR-8-RM-5, four-chamber rocket engine. As did all X-1 rocket engines, the LR-8-RM-5 engine did not have throttle capability, but instead, depended on ignition of any one chamber or group of chambers to vary speed. The X-1A, X-1B, and the X-1D were growth versions of the X-1. They were almost five feet longer, almost 2,500 pounds heavier and had conventional canopies. The X-1A and X-1B were modified to have ejection seats. Their mission was to continue the X-1 studies at higher speeds and altitudes. The X-1A began this research after the X-1D was destroyed in an explosion on a captive flight before it made any research flights. On December 12, 1953, Major Charles Yeager flew the X-1A up to a speed of 1,612 miles per hour (almost two-and-a-half times the speed of sound). Then on August 26, 1954, Major Arthur Murray took the X-1A up to an altitude of 90,440 feet. Those two performances were the records for the X-1 program. Later the X-1A was also destroyed after being jettisoned from the carrier aircraft because of an explosion. The X-1B was fitted with 300 thermocouples for exploratory aerodynamic heating tests. It also

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

    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.

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

    Havlickova, E.; Fundamenski, W.; 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 ra...

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

    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.

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

    Pedersen, U B; Norby, B; Jensen, Anders A.; Schiødt, M; Hansen, A; Suhr-Jessen, P; Scheideler, M; Thastrup, O; Andersen, P H

    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...... 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...

  1. Four 1-D metal-organic polymers self-assembled from semi-flexible benzimidazole-based ligand: Syntheses, structures and fluorescent properties

    Zhou, Chun-lin; Wang, Shi-min; Liu, Sai-nan; Yu, Tian-tian; Li, Rui-ying; Xu, Hong; Liu, Zhong-yi; Sun, Huan; Cheng, Jia-jia; Li, Jin-peng; Hou, Hong-wei; Chang, Jun-biao

    2016-08-01

    Four one-dimensional (1-D) metal-organic polymers based on methylene-bis(1,1‧-benzimidazole)(mbbz), namely, {[Hg(mbbz)(SCN)2]·1/3H2O}n (1), [Co(mbbz)(Cl)2]n (2), {[Co(mbbz)(SO4)]·CH3OH}n (3) and {[Zn(mbbz)(SO4)]·CH3OH}n (4) have been successfully synthesized and structurally characterized. Single-crystal X-ray diffraction reveals that polymers 1 and 2 exhibit interesting 1-D double helical chain structures, while polymers 3 and 4 are 1-D double chain structures due to the bridging effect of mbbz ligands and sulfate anions. These polymers containing the mbbz-based ligand have a high degree of dependence on the corresponding counter anions. Furthermore, the fluorescence properties of the four polymers were also investigated in the solid state, showing the fluorescence signal changes in comparing with that of free ligand mbbz.

  2. Bridged bis-BODIPYs: their synthesis, structures and properties.

    Kesavan, Praseetha E; Das, Sudipta; Lone, Mohsin Y; Jha, Prakash C; Mori, Shigeki; Gupta, Iti

    2015-10-21

    A series of bis-BODIPYs 1-6 bridged via thiophene, furan, N-alkylcarbazole, triphenyl-amine, para- and meta-phenylene groups have been synthesized and characterized by various spectroscopic techniques. The change in the spectroscopic properties of bis-BODIPYs upon varying the size of spacers was studied. X-ray crystal structures of three bis-BODIPYs containing triphenylamine, para- and meta-phenylene bridges were solved. Intermolecular C(H)π and ππ stacking interactions were observed in solid state structures of three bis-BODIPYs. The dihedral angles between the spacer unit and two boron-dipyrrin units were lower in all three compounds as compared to their corresponding monomers. This suggests increased interactions between the two boron-dipyrrin units in molecules which are in turn reflected in the anodic shifts in their reduction potentials. DFT studies indicated effective electronic interactions between spacers and two boron dipyrrin units in all the bis-BODIPYs. The calculated HOMO-LUMO gap was found to be lower for bis-BODIPY having bulky carbazole spacers and higher for bis-BODIPY having smaller furan spacers. Changing the spacer size clearly affected the spectroscopic properties of the bis-BODIPYs and red shifted absorption and emission maxima were observed for bis-BODIPYs with furan and thiophene spacers as compared to bis-BODIPYs with phenylene or bulky aromatic spacers. PMID:26373792

  3. A 1D Double Stranded Chain Complex Based on Barium Ion and 1,3,5-Triazine

    CAO Man-Li; ZHANG Xiu-Lian; YIN Wei

    2012-01-01

    A new coordination compound [Ba(OBPT)2(H2O)2]·H2O was obtained at room temperature by the reaction of 4,6-bis(2-pyridyl)-1,3,5-triazin-2-ol(HOBPT) with BaCl2.It was characterized by elemental analysis,FTIR,TG analysis,powder X-ray diffraction analysis and single-crystal X-ray diffraction analysis.The complex crystallizes in the monoclinic P21/n space group,with a = 16.325(1),b = 6.7977(5),c = 24.164(2) ,β = 104.009(1),V = 2601.8(3) 3,Z =4,C26H22BaN10O5,Mr = 691.88,Dc = 1.766 g/cm3,F(000) = 1376 and μ(MoKα) = 1.587 mm-1.The final R = 0.0282 and wR = 0.0724 for 5095 observed reflections with I 〉 2σ(I) and R = 0.0312 and wR = 0.0744 for all data.In the complex,the barium ion is ten-coordinated with six nitrogen atoms from two ligands,two deprotonated hydroxyl oxygen atoms from another two ligands and two coordinated water molecules to form a double stranded chain.The extensive supramolecular interac-tions lead to the formation of an infinite 2D framework.

  4. SYNTHETIC APPROACHES FOR BIS (INDOLYL METHANES

    Partha Pratim Kaishap* and Chandrajit Dohutia

    2013-04-01

    Full Text Available ABSTRACT: Indole ring system is the most important heterocycle available in natural compounds. Owing to great structural diversity, the indole ring system has become an important structural requirement in many pharmaceutical agents. Indole has been widely identified as a privileged structure or pharmacophore, with its presence in over 3000 natural isolates which are known to possess broad spectrum of biological activities and pharmaceutical applications. The bis (indolyl methane derivatives are found to be very active compounds in pharmacy field. They are found in cruciferous plants and are known to promote beneficial oestrogen metabolism and induce apoptosis in human cancer cells. In recent years, a lots of bis (indolyl methane derivatives have been synthesized and found to possess promising biological activities including anticancer, antimicrobial, antifungal, analgesic, anti-inflammatory, anthelmintic, cardiovascular activities. In the present review several synthetic schemes of these compounds are discussed involving non-toxic catalyst and providing high yields.

  5. Bis-iridoid glucosides from Abelia chinensis.

    Tomassini, L; Foddai, S; Serafini, M; Cometa, M F

    2000-07-01

    Seven bis-iridoid glucosides have been isolated from Abelia chinensis and were characterized by having a secoiridoid residue as unit A esterifying a C(10)-iridoid or a delta-lactone iridoid as unit B. Among these, compounds 1-3 are new and correspond to 7-O-acetyllaciniatoside IV, 7-O-acetyllaciniatoside V, and 7-O-acetylabelioside B, respectively. The structures of 1-3 were elucidated by spectral methods. PMID:10924185

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

    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.

  7. 76 FR 56637 - Airworthiness Directives; Lycoming Engines Model IO-720-A1B Reciprocating Engines

    2011-09-14

    ... Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not affect intrastate aviation in Alaska... Model IO-720-A1B Reciprocating Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final... model IO-720-A1B Lycoming Engines reciprocating engines. This AD requires a crankshaft inspection...

  8. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics

    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

  9. Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B.

    Jin, Tiantian; Yu, Haibo; Huang, Xu-Feng

    2016-01-01

    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. PMID:26865097

  10. Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor

    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).

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

    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. PMID:26214522

  12. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.

    Scheffer, Ingrid E; Harkin, Louise A; Grinton, Bronwyn E; Dibbens, Leanne M; Turner, Samantha J; Zielinski, Marta A; Xu, Ruwei; Jackson, Graeme; Adams, Judith; Connellan, Mary; Petrou, Steven; Wellard, R Mark; Briellmann, Regula S; Wallace, Robyn H; Mulley, John C; Berkovic, Samuel F

    2007-01-01

    SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery. PMID:17020904

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

    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.

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

    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

  15. Evidence against dopamine D1/D2 receptor heteromers

    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

  16. A new general 1-D vadose zone flow solution method

    Ogden, Fred L.; Lai, Wencong; Steinke, Robert C.; Zhu, Jianting; Talbot, Cary A.; Wilson, John L.

    2015-06-01

    We have developed an alternative to the one-dimensional partial differential equation (PDE) attributed to Richards (1931) that describes unsaturated porous media flow in homogeneous soil layers. Our solution is a set of three ordinary differential equations (ODEs) derived from unsaturated flux and mass conservation principles. We used a hodograph transformation, the Method of Lines, and a finite water-content discretization to produce ODEs that accurately simulate infiltration, falling slugs, and groundwater table dynamic effects on vadose zone fluxes. This formulation, which we refer to as "finite water-content", simulates sharp fronts and is guaranteed to conserve mass using a finite-volume solution. Our ODE solution method is explicitly integrable, does not require iterations and therefore has no convergence limits and is computationally efficient. The method accepts boundary fluxes including arbitrary precipitation, bare soil evaporation, and evapotranspiration. The method can simulate heterogeneous soils using layers. Results are presented in terms of fluxes and water content profiles. Comparing our method against analytical solutions, laboratory data, and the Hydrus-1D solver, we find that predictive performance of our finite water-content ODE method is comparable to or in some cases exceeds that of the solution of Richards' equation, with or without a shallow water table. The presented ODE method is transformative in that it offers accuracy comparable to the Richards (1931) PDE numerical solution, without the numerical complexity, in a form that is robust, continuous, and suitable for use in large watershed and land-atmosphere simulation models, including regional-scale models of coupled climate and hydrology.

  17. Molecular characterization of a gilthead sea bream (Sparus aurata) muscle tissue cDNA for carnitine palmitoyltransferase 1B (CPT1B).

    Boukouvala, Evridiki; Leaver, Michael J; Favre-Krey, Laurence; Theodoridou, Maria; Krey, Grigorios

    2010-10-01

    Understanding the control of piscine fatty acid metabolism is important for determining the nutritional requirements of fish, and hence for the production of optimal aquaculture diets. The regulation and expression of carnitine palmitoyltransferase 1 (CPT1; EC No 2.3.1.21) are critical processes in the control of fatty acid metabolism, and here we report a cDNA from gilthead sea bream (Sparus aurata) which encodes a protein with high identity to vertebrate CPT1. This sea bream CPT1 mRNA is predominantly expressed in skeletal and cardiac muscle, with little expression in other tissues. Phylogenetic analysis of other vertebrate CPT1 sequences show that fish genomes contain a single gene related to mammalian CPT1B, and a further two multi-gene families related to mammalian CPT1A. Genes related to mammalian CPT1C are absent in fish. Therefore, based on both functional and evolutionary orthology to mammalian CPT1B, the sea bream CPT1 reported here is a CPT1B isoform. Sea bream CPT1B mRNA expression progressively decreases in heart and muscle up to 12h after last feeding, but returns to initial, non-fasted levels after 72h. In contrast, in liver non-fasted expression is low, but strongly increases at 24 and 72h after last feeding. In white muscle and liver, CPT1B mRNA expression is highly correlated with the expression of peroxisomal proliferator-activated receptor beta (PPARbeta). Thus fatty acid metabolism by CPT1B and its control by PPARs are similar in fish and mammals, but multiple genes for CPT1A-like proteins in fish also suggest different and more complex pathways of lipid utilisation than in mammals. PMID:20601065

  18. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    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.

  19. New Mononuclear Cu(II Complexes and 1D Chains with 4-Amino-4H-1,2,4-triazole

    Marinela M. Dîrtu

    2013-12-01

    Full Text Available The crystal structures of two mononuclear Cu(II NH2trz complexes [Cu(NH2trz4(H2O](AsF62 (I and [Cu(NH2trz4(H2O](PF62 (II as well as two coordination polymers [Cu(μ2-NH2trz2Cl]Cl∙H2O (III and [Cu(μ2-NH2trz2Cl] (SiF60.5∙1.5H2O (IV are presented. Cationic 1D chains with bridging bis-monodentate μ2-coordinated NH2trz and bridging μ2-coordinated chloride ligands are present in III and IV. In these coordination polymers, the Cu(II ions are strongly antiferromagnetically coupled with J = −128.4 cm−1 for III and J = −143 cm−1 for IV (H = −JΣSiSi+1, due to the nature of the bridges between spin centers. Inter-chain interactions present in the crystal structures were taken into consideration, as well as g factors, which were determined experimentally, for the quantitative modeling of their magnetic properties.

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

    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.

  1. Maternal BIS Sensitivity, Overprotective Parenting, and Children's Internalizing Behaviors.

    Kiel, Elizabeth J; Maack, Danielle J

    2012-08-01

    Although sensitivity to the Behavioral Inhibition System within Gray's (1970) reinforcement sensitivity theory relates to individuals' own depressive and anxious symptomatology, less is known about how parental BIS sensitivity relates to early indicators of internalizing problems in young children. Moreover, the extent to which this parental characteristic relates to parenting behavior, and children's internalizing problems above and beyond parenting, remains unknown. The current study assessed maternal BIS sensitivity, overprotective parenting, and toddlers' internalizing behaviors in a sample of 91 mothers while controlling for mothers' own internalizing symptomatology. Heightened BIS sensitivity related to both overprotective parenting and internalizing behaviors. Overprotective parenting partially mediated the relation between BIS sensitivity and children's internalizing behaviors, although BIS sensitivity maintained a marginal relation to internalizing behaviors. Maternal BIS sensitivity and toddler internalizing behaviors may represent a shared disposition towards inhibition that is somewhat accounted for by overprotective parenting. PMID:22904590

  2. PPM1D exerts its oncogenic properties in human pancreatic cancer through multiple mechanisms.

    Wu, Bo; Guo, Bo-Min; Kang, Jie; Deng, Xian-Zhao; Fan, You-Ben; Zhang, Xiao-Ping; Ai, Kai-Xing

    2016-03-01

    Protein phosphatase, Mg(2+)/Mn(2+) dependent, 1D (PPM1D) is emerging as an oncogene by virtue of its negative control on several tumor suppressor pathways. However, the clinical significance of PPM1D in pancreatic cancer (PC) has not been defined. In this study, we determined PPM1D expression in human PC tissues and cell lines and their irrespective noncancerous controls. We subsequently investigated the functional role of PPM1D in the migration, invasion, and apoptosis of MIA PaCa-2 and PANC-1 PC cells in vitro and explored the signaling pathways involved. Furthermore, we examined the role of PPM1D in PC tumorigenesis in vivo. Our results showed that PPM1D is overexpressed in human PC tissues and cell lines and significantly correlated with tumor growth and metastasis. PPM1D promotes PC cell migration and invasion via potentiation of the Wnt/β-catenin pathway through downregulation of apoptosis-stimulating of p53 protein 2 (ASPP2). In contrast to PPM1D, our results showed that ASPP2 is downregulated in PC tissues. Additionally, PPM1D suppresses PC cell apoptosis via inhibition of the p38 MAPK/p53 pathway through both dephosphorylation of p38 MAPK and downregulation of ASPP2. Furthermore, PPM1D promotes PC tumor growth in vivo. Our results demonstrated that PPM1D is an oncogene in PC. PMID:26714478

  3. Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 in human skeletal muscle

    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...... TBC1D4 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...

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

    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. PMID:24803094

  5. 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

    Echwald, Søren M; Riis, Helle Bach; Vestergaard, Henrik; Richelsen, Bjørn; Kristensen, Kurt; Drivsholm, Thomas; Borch-Johnsen, Knut; Hansen, Torben; Pedersen, Oluf

    2002-01-01

    frequency 0.5%, CI 0.1-1.1), showing a significant association to type 2 diabetes (P = 0.036). In vitro, p34 cell division cycle (p34(cdc2)) kinase-directed incorporation of [gamma-(32)P]ATP was reduced in a mutant peptide compared with native peptide (387P: 100% vs. 387L: 28.4 +/- 5.8%; P = 0.0012). In...... summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide....

  6. 77 FR 3284 - Comment Request for Information Collection for the H-1B Technical Skills Training (H-1B) and the...

    2012-01-23

    ... programs and their partnerships with business-related nonprofit organizations, education and training... outcome measures will be used to measure success in the H-1B grants: Entered employment rate, employment... vocational training program. In addition to the three outcome measures, grantees will report on a number...

  7. Sulfone-stabilized carbanions for the reversible covalent capture of a posttranslationally-generated cysteine oxoform found in protein tyrosine phosphatase 1B (PTP1B).

    Parsons, Zachary D; Ruddraraju, Kasi Viswanatharaju; Santo, Nicholas; Gates, Kent S

    2016-06-15

    Redox regulation of protein tyrosine phosphatase 1B (PTP1B) involves oxidative conversion of the active site cysteine thiolate into an electrophilic sulfenyl amide residue. Reduction of the sulfenyl amide by biological thiols regenerates the native cysteine residue. Here we explored fundamental chemical reactions that may enable covalent capture of the sulfenyl amide residue in oxidized PTP1B. Various sulfone-containing carbon acids were found to react readily with a model peptide sulfenyl amide via attack of the sulfonyl carbanion on the electrophilic sulfur center in the sulfenyl amide. Both the products and the rates of these reactions were characterized. The results suggest that capture of a peptide sulfenyl amide residue by sulfone-stabilized carbanions can slow, but not completely prevent, thiol-mediated generation of the corresponding cysteine-containing peptide. Sulfone-containing carbon acids may be useful components in the construction of agents that knock down PTP1B activity in cells via transient covalent capture of the sulfenyl amide oxoform generated during insulin signaling processes. PMID:27132865

  8. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

    Yun Zhao

    2015-09-01

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B, which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1, thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386. Palmitate acid (PA impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt and glycogen synthase kinase 3 beta (GSK3β following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance.

  9. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    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.

  10. DJ-1 can inhibit microtubule associated protein 1 B formed aggregates

    Ding Jianqing

    2011-06-01

    Full Text Available Abstract Background Abnormal accumulation and aggregation of microtubule associated proteins (MAPs plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. Results We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC. Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER stress-induced apoptosis. Conclusion Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD.

  11. Protein Tyrosine Phosphatase-1B Negatively Impacts Host Defense against Pseudomonas aeruginosa Infection.

    Yue, Lei; Xie, Zhongping; Li, Hua; Pang, Zheng; Junkins, Robert D; Tremblay, Michel L; Chen, Xiaochun; Lin, Tong-Jun

    2016-05-01

    Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals. Mechanisms governing immune responses to P. aeruginosa infection remain incompletely defined. Herein, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1B-deficient mice display greatly enhanced bacterial clearance and reduced disease scores, which are accompanied by increased neutrophil infiltration and cytokine production. Interestingly, PTP1B deficiency mainly up-regulates the production of interferon-stimulated response elements-regulated cytokines and chemokines, including chemokine ligand 5 (regulated on activation normal T cell expressed and secreted), CXCL10 (interferon γ-inducible protein 10), and interferon-β production. Further studies reveal that PTP1B deficiency leads to increased interferon regulatory factor 7 (IRF7) expression and activation. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-interferon-stimulated response elements pathway may have broader implications in Toll-like receptor-mediated innate immunity. PMID:27105736

  12. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    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. PMID:26354157

  13. Coumarins from Angelica decursiva inhibit α-glucosidase activity and protein tyrosine phosphatase 1B.

    Ali, Md Yousof; Jannat, Susoma; Jung, Hyun Ah; Jeong, Hyong Oh; Chung, Hae Young; Choi, Jae Sue

    2016-05-25

    In the present study, we investigated the anti-diabetic potential of six natural coumarins, 4-hydroxy Pd-C-III (1), 4'-methoxy Pd-C-I (2), decursinol (3), decursidin (4), umbelliferone 6-carboxylic acid (5), and 2'-isopropyl psoralene (6) isolated from Angelica decursiva and evaluated their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO(-)-mediated protein tyrosine nitration. Coumarins 1-6 showed potent PTP1B and α-glucosidase inhibitory activities with ranges of IC50 values of 5.39-58.90 μM and 65.29-172.10 μM, respectively. In the kinetic study for PTP1B enzyme inhibition, compounds 1, 5, and 6 were competitive, whereas 2 and 4 showed mixed type, and 3 displayed noncompetitive type inhibition. For α-glucosidase enzyme inhibition, compounds 1 and 3 exhibited good mixed-type, while 2, 5, and 6 showed noncompetitive and 4 displayed competitive type inhibition. Furthermore, these coumarins also effectively suppressed ONOO(-)-mediated tyrosine nitration in a dose-dependent manner. To further investigate PTP1B inhibition, we generated a 3D structure of PTP1B using Autodock 4.2 and simulated the binding of compounds 1-6. Docking simulations showed that different residues of PTP1B interacted with different functional groups of compounds 1-6 through hydrogen and hydrophobic interactions. In addition, the binding energies of compounds 1-6 were negative, suggesting that hydrogen bonding may stabilize the open form of the enzyme and potentiate tight binding of the active site of PTP1B, thereby resulting in more effective PTP1B inhibition. These results demonstrate that the whole plant of A. decursiva and its coumarins are useful as potential functional food ingredients for the prevention and treatment of type 2 diabetes. PMID:27085377

  14. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

    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.

  15. Synthesis and Structure of Bis-(o-vanillin)di-pyridine Nickel(Ⅱ)-pyridine Dihydrate

    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.

  16. TBC1D1 Regulates Insulin- and Contraction-Induced Glucose Transport in Mouse Skeletal Muscle

    Toyoda, Taro; Yu, Haiyan; Fujii, Nobuharu; Hirshman, Michael F.; An, Ding Jeff; Goodyear, Laurie Joy; Taylor, Eric B.

    2010-01-01

    OBJECTIVE: TBC1D1 is a member of the TBC1 Rab-GTPase family of proteins and is highly expressed in skeletal muscle. Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known. Genetic linkage analyses show a TBC1D1 R125W missense variant confers risk for severe obesity in humans. The objective of this study was to determine whether TBC1D1 regulates glucose transport in skeletal muscle. RESEARCH DESIGN AND M...

  17. Current Perspectives on Interferon Beta-1b for the Treatment of Multiple Sclerosis

    Marziniak, Martin; Meuth, Sven

    2014-01-01

    Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and i...

  18. Telomere Protection by TPP1 Is Mediated by POT1a and POT1b

    Kibe, Tatsuya; Osawa, Gail A.; Keegan, Catherine E.; de Lange, Titia

    2009-01-01

    Mammalian telomeres are protected by the shelterin complex, which contains single-stranded telomeric DNA binding proteins (POT1a and POT1b in rodents, POT1 in other mammals). Mouse POT1a prevents the activation of the ATR kinase and contributes to the repression of the nonhomologous end-joining pathway (NHEJ) at newly replicated telomeres. POT1b represses unscheduled resection of the 5′-ended telomeric DNA strand, resulting in long 3′ overhangs in POT1b KO cells. Both POT1 proteins bind TPP1,...

  19. Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

    Menon, Lakshmi; Mader, Samantha Ann; Mihailescu, Mihaela-Rita

    2008-01-01

    Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine–glycine–glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA f...

  20. Grid Cell Responses in 1D Environments Assessed as Slices through a 2D Lattice.

    Yoon, KiJung; Lewallen, Sam; Kinkhabwala, Amina A; Tank, David W; Fiete, Ila R

    2016-03-01

    Grid cells, defined by their striking periodic spatial responses in open 2D arenas, appear to respond differently on 1D tracks: the multiple response fields are not periodically arranged, peak amplitudes vary across fields, and the mean spacing between fields is larger than in 2D environments. We ask whether such 1D responses are consistent with the system's 2D dynamics. Combining analytical and numerical methods, we show that the 1D responses of grid cells with stable 1D fields are consistent with a linear slice through a 2D triangular lattice. Further, the 1D responses of comodular cells are well described by parallel slices, and the offsets in the starting points of the 1D slices can predict the measured 2D relative spatial phase between the cells. From these results, we conclude that the 2D dynamics of these cells is preserved in 1D, suggesting a common computation during both types of navigation behavior. PMID:26898777

  1. α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

    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.

  2. Poly[bis[μ-1,4-bis(imidazol-1-ylmethylbenzene]dichloridocadmium(II

    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.

  3. Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata

    Tran Hong Quang

    2015-06-01

    Full Text Available A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1–9 and flavonoids 10–16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1–9 and 13–16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects than the flavonoids, suggesting that they may be promising targets for the future discovery of novel PTP1B inhibitors. Furthermore, kinetic analyses indicated that compounds 1 and 13 inhibited PTP1B in a noncompetitive manner; therefore, they may be potential lead compounds in the development of anti-obesity and -diabetic agents.

  4. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V004

    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)

  5. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V003

    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. GLAS/ICESat L1B Global Waveform-based Range Corrections Data V033

    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...

  7. Dark Matter and Neutrino Masses from Global $U(1)_{B-L}$ Symmetry Breaking

    Lindner, Manfred; Schwetz, Thomas

    2011-01-01

    We present a scenario were neutrino masses and Dark Matter are related due to a global $U(1)_{B-L}$ symmetry. Specifically we consider neutrino mass generation via the Zee{Babu two-loop mecha- nism, augmented by a scalar singlet whose VEV breaks the global $U(1)_{B-L}$ symmetry. In order to obtain a Dark Matter candidate we introduce two Standard Model singlet fermions. They form a pseudo-Dirac particle and are stable because of a remnant $Z_2$ symmetry. Hence, in this model the stability of Dark Matter follows from the global $U(1)_{B-L}$ symmetry. We discuss the Dark Matter phenomenology of the model, and compare it to similar models based on gauged $U(1)_{B-L}$. We argue that in contrast to the gauged versions, the model based on the global symmetry does not suffer from sever constraints from Z' searches.

  8. Nature of Pi1B pulsations as inferred from ground and satellite observations

    Lessard, M. R.; Lund, E. J.; Jones, S. L.; Arnoldy, R. L.; Posch, J. L.; Engebretson, M. J.; Hayashi, K.

    2006-07-01

    The occurrence of Pi1B pulsations is well-documented, including the fact that these pulsations can be observed both on the ground and at geosynchronous orbit at substorm onset, although information about their propagation characteristics has been lacking. In this paper, data are presented from FAST, GOES 9 and various ground stations that show the simultaneous observations of Pi1B pulsations in association with an onset. While the data at GOES 9 show that the pulsations are compressional in nature, data from FAST show the presence of shear mode waves, implying that Pi1B mode conversion of some type must take place in the region between geosynchronous orbit and FAST altitudes. An additional point is that Pi1B pulsations apparently propagate through auroral phenomena routinely, begging the question of what role they may play.

  9. Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

    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.

