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Sample records for antagonist cp-96345 blocks

  1. Tritiation of nonpeptide substance P antagonist CP-96,345 and its azido analogue. Synthetic and characterization details

    Energy Technology Data Exchange (ETDEWEB)

    Egan, J.A..; Filer, C.N. E-mail: crist.filer@perkinelmer.com

    2003-12-01

    CP-96,345 (1) was the first nonpeptide antagonist discovered for the SP receptor and [{sup 3}H] CP-96,345 was required to study the mechanism of receptor action. The radioligand was prepared at high specific activity by catalytic dehalogenation of a dibrominated precursor and this same approach was also used to prepare a photoaffinity analogue.

  2. Evaluation of the effect of the specific CCR1 antagonist CP-481715 on the clinical and cellular responses observed following epicutaneous nickel challenge in human subjects

    DEFF Research Database (Denmark)

    Borregaard, Jeanett; Skov, Lone; Wang, Lisy

    2008-01-01

    BACKGROUND: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1. OBJECTIVES: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs....... CONCLUSIONS: Blocking of CCR1 only partly inhibited clinical manifestations of ACD. Several chemokine receptors are likely relevant for the cellular influx observed in ACD lesions....

  3. Effects of a NR2B Selective NMDA Glutamate Antagonist, CP-101,606, on Dyskinesia and Parkinsonism

    Science.gov (United States)

    Nutt, John G.; Gunzler, Steven A; Kirchhoff, Trish; Hogarth, Penelope; Weaver, Jerry L.; Krams, Michael; Jamerson, Brenda; Menniti, Frank S.; Landen, Jaren W.

    2011-01-01

    Glutamate antagonists decrease dyskinesia and augment the antiparkinsonian effects of levodopa in animal models of Parkinson’s disease (PD). In a randomized, double-blind, placebo-controlled clinical trial we investigated the acute effects of placebo and two doses of a NR2B subunit selective NMDA glutamate antagonist, CP-101,606, on the response to two-hour levodopa infusions in 12 PD subjects with motor fluctuations and dyskinesia. Both doses of CP-101,606 reduced the maximum severity of levodopa-induced dyskinesia approximately 30% but neither dose improved parkinsonism. CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects. PMID:18759356

  4. Radiodinated L-703,606: a potent selective antagonist to the human NK[sub 1] receptor

    Energy Technology Data Exchange (ETDEWEB)

    Francis, B E; Burns, H D [Merck Research Labs., West Point, PA (United States). Dept. of Radiopharmacology; Swain, C; Sabin, V [Merck Sharp and Dohme Research Labs., Harlow (United Kingdom). The Neuroscience Centre

    1994-01-01

    A new, radioiodinated, NK[sub 1] selective radiotracer ([[sup 125]I]L-703,606) was prepared. L-703,606 is an iodinated analog of the NK[sub 1] antagonist CP-96,345 in which the methoxy group has been replaced by an iodine substituent. [[sup 125]I]L-703,606 was made from the corresponding trimethylsilyl compound by treatment with no carrier added Na[sub 125]I and an Iodobead in TFA. The tracer was prepared at a specific activity of approx. 1100 Ci/mmol and preliminary binding studies demonstrated that [[sup 125]I]L=703,606 binds selectively to NK[sub 1] receptors. These results suggest that this radioligand will be useful for the biochemical and pharmacological characterization of the human NK[sub 1] receptor and, if labeled with I-123, may be useful for non-invasive NK[sub 1] receptor imaging via SPECT. (author).

  5. The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis.

    Science.gov (United States)

    Zaretsky, Dmitry V; Zaretskaia, Maria V; Sarkar, Sumit; Rusyniak, Daniel E; DiMicco, Joseph A

    2017-07-13

    The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH 1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105±13 to 278±51pg/ml after 20mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Vitagliano, A; Saccone, G; Noventa, M; Borini, A; Coccia, M E; Nardelli, G B; Saccardi, C; Bifulco, G; Litta, P S; Andrisani, A

    2018-06-03

    Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles. © 2018 Royal College of Obstetricians and Gynaecologists.

  7. Block of the delayed rectifier current (IK) by the 5-HT3 antagonists ondansetron and granisetron in feline ventricular myocytes.