  10. Interleukin 1B Variant -1473G/C (rs1143623) Influences Triglyceride and Interleukin 6 Metabolism

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M; Fuentes, Francisco; Parnell, Laurence D.; Jian SHEN; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J.; Marin, Carmen; Belisle, Sarah E; Rodriguez-Cantalejo, Fernando; Meydani, Simin N.

    2011-01-01

    Healthy young male carriers of the minor allele of IL1B -1473G/C have exaggerated lipid and inflammatory postprandial responses, which could help unravel these relationships during the postprandial state.

  11. TES/Aura L1B Spectra Special Observation Low Resolution V004

    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. The new powder diffractometer D1B of the Institut Laue Langevin

    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

  13. MISR Level 1B1 Local Mode Radiance Data V002

    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...

  14. Detection of the urban heat island in Beijing using HJ-1B satellite imagery

    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.

  15. The new powder diffractometer D1B of the Institut Laue Langevin

    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.

  16. Skin Necrosis Following a Recombinant Interferon-beta-1b Injection

    Chih-Hsun Yang

    2002-11-01

    Full Text Available Recombinant interferon beta-1b (INF-β-1b has been proven to be an effective means oftreating relapsing-remitting multiple sclerosis (MS. Adverse reactions to interferon therapyhave been well documented. The most common side effects are transient influenza-likesymptoms, including fever, fatigue, nausea, and myalgia. Cutaneous necrosis has occasionallybeen reported, mostly involving small and limited lesions. This article describes an MSpatient who developed multiple large, deep cutaneous ulcers on INF-β-1b injection sites,which subsequently required surgical treatment. Vessel thrombosis in the subcutaneous fattylayer and the clinical appearance of livedoid erythema beside the ulcers indicated that INF-β-1b may have caused skin necrosis through its vascular effects.

  17. Trisodium scandium bis­(orthoborate)

    Kunpeng Wang; Jinzhi Fang; Guochun Zhang; Xinyuan Zhang; Jiyong Yao

    2012-01-01

    Single crystals of trisodium scandium bis(orthoborate), Na3Sc(BO3)2, 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...

  18. Synthesis of a Bis(thiophenolate)pyridine Ligand and Its Titanium, Zirconium, and Tantalum Complexes

    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.

  19. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    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

  20. Association Between 5HT1b Receptor Gene and Methamphetamine Dependence

    Ujike, H; Kishimoto, M; Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N

    2011-01-01

    Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis. PMID:21886584

  1. Plant compounds that induce polychlorinated biphenyl biodegradation by Arthrobacter sp. strain B1B.

    Gilbert, E S; Crowley, D. E.

    1997-01-01

    Plant compounds that induced Arthrobacter sp. strain B1B to cometabolize polychlorinated biphenyls (PCBs) were identified by a screening assay based on the formation of a 4,4'-dichlorobiphenyl ring fission product. A chemical component of spearmint (Mentha spicata), l-carvone, induced Arthrobacter sp. strain B1B to cometabolize Aroclor 1242, resulting in significant degradation of 26 peaks in the mixture, including selected tetra- and pentachlorobiphenyls. Evidence for PCB biodegradation incl...

  2. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    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.

  3. Functional properties of Claramine: a novel PTP1B inhibitor and insulin-mimetic compound.

    Qin, Zhaohong; Pandey, Nihar R; Zhou, Xun; Stewart, Chloe A; Hari, Aswin; Huang, Hua; Stewart, Alexandre F R; Brunel, Jean Michel; Chen, Hsiao-Huei

    2015-02-27

    Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling, interfering with its control of glucose homeostasis and metabolism. PTP1B activity is elevated in obesity and type 2 diabetes and is a major cause of insulin resistance. Trodusquemine (MSI-1436) is a "first-in-class" highly selective inhibitor of PTP1B that can cross the blood-brain barrier to suppress feeding and promote insulin sensitivity and glycemic control. Trodusquemine is a naturally occurring cholestane that can be purified from the liver of the dogfish shark, Squalus acanthias, but it can also be manufactured synthetically by a fairly laborious process that requires several weeks. Here, we tested a novel easily and rapidly (2 days) synthesized polyaminosteroid derivative (Claramine) containing a spermino group similar to Trodusquemine for its ability to inhibit PTP1B. Like Trodusquemine, Claramine displayed selective inhibition of PTP1B but not its closest related phosphatase TC-PTP. In cultured neuronal cells, Claramine and Trodusquemine both activated key components of insulin signaling, with increased phosphorylation of insulin receptor-β (IRβ), Akt and GSK3β. Intraperitoneal administration of Claramine or Trodusquemine effectively restored glycemic control in diabetic mice as determined by glucose and insulin tolerance tests. A single intraperitoneal dose of Claramine, like an equivalent dose of Trodusquemine, suppressed feeding and caused weight loss without increasing energy expenditure. In summary, Claramine is an alternative more easily manufactured compound for the treatment of type II diabetes. PMID:25623533

  4. A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery

    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.

  5. Structural and functional analysis of the mouse mdr1b gene promoter.

    Cohen, D; Piekarz, R L; Hsu, S I; DePinho, R A; Carrasco, N; Horwitz, S B

    1991-02-01

    The overproduction of P-glycoprotein, an integral membrane protein thought to function as a drug efflux pump, is the hallmark of the multidrug resistance phenotype. In murine multidrug resistant J774.2 cell lines, distinct mdr genes, mdr1a and mdr1b, encode unique P-glycoprotein isoforms. To examine the transcriptional regulation of the mdr1b gene, its promoter was isolated and characterized. The transcription initiation site was mapped by primer extension, and the 5'-flanking region was sequenced. Several potential regulatory elements were identified in this region. A transient expression vector was constructed by fusion of 540 base pairs of 5'-flanking sequence and part of the first untranslated exon to the chloramphenicol acetyltransferase (CAT) gene. When transfected into monkey kidney COS-1, rat pituitary GH3 or T47D human breast cells, the mdr1b 5'-flanking sequences were capable of driving CAT expression. Transient transfection studies using deletion subclones of the mdr1b-CAT construct were done to locate potential cis-acting sequences. The studies indicate the presence of cis-acting elements in the 5'-flanking region of the mdr1b gene. The implications of these findings for expression and regulation of the mdr1b gene are discussed. PMID:1671222

  6. Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.

    Carpenter, Ashley R; Becknell, M Brian; Ching, Christina B; Cuaresma, Edward J; Chen, Xi; Hains, David S; McHugh, Kirk M

    2016-03-01

    Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract. PMID:26880456

  7. Endogenous N-terminal Domain Cleavage Modulates α1D-Adrenergic Receptor Pharmacodynamics.

    Kountz, Timothy S; Lee, Kyung-Soon; Aggarwal-Howarth, Stacey; Curran, Elizabeth; Park, Ji-Min; Harris, Dorathy-Ann; Stewart, Aaron; Hendrickson, Joseph; Camp, Nathan D; Wolf-Yadlin, Alejandro; Wang, Edith H; Scott, John D; Hague, Chris

    2016-08-26

    The α1D-adrenergic receptor (ADRA1D) is a key regulator of cardiovascular, prostate, and central nervous system functions. This clinically relevant G protein-coupled receptor has proven difficult to study, as it must form an obligate modular homodimer containing the PDZ proteins scribble and syntrophin or become retained in the endoplasmic reticulum as non-functional protein. We previously determined that targeted removal of the N-terminal (NT) 79 amino acids facilitates ADRA1D plasma membrane expression and agonist-stimulated functional responses. However, whether such an event occurs in physiological contexts was unknown. Herein, we report the ADRA1D is subjected to innate NT processing in cultured human cells. SNAP near-infrared imaging and tandem-affinity purification revealed the ADRA1D is expressed as both full-length and NT truncated forms in multiple human cell lines. Serial truncation mapping identified the cleavage site as Leu(90)/Val(91) in the 95-amino acid ADRA1D NT domain, suggesting human cells express a Δ1-91 ADRA1D species. Tandem-affinity purification MS/MS and co-immunoprecipitation analysis indicate NT processing of ADRA1D is not required to form scribble-syntrophin macromolecular complexes. Yet, label-free dynamic mass redistribution signaling assays demonstrate that Δ1-91 ADRA1D agonist responses were greater than WT ADRA1D. Mutagenesis of the cleavage site nullified the processing event, resulting in ADRA1D agonist responses less than the WT receptor. Thus, we propose that processing of the ADRA1D NT domain is a physiological mechanism employed by cells to generate a functional ADRA1D isoform with optimal pharmacodynamic properties. PMID:27382054

  8. BIS Handbook: An Organizational Manual & Directory. Revised Edition.

    Association of Coll. and Research Libraries, Chicago, IL. Bibliographic Instruction Section.

    This handbook was prepared for the officers and committee members of the ACRL (Association of College and Research Libraries) Bibliographic Instruction Section (BIS). Introductory material by Mimi Dudley and James W. Hart traces the history of bibliographic instruction (BI) and the development of BIS. Following a brief discussion of how to get…

  9. Accelerated optical holographic recording using bis-DNO

    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 dipeptid...

  10. Bis-perfluoroalkylation of aromatic compounds with sodium perfluoroalkanesulfinates

    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.

  11. One pot synthesis of bis-silicon-bridged stilbene derivatives

    2007-01-01

    Bis-silicon-bridged stilbene derivatives were synthesized in a modified procedure that combined the preparation of bis[2-(silyl)phenyl]acetylene and its intrmolecular reductive cyclization in one pot. The results indicated that the one pot approach produced target products in a comparable yield to that of the two-step method reported previously.

  12. High-resolution imaging of brain 5-HT{sub 1B} receptors in the rhesus monkey using [{sup 11}C]P943

    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.

  13. Pulsed EPR studies of bis imidazole heme a

    Electron spin echo studies have been performed on the model compound for cytochrome a, bis imidazole heme a, and the results compared with those obtained for bis imidazole protoheme and for cytochrome a. The 14N coupling with the iron in the heme a model compound, as obtained from a study of the nuclear modulation effect, is comparable with that seen for the bis imidazole complex of protoheme. The magnetic field dependence of the linear electric field effect is essentially the same in both bis imidazole complexes, but is markedly different from that observed for cytochrome a. Thus the odd field component of the crystal field in bis imid heme a is different from that in cytochrome a. (author)

  14. 关于图的L(d1,d2)-标号问题%The L(d1, d2)-Labeling Problem on Graphs

    邵振东; 刘家壮

    2006-01-01

    The L(2, 1)-labeling is formulated from the frequency assignment problem. We study the L(d1, d2)- labeling which is a generalization of the L(2, 1)-labeling. Vertex 2-coloring, 2-chromatic number and other related concepts are firstly defined, and the upper bound for 2-chromatic number is given; a very general relationship between λd1 ,d2 (G) and minimum degree δ(G) and maximum degree △(G) is then derived; finally, the upper bounds of L(d1, d2)-labelings of general and planar graphs are given.%图的L(2,1)-标号问题是由频率分配问题归结而来,本文研究作为L(2,1)-标号问题的推广的L(d1,d2)-标号问题.首先定义了顶点2-着色,2-色数及其它有关概念,给出了2-色数的上界.然后得出了λd1,d2(G)与δ(G)和△(G)的一般关系.最后得出了一般图与平面图的λd1,d2(G)的上界.

  15. Spin-crossover studies on a series of 1-D chain and dinuclear iron(II) triazine-dipyridylamine compounds

    Four isostructural one-dimensional polymeric iron(II) spin crossover materials containing the ligand 2-chloro-4,6-bis(dipyrid-2-ylamino)-1,3,5-triazine (cddt) have been synthesized and magnetically and structurally characterized. The polymeric material Fe(NCS)2(cddt)·n(guest) (1), self assembles into three crystallographically distinct phases; the compounds 1b and 1c, [Fe(NCS)2(cddt)]·2(CH3OH), are polymorphs, however, 1a, [Fe(NCS)2(cddt)]·1/2(CHCl3)·(H2O) contains a different solvent system. Each phase shows very different magnetic behavior; phases 1a and 1b remain high spin over all temperatures, whilst phase 1c undergoes a half spin crossover between 225 and 125 K. The structural consequences of the spin transition in 1c have been followed using variable temperature synchrotron powder X-ray diffraction techniques. Variation of the chalcogenide ligand in the complex [Fe(NCSe)2(cddt)]·2(CH3OH), 2, leads to a full one-step spin crossover with a T1/2 of 200 K. Structural analysis of 1c below the transition temperature reveals alternating, crystallographically distinct, HS and LS iron(II) centers (HS: high spin, LS: low spin) along the chain, and structural analysis of 2 below the transition temperature reveals all LS iron(II) centers. Also reported are the structural characterizations of two dinuclear materials, containing the ligand 2,4,6-tris(dipyridin-2-ylamino)-1,3,5-triazine (tdt), of the formula [Fe(tdt)(X)2]2·(ClO4)·(solvent) (X = H2O, Cl- for 3a, 3b) which are analogous to those recently reported by Gamez et al. In addition, the structural characterizations are described for dinuclear materials, containing the ligand cddt, of the formula [Fe(cddt)(Cl)(X)]2·(Y)2·n(solvent) (X: H2O or NCCH3, Y: ClO4-, BF4- 4a, 4b and 4d) and for a cobalt(II) analogue, [Co(cddt)(Cl)(H2O)]2·(BF4)2·n(solvent) (4c)

  16. Upstream ORF affects MYCN translation depending on exon 1b alternative splicing

    The MYCN gene is transcribed into two major mRNAs: one full-length (MYCN) and one exon 1b-spliced (MYCNΔ1b) mRNA. But nothing is known about their respective ability to translate the MYCN protein. Plasmids were prepared to enable translation from the upstream (uORF) and major ORF of the two MYCN transcripts. Translation was studied after transfection in neuroblastoma SH-EP cell line. Impact of the upstream AUG on translation was evaluated after directed mutagenesis. Functional study with the two MYCN mRNAs was conducted by a cell viability assay. Existence of a new protein encoded by the MYCNΔ1b uORF was explored by designing a rabbit polyclonal antibody against a specific epitope of this protein. Both are translated, but higher levels of protein were seen with MYCNΔ1b mRNA. An upstream ORF was shown to have positive cis-regulatory activity on translation from MYCN but not from MYCNΔ1b mRNA. In transfected SH-EP neuroblastoma cells, high MYCN dosage obtained with MYCNΔ1b mRNA translation induces an antiapoptotic effect after serum deprivation that was not observed with low MYCN expression obtained with MYCN mRNA. Here, we showed that MYCNOT: MYCN Overlap Transcript, a new protein of unknown function is translated from the upstream AUG of MYCNΔ1b mRNA. Existence of upstream ORF in MYCN transcripts leads to a new level of MYCN regulation. The resulting MYCN dosage has a weak but significant anti-apoptotic activity after intrinsic apoptosis induction

  17. Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.

    Lalli, Matthew A; Jang, Jiwon; Park, Joo-Hye C; Wang, Yidi; Guzman, Elmer; Zhou, Hongjun; Audouard, Morgane; Bridges, Daniel; Tovar, Kenneth R; Papuc, Sorina M; Tutulan-Cunita, Andreea C; Huang, Yadong; Budisteanu, Magdalena; Arghir, Aurora; Kosik, Kenneth S

    2016-04-01

    Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of WS. In patient-derived stem cells and neurons, we determined the expression profile of the Williams-Beuren syndrome critical region-deleted genes and the genome-wide transcriptional consequences of the hemizygous genomic microdeletion at chromosome 7q11.23. Derived neurons displayed disease-relevant hallmarks and indicated novel aberrant pathways in WS neurons including over-activated Wnt signaling accompanying an incomplete neurogenic commitment. We show that haploinsufficiency of the ATP-dependent chromatin remodeler, BAZ1B, which is deleted in WS, significantly contributes to this differentiation defect. Chromatin-immunoprecipitation (ChIP-seq) revealed BAZ1B target gene functions are enriched for neurogenesis, neuron differentiation and disease-relevant phenotypes. BAZ1B haploinsufficiency caused widespread gene expression changes in neural progenitor cells, and together with BAZ1B ChIP-seq target genes, explained 42% of the transcriptional dysregulation in WS neurons. BAZ1B contributes to regulating the balance between neural precursor self-renewal and differentiation and the differentiation defect caused by BAZ1B haploinsufficiency can be rescued by mitigating over-active Wnt signaling in neural stem cells. Altogether, these results reveal a pivotal role for BAZ1B in neurodevelopment and implicate its haploinsufficiency as a likely contributor to the neurological phenotypes in WS. PMID:26755828

  18. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B

    Yong WU; Jing-ping OU-YANG; Ke WU; Ya WANG; Yun-feng ZHOU; Chong-yuan WEN

    2005-01-01

    Aim: To examine the effects ofAstragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance.Methods: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type Ⅱ diabetes mellitus (TIIDM), were treated with APS (400 mg/kg po) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit. Results: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle,but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR β-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle,but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS. Conclusion: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.

  19. Upstream ORF affects MYCN translation depending on exon 1b alternative splicing

    Tutrone Giovani

    2009-12-01

    Full Text Available Abstract Background The MYCN gene is transcribed into two major mRNAs: one full-length (MYCN and one exon 1b-spliced (MYCNΔ1b mRNA. But nothing is known about their respective ability to translate the MYCN protein. Methods Plasmids were prepared to enable translation from the upstream (uORF and major ORF of the two MYCN transcripts. Translation was studied after transfection in neuroblastoma SH-EP cell line. Impact of the upstream AUG on translation was evaluated after directed mutagenesis. Functional study with the two MYCN mRNAs was conducted by a cell viability assay. Existence of a new protein encoded by the MYCNΔ1b uORF was explored by designing a rabbit polyclonal antibody against a specific epitope of this protein. Results Both are translated, but higher levels of protein were seen with MYCNΔ1b mRNA. An upstream ORF was shown to have positive cis-regulatory activity on translation from MYCN but not from MYCNΔ1b mRNA. In transfected SH-EP neuroblastoma cells, high MYCN dosage obtained with MYCNΔ1b mRNA translation induces an antiapoptotic effect after serum deprivation that was not observed with low MYCN expression obtained with MYCN mRNA. Here, we showed that MYCNOT: MYCN Overlap Transcript, a new protein of unknown function is translated from the upstream AUG of MYCNΔ1b mRNA. Conclusions Existence of upstream ORF in MYCN transcripts leads to a new level of MYCN regulation. The resulting MYCN dosage has a weak but significant anti-apoptotic activity after intrinsic apoptosis induction.

  20. Exercise increases TBC1D1 phosphorylation in human skeletal muscle

    Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders; Goodyear, Laurie J.

    2011-01-01

    Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulatin...

  1. 1D engine simulation of a turbocharged SI engine with CFD computation on components

    Renberg, Ulrica

    2008-01-01

    Techniques that can increase the SI- engine efficiency while keeping the emissions very low is to reduce the engine displacement volume combined with a charging system. Advanced systems are needed for an effective boosting of the engine and today 1D engine simulation tools are often used for their optimization. This thesis concerns 1D engine simulation of a turbocharged SI engine and the introduction of CFD computations on components as a way to assess inaccuracies in the 1D model. 1D engine ...

  2. Bis(μ-bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methanedisilver(I bis(perchlorate

    Hai-Bin Zhu

    2010-12-01

    Full Text Available In the macrocyclic centrosymmetric dinuclear complex, [Ag2(C19H14N6S22](ClO42, the AgI atom, bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methane (2-bppt ligand and perchlorate anion each lie on a twofold rotation axis. The 2-bppt ligand chelates two four-coordinated AgI atoms through its two bipyridine-like arms. The O atoms of the perchlorate anion are disordered each over two positions of equal occupancy. Adjacent complex molecules are linked by π–π interactions between the pyridine and pyrimidine rings [centroid–centroid distance = 3.663 (8 Å].

  3. Comparative effects of nodularin and microcystin-LR in zebrafish: 1. Uptake by organic anion transporting polypeptide Oatp1d1 (Slco1d1).

    Faltermann, Susanne; Prétôt, René; Pernthaler, Jakob; Fent, Karl

    2016-02-01

    Microcystin-LR (MC-LR) and nodularin are hepatotoxins produced by several cyanobacterial species. Their toxicity is based on active cellular uptake and subsequent inhibition of protein phosphatases PP1/2A, leading to hyperphosphorylation and cell death. To date, uptake of MC-LR and nodularin in fish is poorly understood. Here, we investigated the role of the organic anion transporting polypeptide Oatp1d1 in zebrafish (drOatp1d1, Slco1d1) in cellular uptake in zebrafish. We stably transfected CHO and HEK293 cell lines expressing drOatp1d1. In both transfectants, uptake of MC-LR and nodularin was demonstrated by competitive inhibition of uptake with fluorescent substrate lucifer yellow. Direct uptake of MC-LR was demonstrated by immunostaining, and indirectly by the high cytotoxicity in stable transfectants. By means of a synthesized fluorescent labeled MC-LR derivative, direct uptake was further confirmed in HEK293 cells expressing drOatp1d1. Additionally, uptake and toxicity was investigated in the permanent zebrafish liver cell line ZFL. These cells had only a low relative abundance of drOatp1d1, drOatp2b1 and drOatp1f transcripts, which correlated with the lack of MC-LR induced cytotoxicity and transcriptional changes of genes indicative of endoplasmic reticulum stress, a known effect of this toxin. Our study demonstrates that drOatp1d1 functions as an uptake transporter for both MC-LR and nodularin in zebrafish. PMID:26769064

  4. Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain.

    Oscar Fernández

    Full Text Available BACKGROUND: Adherence to interferon β-1b (INFβ-1b therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS. For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%. Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients. CONCLUSION/SIGNIFICANCE: Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

  5. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR

  6. Propagation of dysbindin-1B aggregates: exosome-mediated transmission of neurotoxic deposits.

    Zhu, C-Y; Shen, Y; Xu, Q

    2015-04-16

    Given the detection of aggregated deposits in chronic mental diseases (CMD), the disturbance of proteostasis in those diseases is receiving increasing attention. The study of aggregated proteins can contribute to our understanding of the chronic and progressive condition of such diseases. Dysbindin, encoded by the schizophrenia susceptibility gene DTNBP1, has been reported to co-aggregate with DISC1. However, there has been no evidence to date on the aggregation tendency of dysbindin. Therefore, we investigated the isoform-specific aggregation of dysbindin. We found that dysbindin-1B aggregated into cell-invasive deposits in mice. Because of the efficient propagation of dysbindin-1B, we further studied the mechanism of propagation and identified it as exosome-mediated transmission of the aggregates. In addition, aggregates of dysbindin-1B were toxic. Through exosome-mediated propagation, the deposits of dysbindin-1B exerted toxic effects on recipient neurons a long distance away from the initial aggregation site in mice brain. The rapid long distance propagation of neurotoxic deposits of dysbindin-1B in affected neuronal circuitry indicates a possible mechanism for the progressive deterioration of neurons and cognitive function in CMD. PMID:25704251

  7. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    Turner, Roberta L. [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu [Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Ornelles, David A., E-mail: ornelles@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose) polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.

  8. Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons

    Rui Yan; Tianwen Huang; Zhiqin Xie; Guannan Xia; Hui Qian; Xiaolin Zhao; Leping Cheng

    2013-01-01

    Serotonin (5-HT) neurons synthesize a variety of peptides.How these peptides are controlled during development remains unclear.It has been reported that the co-localization of peptides and 5-HT varies by species.In contrast to the situations in the rostral 5-HT neurons of human and rat brains,several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain.In this study,we found that the peptide substance P and peptide genes,including those encoding peptides thyrotropin-releasing hormone,enkephalin,and calcitonin gene-related peptide,were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons.We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate.Furthermore,we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate.By examining the phenotype of Lmx1b deletion mice,we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons.Together,our results indicate that Lmx1b,a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis,determines some peptide phenotypes in these neurons as well.

  9. Arabidopsis DREB1B in transgenic Salvia miltiorrhiza increased tolerance to drought stress without stunting growth.

    Wei, Tao; Deng, Kejun; Gao, Yonghong; Liu, Yu; Yang, Meiling; Zhang, Lipeng; Zheng, Xuelian; Wang, Chunguo; Song, Wenqin; Chen, Chengbin; Zhang, Yong

    2016-07-01

    Multiple stress response genes are controlled by transcription factors in a coordinated manner; therefore, these factors can be used for molecular plant breeding. CBF1/DREB1B, a known stress-inducible gene, was isolated from Arabidopsis thaliana and introduced into Salvia miltiorrhiza under the control of the CaMV35S or RD29A promoter. Under drought stress, relative water content, chlorophyll content, and the net photosynthetic rate were observed to be higher in the transgenic lines than in the wild type (WT). Moreover, O2(-) and H2O2 accumulation was observed to be lower in the transgenic lines. Additional analyses revealed that the AtDREB1B transgenic plants generally displayed lesser malondialdehyde (MDA) but higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities than the WT under drought stress. Quantitative real-time polymerase chain reaction of a subset of genes involved in photosynthesis, stress response, carbohydrate metabolism, and cell protection further verified that AtDREB1B could enhance tolerance to drought by activating different downstream DREB/CBF genes in the transgenic plants. Furthermore, no growth inhibition was detected in transgenic S. miltiorrhiza plants that expressed AtDREB1B driven by either the constitutive CaMV35S promoter or the stress-inducible RD29A promoter. Together, these results suggest that AtDREB1B is a good candidate gene for increasing drought tolerance in transgenic S. miltiorrhiza. PMID:27002402

  10. Organic anion transporting polypeptide-1B1 haplotypes in Chinese patients

    Lin-yong XU; Hong-hao ZHOU; Zhen-qiu SUN; Yi-jing HE; Wei ZHANG; Sheng Deng; Qing LI; Wei-xia ZHANG; Zhao-qian LIU; Dan WANG; Yuan-fei HUANG

    2007-01-01

    Aim: To detect 388G>A and 521T>C variant alleles in the organic anion transporting polypeptide- 1B 1 (OATP 1B 1, encoding gene SLCOIB1) gene. Methods:One hundred and eleven healthy volunteers were screened for OATPIB 1 alleles in our study. PCR-restriction fragment length polymorphism was used to identify the 388G>A polymorphism and a 1-step tetra-primer method was developed for the determination of 521T>C mutation. Results: The frequencies of the 388G>A and 521T>C variant alleles in the Chinese population were 73.4%and 14.0%,respectively. The frequencies of the SLCO1BI*lb and *15 haplotypes were 59.9% and 14.0%, respectively. Conclusion: The SLCO1B1*1b and SLCO1B1*15 variants are relatively common in the Chinese population. Their frequencies are similar to that in the Japanese, but significantly different from that in Caucasians and blacks.

  11. Atomic layer deposition of molybdenum oxide using bis(tert-butylimido)bis(dimethylamido) molybdenum

    Bertuch, Adam, E-mail: abertuch@ultratech.com; Sundaram, Ganesh [Ultratech/Cambridge NanoTech, 130 Turner Street, Waltham, Massachusetts 02453 (United States); Saly, Mark; Moser, Daniel; Kanjolia, Ravi [SAFC Hitech, 1429 Hilldale Avenue, Haverhill, Massachusetts 01832 (United States)

    2014-01-15

    Molybdenum trioxide films have been deposited using thermal atomic layer deposition techniques with bis(tert-butylimido)bis(dimethylamido)molybdenum. Films were deposited at temperatures from 100 to 300 °C using ozone as the oxidant for the process. The Mo precursor was evaluated for thermal stability and volatility using thermogravimetric analysis and static vapor pressure measurements. Film properties were evaluated with ellipsometry, x-ray photoelectron spectroscopy, secondary ion mass spectroscopy, and secondary electron microscopy. The growth rate per cycle was determined to extend from 0.3 to 2.4 Å/cycle with <4% nonuniformity (1-sigma) with-in-wafer across a 150 mm wafer for the investigated temperature range.

  12. trans-Bis[1,2-bis(dimethylphosphinoethane]bromidonitrosyltungsten(0

    Nataša Avramović

    2008-01-01

    Full Text Available The crystal structure of the title compound, [WBr(NO(C6H16P22], reveals a distorted octahedral geometry around the W centre. The W atom lies on a special position at an inversion centre (the Br and NO ligands are equally disordered. The bis(dimethylphosphinoethane ligand is also severely disordered (site occupancy factors 0.52 and 0.48. This is the first structure of a tungsten species with nitrosyl and bromide ligands.

  13. Molybdenum (VI) Bis(imidoaryl) Complexes Containing the Bis (amonimethyl)aryl 'Pincer' Ligand

    Koten, G. van; Brandts, J.A.M.; Gossage, R.A.; Boersma, J.; Spek, A.L.

    1999-01-01

    The synthesis and characterization of new, five-coordinate molybdenum bis(imido) chloride complexes [MoCl(NCN)(N-t-Bu)2] (2) and [MoCl(2-C,N-NCN)(NAr)2] (3) and the methylated derivative [Mo(2-C,N-NCN)(Me)(NAr)2] (5) (NCN = [C6H3(CH2NMe2)2-2,6]-, Ar = C6H3-i-Pr2-2,6) are reported. Compounds 3 and 5

  14. Three 3D hybrid networks based on octamolybdates and different CuI/CuII-bis(triazole) motifs

    Three 3D compounds based on octamolybdate clusters and various CuI/CuII-bis(triazole) motifs, [CuI2btb][β-Mo8O26]0.5 (1), [CuI2btpe][β-Mo8O26]0.5 (2), and [CuII(btpe)2][β-Mo8O26]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-[Mo8O26]4- clusters via coordinating to CuI cations giving a 3D structure. In 2, the copper(I)-btpe motif exhibits a 'stairs'-like [CuI2btpe]2+ sheet, and the tetradentate β-[Mo8O26]4- clusters interact with two neighboring [CuI2btpe]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-[Mo8O26]4- clusters forming a 3D framework. The thermal stability and luminescent properties of 1-3 are investigated in the solid state. -- Graphical abstract: Three 3D compounds based on β-[Mo8O26]4- clusters with different CuI/CuII-bis(triazole) motifs were synthesized by regularly tuning flexible ligand spacer length and metal coordination preferences. Display Omitted

  15. Mapping of the serotonin 5-HT{sub 1D{alpha}} autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region

    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.

  16. N-Terminal methionine processing by the zinc-activated Plasmodium falciparum methionine aminopeptidase 1b.

    Calcagno, Sarah; Klein, Christian D

    2016-08-01

    The methionine aminopeptidase 1b from Plasmodium falciparum (PfMetAP 1b) was cloned, expressed in Escherichia coli and characterized. Surprisingly, and in contrast to other methionine aminopeptidases (MetAPs) that require heavy-metal cofactors such as cobalt, the enzyme is reliably activated by zinc ions. Immobilization of the enzyme is possible by His-tag metal chelation to iminodiacetic acid-agarose and by covalent binding to chloroacetamido-hexyl-agarose. The covalently immobilized enzyme shows long-term stability, allowing a continuous, heterogenous processing of N-terminal methionines, for example, in recombinant proteins. Activation by zinc, instead of cobalt as for other MetAPs, avoids the introduction of heavy metals with toxicological liabilities and oxidative potential into biotechnological processes. The PfMetAP 1b therefore represents a useful tool for the enzymatic, posttranslational processing of recombinant proteins. PMID:27023914

  17. CLINICAL INFECTION OF TWO CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

    Fuery, Angela; Tan, Jie; Peng, RongSheng; Flanagan, Joseph P; Tocidlowski, Maryanne E; Howard, Lauren L; Ling, Paul D

    2016-03-01

    The ability of prior infection from one elephant endotheliotropic herpesvirus (EEHV) type to protect against clinical or lethal infection from others remains an important question. This report describes viremia and subsequent shedding of EEHV1B in two juvenile 4-yr-old Asian elephants within 3 wk or 2 mo following significant infections caused by the rarely seen EEHV4. High levels of EEHV1B shedding were detected in the first elephant prior to emergence of infection and viremia in the second animal. The EEHV1B virus associated with both infections was identical to the strain causing infection in two herd mates previously. High EEHV viremia correlated with leukopenia and thrombocytopenia, which was followed by leukocytosis and thrombocytosis when clinical signs started to resolve. The observations from these cases should be beneficial for helping other institutions monitor and treat elephants infected with EEHV1, the most common virus associated with lethal hemorrhagic disease. PMID:27010294

  18. Caring from Afar: Asian H1B Migrant Workers and Aging Parents.

    Lee, Yeon-Shim; Chaudhuri, Anoshua; Yoo, Grace J

    2015-09-01

    With the growth in engineering/technology industries, the United States has seen an increase in the arrival of highly skilled temporary migrant workers on H1B visas from various Asian countries. Limited research exists on how these groups maintain family ties from afar including caring for aging parents. This study explores the experiences and challenges that Asian H1B workers face when providing care from a distance. A total of 21 Chinese/Taiwanese, Korean, and Indian H1B workers participated in in-depth qualitative interviews. Key findings indicate that despite distance, caring relationships still continue through regular communications, financial remittances, and return visits, at the same time creating emotional, psychological, and financial challenges for the workers. Findings highlight the need for further research in understanding how the decline of aging parent's health impacts the migrants' adjustment and health in the United States. PMID:26267591

  19. Characteristic Height Growth Pattern in Patients with Pseudohypoparathyroidism: Comparison between Type 1a and Type 1b

    Kinoshita, Kaori; Minagawa, Masanori; Anzai, Michiko; Sato, Yumiko; Kazukawa, Itsuro; Shimohashi, Kyoko; Ota, Setsuo; Kohno, Yoichi

    2007-01-01

    Pseudohypoparathyroidism (PHP) is a metabolic disorder characterized by organ resistance to the action of parathyroid hormone. PHP type 1 is subclassified into two apparent disorders, type 1a (PHP1a) and type 1b (PHP1b). Patients with PHP1a show Albright hereditary osteodystrophy including short stature. Patients with PHP1b have no such skeletal defects, however, literature regarding the growth of PHP1b is not currently available. We evaluated growth charts of PHP patients, including four PHP...

  20. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency

    Sim, J. C. H.; White, S. M.; Fitzpatrick, E.; Wilson, G. R.; Gillies, G.; Pope, K.; Mountford, H. S.; Tørring, Pernille M.; McKee, S.; Vulto-van Silfhout, A. T.; Jhangiani, S. N.; Muzny, D. M.; Leventer, R. J.; Delatycki, M. B.; Amor, D. J.; Lockhart, P. J.

    2014-01-01

    Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the...... predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism. Methods...

  1. Purification, crystallization and preliminary crystallographic analysis of soybean mature glycinin A1bB2

    Soybean mature glycinin was purified and crystallized and its preliminary crystallographic analysis is also reported. Glycinin is one of the most abundant storage-protein molecules in soybean seeds and is composed of five subunits (A1aB1b, A1bB2, A2B1a, A3B4 and A5A4B3). A1bB2 was purified from a mutant soybean cultivar containing glycinin composed of only A5A4B3 and A1bB2. At 281 K the protein formed hexagonal, rectangular and rod-shaped crystals in the first [0.1 M imidazole pH 8.0, 0.2 M MgCl2, 35%(v/v) MPD], second [0.1 M sodium citrate pH 5.6, 0.2 M ammonium acetate, 30%(v/v) MPD] and third (0.1 M phosphate–citrate pH 4.2, 2.0 M ammonium sulfate) crystallization conditions, respectively. X-ray diffraction data were collected to resolutions of 1.85, 1.85 and 2.5 Å from crystals of the three different shapes. The crystals belonged to space groups P6322, P21 and P1, with unit-cell parameters a = b = 143.60, c = 84.54 Å, a = 114.54, b = 105.82, c = 116.67 Å, β = 94.99° and a = 94.45, b = 94.96, c = 100.66 Å, α = 107.02, β = 108.44, γ = 110.71°, respectively. One, six and six subunits of A1bB2 were estimated to be present in the respective asymmetric units. The three-dimensional structure of the A1bB2 hexamer is currently being determined

  2. Protein 4.1B contributes to the organization of peripheral myelinated axons.

    Carmen Cifuentes-Diaz

    Full Text Available Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.

  3. Interferon-β1b Increases Th2 Response in Neuromyelitis Optica

    Toshiaki Hanafusa

    2012-09-01

    Full Text Available A Japanese randomized controlled study showed that Interferon â (IFN-â1b therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS, even in optico-spinal MS (OSMS. However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b treatment was not effective in neuromyelitis optica (NMO patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

  4. CYP1B1 genotype and risk of cardiovascular disease, pulmonary disease, and cancer in 50,000 individuals

    Kaur-Knudsen, D.; Nordestgaard, B.G.; Tybjaerg-Hansen, A.;

    2009-01-01

    OBJECTIVE: Cytochrome P450 (CYP) 1B1 enzymes metabolize tobacco-smoke polycyclic aromatic hydrocarbons and 17beta-estradiol. CYP1B1*3 (rs1056836 = Leu432Val = 4326C>G) and CYP1B1*4 (rs1800440 = Asn453Ser = 4390A>G) influence this metabolism. We, therefore, hypothesized that these two polymorphism...

  5. Thermal conductivity of A1B3C26 ternary compounds and their solid solutions

    Thermal conductivity of ternary compounds A1B3C26 and solid solutions CuGaxIn1-xS2, CuGaxIn1-xSe2, CuInS2xSe2(1-x), was studied by the absolute and relative methods in the temperature range of 300-550 K. Interrelation between thermal conductivity and tetragonal distortion of the ternary compounds A1B3C26 was established. It is shown that concentrational dependence of thermal conductivity for the solid solutions has the minimum near equimolar compositions

  6. Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania tricuspidata

    Tran Hong Quang; Nguyen Thi Thanh Ngan; Chi-Su Yoon; Kwang-Ho Cho; Dae Gill Kang; Ho Sub Lee; Youn-Chul Kim; Hyuncheol Oh

    2015-01-01

    A chemical investigation of the methanol extract from the roots of Cudrania tricuspidata resulted in the isolation of 16 compounds, including prenylated xanthones 1–9 and flavonoids 10–16. Their structures were identified by NMR spectroscopy and mass spectrometry and comparisons with published data. Compounds 1–9 and 13–16 significantly inhibited PTP1B activity in a dose dependent manner, with IC50 values ranging from 1.9–13.6 μM. Prenylated xanthones showed stronger PTP1B inhibitory effects...

  7. Role of Rck-Pat1b binding in assembly of processing-bodies

    Ozgur, Sevim; Stoecklin, Georg

    2013-01-01

    The DEAD box RNA helicase Rck and the scaffold protein Pat1b participate in controlling gene expression at the post-transcriptional level by suppressing mRNA translation and promoting mRNA decapping. In addition, both proteins are required for the assembly of processing (P)-bodies, cytoplasmic foci that contain stalled mRNAs and numerous components of the mRNA decay machinery. The C-terminal RecA-like domain of Rck interacts with the N-terminal acidic domain of Pat1b. Here, we identified poin...

  8. A novel protein tyrosine phosphatase 1B inhibitor from Tinospora sinensis

    Prasoon Gupta; Upasana Sharma; Gupta, Praveen K.; Rakesh Maurya

    2012-01-01

    Bioassay-directed fractionation led to the identification of a new compound, 4-hydroxy-heptadec-6-enoic acid ethyl ester (1) together with three known compounds (2-4) from Tinospora sinensis. The structure of 1 was determined by analysis of spectroscopic data. The isolated compounds were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compounds 1 and 2 displayed significant inhibitory activity with IC 50 values 61.1 and 74.2 μM, respectively

  9. Distinct circuits underlie the effects of 5-HT1B receptors on aggression and impulsivity

    Nautiyal, Katherine M.; Tanaka, Kenji F.; Barr, Mary M.; Tritschler, Laurent; Le Dantec, Yannick; David, Denis J.; Gardier, Alain M.; Blanco, Carlos; Hen, René; Ahmari, Susanne E.

    2015-01-01

    Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B het...

  10. Transit observations at the observatory in Grossschwabhausen: XO-1b and TrES-1

    Vanko, M; Mugrauer, M; Schmidt, T O B; Roell, T; Eisenbeiss, T; Hohle, M; Seifahrt, A; Koeltzsch, A; Broeg, Ch; Koppenhoefer, J; Neuhäuser, R

    2009-01-01

    We report on observations of transit events of the transiting planets XO-1b and TrES-1 with the AIU Jena telescope in Grossschwabhausen. Based on our IR photometry (in March 2007) and available transit timings (SuperWASP, XO and TLC-project-data) we improved the orbital period of XO-1b (P = 3.941497$\\pm$0.000006) and TrES-1 (P = 3.0300737$\\pm$0.000006), respectively. The new ephemeris for the both systems are presented.

  11. Potent water extracts of Indonesian medicinal plants against PTP1B

    Azis Saifudin; Tepy Usia; Subehan AbLallo; Hiroyuki Morita; Ken Tanaka; Yasuhiro Tezuka

    2016-01-01

    Objective: To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine. Methods: Water extracts of 18 plants were prepared through reflux and examined (25 μg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B (PTP1B). The determination of IC50 values was performed for the samples possessing more than 80% inhibition. Meanwhile, those exhibiting IC50 values more than 7.0 μg/mL were further profiled for their chemical const...

  12. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  13. SIMULACIJA TEHNOLOGIJE NADZORA NAD GLOBINO ANESTEZIJE- BIS MONITOR

    Kaučič, Vlasta

    2010-01-01

    V diplomskem delu smo izdelali simulacijsko okolje za predstavitev tehnologije nadzora nad globino anestezije. Preverili smo ali so obstoječi simulatorji ustrezni za simulacijo BIS monitorja. Na svetovnem spletu smo poiskali vsebine v obliki računalniških simulatorjev, ki obravnavajo tehnologijo BIS monitoringa in se osredotočili na ključne učne točke. Diplomsko delo tako predstavlja učbenik za uporabo simulacije tehnologije nadzora nad globino anestezije. Monitor BIS je nev...

  14. High pressure synthesis of BiS2

    Søndergaard-Pedersen, Simone; Nielsen, Morten Bormann; Bremholm, Martin

    possibilities of using high pressure synthesis to discover new phases in the Bi-S binary system were investigated as early as the 1960’s.4 The research led to discovery of a compound with BiS2 stoichiometry, but no structure solution of BiS2 was reported. A reason behind making this new phase is to study the...... contains Bi atoms in distorted square-based pyramidal coordination to five surrounding sulfur atoms. The results will be displayed together with a comparison to other metal dichalcogenide compounds. Experimental details and physical properties will also be presented together with theoretical calculations...

  15. Mono- and bis-thiazolium salts have potent antimalarial activity.

    Hamzé, Abdallah; Rubi, Eric; Arnal, Pascal; Boisbrun, Michel; Carcel, Carole; Salom-Roig, Xavier; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Calas, Michèle

    2005-05-19

    Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50)

  16. Bis-naphtho-γ-pyrones from Fungi and Their Bioactivities

    Shiqiong Lu

    2014-05-01

    Full Text Available Bis-naphtho-γ-pyrones are an important group of aromatic polyketides derived from fungi. They have a variety of biological activities including cytotoxic, antitumor, antimicrobial, tyrosine kinase and HIV-1 integrase inhibition properties, demonstrating their potential applications in medicine and agriculture. At least 59 bis-naphtho-γ-pyrones from fungi have been reported in the past few decades. This mini-review aims to briefly summarize their occurrence, biosynthesis, and structure, as well as their biological activities. Some considerations regarding to synthesis, production, and medicinal and agricultural applications of bis-naphtho-γ-pyrones are also discussed.

  17. Relativistic energy levels and oscillator strengths for the ns(n-1)d 1D-ns21S transitions of the alkaline earth atoms

    A fully relativistic Dirac-Fock method with Breit and QED corrections has been employed to study energy levels and oscillator strengths for the ns(n-1)d 1D-ns21S transitions of the alkaline earth atoms. In calculation, the authors consider significant Breit and QED corrections, the results are in good agreements with recent experimental data and other theoretical values. The results show that it is feasible to obtain the highly Rybderg states of the alkaline earth atoms, especially the autoionization states, by use of quadrupole transitions as an intermediate resonance

  18. Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

    Kathleen M Averette

    Full Text Available NOD-like receptors (NLRs are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT, is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP. The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis.

  19. Homo- and heterodinuclear coordination polymers based on a tritopic cyclam bis-terpyridine unit: Structure and rheological properties

    An innovative coordination polymer based on a tritopic ligand having the bis-terpyridine cyclam (CHTT) unit is explored. Homo- or heteronuclear 1D coordination polymers can be formed with bivalent metal ions such as Co(II) and Ni(II) in solvent DMF. Creep-recovery curves of the (CoII)2CHTT gels formed from 1D coordination polymers were analyzed with the Burgers model and demonstrated an original self-healing property, unusual in the class of molecular gels. The influence of the metal type was studied through the structural features using small-angle neutron scattering (SANS) experiments. In gels, the corresponding network involves genuine fibers (R ≈ 35 Å), bundles of these fibers and also a fraction of finite size aggregates (rods with aspect ratio f ≈ 3–5). We found that the distribution of these latter structural components is sensitive to the metal ions type. Such tritopic 1D coordination polymers exhibit a range of original structural features and a facile control of the developed structures in solutions and gels by tuning their thermodynamic parameters. The versatility associated to the intrinsic dynamic ability of the systems should pave the way to original properties for molecular devices. - Graphical abstract: A tritopic ligand with a bis-terpyridine cyclam (CHTT) unit can form homo- and heterobinuclear coordination polymers with bivalent metal ions in DMF. Gels exhibit a remarkable self-healing property while structures of solutions and gels are studied by small-angle neutron scattering. - Highlights: • Homo- and heteronuclear coordination polymers based on innovative tritopic ligand. • The gels formed from the coordination polymers demonstrated self-healing property. • Influence of the metal type was studied through the structural properties by SANS. • Versatility of the singular system present original properties for molecular device

  20. HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

    White, Christy L.; Whittington, Amy; Barnes, Maria J.; Wang, Zhong; Bray, George A; Morrison, Christopher D.

    2008-01-01

    Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA...

  1. Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk:A meta-analysis

    Akira; Yokoyama; Tetsuji; Yokoyama

    2010-01-01

    AIM:To evaluate the contribution of alcohol dehydrogenase-1B(ADH1B)and aldehyde dehydrogenase-2 (ALDH2)polymorphisms to the risk of esophageal cancer.METHODS:Nineteen articles were included by searching MEDLINE,EMBASE and the Chinese Biomedical Database,13 on ADH1B and 18 on ALDH2.We performed a meta-analysis of case-control studies including 13 studies on ADH1B(cases/controls:2390/7100)and 18 studies on ALDH2(2631/6030).RESULTS:The crude odds ratio[OR(95%confidence interval)]was 2.91(2.04-4.14)for ADH1B*1/...

  2. Synthesis of two mono-deoxy β-cyclodextrin derivatives as useful tools for confirming DIBAL-H promoted bis-de-O-methylation mechanism

    Su Long Xiao; De Min Zhou; Ming Yang; Fei Yu; Li He Zhang; Pierre Sina(y); Yong Min Zhang

    2012-01-01

    Diisobutylaluminium hydride (DIBAL-H) promotes secondary rim regioselective bis-de-O-methylation of permethylated β-cyclodextrin (β-CD) to give diol 2.To gain an insight into the mechanism of this remarkable regioselective behavior,two corresponding permethylated β-CDs with an alcohol function at either 2-or 3-position were synthesized in our previous study.As a step further to this work,the two compounds were subjected to deoxygenation reaction with tributyltin hydride in the present of 2,2'-azobisisobutyronitrile affording the corresponding 2-and 3-deoxy permethylated β-CD derivatives (19 and 16).The structures of these two compounds were characterized by 1D and 2D NMR and HRMS.Compounds 16 and 19 were unable to react with DIBAL-H which suggests that O-2A and O-3B are necessary for DIBAL-H promoted bis-de-O-methylation reaction of permethvlated β-CD.

  3. Study of structural transformations in Fe83W1B16 alloy resulting from natural aging

    Structural transformations taking place in amorphous Fe83W1B16 alloy as a result of its natural aging are investigated by Moessbauer spectroscopy and thermomagnetic analysis methods. Spatial inhomogeneity of changes in the atom closest vicinity and its effect on the alloy magnetization temperature dependence progress are ascertained. 9 refs.; 3 figs

  4. Insertional Mutagenesis Identifies a STAT3/Arid1b/β-catenin Pathway Driving Neurofibroma Initiation

    Jianqiang Wu

    2016-03-01

    Full Text Available To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1 neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs and Schwann cells (SCs prevents neurofibroma formation, decreasing SCP self-renewal and β-catenin activity. β-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and β-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3β and the SWI/SNF gene Arid1b to increase β-catenin. Knockdown of Arid1b or Gsk3β in Stat3fl/fl;Nf1fl/fl;DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/β-catenin pathway inhibitors in neurofibroma therapeutic trials.

  5. Insertional Mutagenesis Identifies a STAT3/Arid1b/β-catenin Pathway Driving Neurofibroma Initiation.

    Wu, Jianqiang; Keng, Vincent W; Patmore, Deanna M; Kendall, Jed J; Patel, Ami V; Jousma, Edwin; Jessen, Walter J; Choi, Kwangmin; Tschida, Barbara R; Silverstein, Kevin A T; Fan, Danhua; Schwartz, Eric B; Fuchs, James R; Zou, Yuanshu; Kim, Mi-Ok; Dombi, Eva; Levy, David E; Huang, Gang; Cancelas, Jose A; Stemmer-Rachamimov, Anat O; Spinner, Robert J; Largaespada, David A; Ratner, Nancy

    2016-03-01

    To identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and β-catenin activity. β-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and β-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3β and the SWI/SNF gene Arid1b to increase β-catenin. Knockdown of Arid1b or Gsk3β in Stat3(fl/fl);Nf1(fl/fl);DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/β-catenin pathway inhibitors in neurofibroma therapeutic trials. PMID:26904939

  6. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy

    Vlaskamp, Danique R.M.; Rump, Patrick; Callenbach, Petra M.C.; Vos, Yvonne J.; Sikkema-Raddatz, Birgit; van Ravenswaaij-Arts, Conny M.A.; Brouwer, Oebele F.

    2016-01-01

    We describe an 18-year-old male patient with myoclonic astatic epilepsy (MAE), moderate to severe intellectual disability, behavioural problems, several dysmorphisms and a 1.2-Mb de novo deletion on chromosome 16p11.2. This deletion results in haploinsufficiency of STX1B and other genes. Recently, v

  7. Isolation of transformation-defective, replication-nondefective early region 1B mutants of adenovirus 12

    The authors isolated three adenovirus 12 early region 1B mutants (in205B, in205C, and dl205) by ligation of the cleaved DNA-protein complex and transfection of human embryo kidney cells with the ligation products. These mutants could replicate efficiently in human embryo kidney or KB cells but showed markedly reduced transforming capacities both in vitro and in vivo. In cells infected with the mutants, the early region 1B gene was transcribed efficiently. In cells infected with in205B, the products corresponding to the early region 1B-coded 19,000-molecular-weight polypeptide was detected by in vitro translation but not immunoprecipitated extract of labeled cells. In cells infected with in205C or dl205, the products corresponding to the same polypeptide were not detected by either in vitro translation or immunoprecipitation of labeled cell extracts. The results suggest that the 19,000-molecular-weight polypeptide encoded by early region 1B is required for cell transformation but not for viral propagation

  8. Human CRISP-3 binds serum alpha(1)B-glycoprotein across species

    Udby, Lene; Johnsen, Anders H; Borregaard, Niels

    2010-01-01

    CRISP-3 was previously shown to be bound to alpha(1)B-glycoprotein (A1BG) in human serum/plasma. All mammalian sera are supposed to contain A1BG, although its presence in rodent sera is not well-documented. Since animal sera are often used to supplement buffers in experiments, in particular such...

  9. Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells.

    César Mattei

    Full Text Available Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and beta-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera.

  10. A complex selection signature at the human AVPR1B gene

    Cagliani Rachele

    2009-06-01

    Full Text Available Abstract Background The vasopressin receptor type 1b (AVPR1B is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common AVPR1B haplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses. Results Here we have analyzed the two exons of the gene and the data we present suggest that AVPR1B has been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg in this region has been subjected to directional selection. Conclusion Although the underlying selective pressure(s remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.

  11. Evidence for protein 4.1B acting as a metastasis suppressor

    Cavanna, T.; Pokorná, Eva; Veselý, Pavel; Gray, C.; Zicha, D.

    2007-01-01

    Roč. 120, č. 4 (2007), s. 606-616. ISSN 0021-9533 Institutional research plan: CEZ:AV0Z50520514 Keywords : 4.1B protein * metastasis * migration Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.383, year: 2007

  12. Mirror Advanced Reactor Study (MARS). Final report. Volume 1-B. Commercial fusion electric plant

    Donohue, M.L.; Price, M.E. (eds.)

    1984-07-01

    Volume 1-B contains the following chapters: (1) blanket and reflector; (2) central cell shield; (3) central cell structure; (4) heat transport and energy conversion; (5) tritium systems; (6) cryogenics; (7) maintenance; (8) safety; (9) radioactivity, activation, and waste disposal; (10) instrumentation and control; (11) balance of plant; (12) plant startup and operation; (13) plant availability; (14) plant construction; and (15) economic analysis.