    Science.gov (United States)

    de Lorenzi, F G; Bridal, T R; Spinelli, W

    1994-01-01

    1. We investigated the effects of two 5-HT3 antagonists, ondansetron and granisetron, on the action potential duration (APD) and the delayed rectifier current (IK) of feline isolated ventricular myocytes. Whole-cell current and action potential recordings were performed at 37 degrees C with the patch clamp technique. 2. Ondansetron and granisetron blocked IK with a KD of 1.7 +/- 1.0 and 4.3 +/- 1.7 microM, respectively. At a higher concentration (30 microM), both drugs blocked the inward rectifier (IKl). 3. The block of IK was dependent on channel activation. Both drugs slowed the decay of IK tail currents and produced a crossover with the pre-drug current trace. These results are consistent with block and unblock from the open state of the channel. 4. Granisetron showed an intrinsic voltage-dependence as the block increased with depolarization. The equivalent voltage-dependency of block (delta) was 0.10 +/- 0.04, suggesting that granisetron blocks from the intracellular side at a binding site located 10% across the transmembrane electrical field. 5. Ondansetron (1 microM) and granisetron (3 microM) prolonged APD by about 30% at 0.5 Hz. The prolongation of APD by ondansetron was abolished at faster frequencies (3 Hz) showing reverse rate dependence. 6. In conclusion, the 5-HT3 antagonists, ondansetron and granisetron, are open state blockers of the ventricular delayed rectifier and show a clear class III action. PMID:7834204

  8. Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

    Directory of Open Access Journals (Sweden)

    Hadley C Bergstrom

    2015-12-01

    Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

  9. NR2B antagonist CP-101,606 abolishes pitch-mediated deviance detection in awake rats

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    Siva eDigavalli

    2014-08-01

    Full Text Available Schizophrenia patients exhibit a decreased ability to detect change in their auditory environment as measured by auditory event related potentials such as mismatch negativity. This deficit has been linked to abnormal NMDA neurotransmission since, among other observations, non-selective channel blockers of NMDA reliably diminish deviance detection in human subjects as well as in animal models. Recent molecular and functional evidence link NR2B receptor subtype to aberrant NMDA transmission in schizophrenia. However, it is unknown if NR2B receptors participate in pre-attentive deviance detection. We recorded event related potentials from the vertex of freely behaving rats in response to frequency mismatch protocols. We saw a robust increase in N1 response to deviants compared to standard as well as control stimuli indicating true deviance detection. Moreover, the increased negativity was highly sensitive to deviant probability. Next, we tested the effect of a non-selective NMDA channel blocker (ketamine, 30 mg/kg and a highly selective NR2B antagonist, CP-101,606 (10 or 30 mg/kg on deviance detection. Ketamine attenuated deviance mainly by increasing the amplitude of the standard ERP. Amplitude and/or latency of several ERP components were also markedly affected. In contrast, CP-101,606 robustly and dose-dependently inhibited the deviant’s N1 amplitude and as a consequence, completely abolished deviance detection. No other ERPs or components were affected. Thus, we report first evidence that NR2B receptors robustly participate in processes of automatic deviance detection in a rodent model. Lastly, our model demonstrates a path forward to test specific pharmacological hypotheses using translational endpoints relevant to aberrant sensory processing in schizophrenia.

  10. Cellular and behavioural profile of the novel, selective neurokinin1 receptor antagonist, vestipitant: a comparison to other agents.

    Science.gov (United States)

    Brocco, Mauricette; Dekeyne, Anne; Mannoury la Cour, Clotilde; Touzard, Manuelle; Girardon, Sylvie; Veiga, Sylvie; de Nanteuil, Guillaume; deJong, Trynke R; Olivier, Berend; Millan, Mark J

    2008-10-01

    This study characterized the novel neurokinin (NK)(1) antagonist, vestipitant, under clinical evaluation for treatment of anxiety and depression. Vestipitant possessed high affinity for human NK(1) receptors (pK(i), 9.4), and potently blocked Substance P-mediated phosphorylation of Extracellular-Regulated-Kinase. In vivo, it occupied central NK(1) receptors in gerbils (Inhibitory Dose(50), 0.11 mg/kg). At similar doses, it abrogated nociception elicited by formalin in gerbils, and blocked foot-tapping and locomotion elicited by the NK(1) agonist, GR73632, in gerbils and guinea pigs, respectively. Further, vestipitant attenuated fear-induced foot-tapping in gerbils, separation-induced distress-vocalizations in guinea pigs, marble-burying behaviour in mice, and displayed anxiolytic actions in Vogel conflict and fear-induced ultrasonic vocalization procedures in rats. These actions were mimicked by CP99,994, L733,060 and GR205,171 which acted stereoselectively vs its less active isomer, GR226,206. In conclusion, vestipitant is a potent NK(1) receptor antagonist: its actions support the utility of NK(1) receptor blockade in the alleviation of anxiety and, possibly, depression.