  13. Synthesis of three bromophenols from red algae as PTP1B inhibitors

    Guo, Shuju; Li, Jing; Li, Ting; Shi, Dayong; Han, Lijun

    2011-01-01

    Bromophenols are a set of natural products widely distributed in seaweed, most of which exhibit interesting and useful biological activities. To develop a reliable and efficient synthetic route to these natural bromophenols, three of them, 3,4-dibromo-5-(2'-bromo-3',4'-dihydroxy-6'-methoxymethyl-benzyl)-benzene-1,2-diol (compound 9), 3,4-dibromo-5-(2'-bromo-6'-ethoxy methyl-3',4'-dihydroxybenzyl)-benzene-1,2-diol (compound 10), and 3-bromo-4-(3'-bromo-4',5'-dihydroxy benzyl)-5-(ethoxymethyl)-benzene-1,2-diol (compound 14), isolated from red marine algae, have been synthesized in eight steps with an overall yield of 14.4%, 14.4%, and 18.2% respectively, via a practical approach employing bromination, Wolff-Kishner-Huang reduction and a Friedel-Crafts reaction as key steps. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the synthetic compounds were evaluated by the colorimetric assay. The results show that these compounds are moderate PTP1B inhibitors. The synthesis of these bromophenol derivatives makes in vivo studies of their structure-activity relationships and inhibition activity against PTP1B possible.

  14. Johnston Atoll Site 1B-P 6/29/2000 14-15M

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 14 and 15 meters along a permanent transect.

  15. Johnston Atoll Site 1B-P 6/29/2000 16-17M

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 16 and 17 meters along a permanent transect.

  16. Johnston Atoll Site 1B-P 6/29/2000 5-6M

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 5 and 6 meters along a permanent transect.

  17. ISEcp1B-Mediated Transposition of blaCTX-M in Escherichia coli

    Poirel, Laurent; Lartigue, Marie-Frédérique; Decousser, Jean-Winoc; Nordmann, Patrice

    2005-01-01

    Several expanded-spectrum β-lactamase blaCTX-M genes are associated with ISEcp1-like elements in Enterobacteriaceae. We found that ISEcp1B was able to mobilize the adjacent blaCTX-M-19 gene by a transpositional mechanism in Escherichia coli by recognizing a variety of DNA sequences as right inverted repeats.

  18. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

  19. Johnston Atoll Site 1B-P 6/29/2000 28-29M

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 28 and 29 meters along a permanent transect.

  20. ISEcp1B-Mediated Transposition of blaCTX-M in Escherichia coli

    Poirel, Laurent; Lartigue, Marie-Frédérique; Decousser, Jean-Winoc; Nordmann, Patrice

    2005-01-01

    Several expanded-spectrum β-lactamase blaCTX-M genes are associated with ISEcp1-like elements in Enterobacteriaceae. We found that ISEcp1B was able to mobilize the adjacent blaCTX-M-19 gene by a transpositional mechanism in Escherichia coli by recognizing a variety of DNA sequences as right inverted repeats. PMID:15616333

  1. Mirror Advanced Reactor Study (MARS). Final report. Volume 1-B. Commercial fusion electric plant

    Volume 1-B contains the following chapters: (1) blanket and reflector; (2) central cell shield; (3) central cell structure; (4) heat transport and energy conversion; (5) tritium systems; (6) cryogenics; (7) maintenance; (8) safety; (9) radioactivity, activation, and waste disposal; (10) instrumentation and control; (11) balance of plant; (12) plant startup and operation; (13) plant availability; (14) plant construction; and (15) economic analysis

  2. 2D numerical comparison of trailing edge flaps - UpWind WP1B3

    Buhl, Thomas; Andersen, Peter Bjørn; Barlas, T.K.

    This report covers the investigations and comparisons of trailing edge flaps carried out by Delft and Risø. The work is a part of the W1B3 work package of the UpWind EU-project. This report covers only 2D test cases with simple control of the trailing edge flap with the objective of keeping CL...

  3. Patient satisfaction with the BETACONNECT™ autoinjector for interferon beta-1b

    Weller I

    2015-07-01

    Full Text Available Ivonne Weller,1 Anna Saake,1 Thomas Schreiner,1 Julika Vogelreuter,1 Nicolas Petroff2 1Bayer Vital GmbH, Leverkusen, Germany; 2Vitartis Medizin-Service GmbH, Göttingen, Germany Purpose: Multiple sclerosis (MS is a chronic demyelinating, degenerative disease requiring long-term treatment. Patient adherence to treatment may be challenging in such scenarios, especially since treatment often involves self-injection, for example, with interferon beta-1b during therapy. BETACONNECT™ is a novel electronic autoinjector for patient support in interferon beta-1b administration. The purpose of this survey was to assess patient satisfaction with the BETACONNECT™ device and its features.Patients and methods: A total of 2,299 MS patients using the BETACONNECT™ device were asked to participate in a survey in October 2014. All of these candidates participated in the BETAPLUS® program and had provided written informed consent. The participants were asked to answer 13 device-related questions.Results: Of these candidates, 1,365 replied to the questionnaire, with more than 60% of the participants being 40–59 years of age. Among them, 69% were women and 21% were men (10% not specified. Approximately half of the participants received treatment with interferon beta-1b for more than 5 years. Most participants (85% had used self-injection devices before, with 59% previously using BETACOMFORT®, 23% using BETAJECT® Comfort, and 3% using BETAJECT® Lite, while less than 4% manually injected interferon beta-1b. The majority of the participants had received the BETACONNECT™ device from a BETAPLUS® nurse (87% and 48% had already used the device for more than 2 months (49% for 2 months or less. Among the participants, more than 90% evaluated the BETACONNECT™ device as “very helpful” or “helpful” in supporting their interferon beta-1b therapy with only marginal sex differences. Features that were rated “very important” by more than half of the

  4. Estimation of evapotranspiration over heterogeneous surfaces based on HJ1B satellite data in China

    Xin, Xiaozhou; Jiao, Jingjun

    2014-05-01

    The HJ1B satellite of China is equipped with two CCD cameras with 30m resolution and one infrared multispectral camera with 300m resolution. And the revisit period of HJ1B satellite is 4 days. Compared to MODIS or TM, HJ1B data has the advantage of high spatial-temporal resolution. Methodology based on the one-source energy balance model was developed for net radiation (Rn), soil heat flux (G), sensible heat flux (H) and latent heat flux (LE) estimation from HI1B data. The core procedure is a scheme that was designed for correcting the spatial scale error over heterogeneous surfaces by taking advantage of the HJ1B data characteristics, i.e., high resolution CCD data (30m) along with thermal data (300m). First of all, a regression relationship between Ts and NDVI was built up at 300m resolution based on the data of Ts and NDVI of the selected "pure" pixels. And then the relationship function was applied at 30m resolution to derive Ts at high resolution, i.e., at the subpixel level. Furthermore, the 30m land class data was also used in the parameterization of surface energy balance and surface aerodynamic transfer, which is important since significant error may be resulted by using one land class type to represent the whole mixed pixel. By using high resolution NDVI and land class data, we are able to mitigate the spatial scale error of the mixed pixels at 300m resolution. At last, the 300m surface energy fluxes were obtained by aggregation of the 30m estimation. HJ1B data at Hai river basin in north China in 2010 were used to verify this method. The eddy-correlation system data were used as validation. The results of the method were compared with the results of a simple method that estimates the fluxes at 300m by aggregating all of the input parameters to 300m. It is shown that the method proposed in this study shows higher agreement with in-suit measurement, and the fluxes maps also show much more details of the spatial variation. By using this method, it can be

  5. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

    Zhang, Minli; Zhou, Diansong; Wang, Yi; Maier, Donna L; Widzowski, Daniel V; Sobotka-Briner, Cynthia D; Brockel, Becky J; Potts, William M; Shenvi, Ashok B; Bernstein, Peter R; Pierson, M Edward

    2011-11-01

    The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients. PMID:21825000

  6. Spatial-Temporal Study of Rab1b Dynamics and Function at the ER-Golgi Interface

    Martinez, Hernán; García, Iris A.; Sampieri, Luciana

    2016-01-01

    The GTPase Rab1b is involved in ER to Golgi transport, with multiple Rab1b effectors (located at ERES, VTCs and the Golgi complex) being required for its function. In this study, we performed live-cell dual-expression studies to analyze the dynamics of Rab1b and some effectors located at the ERES-Golgi interface. Rab1b occupied widely distributed mobile punctate and tubular structures, displaying a transient overlaps with its effectors and showing that these overlaps occurred at the same time in spatially distinct steps of ER to Golgi transport. In addition, we assessed Rab1b dynamics during cargo sorting by analyzing the concentration at ERES of a Golgi protein (SialT2-CFP) during Brefeldin A washout (BFA WO). Rab1b was associated to most of the ERES structures, but at different times during BFA WO, and recurrently SialT2-CFP was sorted in the ERES-Rab1b positive structures. Furthermore, we reveal for first time that Rab1b localization time at ERES depended on GBF1, a Rab1b effector that acts as the guanine nucleotide exchange factor of Arf1, and that Rab1b membrane association/dissociation dynamics at ERES was dependent on the GBF1 membrane association and activity, which strongly suggests that GBF1 activity modulates Rab1b membrane cycling dynamic. PMID:27500526

  7. The Polycomb protein and E3 ubiquitin ligase Ring1B harbors an IRES in its highly conserved 5' UTR.

    Erwin Boutsma

    Full Text Available Ring1B is an essential member of the highly conserved Polycomb group proteins, which orchestrate developmental processes, cell growth and stem cell fate by modifying local chromatin structure. Ring1B was found to be the E3 ligase that monoubiquitinates histone H2A, which adds a new level of chromatin modification to Polycomb group proteins. Here we report that Ring1B belongs to the exclusive group of proteins that for their translation depend on a stable 5' UTR sequence in their mRNA known as an Internal Ribosome Entry Site (IRES. In cell transfection assays the Ring1B IRES confers significantly higher expression levels of Ring1B than a Ring1B cDNA without the IRES. Also, dual luciferase assays show strong activity of the Ring1B IRES. Although our findings indicate Ring1B can be translated under conditions where cap-dependent translation is impaired, we found the Ring1B IRES to be cap-dependent. This raises the possibility that translational control of Ring1B is a multi-layered process and that translation of Ring1B needs to be maintained under varying conditions, which is in line with its essential role as an E3 ligase for monoubiquitination of histone H2A in the PRC1 Polycomb protein complex.

  8. Cryptochrome 1b: a possible inducer of visual lateralization in pigeons?

    Ströckens, Felix; Güntürkün, Onur

    2016-01-01

    The visual system of adult pigeons shows a lateralization of object discrimination with a left hemispheric dominance on the behavioural, physiological and anatomical levels. The crucial trigger for the establishment of this asymmetry is the position of the embryo inside the egg, which exposes the right eye to light falling through the egg shell. As a result, the right-sided retina is more strongly stimulated with light during embryonic development. However, it is unknown how this embryonic light stimulation is transduced to the brain as rods and cones are not yet functional. A possible solution could be the blue-light-sensitive molecule cryptochrome 1 (Cry1), which is expressed in retinal ganglion cells (RGCs) of several mammalian and avian species. RGCs have been shown to be functional during the time of induction of asymmetry and possess projections to primary visual areas. Therefore, Cry1-containing RGCs could be responsible for induction of asymmetry. The aim of this study was to identify the expression pattern of the Cry1 subtype Cry1b in the retina of embryonic, post-hatch and adult pigeons by immunohistochemical staining and to show whether Cry1b-containing RGCs project to the optic tectum. Cry1b-positive cells were indeed mainly found in the RGC layer and to lesser extent in the inner nuclear layer at all ages, including the embryonic stage. Tracing in adult animals revealed that at least a subset of Cry1b-containing RGCs project to the optic tectum. Thus, Cry1b-containing RGCs within the embryonic retina could be involved in the induction of asymmetries in the visual system of pigeons. PMID:26535920

  9. Interleukin 1B Variant -1473G/C (rs1143623) Influences Triglyceride and Interleukin 6 Metabolism

    Delgado-Lista, Javier; Garcia-Rios, Antonio; Perez-Martinez, Pablo; Solivera, Juan; Yubero-Serrano, Elena M.; Fuentes, Francisco; Parnell, Laurence D.; Shen, Jian; Gomez, Purificacion; Jimenez-Gomez, Yolanda; Gomez-Luna, Maria J.; Marin, Carmen; Belisle, Sarah E.; Rodriguez-Cantalejo, Fernando; Meydani, Simin N.; Ordovas, Jose M.; Perez-Jimenez, Francisco

    2011-01-01

    Context: IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility. Objective: We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6. Design, Setting, and Participants: A total of 477 people over age 65 yr were genotyped for IL1B -1473G/C, and we evaluated fasting lipids depending on genotype. Then, 88 healthy young men were also genotyped and were fed a saturated fatty acid-rich meal. Serial blood samples were drawn for 11 h after the meal, and lipid fractions and IL6 were assayed. Main Outcome and Interventions: Fasting lipids were studied in the aged persons. Fasting and postprandial measurements of lipids and IL6 were performed in the healthy young men. Results: In the aged persons, CC subjects (minor allele homozygotes) showed higher triglyceride (P = 0.002) and cholesterol (P = 0.011) levels. Healthy young male carriers of the minor C allele showed higher postprandial triglycerides (P = 0.037), and those carried into large triglyceride-rich lipoproteins (P = 0.004). In addition, they showed higher postprandial IL6 concentrations (P = 0.008). Conclusions: Our work shows that inflammatory genes may regulate fasting and postprandial lipids because the carriers of the minor allele of an IL gene variant have altered lipid metabolism. To reinforce these gene-phenotype findings, IL6 (the natural effector of IL1B) was increased in these persons. PMID:21307135

  10. Potent water extracts of Indonesian medicinal plants against PTP1B

    Azis Saifudin; Tepy Usia; Subehan AbLallo; Hiroyuki Morita; Ken Tanaka; Yasuhiro Tezuka

    2016-01-01

    Objective: To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine. Methods: Water extracts of 18 plants were prepared through reflux and examined (25 mg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B (PTP1B). The determination of IC50 values was performed for the samples possessing more than 80% inhibition. Meanwhile, those exhibiting IC50 values more than 7.0 mg/mL were further profiled for their chemical constituents through nuclear magnetic resonance (NMR) measurement. Results: About 44% (8) of the examined samples showed more than 80% inhibition against PTP1B. The water extracts of Elephantopus scaber, Helicteres isora aerial parts, Elaeocarpus grandiflorus (E. grandiflorus) fruits, Melaleuca leucadendron leaves, and Quercus infectoria gum had IC50 values ranging from 2.05 to 6.90 mg/mL. Meanwhile, Andropogon nardus and Centella asiatica were at the area of d 3.0–4.0 ppm. Further, the 13C NMR observation of samples possessing the most intensive signals in their proton NMR Cinnamomum burmannii and E. grandiflorus showed the peaks at the area of d 60–90 ppm as the supportive evidence for sugar group signals. Intriguingly, a disaccharide from E. grandiflorus could be an active inhibitor towards PTB1B. Conclusions: In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia, pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines. In addition, the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1B.

  11. Use of optimized 1D TOCSY NMR for improved quantitation and metabolomic analysis of biofluids

    Sandusky, Peter [Eckerd College, Department of Chemistry (United States); Appiah-Amponsah, Emmanuel; Raftery, Daniel, E-mail: raftery@purdue.edu [Purdue University, Department of Chemistry (United States)

    2011-04-15

    One dimensional selective TOCSY experiments have been shown to be advantageous in providing improved data inputs for principle component analysis (PCA) (Sandusky and Raftery 2005a, b). Better subpopulation cluster resolution in the observed scores plots results from the ability to isolate metabolite signals of interest via the TOCSY based filtering approach. This report reexamines the quantitative aspects of this approach, first by optimizing the 1D TOCSY experiment as it relates to the measurement of biofluid constituent concentrations, and second by comparing the integration of 1D TOCSY read peaks to the bucket integration of 1D proton NMR spectra in terms of precision and accuracy. This comparison indicates that, because of the extensive peak overlap that occurs in the 1D proton NMR spectra of biofluid samples, bucket integrals are often far less accurate as measures of individual constituent concentrations than 1D TOCSY read peaks. Even spectral fitting approaches have proven difficult in the analysis of significantly overlapped spectral regions. Measurements of endogenous taurine made over a sample population of human urine demonstrates that, due to background signals from other constituents, bucket integrals of 1D proton spectra routinely overestimate the taurine concentrations and distort its variation over the sample population. As a result, PCA calculations performed using data matrices incorporating 1D TOCSY determined taurine concentrations produce better scores plot subpopulation cluster resolution.

  12. 40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100... Substances § 721.8100 Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis...

  13. Charge Transport in 1-D Nanostructured CdS Dye Sensitized Solar Cell

    Charge transport in eosin yellow sensitized CdS 1-D nanostructures is studied. Direct conduction pathway for electron transport in nanowires enhances Voc in CdS nanowires compared to nanorods and nanoparticles. J-V characterization of nanowires results in improved efficiency of 0.184% due to fewer interparticle connections. Increase in Jsc is observed by coating CdS 1-D nanostructures on TiO2 substrate which reduces rate of recombination and photocorrosive nature of CdS photoanodes. Enhancement in efficiency up to 0.501% is achieved for CdS 1-D nanostructures DSSCs on TiO2 substrate.

  14. Non-uniform black strings and the critical dimension in the $1/D$ expansion

    Suzuki, Ryotaku; Tanabe, Kentaro

    2015-01-01

    Non-uniform black strings (NUBS) are studied by the large $D$ effective theory approach. By solving the near-horizon geometry in the $1/D$ expansion, we obtain the effective equation for the deformed horizon up to the next-to-next-to-leading order (NNLO) in $1/D$. We also solve the far-zone geometry by the Newtonian approximation. Matching the near and far zones, the thermodynamic variables are computed in the $1/D$ expansion. As the result, the large $D$ analysis gives a critical dimension $...

  15. Development of a 1D neutron transport code employing the method of characteristics

    To investigate the 2D/1D fusion core analysis method, a 1D neutron transport problem solver, PEACH-ID, is developed. It is a code of method of characteristics (MOC), both the usual fiat-source step characteristics (SC) scheme and linear source (LS) approximation scheme are adopted for tracking calculation along the neutron flying trajectory. Exponential function interpolation table and fission source extrapolation are adopted as two major methods to accelerate the computational process. Numerical results demonstrate that PEACH-1D is accurate and efficient, and the proposed LS scheme is able to handle quite larger mesh division and deserves much more application in the MOC codes. (authors)

  16. CD1d and invariant NKT cells at the human maternal–fetal interface

    Boyson, Jonathan E.; Rybalov, Basya; Koopman, Louise A.; Exley, Mark; Balk, Steven P.; Racke, Frederick K.; Schatz, Frederick; Masch, Rachel; Wilson, S. Brian; Strominger, Jack L.

    2002-01-01

    Invariant CD1d-restricted natural killer T (iNKT) cells comprise a small, but significant, immunoregulatory T cell subset. Here, the presence of these cells and their CD1d ligand at the human maternal–fetal interface was investigated. Immunohistochemical staining of human decidua revealed the expression of CD1d on both villous and extravillous trophoblasts, the fetal cells that invade the maternal decidua. Decidual iNKT cells comprised 0.48% of the decidual CD3+ T cell population, a frequency...

  17. Construction of copper-based coordination polymers with 1D chain, 2D plane and wavy networks: Syntheses, structures, thermal behaviors and photoluminescence properties

    Jianghua Li; Chi Zhang

    2015-11-01

    Three Cu-based coordination polymers (CPs), including [CuII ( -1 -NCS)2 (O-1 -DMF)2 (2 -3,3’-bptz)] (1), [CuI (1,3-2-NCS)(2-3,3’-bptz)] (2) and [(CuI (1,3-μ2- NCS))(2-4,4’-bptz)] (3) (DMF = , -dimethyl formamide, 3,3’-bptz = 3,6-bis(3-pyridyl)tetrazine and 4,4’-bptz = 3,6-bis(4-pyridyl)tetrazine) have been successfully constructed by solution diffusion reactions by using Cu(NO3)2 ·3H2O or CuNCS and KNCS with 3,3’-bptz / 4,4’-bptz ligands, respectively. The resulting crystalline materials have been characterized by the single-crystal X-ray diffraction analyses, elemental analyses, FT-IR spectra, thermogravimetric analyses and powder X-ray diffraction (PXRD). Single crystal X-ray analyses revealed that CP 1 is organized in one-dimensional (1D) chain in which the Cu(II) ions are coordinated by 1 -NCS− anions and 1-DMF molecules, and linked by 2-3,3’-bptz bridging ligands. CPs ,2 and 3 are structural isomers. CP 2 exhibits two-dimensional (2D) (4,4)-plane-like network in which Cu(I) ions are linked by 2-NCS − and 2-3,3’-bptz ligands. In CP 3, Cu(I) ions are connected by 2 -NCS − and 2-4,4’-bptz ligands to form 2D saw-tooth wavy network. In addition, the photoluminescence properties of CPs 1-3 were also investigated in the solid state at room temperature.

  18. Safety assessment of bis-diglyceryl polyacyladipate-2 and bis-diglyceryl polyacyladipate-1 as used in cosmetics.

    Fiume, Monice M; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2013-01-01

    The Cosmetic Ingredient Review Expert Panel assessed the safety of bis-diglyceryl polyacyladipate-2 and bis-diglyceryl polyacyladipate-1 as used in cosmetics, finding that these ingredients are safe in cosmetic formulations in the present practices of use and concentration. Both ingredients are lanolin substitutes and are reported to function in cosmetics as skin-conditioning agents--emollients. The Panel reviewed available animal and clinical data in making its determination of safety. PMID:24174474

  19. Synergistic extraction of Eu(III) with N-phosphorylated bis-ureas and chlorinated cobalt bis(dicarbollide) ion

    Selucký, P.; Bubeníková, M.; Rais, J.; Grüner, Bohumír; Brusko, V.V.

    2013-01-01

    Roč. 101, č. 1 (2013), s. 27-31. ISSN 0033-8230 R&D Projects: GA ČR GA104/09/0668 Institutional support: RVO:61388980 Keywords : liquid-liquid extraction * lanthanides * actinides * N-phosphorylated bis-ureas * chlorinated cobalt bis(dicarbollide) ion * high level liquid waste Subject RIV: CA - Inorganic Chemistry Impact factor: 1.411, year: 2013

  20. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of OATP1B1.

    van de Steeg, E; Greupink, R; Schreurs, M; Nooijen, I H G; Verhoeckx, 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

    2013-03-01

    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 oral antidiabetics in the clinic. The aim of this study was to investigate possible drug-drug interactions between these drugs at the level of OATP1B1 and OATP1B1*15. We generated human embryonic kidney (HEK)293 cells stably overexpressing OATP1B1 or OATP1B1*15 that showed similar protein expression levels of OATP1B1 and OATP1B1*15 at the cell membrane as measured by liquid chromatography-tandem mass spectrometry. In HEK-OATP1B1*15 cells, the V(max) for OATP1B1-mediated transport of E(2)17β-G (estradiol 17β-d-glucuronide) was decreased >60%, whereas K(m) values (Michaelis constant) were comparable. Uptake of rosuvastatin in HEK-OATP1B1 cells (K(m) 13.1 ± 0.43 μM) was nearly absent in HEK-OATP1B1*15 cells. Interestingly, several oral antidiabetics (glyburide, glimepiride, troglitazone, pioglitazone, glipizide, gliclazide, and tolbutamide), but not metformin, were identified as significant inhibitors of the OATP1B1-mediated transport of rosuvastatin. The IC(50) values for inhibition of E(2)17β-G uptake were similar between OATP1B1 and OATP1B1*15. In conclusion, these studies indicate that several oral antidiabetic drugs affect the OATP1B1-mediated uptake of rosuvastatin in vitro. The next step will be to translate these data to the clinical situation, as it remains to be established whether the studied oral antidiabetics indeed affect the clinical pharmacokinetic profile of rosuvastatin in patients. PMID:23248200

  1. Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is regulated by protein palmitoylation

    Kong, Chen; Lange, Jeffrey J.; Samovski, Dmitri [Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Su, Xiong [Department of Internal Medicine, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO 63110 (United States); Liu, Jialiu [Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Sundaresan, Sinju [Department of Internal Medicine, Center for Human Nutrition Washington University School of Medicine, St. Louis, MO 63110 (United States); Stahl, Philip D., E-mail: pstahl@wustl.edu [Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2013-05-03

    Highlights: •Hominoid-specific oncogene TBC1D3 is targeted to plasma membrane by palmitoylation. •TBC1D3 is palmitoylated on two cysteine residues: 318 and 325. •TBC1D3 palmitoylation governs growth factors-induced TBC1D3 degradation. •Post-translational modifications may regulate oncogenic properties of TBC1D3. -- Abstract: Expression of the hominoid-specific oncoprotein TBC1D3 promotes enhanced cell growth and proliferation by increased activation of signal transduction through several growth factors. Recently we documented the role of CUL7 E3 ligase in growth factors-induced ubiquitination and degradation of TBC1D3. Here we expanded our study to discover additional molecular mechanisms that control TBC1D3 protein turnover. We report that TBC1D3 is palmitoylated on two cysteine residues: 318 and 325. The expression of double palmitoylation mutant TBC1D3:C318/325S resulted in protein mislocalization and enhanced growth factors-induced TBC1D3 degradation. Moreover, ubiquitination of TBC1D3 via CUL7 E3 ligase complex was increased by mutating the palmitoylation sites, suggesting that depalmitoylation of TBC1D3 makes the protein more available for ubiquitination and degradation. The results reported here provide novel insights into the molecular mechanisms that govern TBC1D3 protein degradation. Dysregulation of these mechanisms in vivo could potentially result in aberrant TBC1D3 expression and promote oncogenesis.

  2. Non-uniform black strings and the critical dimension in the $1/D$ expansion

    Suzuki, Ryotaku

    2015-01-01

    Non-uniform black strings (NUBS) are studied by the large $D$ effective theory approach. By solving the near-horizon geometry in the $1/D$ expansion, we obtain the effective equation for the deformed horizon up to the next-to-next-to-leading order (NNLO) in $1/D$. We also solve the far-zone geometry by the Newtonian approximation. Matching the near and far zones, the thermodynamic variables are computed in the $1/D$ expansion. As the result, the large $D$ analysis gives a critical dimension $D_*\\simeq13.5$ at which the translation-symmetry-breaking phase transition changes between first and second order. This value of $D_*$ agrees perfectly, within the precision of the $1/D$ expansion, with the result previously obtained by E. Sorkin through the numerical resolution. We also compare our NNLO results for the thermodynamics of NUBS to earlier numerical calculations, and find good agreement within the expected precision.

  3. Non-uniform black strings and the critical dimension in the 1/D expansion

    Suzuki, Ryotaku; Tanabe, Kentaro

    2015-10-01

    Non-uniform black strings (NUBS) are studied by the large D effective theory approach. By solving the near-horizon geometry in the 1 /D expansion, we obtain the effective equation for the deformed horizon up to the next-to-next-to-leading order (NNLO) in 1 /D. We also solve the far-zone geometry by the Newtonian approximation. Matching the near and far zones, the thermodynamic variables are computed in the 1 /D expansion. As the result, the large D analysis gives a critical dimension D * ≃ 13 .5 at which the translation-symmetry-breaking phase transition changes between first and second order. This value of D * agrees perfectly, within the precision of the 1 /D expansion, with the result previously obtained by E. Sorkin through the numerical resolution. We also compare our NNLO results for the thermodynamics of NUBS to earlier numerical calculations, and find good agreement within the expected precision.