  11. P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

    Science.gov (United States)

    Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

    2015-09-01

    HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

  12. Two-body wear rate of CAD/CAM resin blocks and their enamel antagonists.

    Science.gov (United States)

    Stawarczyk, Bogna; Özcan, Mutlu; Trottmann, Albert; Schmutz, Felix; Roos, Malgorzata; Hämmerle, Christoph

    2013-05-01

    Computer-aided design and computer-aided manufacturing (CAD/CAM) resins exhibit good mechanical properties and can be used as long-term restorations. The wear rate of such resins and their enamel antagonists is unknown. The purpose of this study was to test and compare the 2-body wear rate of CAD/CAM resin blocks. Wear specimens (N=42, n=6) were made from 5 CAD/CAM resins: ZENO PMMA (ZP), artBloc Temp (AT), Telio CAD (TC), Blanc High-class (HC), CAD-Temp (CT); 1 manually polymerized resin: Integral esthetic press (negative control group, IEP); and 1 glass-ceramic: VITA Mark II (positive control group, VM2). The specimens for the wear resistance were aged in a thermomechanical loading machine (49 N, 1.67 Hz, 5/50°C) with human enamel antagonists. The material loss of all specimens before, during, and after aging was evaluated with a 3DS profilometer. The measured material loss data of all tested groups were statistically evaluated with linear mixed model analysis (a=.05). Manually polymerized resin showed significantly higher material wear (P<.001) than all other tested groups. Glass-ceramic showed significantly lower wear values (P<.001) than CAD/CAM resins ZP, AT, HC, CT, and IES. CAD/CAM resin TC was not significantly different from the positive control group. Glass-ceramic showed the highest enamel wear values (P<.001) of all tested resins. No differences were found in the enamel wear among all resins. The glass-ceramic group showed damage in the form of cracks on the worn enamel surface in 50% of specimens. CAD/CAM resins showed lower wear rates than those conventionally polymerized. Only one CAD/CAM resin, TC, presented material wear values comparable with glass-ceramic. The tested glass-ceramic developed cracks in the enamel antagonist and showed the highest enamel wear values of all other tested groups. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  13. Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

    International Nuclear Information System (INIS)

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-01-01

    Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  14. SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor.

    Science.gov (United States)

    Rinaldi-Carmona, M; Barth, F; Millan, J; Derocq, J M; Casellas, P; Congy, C; Oustric, D; Sarran, M; Bouaboula, M; Calandra, B; Portier, M; Shire, D; Brelière, J C; Le Fur, G L

    1998-02-01

    Based on both binding and functional data, this study introduces SR 144528 as the first, highly potent, selective and orally active antagonist for the CB2 receptor. This compound which displays subnanomolar affinity (Ki = 0.6 nM) for both the rat spleen and cloned human CB2 receptors has a 700-fold lower affinity (Ki = 400 nM) for both the rat brain and cloned human CB1 receptors. Furthermore it shows no affinity for any of the more than 70 receptors, ion channels or enzymes investigated (IC50 > 10 microM). In vitro, SR 144528 antagonizes the inhibitory effects of the cannabinoid receptor agonist CP 55,940 on forskolin-stimulated adenylyl cyclase activity in cell lines permanently expressing the h CB2 receptor (EC50 = 10 nM) but not in cells expressing the h CB1 (no effect at 10 microM). Furthermore, SR 144528 is able to selectively block the mitogen-activated protein kinase activity induced by CP 55,940 in cell lines expressing h CB2 (IC50 = 39 nM) whereas in cells expressing h CB1 an IC50 value of more than 1 microM is found. In addition, SR 144528 is shown to antagonize the stimulating effects of CP 55,940 on human tonsillar B-cell activation evoked by cross-linking of surface Igs (IC50 = 20 nM). In vivo, after oral administration SR 144528 totally displaced the ex vivo [3H]-CP 55,940 binding to mouse spleen membranes (ED50 = 0.35 mg/kg) with a long duration of action. In contrast, after the oral route it does not interact with the cannabinoid receptor expressed in the mouse brain (CB1). It is expected that SR 144528 will provide a powerful tool to investigate the in vivo functions of the cannabinoid system in the immune response.