  4. Modeling blood flow circulation in intracranial arterial networks: a comparative 3D/1D simulation study.

    Grinberg, L; Cheever, E; Anor, T; Madsen, J R; Karniadakis, G E

    2011-01-01

    We compare results from numerical simulations of pulsatile blood flow in two patient-specific intracranial arterial networks using one-dimensional (1D) and three-dimensional (3D) models. Specifically, we focus on the pressure and flowrate distribution at different segments of the network computed by the two models. Results obtained with 1D and 3D models with rigid walls show good agreement in massflow distribution at tens of arterial junctions and also in pressure drop along the arteries. The 3D simulations with the rigid walls predict higher amplitude of the flowrate and pressure temporal oscillations than the 1D simulations with compliant walls at various segments even for small time-variations in the arterial cross-sectional areas. Sensitivity of the flow and pressure with respect to variation in the elasticity parameters is investigated with the 1D model. PMID:20661645

  5. Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

    The labeling method for 177Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

  6. 1D model for the dynamics and expansion of elongated Bose-Einstein condensates

    Massignan, Pietro; Modugno, Michele

    2002-01-01

    We present a 1D effective model for the evolution of a cigar-shaped Bose-Einstein condensate in time dependent potentials whose radial component is harmonic. We apply this model to investigate the dynamics and expansion of condensates in 1D optical lattices, by comparing our predictions with recent experimental data and theoretical results. We also discuss negative-mass effects which could be probed during the expansion of a condensate moving in an optical lattice.

  7. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

    Kayserili Karabey, Hülya; Schmidts, Miriam; Hou, Yuqing; Cortes, Claudio R.; Mans, Dorus A.; Huber, Celine; Boldt, Karsten; Patel, Mitali; van Reeuwijk, Jeroen; Plaza, Jean-Marc; van Beersum, Sylvia E. C.; Yap, Zhi Min; Letteboer, Stef J. F.; Taylor, S. Paige; Herridge, Warren; Johnson, Colin A.; Scambler, Peter J.; Ueffing, Marius; Krakow, Deborah; King, Stephen M.; Beales, Philip L.; Al-Gazali, Lihadh; Wicking, Carol; Cormier-Daire, Valerie; Roepman, Ronald; Mitchison, Hannah M.; Witman, George B.

    2015-01-01

    The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. W...

  8. Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1).

    Hayashi, Ryo; Tanoue, Kan; Durell, Stewart R; Chatterjee, Deb K; Jenkins, Lisa M Miller; Appella, Daniel H; Appella, Ettore

    2011-05-31

    PPM1D (PP2Cδ or Wip1) was identified as a wild-type p53-induced Ser/Thr phosphatase that accumulates after DNA damage and classified into the PP2C family. It dephosphorylates and inactivates several proteins critical for cellular stress responses, including p38 MAPK, p53, and ATM. Furthermore, PPM1D is amplified and/or overexpressed in a number of human cancers. Thus, inhibition of its activity could constitute an important new strategy for therapeutic intervention to halt the progression of several different cancers. Previously, we reported the development of a cyclic thioether peptide with low micromolar inhibitory activity toward PPM1D. Here, we describe important improvements in the inhibitory activity of this class of cyclic peptides and also present a binding model based upon the results. We found that specific interaction of an aromatic ring at the X1 position and negative charge at the X5 and X6 positions significantly increased the inhibitory activity of the cyclic peptide, with the optimized molecule having a K(i) of 110 nM. To the best of our knowledge, this represents the highest inhibitory activity reported for an inhibitor of PPM1D. We further developed an inhibitor selective for PPM1D over PPM1A with a K(i) of 2.9 μM. Optimization of the cyclic peptide and mutagenesis experiments suggest that a highly basic loop unique to PPM1D is related to substrate specificity. We propose a new model for the catalytic site of PPM1D and inhibition by the cyclic peptides that will be useful both for the subsequent design of PPM1D inhibitors and for identification of new substrates. PMID:21528848

  9. Momentum Conservation Implies Anomalous Energy Transport in 1D Classical Lattices

    Under quite general conditions, we prove that for classical many-body lattice Hamiltonians in one dimension (1D) total momentum conservation implies anomalous conductivity in the sense of the divergence of the Kubo expression for the coefficient of thermal conductivity, κ . Our results provide rigorous confirmation and explanation of many of the existing ''surprising'' numerical studies of anomalous conductivity in 1D classical lattices, including the celebrated Fermi-Pasta-Ulam problem. (c) 2000 The American Physical Society

  10. Momentum conservation implies anomalous energy transport in 1d classical lattices

    Prosen, T; Prosen, Tomaz; Campbell, David K.

    2000-01-01

    Under quite general conditions, we prove that for classical many-body lattice Hamiltonians in one dimension (1D) total momentum conservation implies anomalous conductivity in the sense of the divergence of the Kubo expression for the coefficient of thermal conductivity, $\\kappa$. Our results provide rigorous confirmation and explanation of many of the existing ``surprising'' numerical studies of anomalous conductivity in 1D classical lattices, including the celebrated Fermi-Pasta-Ulam problem.

  11. User's manual of the REFLA-1D/MODE4 reflood thermo-hydrodynamic analysis code

    REFLA-1D/MODE4 code has been developed by incorporating local power effect model and fuel temperature profile effect model into REFLA-1D/MODE3 code. This code can calculate the temperature transient of local rod by considering radial power profile effect in core and simulate the thermal characteristics of the nuclear fuel rod. This manual describes the outline of incorporated models, modification of the code with incorporating models and provides application information required to utilize the code. (author)

  12. *609850 TBC1 DOMAIN FAMILY, MEMBER 1; TBC1D1 [OMIM

    Full Text Available FIELD NO 609850 FIELD TI 609850 TBC1 DOMAIN FAMILY, MEMBER 1; TBC1D1 ;;KIAA1108 FIELD TX DESCRIP ... o obesity, see BMIQ7 (608410). ANIMAL MODEL In the lean ... Swiss Jim Lambert (SJL) strain of obesity-resistan ... .; Joost, H.-G.; Al-Hasani, H.: Tbc1d1 mutation in lean ... mouse strain confers lean ness and protects from di ...

  13. Protective mucosal immunity mediated by epithelial CD1d and IL-10.

    Olszak, Torsten; Neves, Joana F; Dowds, C Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito; Nagata, Kazuhiro; Müller, Werner; Snapper, Scott B; Schreiber, Stefan; Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S

    2014-05-22

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease. As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref. 9), decreased epithelial CD1d expression--as observed in inflammatory bowel disease--may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1d elicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP), as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease. PMID:24717441

  14. Protective mucosal immunity mediated by epithelial CD1d and IL-10

    Olszak, Torsten; Neves, Joana F.; Dowds, C. Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito

    2014-01-01

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host1,2. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease3–8. As CD1d crosslinking on ...

  15. Simple model of the density of states in 1D photonic crystal

    Rudziński, Adam; Tyszka-Zawadzka, Anna; Szczepański, Paweł

    2010-01-01

    In this paper, we present a simple, yet versatile, analytical model of one-dimensional photonic crystal (1D PC). In our theoretical model, we take into account direction of propagation and therefore do not neglect anisotropic nature of photonic crystals. We derive analytical expressions for mode spectrum and density of states in 1D photonic crystal. With those formulas, we obtain mode spectrum characteristics, which depict formation of photonic band gap and reveal properties of photonic cryst...

  16. Melatonin receptor 1B gene associated with hyperglycemia in bipolar disorder.

    Hukic, Dzana S; Lavebratt, Catharina; Frisén, Louise; Backlund, Lena; Hilding, Agneta; Gu, Harvest F; Östenson, Claes-Göran; Erlinge, David; Ehrenborg, Ewa; Schalling, Martin; Ösby, Urban

    2016-06-01

    Bipolar patients are at a higher risk of developing metabolic disorders. Cardiovascular morbidity and mortality is twice the rate reported in the population. Antipsychotic medication increases the risk of metabolic abnormalities. However, bipolar disorder and schizophrenia have a similarly increased mortality from cardiovascular causes of death, although bipolar patients medicate with antipsychotic drugs to a much smaller extent than schizophrenic patients. Bipolar disorder and schizophrenia share substantial genetic risk components; thus, increased metabolic abnormalities is hypothesized to be an effect of specific sets of metabolic risk genes, which might overlap with the metabolic risk genes in schizophrenia. This study reports that a functional genetic variant of MTNR1B, previously implicated in the impairment of glucose-stimulated insulin release also in schizophrenia, was associated with elevated fasting glucose levels in bipolar patients and controls. This finding suggests that the MTNR1B-dependent vulnerability for elevated fasting plasma glucose levels is shared between bipolar disorder and schizophrenia. PMID:26991397

  17. Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.

    Kumar, Sujeet; Gopalakrishnan, Vidya; Hegde, Mahesh; Rana, Vivek; Dhepe, Sharad S; Ramareddy, Sureshbabu A; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Srivastava, Mrinal; Raghavan, Sathees C; Karki, Subhas S

    2014-10-01

    A series of 2,5,6-substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of apoptosis, however, without affecting cell cycle progression. PMID:25205189

  18. Intrinsic fluorescence spectra characteristics of vitamin B1, B2, and B6

    Yang, Hui; Xiao, Xue; Zhao, Xuesong; Hu, Lan; Lv, Caofang; Yin, Zhangkun

    2015-11-01

    This paper presents the intrinsic fluorescence characteristics of vitamin B1, B2 and B6 measured with 3D fluorescence Spectrophotometer. Three strong fluorescence areas of vitamin B2 locate at λex/λem=270/525nm, 370/525nm and 450/525nm, one fluorescence areas of vitamin B1 locates at λex/λem=370/460nm, two fluorescence areas of vitamin B6 locates at λex/λem=250/370nm and 325/370nm were found. The influence of pH of solution to the fluorescence profile was also discussed. Using the PARAFAC algorithm, 10 vitamin B1, B2 and B6 mixed solutions were successfully decomposed, and the emission profiles, excitation profiles, central wavelengths and the concentration of the three components were retrieved precisely through about 5 iteration times.

  19. Minimal gauged U(1) B-L model with spontaneous R parity violation.

    Barger, Vernon; Pérez, Pavel Fileviez; Spinner, Sogee

    2009-05-01

    We study the minimal gauged U(1) B-L supersymmetric model and show that it provides an attractive theory for spontaneous R-parity violation. Both U(1) B-L and R parity are broken by the vacuum expectation value of the right-handed sneutrino (proportional to the soft supersymmetry masses), thereby linking the B-L and soft SUSY scales. In this context we find a consistent mechanism for generating neutrino masses and a realistic mass spectrum, all without extending the Higgs sector of the minimal supersymmetry standard model. We discuss the most relevant collider signals and the connection between the Z' gauge boson and R-parity violation. PMID:19518859

  20. Structure and thermal behavior of a nickel complex based on a V-shaped bis(4-(1H-imidazol-1-yl)phenyl)amine ligand

    Jiao, Yan, E-mail: felixjiao@163.com; Wang, Zhe; Qiu, Yu; He, Jing-Man; Chen, Min-dong [Nanjing University of Information Science & Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Innovative Research Laboratory of Energy & Environmental Catalysis, School of Environmental Science and Engineering (China)

    2015-12-15

    A new coordination polymer ([Ni(BIPA)(bpdc)(H{sub 2}O){sub 2}]){sub n} has been prepared based on a new V-shaped bis(4-(1H-imidazol-1-yl)phenyl)amine (BIPA) ligand. Complex was characterized by elemental analysis, IR spectra, X-ray powder diffraction, thermal analysis and single crystal X-ray analysis. Complex exhibits a 1D → 3D structure. Hydrogen bonds play an important role in the formation of supramolecular network structure. Thermal analysis indicates that complex exhibits a high thermal stability.

  1. Structure and thermal behavior of a nickel complex based on a V-shaped bis(4-(1H-imidazol-1-yl)phenyl)amine ligand

    A new coordination polymer ([Ni(BIPA)(bpdc)(H2O)2])n has been prepared based on a new V-shaped bis(4-(1H-imidazol-1-yl)phenyl)amine (BIPA) ligand. Complex was characterized by elemental analysis, IR spectra, X-ray powder diffraction, thermal analysis and single crystal X-ray analysis. Complex exhibits a 1D → 3D structure. Hydrogen bonds play an important role in the formation of supramolecular network structure. Thermal analysis indicates that complex exhibits a high thermal stability

  2. One-Dimensional (1D) ZnS Nanomaterials and Nanostructures

    Xiaosheng FANG; Lide ZHANG

    2006-01-01

    One-dimensional (1D) nanomaterials and nanostructures have received much attention due to their potential interest for understanding fundamental physical concepts and for applications in constructing nanoscale electric and optoelectronic devices. Zinc sulfide (ZnS) is an important semiconductor compound of Ⅱ-Ⅵ group,and the synthesis of 1D ZnS nanomaterials and nanostructures has been of growing interest owing to their promising application in nanoscale optoelectronic devices. This paper reviews the recent progress on 1D ZnS nanomaterials and nanostructures, including nanowires, nanowire arrays, nanorods, nanobelts or nanoribbons,nanocables, and hierarchical nanostructures etc. This article begins with a survey of various methods that have been developed for generating 1D nanomaterials and nanostructures, and then mainly focuses on structures,synthesis, characterization, formation mechanisms and optical property tuning, and luminescence mechanisms of 1D ZnS nanomaterials and nanostructures. Finally, this review concludes with personal views towards future research on 1D ZnS nanomaterials and nanostructures.

  3. Dynamics of reactions O((1)D)+C(6)H(6) and C(6)D(6).

    Chen, Hui-Fen; Liang, Chi-Wei; Lin, Jim J; Lee, Yuan-Pern; Ogilvie, J F; Xu, Z F; Lin, M C

    2008-11-01

    The reaction between O((1)D) and C(6)H(6) (or C(6)D(6)) was investigated with crossed-molecular-beam reactive scattering and time-resolved Fourier-transform infrared spectroscopy. From the crossed-molecular-beam experiments, four product channels were identified. The major channel is the formation of three fragments CO+C(5)H(5)+H; the channels for formation of C(5)H(6)+CO and C(6)H(5)O+H from O((1)D)+C(6)H(6) and OD+C(6)D(5) from O((1)D)+C(6)D(6) are minor. The angular distributions for the formation of CO and H indicate a mechanism involving a long-lived collision complex. Rotationally resolved infrared emission spectra of CO (1ratio of [CO]/[OH]=2.1+/-0.4 for O((1)D)+C(6)H(6) and [CO]/[OD]>2.9 for O((1)D)+C(6)D(6) is consistent with the expectation for an abstraction reaction. The mechanism of the reaction may be understood from considering the energetics of the intermediate species and transition states calculated at the G2M(CC5) level of theory for the O((1)D)+C(6)H(6) reaction. The experimentally observed branching ratios and deuterium isotope effect are consistent with those predicted from calculations. PMID:19045343

  4. A Cadmium-transporting P1B-type ATPase in Yeast Saccharomyces cerevisiae*

    Adle, David J.; Sinani, Devis; Kim, Heejeong; Lee, Jaekwon

    2006-01-01

    Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpe...

  5. Condensation of rye chromatin in somatic interphase nuclei of Ph1 and ph1b wheat

    Kopecký, David; Allen, D.C.; Duchoslav, M.; Doležel, Jaroslav; Lukaszewski, A.J.

    2007-01-01

    Roč. 119, 3-4 (2007), s. 263-267. ISSN 1424-8581 R&D Projects: GA MŠk(CZ) LC06004 Institutional research plan: CEZ:AV0Z50380511 Source of funding: V - iné verejné zdroje Keywords : hexaploid wheat * Ph1 and ph1b * rye chromatin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.402, year: 2007

  6. Carnitine Palmitoyltransferase 1b Deficient Mice Develop Severe Insulin Resistance After Prolonged High Fat Diet Feeding

    Kim, Teayoun; Moore, John F.; Sharer, Jon D.; Yang, Kevin; Wood, Philip A.; Yang, Qinglin

    2014-01-01

    Background Carnitine palmitoyltransferase 1 (CPT1) is the rate-limiting enzyme governing the entry of long-chain acyl-CoAs into mitochondria. Treatments with CPT1 inhibitors protect against insulin resistance in short-term preclinical animal studies. We recently reported that mice with muscle isoform CPT1b deficiency demonstrated improved insulin sensitivity when fed a High Fat-Diet (HFD) for up to 5 months. In this follow up study, we further investigated whether the insulin sensitizing effe...

  7. Regulation of cytochrome P450 1B1 under proinflammatory conditions

    Umannová, Lenka; Machala, M.; Kozubík, Alois; Vondráček, Jan

    Trenčianske Teplice, 2008. s. 117. ISSN 1337-6853. [TOXCON 2008, Integration of Toxicological Research Within V4, 13th Interdisciplinary Toxicology Conference. 27.05.2008-30.05.2008, Trenčianske Teplice] R&D Projects: GA ČR(CZ) GA524/06/0517 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : CYP1B1 * TNF-alpha * inflammation Subject RIV: BO - Biophysics

  8. Regulation of cytochrome P450 1B1 in rat liver progenitor cells

    Umannová, Lenka; Machala, M.; Kozubík, Alois; Vondráček, Jan

    Rhodes : Elsevier, 2008. S43. ISSN 0378-4274. [45th Congress of the European Societies of Toxicology. 05.10.2008-08.10.2008, Rhodes] R&D Projects: GA ČR(CZ) GA524/06/0517 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : CYP1B1 * TNF-alpha * inflammation Subject RIV: BO - Biophysics

  9. Regulation of cytochrome P450 1B1 under inflammatory condition

    Umannová, Lenka; Machala, M.; Kozubík, Alois; Vondráček, Jan

    Mikulov, 2009. s. 13. [XXV. Xenobiochemické symposium. 22.09.2009-25.09.2009, Mikulov] R&D Projects: GA ČR(CZ) GA524/09/1337; GA ČR(CZ) GD204/09/H058 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : CYP1B1 * inflammation * environmental pollutants Subject RIV: BO - Biophysics

  10. Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

    Yang Jae-Hyug

    2011-06-01

    Full Text Available Abstract Backgrounds Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM in previous studies. Since T2DM and gestational diabetes mellitus (GDM share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. Methods A total of 1,918 subjects (928 GDM patients and 990 controls were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs, 95% confidence intervals (CIs, and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. Results We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. Conclusion There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

  11. Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract

    Raaijmakers, Anke; Corveleyn, Anniek; Devriendt, Koenraad; van Tienoven, Theun Pieter; Allegaert, Karel; Van Dyck, Mieke; van den Heuvel, Bert; Kuypers, Dirk; Claes, Kathleen; Mekahli, Djalila; Levtchenko, Elena

    2015-01-01

    Congenital anomalies of kidneys and urinary tract (CAKUT) are the most predominant developmental disorders comprising ∼20-30% of all anomalies identified in the prenatal period. Mutations in hepatocyte nuclear factor 1-beta (HNF-1β) involved in the development of kidneys, liver, pancreas and urogenital tract are currently the most frequent monogenetic cause of CAKUT found in 10-30% of patients depending on screening policy and study design. We aimed to validate criteria for analysis of HNF1B ...

  12. Geochemical variations detected with continuous XRF measurements on ANDRILL AND-1B core - preliminary results

    Helling, D.; Kuhn, Gerhard

    2007-01-01

    Antarctica and especially its ice sheets play a major role in both the global ocean current system andclimate. The ANDRILL (Antarctic Geological Drilling) MIS deep drilling project (McMurdo Sound, NE Ross Ice Shelf, drilled core AND-1B during austral summer 2006/2007) is located in a flexural moat basin filled with glaciomarine, terrigenous, volcanic, and biogenic sediments (Horgan et al., 2005). This basin contains a well-preserved outstanding record of paleoclimate history. During the drill...

  13. Der Einfluss der selektiven Serotonin 1 B/D-Agonisten auf die Thrombozyten- und Erythrozytenfunktion

    Heuel, T. (Thomas)

    2005-01-01

    Der Einfluss von selektiven und unselektiven Serotonin 1 B/D Agonisten auf die Thrombozyten und Erythrozytenfunktion wurde in einer einfachblinden, placebokontrollierten Studie an 20 Probanden untersucht. Getestet wurden 2,5 mg Zolmitriptan, 100 mg Sumatriptan, 2 mg Ergotamintartrat und 1000 mg Acetylsalicylsäure. Hierbei zeigte sich nach Einnahme von Placebo, Sumatriptan und Zolmitriptan keine signifikante Änderung der Plättchenreaktivität (PR) oder Erythrozytenaggregation (ER). Nach Einnahm...

  14. Free Fatty Acids Inhibit Protein Tyrosine Phosphatase 1B and Activate Akt

    Eisuke Shibata

    2013-09-01

    Full Text Available Background/Aims: Accumulating evidence has suggested that free fatty acids (FFAs interact with protein kinases and protein phosphatases. The present study examined the effect of FFAs on protein phosphatases and Akt. Methods: Activities of protein phosphatase 1 (PP1, protein phosphatase 2A (PP2A, and protein tyrosine phosphatase 1B (PTP1B were assayed under the cell-free conditions. Phosphorylation of Akt was monitored in MSTO-211H human malignant pleural mesothelioma cells without and with knocking-down phosphatidylinositol 3 kinase (PI3K or 3-phosphoinositide-dependent protein kinase-1 (PDK1. Results: In the cell-free assay, unsaturated FFAs (uFFAs such as oleic, linoleic and linolenic acid and saturated FFAs (sFFAs such as stearic, palmitic, myristic, and behenic acid markedly reduced PTP1B activity, with the potential for uFFAs greater than that for sFFAs. All the investigated sFFAs inhibited PP2A activity, but otherwise no inhibition was obtained with uFFAs. Both uFFAs and sFFAs had no effect on PP1 activity. Oleic acid phosphorylated Akt both on Thr308 and Ser473, while stearic acid phosphorylated Akt on Thr308 alone. The effects of oleic and stearic acid on Akt phosphorylation were abrogated by the PI3K inhibitor wortmannin or the PDK1 inhibitor BX912 and also by knocking-down PI3K or PDK1. Conclusion: The results of the present study indicate that uFFAs and sFFAs could activate Akt through a pathway along a PI3K/PDK1/Akt axis in association with PTP1B inhibition.

  15. Antimicrobial Resistance of Shigella flexneri Serotype 1b Isolates in China.

    Xianyan Cui

    Full Text Available Shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. However, only limited data is available on the global phenotypic and genotypic characteristics of S. flexneri 1b. In the present study, 40 S. flexneri 1b isolates from different regions of China were confirmed by serotyping and biochemical characterization. Antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susceptibility profiles varied between geographical locations. Strains from Yunnan were far more resistant than those from Xinjiang, while only one strain from Shanghai was resistant to ceftazidime and aztreonam. Fifteen cephalosporin resistant isolates were identified in this study. ESBL genes (blaSHV, blaTEM, blaOXA, and blaCTX-M and ampC genes (blaMOX, blaFOX, blaMIR(ACT-1, blaDHA, blaCIT and blaACC were subsequently detected among the 15 isolates. The results showed that these strains were positive only for blaTEM, blaOXA, blaCTX-M, intI1, and intI2. Furthermore, pulsed-field gel electrophoresis (PFGE analysis showed that the 40 isolates formed different profiles, and the PFGE patterns of Xinjiang isolates were distinct from Yunnan and Shanghai isolates by one obvious, large, missing band. In summary, similarities in resistance patterns were observed in strains with the same PFGE pattern. Overall, the results supported the need for more prudent selection and use of antibiotics in China. We suggest that antibiotic susceptibility testing should be performed at the start of an outbreak, and antibiotic use should be restricted to severe Shigella cases, based on resistance pattern variations observed in different regions. The data obtained in the current study might help to develop a strategy for the treatment of infections caused by S. flexneri 1b in China.

  16. Potent water extracts of Indonesian medicinal plants against PTP1B

    Azis Saifudin

    2016-01-01

    Conclusions: In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia, pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines. In addition, the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1B.

  17. Cardioembolic stroke related to limb-girdle muscular dystrophy 1B

    Chen, Chih-Hao; Tang, Sung-Chun; Su, Yi-Ning; Yang, Chih-Chao; Jeng, Jiann-Shing

    2013-01-01

    Background Cardioembolic stroke is an under-recognized complication in patients with limb-girdle muscular dystrophy 1B. Here we present a young stroke patient who had a novel lamin A/C gene (LMNA) mutation. Case presentation This is a 39-year-old man who had slowly progressive proximal muscle weakness and cardiac arrhythmia since adolescent and a family history of similar manifestation. He sustained acute ischemic stroke in the left middle cerebral artery territory. Intravenous recombinant ti...

  18. BOREAS RSS-2 Level-1B ASAS Image Data: At-Sensor Radiance in BSQ Format

    Russell, C.; Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Dabney, P. W.; Kovalick, W.; Graham, D.; Bur, Michael; Irons, James R.; Tierney, M.

    2000-01-01

    The BOREAS RSS-2 team used the ASAS instrument, mounted on the NASA C-130 aircraft, to create at-sensor radiance images of various sites as a function of spectral wavelength, view geometry (combinations of view zenith angle, view azimuth angle, solar zenith angle, and solar azimuth angle), and altitude. The level-1b ASAS images of the BOREAS study areas were collected from April to September 1994 and March to July 1996.

  19. Synthesis, properties and supramolecular structure of di(aqua)bis(ethylenediamine)nickel(II) bis(4-nitrobenzoate)

    Bikshandarkoil R Srinivasan; Gayatri K Rane

    2009-03-01

    The reaction of the sodium salt of 4-nitrobenzoic acid (4-nbaH) with [Ni(H2O)6]Cl2 or [Ni(en)3]Cl2.2H2O (en is ethylenediamine) results in the formation of the known octahedral compound [Ni(H2O)4(1-4-nba)2].2H2O (4-nba = 4-nitrobenzoate) 1 or the title compound di(aqua)bis(ethylenediamine) nickel(II) bis(4-nitrobenzoate) 2 respectively. Compounds 1 and 2 were characterized by elemental analysis, infrared spectra, DSC thermograms, weight loss studies and the structure of 2 was determined. Both 1 and 2 can be thermally decomposed to green NiO. The title compound [Ni(H2O)2(en)2](4-nba)2 2 crystallizes in the centrosymmetric monoclinic space group 21/ with the Ni(II) situated on an inversion center. The crystal structure of 2 consists of a hexacoordinated Ni(II) complex cation and an uncoordinated 4-nba anion. In the octahedral complex cation, the central metal is linked to two symmetry related bidentate en ligands and two water molecules. In the crystal structure, the cations and anions are linked by three varieties of hydrogen bonding interactions. A comparative study of seven nickel 4-nitrobenzoate compounds is described.

  20. Estructura molecular y cristalina del bis (bis(dietilamino glioximato níquel (II

    Luis Alejandro Nuvan

    2009-07-01

    Full Text Available Ni(CioH2lN4022- monoclínico, grupo espacial P2i/a, a = 15.760 (2, b = 11.793 (3, c = 7.297 (1 A°, j3 = 99.10 (1°, V = 1339.0 (7 A°3, Z = 2 , De = 1.28 Mg M " \\ M = 765 M " ' . La estructura fue resuelta por el método del átomo pesado y afinada por mínimos cuadrados, utilizando la matriz completa, hasta obtener una concordancia R = 0.068 para todas las reflexiones observadas. El átomo de níquel está localizado en un centro de inversión y presenta una coordinación cuadrado planar. El complejo Bis (Bis (Dietilamino Glioximato Níquel (II es casi planar y el desplazamiento de los grupos etil con respecto al plano es producido por efectos estéricos. Las moléculas planares se apilan a lo largo de c, las normales a los planos forman con este eje un ángulo de 41.53 . Existen interacciones axiales entre el níquel y los grupos amino de las moléculas adyacentes de la columna.

  1. Minimal Flavor Violation in the Minimal $U(1)_{B-L}$ Model and Resonant Leptogenesis

    Okada, Nobuchika; Yamada, Toshifumi

    2012-01-01

    We investigate the resonant leptogenesis scenario in the minimally $U(1)_{B-L}$ extended standard model with minimal flavor violation. In our model, the $U(1)_{B-L}$ gauge symmetry is broken at the TeV scale and standard model singlet neutrinos gain Majorana masses of order TeV. In addition, we introduce a flavor symmetry on the singlet neutrinos at a scale higher than TeV. The flavor symmetry is explicitly broken by the neutrino Dirac Yukawa coupling, which induces splittings in the singlet neutrino Majorana masses at lower scales through renormalization group evolutions. We call this setup "minimal flavor violation". The mass-splittings are proportional to the tiny Dirac Yukawa coupling, and hence they automatically enhance the CP asymmetry parameter necessary for the resonant leptogenesis mechanism. In this paper, we calculate the baryon number yield by solving the Boltzmann equations, including the effects of $U(1)_{B-L}$ gauge boson that also has TeV scale mass and causes washing-out of the singlet neutr...

  2. Significance of 1B and 2B domains in modulating elastic properties of lamin A

    Bera, Manindra; Ainavarapu, Sri Rama Koti; Sengupta, Kaushik

    2016-01-01

    Nuclear lamins are type V intermediate filament proteins which form an elastic meshwork underlying the inner nuclear membrane. Lamins directly contribute to maintain the nuclear shape and elasticity. More than 400 mutations have been reported in lamin A that are involved in diseases known as laminopathies. These mutations are scattered mainly in the lamin rod domain along with some in its C-terminal domain. The contribution of the rod domain towards the elasticity of lamin A molecule was hitherto unknown. Here, we have elucidated the significance of the 1B and 2B domains of the rod in modulating the elastic behavior of lamin A by single-molecule force spectroscopy. In addition, we have also studied the network forming capacity of these domains and their corresponding viscoelastic behavior. We have shown that the 1B domain has the ability to form a lamin-like network and resists larger deformation. However at the single-molecular level, both the domains have comparable mechanical properties. The self-assembly of the 1B domain contributes to the elasticity of the lamin A network. PMID:27301336

  3. Construction and in vitro Study of an E1B-Defective Adenovirus

    Xue Feng; Joshua Mallam Nock; Zhu Hua-bin; Dong Chang-yuan; Qi Yi-peng

    2004-01-01

    An E1B-defective adenovirus named r1/Ad was constructed by homologous recombination. The construction, selection and propagation of recombinant virus was done in the human embryonic kidney 293 cells (HEK293). The in vitro study demonstrated that the recombinant virus has the ability to replicate in and lyse some p53-deficient human tumor cells such as the human glioblastoma tumor cells (U251) and human bladder tumer cells (EJ) but not in the normal cells with functional p53 such as the human fibroblast cells (MRC-5). Also, based on the cytopathic effect (CPE), it was demonstrated that the U251 cells were more sensitive to the infection of r1/Ad than that of EJ cells under identical conditions. In this paper, it was found that r1/Ad could be very useful in studying the in vitro selective replication of E1B-defective adenovirus. This may help to determine the safety of using any E1B-defective adenoviruses in cancer gene therapy.

  4. A de novo microdeletion involving PAFAH1B (LIS1 related to lissencephaly phenotype

    Keiko Shimojima

    2015-09-01

    Full Text Available Lissencephaly is a type of the congenital malformation of the brain. Due to the impairments of neuronal migration, patients show absence of brain convolution manifesting smooth brain surfaces. One of the human genes responsible for lissencephaly is the platelet-activating factor acetylhydrolase 1b gene (PAFAH1B; also known as LIS1 located on 17p13.3. Patients with heterozygous deletion of this chromosomal region exhibit lissencephaly. Recently, we encountered a male patient who showed typical lissencephaly. Using a microarray analysis, we identified a 1.3 Mb submicroscopic deletion in 17p13.3. This deletion included PAFAH1B. Both of the parents showed no deletion in this region. Therefore, this was determined to be derived from de novo origin. After obtaining the written informed consent, skin fibroblasts were provided from this patient and disease-specific induced pluripotent stem (iPS cells were generated and used for medical research (Shimojima K, Okumura A, Hayashi M, Kondo T, Inoue H, and Yamamoto T. CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly. Genomics, in press.

  5. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    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. We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations

  6. Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene.

    Ronzoni, Luisa; Tagliaferri, Francesco; Tucci, Arianna; Baccarin, Marco; Esposito, Susanna; Milani, Donatella

    2016-05-01

    Interstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It has been hypothesized that haploinsufficiency of these genes impairs normal development of the brain and is responsible for the phenotype. This case report describes a girl presenting with typical features of 6q microdeletion syndrome, including global developmental delay, speech impairment, distinct dysmorphic features, dysgenesis of the corpus callosum, common limb anomalies, and hearing loss. Chromosome analysis by array-CGH revealed a small interstitial 6q deletion spanning approximately 1.1 Mb of DNA and containing only one coding gene, ARID1B. We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations. © 2016 Wiley Periodicals, Inc. PMID:26754677

  7. The PSACOIN level 1B exercise: A probabilistic code intercomparison involving a four compartment biosphere model

    The probabilistic Systems Assessment Code (PSAC) User Group of the OECD Nuclear Energy Agency has organised a series of code intercomparison studies of relevance to the performance assessment of underground repositories for radioactive wastes - known collectively by the name PSACOIN. The latest of these to be undertaken is designated PSACOIN Level 1b, and the case specification provides a complete assessment model of the behaviour of radionuclides following release into the biosphere. PSACOIN Level 1b differs from other biosphere oriented intercomparison exercises in that individual dose is the end point of the calculations as opposed to any other intermediate quantity. The PSACOIN Level 1b case specification describes a simple source term which is used to simulate the release of activity to the biosphere from certain types of near surface waste repository, the transport of radionuclides through the biosphere and their eventual uptake by humankind. The biosphere sub model comprises 4 compartments representing top and deep soil layers, river water and river sediment. The transport of radionuclides between the physical compartments is described by ten transfer coefficients and doses to humankind arise from the simultaneous consumption of water, fish, meat, milk, and grain as well as from dust inhalation and external γ-irradiation. The parameters of the exposure pathway sub model are chosen to be representative of an individual living in a small agrarian community. (13 refs., 3 figs., 2 tabs.)

  8. Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells.

    Yahoo, Neda; Pournasr, Behshad; Rostamzadeh, Jalal; Hakhamaneshi, Mohammad Saeed; Ebadifar, Asghar; Fathi, Fardin; Baharvand, Hossein

    2016-05-20

    Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells. We screened the effects of candidate transcription factors Hnf1b, Hnf1a, Hnf4a, Foxa1, Foxa3 and Hex, and determined that the combination of Hnf1b/Foxa3 promoted expression of several hepatic lineage-specific markers and proteins, in addition to glycogen storage, ICG uptake, and secretion of albumin and urea. The differentiated cells were engraftable and expressed albumin when transplanted into a carbon tetrachloride-injured mouse model. These results demonstrated the crucial role of Hnf1b and Foxa3 in hepatogenesis in vitro and provided a valuable tool for the efficient differentiation of HLCs from ES cells. PMID:27107701

  9. HNF1B-associated clinical phenotypes: the kidney and beyond.

    Bockenhauer, Detlef; Jaureguiberry, Graciana

    2016-05-01

    Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management. PMID:26160100

  10. The thermal emission of the exoplanets WASP-1b and WASP-2b

    Wheatley, Peter J; Harrington, Joseph; Fortney, Jonathan J; Simpson, James M; Anderson, David R; Smith, Alexis M S; Aigrain, Suzanne; Clarkson, William I; Gillon, Michael; Haswell, Carole A; Hebb, Leslie; Hébrard, Guillaume; Hellier, Coel; Hodgkin, Simon T; Horne, Keith D; Kane, Stephen R; Maxted, Pierre F L; Norton, Andrew J; Pollacco, Don L; Pont, Frederic; Skillen, Ian; Smalley, Barry; Street, Rachel A; Udry, Stephane; West, Richard G; Wilson, David M

    2010-01-01

    We present a comparative study of the thermal emission of the transiting exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two planets have very similar masses but suffer different levels of irradiation and are predicted to fall either side of a sharp transition between planets with and without hot stratospheres. WASP-1b is one of the most highly irradiated planets studied to date. We measure planet/star contrast ratios in all four of the IRAC bands for both planets (3.6-8.0um), and our results indicate the presence of a strong temperature inversion in the atmosphere of WASP-1b, particularly apparent at 8um, and no inversion in WASP-2b. In both cases the measured eclipse depths favor models in which incident energy is not redistributed efficiently from the day side to the night side of the planet. We fit the Spitzer light curves simultaneously with the best available radial velocity curves and transit photometry in order to provide updated measurements of system parameters. We do not find ...

  11. Evaluation of LLTR Series II tests A-1A and A-1B test results

    The standard methodology, with minor modifications provides conservative yet realistic predictions of leaksite and other sodium system pressures in the LLTR Series II vessel and piping. The good agreement between predicted and measured pressures indicates that the TRANSWRAP/RELAP modeling developed from the Series I tests is applicable to larger scale units prototypical of the Clinch River steam generator design. Calculated sodium system pressures are sensitive to several modeling parameters including rupture disc modeling, acoustic velocity in the test vessel, and flow rate from the rupture tube. The acoustic velocity which produced best agreement with leaksite pressures was calculated based on the shroud diameter and shroud wall thickness. The corresponding rupture tube discharge coefficient was that of the standard design methodology developed from Series I testing. As found in Series I testing, the Series II data suggests that the leading edge of the flow in the relief line is two phase for a single, doubled-ended guillotine tube rupture. The steam generator shroud acts as if it is relatively transparent to the transmission of radial pressures to the vessel wall. Slightly lower sodium system maximum pressures measured during Test A-1b compared to Test A-1a are attributed to premature failure (failure at a lower pressure) of the rupture disc in contact with the sodium for test A-1b. The delay in failure of the second disc in Test A-1b, which was successfully modeled with TRANSWRAP, is attributed to the limited energy in the nitrogen injection

  12. HERMES Precision Results on g1p, g1d and g1n and the First Measurement of the Tensor Structure Function b1d

    Riedl, C; Akopov, Z; Amarian, M; Ammosov, V V; Andrus, A; Aschenauer, E C; Augustyniak, W; Avakian, R; Avetisian, A; Avetissian, E; Bailey, P; Baturin, V; Baumgarten, C; Beckmann, M; Belostotskii, S; Bernreuther, S; Bianchi, N; Blok, H P; Böttcher, Helmut B; Borisov, A; Bouwhuis, M; Brack, J; Brüll, A; Bryzgalov, V V; Capitani, G P; Chiang, H C; Ciullo, G; Contalbrigo, M; Dalpiaz, P F; De Leo, R; De Nardo, L; De Sanctis, E; Devitsin, E G; Di Nezza, P; Düren, M; Ehrenfried, M; Elalaoui-Moulay, A; Elbakian, G M; Ellinghaus, F; Elschenbroich, U; Ely, J; Fabbri, R; Fantoni, A; Feshchenko, A; Felawka, L; Fox, B; Franz, J; Frullani, S; Gärber, Y; Gapienko, G; Gapienko, V; Garibaldi, F; Garrow, K; Garutti, E; Gaskell, D; Gavrilov, G E; Karibian, V; Graw, G; Grebenyuk, O; Greeniaus, L G; Hafidi, K; Hartig, M; Hasch, D; Heesbeen, D; Henoch, M; Hertenberger, R; Hesselink, W H A; Hillenbrand, A; Hoek, M; Holler, Y; Hommez, B; Iarygin, G; Ivanilov, A; Izotov, A; Jackson, H E; Jgoun, A; Kaiser, R; Kinney, E; Kiselev, A; Königsmann, K C; Kopytin, M; Korotkov, V A; Kozlov, V; Krauss, B; Krivokhizhin, V G; Lagamba, L; Lapikas, L; Laziev, A; Lenisa, P; Liebing, P; Lindemann, T; Lipka, K; Lorenzon, W; Lü, J; Maiheu, B; Makins, N C R; Marianski, B; Marukyan, H O; Masoli, F; Mexner, V; Meyners, N; Miklukho, O; Miller, C A; Miyachi, Y; Muccifora, V; Nagaitsev, A; Nappi, E; Naryshkin, Yu; Nass, A; Negodaev, M A; Nowak, Wolf-Dieter; Oganessyan, K; Ohsuga, H; Orlandi, G; Pickert, N; Potashov, S Yu; Potterveld, D H; Raithel, M; Reggiani, D; Reimer, P E; Reischl, A; Reolon, A R; Rith, K; Airapetian, A; Rosner, G; Rostomyan, A; Rubacek, L; Ryckbosch, D; Salomatin, Yu I; Sanjiev, I; Savin, I; Scarlett, C; Schäfer, A; Schill, C; Schnell, G; Schüler, K P; Schwind, A; Seele, J; Seidl, R; Seitz, B; Shanidze, R G; Shearer, C; Shibata, T A; Shutov, V B; Simani, M C; Sinram, K; Stancari, M D; Statera, M; Steffens, E; Steijger, J J M; Stewart, J; Stösslein, U; Tait, P; Tanaka, H; Taroian, S P; Tchuiko, B; Terkulov, A R; Tkabladze, A V; Trzcinski, A; Tytgat, M; Vandenbroucke, A; Van der Nat, P B; van der Steenhoven, G; Vetterli, Martin C; Vikhrov, V; Vincter, M G; Visser, J; Vogel, C; Vogt, M; Volmer, J; Weiskopf, C; Wendland, J; Wilbert, J; Ybeles-Smit, G V; Yen, S; Zihlmann, B; Zohrabyan, H G; Zupranski, P; Riedl, Caroline

    2005-01-01

    Final HERMES results on the proton, deuteron and neutron structure function g1 are presented in the kinematic range 0.00211d are presented.

  13. Stable Interacting $(2 + 1)d$ Conformal Field Theories at the Boundary of a class of $(3 + 1)d$ Symmetry Protected Topological Phases

    Bi, Zhen; BenTov, Yoni; Xu, Cenke

    2016-01-01

    Motivated by recent studies of symmetry protected topological (SPT) phases, we explore the possible gapless quantum disordered phases in the $(2+1)d$ nonlinear sigma model defined on the Grassmannian manifold $\\frac{U(N)}{U(n)\\times U(N - n)}$ with a Wess-Zumino-Witten (WZW) term at level $k$, which is the effective low energy field theory of the boundary of certain $(3+1)d$ SPT states. With $k = 0$, this model has a well-controlled large-$N$ limit, $i.e.$ its renormalization group equations can be computed exactly with large-$N$. However, with the WZW term, the large-$N$ and large-$k$ limit alone is not sufficient for a reliable study of the nature of the quantum disordered phase. We demonstrate that at least for $n = 1$, through a combined large-$N$, large-$k$ and $3-\\epsilon$ generalization, a stable fixed point in the quantum disordered phase can be reliably located, which corresponds to a $(2+1)d$ strongly interacting conformal field theory. Extension of our method to $n > 1$ will also be discussed.

  14. Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

    Borrell-Pagès, Maria; Canals, Josep M.; Cordelières, Fabrice P; Parker, J. Alex; Pineda, José R.; Grange, Ghislaine; Bryson, Elzbieta A.; Guillermier, Martine; Hirsch, Etienne; Hantraye, Philippe; Cheetham, Michael E.; Néri, Christian; Alberch, Jordi; Brouillet, Emmanuel; Saudou, Frédéric

    2006-01-01

    There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin–induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway thro...

  15. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  16. Influence of ADH1B polymorphism on alcohol use and its subjective effects in a Jewish population.

    Carr, Lucinda G; Foroud, Tatiana; Stewart, Trent; Castelluccio, Peter; Edenberg, Howard J; Li, Ting-Kai

    2002-10-01

    Class I alcohol dehydrogenases (ADHs) are the principal enzymes responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH1B locus (old nomenclature ADH2) results in isozymes with quite different catalytic properties. The frequency of the ADH1B*2 allele varies among ethnic groups. ADH1B*2 is most often observed in Asian populations, and has been shown to be protective against alcoholism. The Jewish population has a higher frequency of the ADH1B*2 allele and lower rates of alcohol-related problems as compared to other Caucasian populations. Thus, it would be of interest to determine whether the ADH1B*2 allele is associated with alcohol consumption and its subjective effects in this group. Four groups of Jewish subjects (male and female college-age samples, and male and female general samples) were recruited from the same region of the United States. All subjects completed a questionnaire to delineate alcohol consumption and its subjective consequences. Genotype at the ADH1B locus was determined for each participant. ADH1B*2 allele frequencies were similar for the Jewish college-age and general population samples. Men in both the college-age and general population in the ADH1B*2 group reported more unpleasant reactions following alcohol consumption than men in the ADH1B*1 group. Men in the general population in the ADH1B*2 group drank alcohol less frequently than men who were homozygous ADH1B*1; there was a similar trend among the women. The ADH1B polymorphism is associated with unpleasant reactions after alcohol consumption, and frequency of alcohol consumption in these Jewish samples. PMID:12244546

  17. A novel and facile synthesis of 3-(2-benzofuroyl- and 3,6-bis(2-benzofuroylcarbazole derivatives

    Wentao Gao

    2011-11-01

    Full Text Available A facile synthesis of hitherto unreported 3-(2-benzofuroylcarbazoles 3a–k, 3,6-bis(2-benzofuroylcarbazoles 5a–k, and naphtho[2,1-b]furoylcarbazoles 3l and 5l is described. The synthesis mainly relies on the ultrasound-assisted Rap–Stoermer reaction of 3-chloroacetyl- (1 or 3,6-dichloroacetyl-9-ethyl-9H-carbazole (4 with various salicylaldehydes 2a–k as well as 2-hydroxy-1-naphthaldehyde (2l in CH3CN with the presence of PEG-400 as catalyst. The procedure offers easy access to benzofuroylcarbazoles in short reaction times and the products are obtained in moderate to good yields.

  18. A common haplotype of carnitine palmitoyltransferase 1b is associated with the metabolic syndrome.

    Auinger, A; Rubin, D; Sabandal, M; Helwig, U; Rüther, A; Schreiber, S; Foelsch, U R; Döring, F; Schrezenmeir, J

    2013-03-14

    The carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into mitochondria to provide substrates for β-oxidation. We performed an analysis including three coding SNP in the muscle isoform of the CPT1b gene (rs3213445, rs2269383 and rs470117) and one coding SNP in the CPT2 gene (rs1799821) to find associations with traits of the metabolic syndrome (MetS). Male participants (n 755) from the Metabolic Intervention Cohort Kiel were genotyped and phenotyped for features of the MetS. Participants underwent a glucose tolerance test and a postprandial assessment of metabolic variables after a standardised mixed meal. Carriers of the rare CPT1b 66V (rs3213445) allele had significantly higher γ-glutamyl transpeptidase (GGT), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) activities (P< 0·0001, P= 0·03 and P= 0·048, respectively) and a higher fatty liver index (FLI, P= 0·026). Fasting and postprandial TAG (P= 0·007 and P= 0·009, respectively) and fasting glucose (P= 0·012) were significantly higher in 66V-allele carriers. The insulin sensitivity index determined after a glucose load was lower in those subjects (P= 0·005). Total cholesterol (P= 0·051) and LDL-cholesterol (P= 0·062) tended to be higher in 66V-allele carriers when compared with I66I homozygotes. Homozygosity of the rare K531E allele presented with lower GGT and GOT activities (P= 0·011 and P= 0·027, respectively). E531E homozygotes tended to have lower GPT and FLI (P= 0·078 and P= 0·052, respectively). CPT2 V368I (rs1799821) genotypic groups did not differ in the investigated anthropometric and metabolic parameters. The present results confirm the association of CPT1b coding polymorphisms with the MetS, with a deleterious effect of the CPT1b I66V and a protective impact of the CPT1b K531E SNP, whereas haplotype analysis indicates a relevance of the E531K polymorphism only. PMID:22809552

  19. Polymorphisms in the ANKS1B gene are associated with cancer, obesity and type 2 diabetes

    Ke-Sheng Wang

    2015-08-01

    Full Text Available Obesity and type 2 diabetes (T2D are comorbidities with cancer which may be partially due to shared genetic variants. Genetic variants in the ankyrin repeat and sterile alpha motif domain containing 1B (ANKS1B gene may play a role in cancer, adiposity, body mass index (BMI, and body weight. However, few studies focused on the associations of ANKS1B with obesity and T2D. We examined genetic associations of 272 single nucleotide polymorphisms (SNPs within the ANKS1B with the cancer (any diagnosed cancer omitting minor skin cancer, obesity and T2D using the Marshfield sample (716 individuals with cancers, 1442 individuals with obesity, and 878 individuals with T2D. The Health Aging and Body Composition (Health ABC sample (305 obese and 1336 controls was used for replication. Multiple logistic regression analysis was performed using the PLINK software. Odds ratios (ORs and 95% confidence intervals (CIs were calculated. We identified 25 SNPs within the ANKS1B gene associated with cancer, 34 SNPs associated with obesity, and 12 SNPs associated with T2D (p < 0.05. The most significant SNPs associated with cancer, T2D, and obesity were rs2373013 (p = 2.21 × 10-4, rs10860548 (p = 1.92 × 10-3, and rs7139028 (p = 1.94 × 10-6, respectively. Interestingly, rs3759214 was identified for both cancer and T2D (p = 0.0161 and 0.044, respectively. Furthermore, seven SNPs were associated with both cancer and obesity (top SNP rs2372719 with p = 0.0161 and 0.0206, respectively; six SNPs were associated with both T2D and obesity (top SNP rs7139028 with p = 0.0231 and 1.94 × 10-6, respectively. In the Health ABC sample, 18 SNPs were associated with obesity, 5 of which were associated with cancer in the Marshfield sample. In addition, three SNPs (rs616804, rs7295102, and rs201421 were associated with obesity in meta-analysis using both samples. These findings provide evidence of common genetic variants in the ANKS1B gene influencing the risk of cancer, obesity, and

  20. Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells.

    Ha, Sun-Hyung; Lee, Ji-Min; Kwon, Kyung-Min; Kwak, Choong-Hwan; Abekura, Fukushi; Park, Jun-Young; Cho, Seung-Hak; Lee, Kichoon; Chang, Young-Chae; Lee, Young-Choon; Choi, Hee-Jung; Chung, Tae-Wook; Ha, Ki-Tae; Chang, Hyeun-Wook; Kim, Cheorl-Ho

    2016-01-01

    Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI) staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose) polymerase), without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2) gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis. PMID:27144558

  1. Analysen zur Funktion des E1B-55K-Proteins von Adenovirus Typ 5 im lytischen Replikationszyklus

    Kindsmüller, Kathrin

    2007-01-01

    Das E1B-55K-Protein von Adenovirus Typ 5 ist ein multifunktionelles Phosphoprotein, das eine zentrale Rolle im produktiven Replikationszyklus von Ad5 einnimmt. Die lytischen Aktivitäten des E1B-Proteins werden zumindest teilweise im Komplex mit dem viralen Protein E4orf6 vermittelt. Soweit bekannt fördert der E1B-55K/E4orf6-Komplex (E1B/E4-Komplex) den nukleozytoplasmatischen Transport viraler mRNAs und fördert somit die Synthese viraler Kapsidproteine bzw. die Produktion von Nachkommenviren....

  2. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    Sharawan Yadav; Naveen Kumar Singhal; Virendra Singh; Neeraj Rastogi; Pramod Kumar Srivastava; Mahendra Pratap Singh

    2009-01-01

    Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of ...

  3. Sex Bias in Primary Congenital Glaucoma Patients with and without CYP1B1 Mutations

    Fatemeh Suri

    2009-04-01

    Full Text Available

    PURPOSE: To investigate variations in sex ratio among Iranian primary congenital glaucoma (PCG patients with and without mutations in the CYP1B1 gene and to evaluate possible clinical variations associated with sex in these two groups. METHODS: Phenotypical data on 104 unrelated Iranian PCG patients who had previously been screened for CYP1B1 mutations were analyzed. Emphasis was placed on analysis of sex ratios among patients with and without CYP1B1 mutations. In addition to sex, familial and sporadic incidence and clinical features including age at onset, bilateral/unilateral involvement, corneal diameter, intraocular pressure, and cup-disc ratios were compared between these two groups. Information on phenotypical parameters was available for most but not all patients. RESULTS: Among the 93 PCG patients whose sex was recorded, 57 were male (61.3% and 36 were female (38.7% (P=0.03. Patients with CYP1B1 mutations included 37 male (66.1% and 29 female (43.9% subjects (P=0.30, while patients without the mutation included 20 (74.1% male and 7 (25.9% female individuals (P=0.013. Our data did not provide conclusive evidence on difference in severity of the disease between those

  4. Benchmarks and models for 1-D radiation transport in stochastic participating media

    Miller, D S

    2000-08-21

    Benchmark calculations for radiation transport coupled to a material temperature equation in a 1-D slab and 1-D spherical geometry binary random media are presented. The mixing statistics are taken to be homogeneous Markov statistics in the 1-D slab but only approximately Markov statistics in the 1-D sphere. The material chunk sizes are described by Poisson distribution functions. The material opacities are first taken to be constant and then allowed to vary as a strong function of material temperature. Benchmark values and variances for time evolution of the ensemble average of material temperature energy density and radiation transmission are computed via a Monte Carlo type method. These benchmarks are used as a basis for comparison with three other approximate methods of solution. One of these approximate methods is simple atomic mix. The second approximate model is an adaptation of what is commonly called the Levermore-Pomraning model and which is referred to here as the standard model. It is shown that recasting the temperature coupling as a type of effective scattering can be useful in formulating the third approximate model, an adaptation of a model due to Su and Pomraning which attempts to account for the effects of scattering in a stochastic context. This last adaptation shows consistent improvement over both the atomic mix and standard models when used in the 1-D slab geometry but shows limited improvement in the 1-D spherical geometry. Benchmark values are also computed for radiation transmission from the 1-D sphere without material heating present. This is to evaluate the performance of the standard model on this geometry--something which has never been done before. All of the various tests demonstrate the importance of stochastic structure on the solution. Also demonstrated are the range of usefulness and limitations of a simple atomic mix formulation.