  15. Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

    Science.gov (United States)

    Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

    2015-01-01

    The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

  16. Does protein binding modulate the effect of angiotensin II receptor antagonists?

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    Marc P Maillard

    2001-03-01

    Full Text Available IntroductionAngiotensin II AT 1-receptor antagonists are highly bound to plasma proteins (≥ 99%. With some antagonists, such as DuP-532, the protein binding was such that no efficacy of the drug could be demonstrated clinically. Whether protein binding interferes with the efficacy of other antagonists is not known. We have therefore investigated in vitro how plasma proteins may affect the antagonistic effect of different AT1-receptor antagonists.MethodsA radio-receptor binding assay was used to analyse the interaction between proteins and the ability of various angiotensin II (Ang II antagonists to block AT1-receptors. In addition, the Biacore technology, a new technique which enables the real-time monitoring of binding events between two molecules, was used to evaluate the dissociation rate constants of five AT1-receptor antagonists from human serum albumin.ResultsThe in vitro AT 1-antagonistic effects of different Ang II receptor antagonists were differentially affected by the presence of human plasma, with rightward shifts of the IC50 ranging from one to several orders of magnitude. The importance of the shift correlates with the dissociation rate constants of these drugs from albumin. Our experiments also show that the way that AT1-receptor antagonists bind to proteins differs from one compound to another. These results suggest that the interaction with plasma proteins appears to modulate the efficacy of some Ang II antagonists.ConclusionAlthough the high binding level of Ang II receptor antagonist to plasma proteins appears to be a feature common to this class of compounds, the kinetics and characteristics of this binding is of great importance. With some antagonists, protein binding interferes markedly with their efficacy to block AT1-receptors.

  17. Standard Model CP-violation and baryon asymmetry

    CERN Document Server

    Gavela, M.B.; Orloff, J.; Pene, O.

    1994-01-01

    Simply based on CP arguments, we argue against a Standard Model explanation of the baryon asymmetry of the universe in the presence of a first order phase transition. A CP-asymmetry is found in the reflection coefficients of quarks hitting the phase boundary created during the electroweak transition. The problem is analyzed both in an academic zero temperature case and in the realistic finite temperature one. The building blocks are similar in both cases: Kobayashi-Maskawa CP-violation, CP-even phases in the reflection coefficients of quarks, and physical transitions due to fermion self-energies. In both cases an effect is present at order $\\alpha_W^2$ in rate. A standard GIM behaviour is found as intuitively expected. In the finite temperature case, a crucial role is played by the damping rate of quasi-particles in a hot plasma, which is a relevant scale together with $M_W$ and the temperature. The effect is many orders of magnitude below what observation requires, and indicates that non standard physics is ...

  18. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nabulsi, Nabeel; Huang Yiyun; Weinzimmer, David; Ropchan, Jim; Frost, James J. [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States); McCarthy, Timothy [Pfizer Global R and D, Groton, CT 06340 (United States); Carson, Richard E.; Ding Yushin [Yale PET Center, Department of Diagnostic Radiology and Psychiatry, Yale University School of Medicine, P.O. Box 208048, New Haven, CT 06520-8048 (United States)

    2010-02-15

    The serotonin 5-HT{sub 1B} receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [{sup 11}C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT{sub 1B} receptor. [{sup 11}C]P943 was synthesized via N-methylation of the precursor with [{sup 11}C]methyl iodide or [{sup 11}C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8{+-}3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP{sub ND}) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT{sub 1B} receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP{sub ND} values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT{sub 1B}/5-HT{sub 1D} antagonist, resulted in reduction of BP{sub ND} values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [{sup 11}C]P943 for 5-HT{sub 1B} receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT{sub 1B} receptor system in humans.