  5. TNFα increases hypothalamic PTP1B activity via the NFκB pathway in rat hypothalamic organotypic cultures.

    Ito, Yoshihiro; Banno, Ryoichi; Hagimoto, Shigeru; Ozawa, Yoshiharu; Arima, Hiroshi; Oiso, Yutaka

    2012-02-10

    In obesity, levels of tumor necrosis-factor α (TNFα) are well known to be elevated in adipose tissues or serum, and a high-fat diet (HFD) reportedly increases TNFα expression in the hypothalamus. The expression levels of hypothalamic protein tyrosine phosphatase 1B (PTP1B), a negative regulator of leptin and insulin signaling, are also elevated by HFD, and several lines of evidence support a relationship between TNFα and PTP1B. It remains unclear however how TNFα acts locally in the hypothalamus to regulate hypothalamic PTP1B expression and activity. In this study, we examined whether TNFα can regulate PTP1B expression and activity using rat hypothalamic organotypic cultures. Incubation of cultures with TNFα resulted in increases in mRNA expression, protein levels and activity of PTP1B in a dose- and time-dependent manner, respectively compared with controls. TNFα-induced PTP1B protein levels were not influenced by co-incubation with the sodium channel blocker tetrodotoxin, indicating that the action of TNFα is independent of action potentials. TNFα also increased phosphorylation of p65, a subunit of nuclear factor-κB (NFκB), in a dose- and time-dependent manner. While incubation with inhibitors of NFκB did not affect basal levels of either p65 phosphorylation or PTP1B expression, it markedly suppressed both TNFα-induced p65 phosphorylation and PTP1B expression to almost basal levels. These data suggest that TNFα acts on the hypothalamus to increase hypothalamic PTP1B expression and activity via the NFκB pathway, and that TNFα-mediated induction of NFκB in the hypothalamus may cause leptin and insulin resistance in the hypothalamus by increasing hypothalamic PTP1B activity. PMID:22166493

  6. A Mathematical Model of T1D Acceleration and Delay by Viral Infection.

    Moore, James R; Adler, Fred

    2016-03-01

    Type 1 diabetes (T1D) is often triggered by a viral infection, but the T1D prevalence is rising among populations that have a lower exposure to viral infection. In an animal model of T1D, the NOD mouse, viral infection at different ages may either accelerate or delay disease depending on the age of infection and the type of virus. Viral infection may affect the progression of T1D via multiple mechanisms: triggering inflammation, bystander activation of self-reactive T-cells, inducing a competitive immune response, or inducing a regulatory immune response. In this paper, we create mathematical models of the interaction of viral infection with T1D progression, incorporating each of these four mechanisms. Our goal is to understand how each viral mechanism interacts with the age of infection. The model predicts that each viral mechanism has a unique pattern of interaction with disease progression. Viral inflammation always accelerates disease, but the effect decreases with age of infection. Bystander activation has little effect at younger ages and actually decreases incidence at later ages while accelerating disease in mice that do get the disease. A competitive immune response to infection can decrease incidence at young ages and increase it at older ages, with the effect decreasing over time. Finally, an induced Treg response decreases incidence at any age of infection, but the effect decreases with age. Some of these patterns resemble those seen experimentally. PMID:27030351

  7. Epitaxial 1D electron transport layers for high-performance perovskite solar cells.

    Han, Gill Sang; Chung, Hyun Suk; Kim, Dong Hoe; Kim, Byeong Jo; Lee, Jin-Wook; Park, Nam-Gyu; Cho, In Sun; Lee, Jung-Kun; Lee, Sangwook; Jung, Hyun Suk

    2015-10-01

    We demonstrate high-performance perovskite solar cells with excellent electron transport properties using a one-dimensional (1D) electron transport layer (ETL). The 1D array-based ETL is comprised of 1D SnO2 nanowires (NWs) array grown on a F:SnO2 transparent conducting oxide substrate and rutile TiO2 nanoshells epitaxially grown on the surface of the 1D SnO2 NWs. The optimized devices show more than 95% internal quantum yield at 750 nm, and a power conversion efficiency (PCE) of 14.2%. The high quantum yield is attributed to dramatically enhanced electron transport in the epitaxial TiO2 layer, compared to that in conventional nanoparticle-based mesoporous TiO2 (mp-TiO2) layers. In addition, the open space in the 1D array-based ETL increases the prevalence of uniform TiO2/perovskite junctions, leading to reproducible device performance with a high fill factor. This work offers a method to achieve reproducible, high-efficiency perovskite solar cells with high-speed electron transport. PMID:26324759

  8. Deconvolution of Complex 1D NMR Spectra Using Objective Model Selection.

    Travis S Hughes

    Full Text Available Fluorine (19F NMR has emerged as a useful tool for characterization of slow dynamics in 19F-labeled proteins. One-dimensional (1D 19F NMR spectra of proteins can be broad, irregular and complex, due to exchange of probe nuclei between distinct electrostatic environments; and therefore cannot be deconvoluted and analyzed in an objective way using currently available software. We have developed a Python-based deconvolution program, decon1d, which uses Bayesian information criteria (BIC to objectively determine which model (number of peaks would most likely produce the experimentally obtained data. The method also allows for fitting of intermediate exchange spectra, which is not supported by current software in the absence of a specific kinetic model. In current methods, determination of the deconvolution model best supported by the data is done manually through comparison of residual error values, which can be time consuming and requires model selection by the user. In contrast, the BIC method used by decond1d provides a quantitative method for model comparison that penalizes for model complexity helping to prevent over-fitting of the data and allows identification of the most parsimonious model. The decon1d program is freely available as a downloadable Python script at the project website (https://github.com/hughests/decon1d/.

  9. Possible Dimensional Crossover to 1D of ^3He Fluid in Nanochannels Observed in Susceptibilities

    Matsushita, Taku; Kurebayashi, Katsuya; Shibatsuji, Ryosuke; Hieda, Mitsunori; Wada, Nobuo

    2016-05-01

    Dimensional crossover to the one-dimensional (1D) state from higher dimensions has been studied for dilute ^3He fluid adsorbed in 2.4 nm ^4He-preplated nanochannels, by susceptibility measurements down to 70 mK using 4.29 MHz nuclear magnetic resonance. In nanochannels, since energy states of ^3He motion perpendicular to the channel axis are discrete, a genuine 1D ^3He fluid is expected when the Fermi energy is less than the first excitation Δ _{01} for azimuthal motion. The susceptibilities χ above 0.3 K show the Curie-law susceptibilities independent of the ^3He density, which are characteristic of nondegenerate fluid in higher dimensions. With decreasing the temperature, a significant reduction of χ T was observed from about 0.3 K for all ^3He densities. It is considered to be due to the dimensional crossover below Δ _{01}˜ 0.5 K to the 1D ^3He state in the semi-degenerate regime above the Fermi temperature. In the 1D state at lower temperatures, T-independent χ were observed for ^3He of 0.019 layers below 0.1 K. It suggests that the 1D ^3He fluid enters the quantum degenerate regime.

  10. Aromatic carboxylate effect on dimensionality of three bis(benzimidazole)-based cobalt(II) coordination polymers: Syntheses, structures and properties

    Zhang, Ju-Wen; Gong, Chun-Hua; Hou, Li-Li; Tian, Ai-Xiang; Wang, Xiu-Li, E-mail: wangxiuli@bhu.edu.cn

    2013-09-15

    Three new metal-organic coordination polymers [Co(4-bbc){sub 2}(bbbm)] (1), [Co(3,5-pdc)(bbbm)]·2H{sub 2}O (2) and [Co(1,4-ndc)(bbbm)] (3) (4-Hbbc=4-bromobenzoic acid, 3,5-H{sub 2}pdc=3,5-pyridinedicarboxylic acid, 1,4-H{sub 2}ndc=1,4-naphthalenedicarboxylic acid and bbbm=1,1-(1,4-butanediyl)bis-1H-benzimidazole) were hydrothermally synthesized and structurally characterized. Polymer 1 is a 1D chain formed by the bbbm ligands and Co{sup II} ions. Polymer 2 exhibits a 2D network with a (3·4·5)(3{sup 2}·4·5·6{sup 2}·7{sup 4}) topology. Polymer 3 possesses a 3D three-fold interpenetrating framework. The versatile structures of title polymers indicate that the aromatic carboxylates have an important influence on the dimensionality of 1–3. Moreover, the thermal stability, electrochemical and luminescent properties of 1–3 were investigated. - graphical abstract: Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were hydrothermally synthesized and structurally characterized. The aromatic carboxylates play a key role in the dimensionality of three polymers. The electrochemical and luminescent properties of three polymers were investigated. Display Omitted - Highlights: • Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were obtained. • The aromatic carboxylates have an important influence on the dimensionality of three polymers. • The electrochemical and luminescent properties of three polymers were investigated.

  11. Structural modulation of Co(II) coordination polymers with flexible bis(benzimidazole) and different dicarboxylate ligands

    Qin, Li; Wang, Li-na; Ma, Pei-juan; Cui, Guang-hua

    2014-02-01

    Two complexes [Co2(L)2(npht)2·H2O]n (1) and [Co(L)(mip)·0.5H2O]n (2) (H2npht = 3-nitrophthalic acid, L = 1,3-bis(5,6-dimethylbenzimidazol)propane, H2mip = 5-methylisophthalic acid) were obtained under hydrothermal conditions. In compound 1, two npht2- ligands connect two crystallographically independent Co atoms to form a binuclear [Co2(npht)]2 subunit, further linked by L ligands to generate a 1D ladder-like chain, which is arranged into a 2D supramolecular layer through face-to-face π-π stacking interactions. Compound 2 exhibits a 2D 4-connected coordination network. The fluorescence properties of 1 and 2 have been investigated in the solid-state. Both complexes show higher catalytic behaviors for degradation of methyl orange dye.

  12. Synthesis and biological study of novel methylene-bis-benzofuranyl-

    Sanjeeva R. Cherkupally

    2008-12-01

    Full Text Available A series of novel methylene-bis-[1,5]-benzothiazepines 4 and methylene-bis-benzofuranyl-[1,5]-benzothiazepines 5 were prepared by the reaction of methylene-bis-chalcones 3 with 2-aminothiophenolfollowed by the condensation with -bromoacetophenone. The structures of the synthesized compounds wereconfirmed by their IR, 1H, 13C NMR and Mass spectral analyses. All the synthesized compounds were tested fortheir antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. Among the synthesizedcompounds, the compounds 4f, 4g, 5f and 5g were found to be the most active against Bacillus subtilis, Bacillussphaericus, Staphylococcus aureus, Klebsiella aerogenes and Chromobacterium violaceum. Similarly thesecompounds showed potent antifungal effect against Candida albicans, Aspergillus fumigatus, Trichophytonrubrum, and Trichophyton mentagrophytes. It is interesting to note that the compounds with heterocyclic ringsubstituents at the 4th position of benzothiazepine system displayed notable antibacterial activity, almost equalto that of streptomycin and penicillin.

  13. Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B

    Kuypers, M. M.; Kuypers, M. M.; Blokker, P.; Erbacher, J.; Kinkel, H.; Pancost, R. D.; Pancost, R. D.; Schouten, S.; Sinninghe Damsté, J. S.

    2001-12-01

    Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC) burial during the early Albian OAE1b (~112 My) was caused by a different process. Combined biogeochemical and stable carbon isotopic analyses indicate that black shales from this period contain up to 80% of OC derived from archaea. Archaea-derived isoprenoidal tetraether membrane lipids and free and macromolecularly bound isoprenoid alkanes are abundantly present in these black shales. More specifically the presence of certain ether lipids (cyclic biphytane tetraethers) indicates representatives of the pelagic archaea. To the best of our knowledge this is the earliest fossil evidence for marine planktonic archaea, extending their geological record by more than 60 million years. The diversity of archaeal lipids recovered from the OAE1b black shales suggests that they derive from a multitude of archaeal species. However, the specific 13C enrichment of all such lipids indicates a common `heavy' (13C-rich) carbon source for the archaea and/or a common pathway of carbon-fixation with a reduced 13C fractionation effect compared to the Calvin cycle used by algae, cyanobacteria and higher plants. The large differences (up to 12%) in 13C/12C ratios between the algal biomarkers and the much more abundant archaeal molecular fossils suggest that the latter were not living heterotrophically on photoautotrophic biomass. It seems likely that the archaea present during OAE1b used a chemical energy source (possibly ammonium) for carbon fixation since photoautotrophy within the domain of the Archaea is restricted to only a few species from hypersaline

  14. In vitro study of vitamins B1, B2 and B6 adsorption on zeolite

    Basić Zorica

    2011-01-01

    Full Text Available Background/Aim. Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitivness. Methods. The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7, concentration of vitamin solution (1, 2 and 5 mg/L, the lenght of contact with zeolite (10-180 min and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37°C. Jon competitiveness was examined by adding commercial feed mixture (grower with a defined content of the examined vitamines in zeolite solutions the pH = 2 and pH = 7. Results. Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37°C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations testch. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed

  15. The light chain 1 subunit of the microtubule-associated protein 1B (MAP1B is responsible for Tiam1 binding and Rac1 activation in neuronal cells.

    Daniel R Henríquez

    Full Text Available Microtubule-associated protein 1B (MAP1B is a neuronal protein involved in the stabilization of microtubules both in the axon and somatodendritic compartments. Acute, genetic inactivation of MAP1B leads to delayed axonal outgrowth, most likely due to changes in the post-translational modification of tubulin subunits, which enhances microtubule polymerization. Furthermore, MAP1B deficiency is accompanied by abnormal actin microfilament polymerization and dramatic changes in the activity of small GTPases controlling the actin cytoskeleton. In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1. These proteins co-segregated in neurons, and interact in both heterologous expression systems and primary neurons. We dissected the molecular domains involved in the MAP1B-Tiam1 interaction, and demonstrated that pleckstrin homology (PH domains in Tiam1 are responsible for MAP1B binding. Interestingly, only the light chain 1 (LC1 of MAP1B was able to interact with Tiam1. Moreover, it was able to increase the activity of the small GTPase, Rac1. These results suggest that the interaction between Tiam1 and MAP1B, is produced by the binding of LC1 with PH domains in Tiam1. The formation of such a complex impacts on the activation levels of Rac1 confirming a novel function of MAP1B related with the control of small GTPases. These results also support the idea of cross-talk between cytoskeleton compartments inside neuronal cells.

  16. Bis(2-{[bis(dimethylaminomethylidene]amino-κN}benzenesulfonato-κNcopper(II

    Adam Neuba

    2012-12-01

    Full Text Available The molecular structure of the title compound, [Cu(C11H16N3O3S2], shows the CuII atom with a distorted square-planar coordination geometry from the N2O2 donor set of the two chelating 2-{[bis(dimethylaminomethylidene]amino}benzenesulfonate ligands. The CuII atom lies 0.065 (1 Å above the N2O2 plane and the Cu—O [2 × 1.945 (2 Å] and Cu—N bond lengths [1.968 (3 and 1.962 (3 Å] lie in expected ranges. The two aromatic ring planes make a dihedral angle of 85.48 (1°.

  17. trans-Tetraaquabis[bis(pyridin-3-ylmethanone-κN]manganese(II bis(perchlorate

    Bin Liu

    2012-01-01

    Full Text Available In the title complex, [Mn(C11H8N2O2(H2O4](ClO42, the Mn2+ ion is located on an inversion center with the slightly distorted N2O4 octahedral coordination sphere comprising N-atom donors from two monodentate trans-related bis(pyridin-3-ylmethanone ligands and four water ligands. The two perchlorate anions are linked to the mononuclear complex molecule through water O—H...O hydrogen bonds while inter-complex water O—H...N(pyridine interactions form an infinite chain structure extending along the b axis. The perchlorate anions also function as inter-unit links through water O—H...O hydrogen bonds which, together with water O—H...O(carbonyl interactions, give a three-dimensional framework structure.

  18. Synthesis of δ-Oxo-1,1-bis(triflyl)alkanes and Their Acidities

    Hikaru Yanai; Masaya Fujita; Arata Takahashi; Min Zhang; Masaaki Mishima; Akira Kotani; Takashi Matsumoto; Takeo Taguchi

    2013-01-01

    The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable carbonyls yielded δ-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities in both the gas and solution phases were determined.

  19. Short-Term Dynamic and Local Epidemiological Trends in the South American HIV-1B Epidemic

    Junqueira, Dennis Maletich; de Medeiros, Rubia Marília; Gräf, Tiago; Almeida, Sabrina Esteves de Matos

    2016-01-01

    The human displacement and sexual behavior are the main factors driving the HIV-1 pandemic to the current profile. The intrinsic structure of the HIV transmission among different individuals has valuable importance for the understanding of the epidemic and for the public health response. The aim of this study was to characterize the HIV-1 subtype B (HIV-1B) epidemic in South America through the identification of transmission links and infer trends about geographical patterns and median time of transmission between individuals. Sequences of the protease and reverse transcriptase coding regions from 4,810 individuals were selected from GenBank. Maximum likelihood phylogenies were inferred and submitted to ClusterPicker to identify transmission links. Bayesian analyses were applied only for clusters including ≥5 dated samples in order to estimate the median maximum inter-transmission interval. This study analyzed sequences sampled from 12 South American countries, from individuals of different exposure categories, under different antiretroviral profiles, and from a wide period of time (1989–2013). Continentally, Brazil, Argentina and Venezuela were revealed important sites for the spread of HIV-1B among countries inside South America. Of note, from all the clusters identified about 70% of the HIV-1B infections are primarily occurring among individuals living in the same geographic region. In addition, these transmissions seem to occur early after the infection of an individual, taking in average 2.39 years (95% CI 1.48–3.30) to succeed. Homosexual/Bisexual individuals transmit the virus as quickly as almost half time of that estimated for the general population sampled here. Public health services can be broadly benefitted from this kind of information whether to focus on specific programs of response to the epidemic whether as guiding of prevention campaigns to specific risk groups. PMID:27258369

  20. Identification of protein tyrosine phosphatase 1B and casein as substrates for 124-v-Mos

    Stabel Silvia

    2002-04-01

    Full Text Available Abstract Background The mos proto-oncogene encodes a cytoplasmic serine/threonine-specific protein kinase with crucial function during meiotic cell division in vertebrates. Based on oncogenic amino acid substitutions the viral derivative, 124-v-Mos, displays constitutive protein kinase activity and functions independent of unknown upstream effectors of mos protein kinase. We have utilized this property of 124-v-Mos and screened for novel mos substrates in immunocomplex kinase assays in vitro. Results We generated recombinant 124-v-Mos using the baculovirus expression system in Spodoptera frugiperda cells and demonstrated constitutive kinase activity by the ability of 124-v-Mos to auto-phosphorylate and to phosphorylate vimentin, a known substrate of c-Mos. Using this approach we analyzed a panel of acidic and basic substrates in immunocomplex protein kinase assays and identified novel in vitro substrates for 124-v-Mos, the protein tyrosine phosphatase 1B (PTP1B, alpha-casein and beta-casein. We controlled mos-specific phosphorylation of PTP1B and casein in comparative assays using a synthetic kinase-inactive 124-v-Mos mutant and further, tryptic digests of mos-phosphorylated beta-casein identified a phosphopeptide specifically targeted by wild-type 124-v-Mos. Two-dimensional phosphoamino acid analyses showed that 124-v-mos targets serine and threonine residues for phosphorylation in casein at a 1:1 ratio but auto-phosphorylation occurs predominantly on serine residues. Conclusion The mos substrates identified in this study represent a basis to approach the identification of the mos-consensus phosphorylation motif, important for the development of specific inhibitors of the Mos protein kinase.

  1. Short-Term Dynamic and Local Epidemiological Trends in the South American HIV-1B Epidemic.

    Junqueira, Dennis Maletich; de Medeiros, Rubia Marília; Gräf, Tiago; Almeida, Sabrina Esteves de Matos

    2016-01-01

    The human displacement and sexual behavior are the main factors driving the HIV-1 pandemic to the current profile. The intrinsic structure of the HIV transmission among different individuals has valuable importance for the understanding of the epidemic and for the public health response. The aim of this study was to characterize the HIV-1 subtype B (HIV-1B) epidemic in South America through the identification of transmission links and infer trends about geographical patterns and median time of transmission between individuals. Sequences of the protease and reverse transcriptase coding regions from 4,810 individuals were selected from GenBank. Maximum likelihood phylogenies were inferred and submitted to ClusterPicker to identify transmission links. Bayesian analyses were applied only for clusters including ≥5 dated samples in order to estimate the median maximum inter-transmission interval. This study analyzed sequences sampled from 12 South American countries, from individuals of different exposure categories, under different antiretroviral profiles, and from a wide period of time (1989-2013). Continentally, Brazil, Argentina and Venezuela were revealed important sites for the spread of HIV-1B among countries inside South America. Of note, from all the clusters identified about 70% of the HIV-1B infections are primarily occurring among individuals living in the same geographic region. In addition, these transmissions seem to occur early after the infection of an individual, taking in average 2.39 years (95% CI 1.48-3.30) to succeed. Homosexual/Bisexual individuals transmit the virus as quickly as almost half time of that estimated for the general population sampled here. Public health services can be broadly benefitted from this kind of information whether to focus on specific programs of response to the epidemic whether as guiding of prevention campaigns to specific risk groups. PMID:27258369

  2. Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice

    Postma Dirkje S

    2007-07-01

    Full Text Available Abstract Background Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD, though the mechanisms of its toxicity are still unclear. The ABC transporters multidrug resistance-associated protein 1 (MRP1 and P-glycoprotein (P-gp/MDR1 extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium. Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke. Methods We examined whether triple knock-out (TKO mice lacking the genes for Mrp1 and Mdr1a/1b are more susceptible to develop COPD features than their wild-type (WT littermates. TKO and WT mice (six per group were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months. Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept. Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences. Results TKO mice had lower levels of interleukin (IL-7, KC (mouse IL-8, IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (P P P Conclusion Mrp1/Mdr1a/1b knock-out mice have a reduced inflammatory response to cigarette smoke. In addition, the expression levels of several cytokines and chemokines were also lower in lungs of Mrp1/Mdr1a/1b knock-out mice independent of smoke exposure. Further studies are required to determine whether dysfunction of MRP1 and/or P-gp contribute to the pathogenesis of COPD.

  3. TC-PTP and PTP1B: Regulating JAK-STAT signaling, controlling lymphoid malignancies.

    Pike, Kelly A; Tremblay, Michel L

    2016-06-01

    Lymphoid malignancies are characterized by an accumulation of genetic lesions that act co-operatively to perturb signaling pathways and alter gene expression programs. The Janus kinases (JAK)-signal transducers and activators of transcription (STATs) pathway is one such pathway that is frequently mutated in leukemia and lymphoma. In response to cytokines and growth factors, a cascade of reversible tyrosine phosphorylation events propagates the JAK-STAT pathway from the cell surface to the nucleus. Activated STAT family members then play a fundamental role in establishing the transcriptional landscape of the cell. In leukemia and lymphoma, somatic mutations have been identified in JAK and STAT family members, as well as, negative regulators of the pathway. Most recently, inactivating mutations in the protein tyrosine phosphatase (PTP) genes PTPN1 (PTP1B) and PTPN2 (TC-PTP) were sequenced in B cell lymphoma and T cell acute lymphoblastic leukemia (T-ALL) respectively. The loss of PTP1B and TC-PTP phosphatase activity is associated with an increase in cytokine sensitivity, elevated JAK-STAT signaling, and changes in gene expression. As inactivation mutations in PTPN1 and PTPN2 are restricted to distinct subsets of leukemia and lymphoma, a future challenge will be to identify in which cellular contexts do they contributing to the initiation or maintenance of leukemogenesis or lymphomagenesis. As well, the molecular mechanisms by which PTP1B and TC-PTP loss co-operates with other genetic aberrations will need to be elucidated to design more effective therapeutic strategies. PMID:26817397

  4. 2-Isobutyl-6-(4-methoxyphenylimidazo[2,1-b][1,3,4]thiadiazole

    Hoong-Kun Fun

    2011-02-01

    Full Text Available In the title compound, C15H17N3OS, the dihedral angle between the statistically planar imidazo[2,1-b][1,3,4]thiadiazole fused-ring system (r.m.s. deviation = 0.002 Å and the methyoxbenzene ring is 4.52 (6°. In the crystal, molecules are arranged into columns and stacked down the a axis. The crystal structure is stabilized by weak C—H...π and π–π interactions [centroid–centroid separations = 3.6053 (8 and 3.7088 (7 Å].

  5. Sterile neutrino portal to Dark Matter I: The $U(1)_{B-L}$ case

    Escudero, Miguel; Rius, Nuria; Sanz, Verónica

    2016-01-01

    In this paper we explore the possibility that the sterile neutrino and Dark Matter sectors in the Universe have a common origin. We study the consequences of this assumption in the simple case of coupling the dark sector to the Standard Model via a global $U(1)_{B-L}$, broken down spontaneously by a dark scalar. This dark scalar provides masses to the dark fermions and communicates with the Higgs via a Higgs portal coupling. We find an interesting interplay between Dark Matter annihilation to...

  6. Nail-patella syndrome—a novel mutation in the LMX1B gene

    Nair, Rajesh R.; Unni, Vavullipathy N.; Indu, Kadevalappil N.; Nampoothiri, Sheela; Mathew, Anil; Kurian, George; Vimala, Avadaiammal

    2013-01-01

    Nail-patella syndrome (NPS) is an autosomal-dominant pleiotropic disorder characterized by dyplasia of finger nails, skeletal anomalies and frequently renal disease. In the reported case, genetic analysis revealed a new missense mutation in the homeodomain of LMX1B, presumed to abolish DNA binding (c.725T>C, p.Val242Ala). A missense mutation at codon 725 was identified, where thymine was replaced by cytosine which led to the replacement of valine by alanine at position 242. It was not detecte...

  7. LEUPROLIDE INHIBITS MARBLE-BURYING BEHAVIOR VIA MODULATION OF 5-HT1B RECEPTOR

    Parle Milind; Gaikwad Uday

    2011-01-01

    Obsessive compulsive disorder (OCD) is characterized by intrusive thoughts followed by repetitive behaviors. Serotonin-related genes found in OCD include those required for coding of 5-HT transporter and 5-HT receptors (5-HT2A, 5-HT2B, 5-HT2C and 5-HT1B). Marble-burying behavior of mice is a well-accepted paradigm to screen anti-compulsive activity. The aim of this study was to evaluate the effect of leuprolide alone and it’s combination with sumatriptan or ondansetron on marble-burying behav...

  8. Four Years of Realtime GRB Followup by BOOTES-1B (2005-2008)

    Jelinek, Martin; Postigo, Antonio de Ugarte; Kubanek, Petr; Guziy, Sergei; Gorosabel, Javier; Cunniffe, Ronan; Vitek, Stanislav; Hudec, Rene; Reglero, Victor; Sabau-Graziati, Lola

    2010-01-01

    Four years of BOOTES-1B GRB follow-up history are summarised for the first time in the form of a table. The successfully followed events are described case by case. Further, the data are used to show the GRB trigger rate in Spain on a per-year basis, resulting in an estimate of 18 triggers and about 51 h of telescope time per year for real time triggers. These numbers grow to about 22 triggers and 77 h per year if we include also the GRBs observable within 2 hours after the trigger.

  9. Identification of Bmpr-1b and Bmp15 gene mutations in fat tail sheep

    Maskur .; Chairussyuhur Arman

    2012-01-01

    Fat tail sheep (FTS) is regarded as highly prolific local sheep and have been well adapted under tropical climate of Lombok island. BMPR-1B and BMP15 genes that controll reproductive traits such as ovulation rate and litter size in different type of sheep will be studied as candidate genes for prolific traits in FTS. These genes  have been reported by various investigators have different prolificacy mechanism between several breeds of sheep, and it is very likely will occur in FTS. This study...

  10. REAL-TIME FLOOD FORECASTING METHOD WITH 1-D UNSTEADY FLOW MODEL

    MU Jin-bin; ZHANG Xiao-feng

    2007-01-01

    A real-time forecasting method coupled with the 1-D unsteady flow model with the recursive least-square method was developed. The 1-D unsteady flow model was modified by using the time-variant parameter and revising it dynamically through introducing a variable weighted forgetting factor, such that the output of the model could be adjusted for the real time forecasting of floods. The application of the new real time forecasting model in the reach from Yichang to Luoshan of the Yangtze River was demonstrated. Computational result shows that the forecasting accuracy of the new model is much higher than that of the original 1-D unsteady flow model. The method developed is effective for flood forecasting, and can be used for practical operation in the flood forecasting.

  11. A comparison of 1D and 2D LSTM architectures for the recognition of handwritten Arabic

    Yousefi, Mohammad Reza; Soheili, Mohammad Reza; Breuel, Thomas M.; Stricker, Didier

    2015-01-01

    In this paper, we present an Arabic handwriting recognition method based on recurrent neural network. We use the Long Short Term Memory (LSTM) architecture, that have proven successful in different printed and handwritten OCR tasks. Applications of LSTM for handwriting recognition employ the two-dimensional architecture to deal with the variations in both vertical and horizontal axis. However, we show that using a simple pre-processing step that normalizes the position and baseline of letters, we can make use of 1D LSTM, which is faster in learning and convergence, and yet achieve superior performance. In a series of experiments on IFN/ENIT database for Arabic handwriting recognition, we demonstrate that our proposed pipeline can outperform 2D LSTM networks. Furthermore, we provide comparisons with 1D LSTM networks trained with manually crafted features to show that the automatically learned features in a globally trained 1D LSTM network with our normalization step can even outperform such systems.

  12. Transparent Conducting Electrodes based on 1D and 2D Ag Nanogratings for Organic Photovoltaics

    Zeng, Beibei; Bartoli, Filbert J

    2014-01-01

    The optical and electrical properties of optically-thin one-dimensional (1D) Ag nanogratings and two-dimensional (2D) Ag nanogrids are studied, and their use as transparent electrodes in organic photovoltaics are explored. A large broadband and polarization-insensitive optical absorption enhancement in the organic light-harvesting layers is theoretically and numerically demonstrated using either single-layer 2D Ag nanogrids or two perpendicular 1D Ag nanogratings, and is attributed to the excitation of surface plasmon resonances and plasmonic cavity modes. Total photon absorption enhancements of 150% and 200% are achieved for the optimized single-layer 2D Ag nanogrids and double (top and bottom) perpendicular 1D Ag nanogratings, respectively.

  13. Periodic Properties of 1D FE Discrete Models in High Frequency Dynamics

    A. Żak

    2016-01-01

    Full Text Available Finite element discrete models of various engineering 1D structures may be considered as structures of certain periodic characteristics. The source of this periodicity comes from the discontinuity of stress/strain field between the elements. This behaviour remains unnoticeable, when low frequency dynamics of these structures is investigated. At high frequency regimes, however, its influence may be strong enough to dominate calculated structural responses distorting or even falsifying them completely. In this paper, certain computational aspects of structural periodicity of 1D FE discrete models are discussed by the authors. In this discussion, the authors focus their attention on an exemplary problem of 1D rod modelled according to the elementary theory.

  14. PC-1D installation manual and user's guide

    Basore, P.A.

    1991-05-01

    PC-1D is a software package for personal computers that uses finite-element analysis to solve the fully-coupled two-carrier semiconductor transport equations in one dimension. This program is particularly useful for analyzing the performance of optoelectronic devices such as solar cells, but can be applied to any bipolar device whose carrier flows are primarily one-dimensional. This User's Guide provides the information necessary to install PC-1D, define a problem for solution, solve the problem, and examine the results. Example problems are presented which illustrate these steps. The physical models and numerical methods utilized are presented in detail. This document supports version 3.1 of PC-1D, which incorporates faster numerical algorithms with better convergence properties than previous versions of the program. 51 refs., 17 figs., 5 tabs.

  15. Spin Excitations and Phonon Anomaly in Quasi-1D Spiral Magneti CuBr2

    Li, Yuan; Wang, Chong; Yu, Daiwei; Wang, Lichen; Wang, Fa; Iida, Kazuki; Kamazawa, Kazuya; Wakimoto, Shuichi

    CuBr2 can be considered as a model quasi-one-dimensional (quasi-1D) spin-1/2 magnet, in which the frustrating ferromagnetic nearest-neighbor and antiferromagnetic next-nearest-neighbor exchange interactions give rise to a cycloidal magnetic order below TN = 73 K. The removal of inversion symmetry by the magnetic order also makes the material a type-II multiferroic system with a remarkably simple crystal structure. Using time-of-flight inelastic neutron scattering spectroscopy, we have determined the spin-wave as well as phonon spectra throughout the entire Brillouin zone. The spin-wave spectrum exhibits pronounced anisotropy and magnon damping, consistent with the material's quasi-1D nature and the non-colinear spin structure. The phonon spectrum exhibits dramatic discontinuities in the dispersion across the quasi-1D magnetic wave vector, indicative of strong magnetoelastic coupling and possibly of a spin-orbital texture that comes along with the spin correlations.

  16. Solution to 1-D consolidation of non-homogeneous soft clay

    XIE Kang-he; WEN Jie-bang; XIA Jian-zhong

    2005-01-01

    In this work, semi-analytical methods were used to solve the problem of 1-D consolidation of non-homogeneous soft clay with spatially varying coefficients of permeability and compressibility. The semi-analytical solution was programmed and then verified by comparison with the obtained analytical solution of a special case. Based on the results of some computations and comparisons with the 1-D homogeneous consolidation (by Terzaghi) and the 1-D non-linear consolidation theory (by Davis et al.)of soft clay, some diagrams were prepared and the relevant consolidation behavior of non-homogeneous soils is discussed. It was shown that the result obtained differs greatly from Terzaghi's theory and that of the non-linear consolidation theory when the coefficients of permeability and compressibility vary greatly.

  17. DEVELOPMENT OF COUPLED 1D-2D MATHEMATICAL MODELS FOR TIDAL RIVERS

    XU Zu-xin; YIN Hai-long

    2004-01-01

    Some coupled 1D-2D hydrodynamic and water quality models depicting tidal water bodies with complex topography were presented. For the coupled models, finite element method was used to solve the governing equations so as to study tidal rivers with complex topography. Since the 1D and 2D models were coupled, the principle of model coupling was proposed to account appropriately for the factors of water level, flow and pollutant flux and the related dynamical behavior was simulated. Specifically the models were used to probe quantitative pollution contribution of receiving water from neighboring Jiangsu and Zhejiang Provinces to the pollution in the Huangpu River passing through Shanghai City. Numerical examples indicated that the developed coupled 1D-2D models are applicable in tidal river network region of Shanghai.

  18. Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion.

    de Lange, Iris M; Verrijn Stuart, Annemarie A; van der Luijt, Rob B; Ploos van Amstel, Hans Kristian; van Haelst, Mieke M

    2016-09-01

    Pseudohypoparathyroidism (PHP) is a genetic disorder with resistance to parathyroid hormone (PTH) as most important feature. Main subtypes of the disease are pseudohypoparathyroidism 1b (PHP1b) and pseudohypoparathyroidism 1a (PHP1a). PHP1b is characterized by PTH resistance of the renal cortex due to reduced activity of the stimulatory G protein α subunit (Gsα) of the PTH receptor. In addition to resistance to PTH, PHP1a patients also lack sensitivity for other hormones that signal their actions through G protein-coupled receptors and display physical features of Albright hereditary osteodystrophy (AHO), which is not classically seen in PHP1b patients. PHP1a is caused by heterozygous loss-of-function mutations in maternally inherited GNAS exons 1-13, which encode Gsα. PHP1b is often caused by deletion of the STX16 gene, which is thought to have an important role in controlling the methylation and thus imprinting at part of the GNAS locus. Here we present a patient with PHP1b caused by the previously described recurrent 3-kb STX16 deletion. The patient's first symptoms were macrosomia, early onset obesity, and macrocephaly. Since this is an atypical but previously described rare presentation of PHP1b, we reemphasize STX16 deletions and PHP1b as a rare cause for early onset obesity and macrosomia. © 2016 Wiley Periodicals, Inc. PMID:27338644

  19. Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen

    Blanquart, Christophe; Karouri, Salah-Eddine [Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris (France); Inserm, U567, Paris (France); Issad, Tarik, E-mail: tarik.issad@inserm.fr [Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris (France); Inserm, U567, Paris (France)

    2009-10-02

    The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.

  20. Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line.

    Viall, A K; Goodall, C P; Stang, B; Marley, K; Chappell, P E; Bracha, S

    2016-06-01

    Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target. PMID:24916076

  1. 76 FR 11686 - Registration Requirement for Petitioners Seeking to File H-1B Petitions on Behalf of Aliens...

    2011-03-03

    ... random selection process on March 24, 2008. See 73 FR 15389. Although the current regulations at 8 CFR...-1B Petitions on Behalf of Aliens Subject to the Numerical Limitations AGENCY: U.S. Citizenship and... is proposing to amend its regulations governing petitions filed on behalf of H-1B alien...

  2. Complete Genome Sequence of Bovine Viral Diarrhea Virus-1 Strain Egy/Ismailia/2014, Subtype 1b

    Soltan, Mohamed A.; Wilkes, Rebecca P.; Elsheery, Mohamed N.; Elhaig, Mahmoud M.; Riley, Matthew C.; Melissa A. Kennedy

    2015-01-01

    Here, we report the complete genome sequence of bovine viral diarrhea virus-1b (BVDV-1b), strain Egy/Ismailia/2014. The virus genome is composed of 12,217 nucleotides organized as one open reading frame encoding 3,898 amino acids. This report will assist efforts in diagnostics, studying molecular epidemiology, and control of BVDV in Egypt.

  3. Complete Genome Sequence of Bovine Viral Diarrhea Virus-1 Strain Egy/Ismailia/2014, Subtype 1b.

    Soltan, Mohamed A; Wilkes, Rebecca P; Elsheery, Mohamed N; Elhaig, Mahmoud M; Riley, Matthew C; Kennedy, Melissa A

    2015-01-01

    Here, we report the complete genome sequence of bovine viral diarrhea virus-1b (BVDV-1b), strain Egy/Ismailia/2014. The virus genome is composed of 12,217 nucleotides organized as one open reading frame encoding 3,898 amino acids. This report will assist efforts in diagnostics, studying molecular epidemiology, and control of BVDV in Egypt. PMID:26701085

  4. 76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

    2011-07-06

    ... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not affect intrastate aviation... Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55 Series Helicopters AGENCY: Federal Aviation... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No....

  5. Interaction of novel bis(platinum) complexes with DNA.

    Roberts, J. D.; Van Houten, B; Qu, Y.; Farrell, N P

    1989-01-01

    Bis(platinum) complexes [[cis-PtCl2(NH3)]2H2N(CH2)nNH2] are a novel series of potential anticancer agents in which two cis-diamine(platinum) groups are linked by an alkyldiamine of variable length. These complexes are potentially tetrafunctional, a unique feature in comparison with known anticancer agents. Studies of DNA interactions of bis(platinum) complexes in comparison with cisplatin demonstrate significant differences. Investigations of interstrand crosslink formation in which crosslink...

  6. Biodistribution of bis(short-chain-amino)-ortho-dicarbaborane hydrochloride

    Bis(aminomethyl)-ortho-dicarbaborane hydrochloride and their nido-derivates, which may potentially be used as boron neutron capture therapy agents, have been synthesized from corresponding bis(short-chain-phthalimido)acetylenes in 81% yield. The pharmacokinetics of the type compounds is studied in healthy mice. Blood, liver, lung and spleen samples are collected at 8, 16, 30 and 48 hours after intra-peritoneal administration of the compound in healthy mice. In the study, the compound has been well absorbed and peak much earlier. (author)

  7. Carboxyl terminus-truncated α1D-adrenoceptors inhibit the ERK pathway.

    Alfonzo-Méndez, Marco A; Castillo-Badillo, Jean A; Romero-Ávila, M Teresa; Rivera, Richard; Chun, Jerold; García-Sáinz, J Adolfo

    2016-08-01

    Human α1D-adrenoceptors are G protein-coupled receptors that mediate adrenaline/noradrenaline actions. There is a growing interest in identifying regulatory domains in these receptors and determining how they function. In this work, we show that the absence of the human α1D-adrenoceptor carboxyl tail results in altered ERK (extracellular signal-regulated kinase) and p38 phosphorylation states. Amino terminus-truncated and both amino and carboxyl termini-truncated α1D-adrenoceptors were transfected into Rat-1, HEK293, and B103 cells, and changes in the phosphorylation state of extracellular signal-regulated kinase was assessed using biochemical and biophysical approaches. The phosphorylation state of other protein kinases (p38, MEK1, and Raf-1) was also studied. Noradrenaline-induced ERK phosphorylation in Rat-1 fibroblasts expressing amino termini-truncated α1D-adrenoceptors. However, in cells expressing receptors with both amino and carboxyl termini truncations, noradrenaline-induced activation was abrogated. Interestingly, ERK phosphorylation that normally occurs through activation of endogenous G protein-coupled receptors, EGF receptors, and protein kinase C, was also decreased, suggesting that downstream steps in the mitogen-activated protein kinase pathway were affected. A similar effect was observed in B103 cells but not in HEK 293 cells. Phosphorylation of Raf-1 and MEK1 was also diminished in Rat-1 fibroblasts expressing amino- and carboxyl-truncated α1D-adrenoceptors. Our data indicate that expression of carboxyl terminus-truncated α1D-adrenoceptors alters ERK and p38 phosphorylation state. PMID:27146292

  8. Modelling turbulent vertical mixing sensitivity using a 1-D version of NEMO

    G. Reffray

    2014-08-01

    Full Text Available Through two numerical experiments, a 1-D vertical model called NEMO1D was used to investigate physical and numerical turbulent-mixing behaviour. The results show that all the turbulent closures tested (k + l from Blanke and Delecluse, 1993 and two equation models: Generic Lengh Scale closures from Umlauf and Burchard, 2003 are able to correctly reproduce the classical test of Kato and Phillips (1969 under favourable numerical conditions while some solutions may diverge depending on the degradation of the spatial and time discretization. The performances of turbulence models were then compared with data measured over a one-year period (mid-2010 to mid-2011 at the PAPA station, located in the North Pacific Ocean. The modelled temperature and salinity were in good agreement with the observations, with a maximum temperature error between −2 and 2 °C during the stratified period (June to October. However the results also depend on the numerical conditions. The vertical RMSE varied, for different turbulent closures, from 0.1 to 0.3 °C during the stratified period and from 0.03 to 0.15 °C during the homogeneous period. This 1-D configuration at the PAPA station (called PAPA1D is now available in NEMO as a reference configuration including the input files and atmospheric forcing set described in this paper. Thus, all the results described can be recovered by downloading and launching PAPA1D. The configuration is described on the NEMO site (http://www.nemo-ocean.eu/Using-NEMO/Configurations/C1D_PAPA. This package is a good starting point for further investigation of vertical processes.

  9. Expression of organic anion-transporting polypeptides 1B3, 1B1, and 1A2 in human pancreatic cancer reveals a new class of potential therapeutic targets

    Kounnis V

    2011-04-01

    Full Text Available Valentinos Kounnis1, Elli Ioachim2, Martin Svoboda3, Andreas Tzakos4, Ioannis Sainis1, Theresia Thalhammer3, Georg Steiner5, Evangelos Briasoulis11Cancer Biobank Center of the University of Ioannina, Greece; 2Pathology Department of Hatzikosta General Hospital, Ioannina Greece; 3Department of Pathophysiology and Allergy Research, Medical University of Vienna, Austria; 4Department of Chemistry, University of Ioannina, Greece; 5TissueGnostics GmbH, Vienna, AustriaBackground: Organic anion-transporting polypeptides (OATPs are influx transporters that mediate intracellular uptake of selective endogenous and xenobiotic compounds. Identification of new molecular targets and discovery of novel targeted therapies is top priority for pancreatic cancer, which lacks any effective therapy.Materials and methods: We studied expression of OATP 1A2, 1B1, and 1B3 in pancreatic cancer tissue and in cell lines. Formalin-fixed paraffin-embedded biopsy material of 12 human pancreatic cancers was immunohistochemically assessed for protein expression of the three studied influx transporters. Immunohistochemistry was evaluated by experienced pathologists and quantified by use of an automated image analysis system. BxPC-3 and MIA PaCa-2 pancreatic cancer cell lines were used to quantify transcripts of OATP 1B1 and 1B3.Results: OATP 1A2, 1B1, and 1B3 proteins were found ubiquitously expressed in all studied cases. Quantification performed by HistoQuest system revealed that mean intensity was 53 for 1A2, 45 for 1B1, and 167 for OATP 1B1/1B3 on a range scale 0–250 units. At mRNA level, 1B1 and 1B3 were overexpressed in both studied cancer cell lines but not in normal pancreatic tissue.Conclusion: OATPs 1A2, 1B1, and 1B3 are highly expressed in pancreatic adenocarcinoma. We suggest that expression of these transporters in pancreatic cancer justify research efforts towards discovery of novel therapeutics targeting OATPs.Keywords: organic anion-transporting polypeptides

  10. Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity.

    Liu, Peihong; Du, Yongli; Song, Lianhua; Shen, Jingkang; Li, Qunyi

    2016-08-01

    Protein tyrosine phosphatase 1B (PTP1B) as a key negative regulator of both insulin and leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated insulin receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake. PMID:27123900

  11. Investigating the Impact of Asp181 Point Mutations on Interactions between PTP1B and Phosphotyrosine Substrate

    Liu, Mengyuan; Wang, Lushan; Sun, Xun; Zhao, Xian

    2014-05-01

    Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling, which suggests that it is an attractive therapeutic target in type II diabetes and obesity. The aim of this research is to explore residues which interact with phosphotyrosine substrate can be affected by D181 point mutations and lead to increased substrate binding. To achieve this goal, molecular dynamics simulations were performed on wild type (WT) and two mutated PTP1B/substrate complexes. The cross-correlation and principal component analyses show that point mutations can affect the motions of some residues in the active site of PTP1B. Moreover, the hydrogen bond and energy decomposition analyses indicate that apart from residue 181, point mutations have influence on the interactions of substrate with several residues in the active site of PTP1B.

  12. MYELOMA CELL CKS1B EXPRESSION IN 171 NEWLY DIAGNOSED PATIENTS IS NOT ASSOCIATED WITH INFERIOR SURVIVAL

    Christensen, Jacob Haaber; Abildgaard, Niels; Meldgaard Knudsen, Lene;

    2007-01-01

    cells from 171 untreated, newly diagnosed MM-patients. 36% of the patients (stem cell support. 56% (>65 years) were treated with standard melphalan and prednisolone,  and 8% were untreated. Median follow-up was 53 months. The clonal...... the overall survival was similar in patients with or without up-reulated CKS1B expression. In patients treated with conventional chemotherapy expression of CKS1B showed a trend towards a survival benefit (p=0.05). So, our data do not confirm that myeloma celle over-expression of CKS1B is associated with af......Introduction. In recent years global gene expression profiling studies introduce several new potential prognostic markers in multiple myeloma (MM). Up-regulation and amplification of the gene CKS1B in myeloma cells has lately been associated with a poor prognosis in MM patients. The CKS1B gene...

  13. Column Testing and 1D Reactive Transport Modeling to Evaluate Uranium Plume Persistence Processes

    Johnson, Raymond H. [Navarro Research and Engineering, Inc.; Morrison, Stan [Navarro Research and Engineering, Inc.; Morris, Sarah [Navarro Research and Engineering, Inc.; Tigar, Aaron [Navarro Research and Engineering, Inc.; Dam, William [U.S. Department of Energy, Office of Legacy Management; Dayvault, Jalena [U.S. Department of Energy, Office of Legacy Management

    2016-04-26

    Motivation for Study: Natural flushing of contaminants at various U.S. Department of Energy Office of Legacy Management sites is not proceeding as quickly as predicted (plume persistence) Objectives: Help determine natural flushing rates using column tests. Use 1D reactive transport modeling to better understand the major processes that are creating plume persistence Approach: Core samples from under a former mill tailings area Tailings have been removed. Column leaching using lab-prepared water similar to nearby Gunnison River water. 1D reactive transport modeling to evaluate processes

  14. Refractive index sensor based on a 1D photonic crystal in a microfluidic channel

    Rodrigues de Sousa Nunes, Pedro André; Mortensen, Asger; Kutter, Jörg Peter;

    2010-01-01

    A refractive index sensor has been fabricated in silicon oxynitride by standard UV lithography and dry etching processes. The refractive index sensor consists of a 1D photonic crystal (PhC) embedded in a microfluidic channel addressed by fiber-terminated planar waveguides. Experimental demonstrat......A refractive index sensor has been fabricated in silicon oxynitride by standard UV lithography and dry etching processes. The refractive index sensor consists of a 1D photonic crystal (PhC) embedded in a microfluidic channel addressed by fiber-terminated planar waveguides. Experimental...

  15. AM1/d parameters for Magnesium in Metalloenzymes. Journal of Chemical Theory and Computation

    Imhof, Petra [University of Heidelberg; Noe, F [University of Heidelberg; Fischer, S. [University of Heidelberg; Smith, Jeremy C [ORNL

    2006-06-01

    AM1/d parameters are derived for magnesium, optimized for modeling reactions in metalloenzymes. The parameters are optimized with a Monte Carlo procedure so as to reproduce the geometries and energies of a training set calculated with density functional theory. The training set consists of compounds with magnesium coordinated to the oxygen atom of typical biological ligands. Optimization of AM1 parameters without extension to d functions leaves serious errors. The new AM1/d parameters provide a clear improvement in accuracy compared to the standard semiempirical methods AM1 and MNDO/d and will be particularly useful for modeling reactions in large biological systems at low computational cost.

  16. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance

    Hasbi Ahmed

    2011-06-01

    Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

  17. Synthesis and structure of bis(diethyldithiocarbamato)nitridotechnetium(v): a technetium-nitrogen triple bond

    The compound bis(diethyldithiocarbamato)nitridotechnetium(V), (dtc)2TcN, has been prepared by the reduction of ammonium pertechnetate with hydrazine followed by reaction with sodium diethyldithiocarbamate. The crystal structure of (dtc)2TcN has been determined by single-crystal X-ray diffraction methods at 17 deg. C. Crystals are monoclinic, space group P21/c, Z = 4, a = 14.823 (1), b = 9.159(1), c = 12.865(1) A, β = 107.98(1) deg. Diffractometry has provided significant Bragg intensities for 2152 independent reflections and the structure has been refined by full-matrix least-squares methods to R 0.042. The compound, which is isostructural with the rhenium analogue, consists of discrete (dtc) 2TcN molecules, each containing a terminal N3- group. The technetium atom has a distorted square-pyramidal environment with the nitrogen atom in the apical position and four sulphur atoms forming the base

  18. PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

    Jian Wei

    2012-08-01

    Full Text Available Activated inhibitor of nuclear factor-κB kinase β (IKKβ is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg2+/Mn2+-dependent protein phosphatase 1B (PPM1B inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control, 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

  19. PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

    Wei, Jian; Liang, Bing-Sheng [Department of Orthopedics, the Second Hospital, Shanxi Medical University, Taiyuan (China)

    2012-05-18

    Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg{sup 2+}/Mn{sup 2+}-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

  20. Interaction between genetic polymorphism of cytochrome P450-1B1 and environmental pollutants in breast cancer risk.

    Saintot, M; Malaveille, C; Hautefeuille, A; Gerber, M

    2004-02-01

    Cytochrome P450 1B1 (CYP1B1) is implicated in the activation of potentially carcinogenic xenobiotics and oestrogens. The polymorphism of the CYP1B1 gene at codon 432 (Val-->Leu) is associated with change in catalytic function. In a case-series study of breast cancer patients, we investigated the interaction between this polymorphism and environmental exposure. The women carrying the Val CYP1B1 allele and who had lived near to a waste incinerator for more than 10 years had a higher risk of breast cancer than those never exposed with the Leu/Leu genotype (odds ratio of interactions (ORi)=3.26, 95% confidence interval (CI) 1.20-8.84). Also, the Val CYP1B1 allele increased the susceptibility to breast cancer for women exposed during their life to agricultural products used in farming (ORi = 2.18, 95% CI 1.10-4.32). These xenobiotics, mainly organochlorine hydrocarbons, are known to bind to the aromatic hydrocarbon receptor (AhR), and to induce the expression of CYP1B1 enzyme. The excess risk for exposed women with a Val CYP1B1 homo/heterozygous genotype could result from a higher exposure to activated metabolites of pesticides or dioxin-like substances. Also, a higher induction of CYP1B1 enzyme by xenobiotics could increase the formation of genotoxic catechol-oestrogens among exposed women carrying the Val CYP1B1 allele. Our results suggested that the Val CYP1B1 allele increases the susceptibility to breast cancer in women exposed to waste incinerator or agricultural pollutants. PMID:15075793