  20. CP violation with an unbroken CP transformation

    Energy Technology Data Exchange (ETDEWEB)

    Ratz, Michael [Department of Physics and Astronomy, University of California,Irvine, California 92697-4575 (United States); Trautner, Andreas [Bethe Center for Theoretical Physics und Physikalisches Institut der Universität Bonn,Nussallee 12, 53115 Bonn (Germany)

    2017-02-21

    A CP conserving SU(3) gauge theory is spontaneously broken to T{sub 7} by the vacuum expectation value (VEV) of a 15-plet. Even though the SU(3)-CP transformation is not broken by the VEV, the theory exhibits physical CP violation in the broken phase. This is because the SU(3)-CP transformation corresponds to the unique order-two outer automorphism of T{sub 7}, which is not a physical CP transformation for the T{sub 7} states, and there is no other possible CP transformation. We explicitly demonstrate that CP is violated by calculating a CP odd decay asymmetry in the broken phase. This scenario provides us with a natural protection for topological vacuum terms, ensuring that θ G{sub μν}G̃{sup μν} is absent even though CP is violated for the physical states of the model.

  1. The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.

    Science.gov (United States)

    Sirohi, Sunil; Dighe, Shveta V; Madia, Priyanka A; Yoburn, Byron C

    2009-08-01

    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.

  2. Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

    Science.gov (United States)

    Herrera, José A; Ward, Christopher S; Wehrens, Xander H T; Neul, Jeffrey L

    2016-11-15

    Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

  3. Multiple blocking sets in PG(n,q), n>=3

    DEFF Research Database (Denmark)

    Barat, Janos

    2004-01-01

    This article discusses minimal s-fold blocking sets B in PG (n, q), q = ph, p prime, q > 661, n > 3, of size |B| > sq + cp q2/3 - (s - 1) (s - 2)/2 (s > min (cp q1/6, q1/4/2)). It is shown that these s-fold blocking sets contain the disjoint union of a collection of s lines and/or Baer subplanes....... To obtain these results, we extend results of Blokhuis–Storme–Szönyi on s-fold blocking sets in PG(2, q) to s-fold blocking sets having points to which a multiplicity is given. Then the results in PG(n, q), n ≥ 3, are obtained using projection arguments. The results of this article also improve results...

  4. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.

    Science.gov (United States)

    Garami, Andras; Shimansky, Yury P; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Romanovsky, Andrej A

    2010-01-27

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.

  5. Characterization of Pseudomonas chlororaphis from Theobroma cacao L. rhizosphere with antagonistic activity against Phytophthora palmivora (Butler).

    Science.gov (United States)

    Acebo-Guerrero, Y; Hernández-Rodríguez, A; Vandeputte, O; Miguélez-Sierra, Y; Heydrich-Pérez, M; Ye, L; Cornelis, P; Bertin, P; El Jaziri, M

    2015-10-01

    To isolate and characterize rhizobacteria from Theobroma cacao with antagonistic activity against Phytophthora palmivora, the causal agent of the black pod rot, which is one of the most important diseases of T. cacao. Among 127 rhizobacteria isolated from cacao rhizosphere, three isolates (CP07, CP24 and CP30) identified as Pseudomonas chlororaphis, showed in vitro antagonistic activity against P. palmivora. Direct antagonism tested in cacao detached leaves revealed that the isolated rhizobacteria were able to reduce symptom severity upon infection with P. palmivora Mab1, with Ps. chlororaphis CP07 standing out as a potential biocontrol agent. Besides, reduced symptom severity on leaves was also observed in planta where cacao root system was pretreated with the isolated rhizobacteria followed by leaf infection with P. palmivora Mab1. The production of lytic enzymes, siderophores, biosurfactants and HCN, as well as the detection of genes encoding antibiotics, the formation of biofilm, and bacterial motility were also assessed for all three rhizobacterial strains. By using a mutant impaired in viscosin production, derived from CP07, it was found that this particular biosurfactant turned out to be crucial for both motility and biofilm formation, but not for the in vitro antagonism against Phytophthora, although it may contribute to the bioprotection of T. cacao. In the rhizosphere of T. cacao, there are rhizobacteria, such as Ps. chlororaphis, able to protect plants against P. palmivora. This study provides a theoretical basis for the potential use of Ps. chlororaphis CP07 as a biocontrol agent for the protection of cacao plants from P. palmivora infection. © 2015 The Society for Applied Microbiology.

  6. CP violation

    CERN Document Server

    1989-01-01

    Contents: CP Phenomenology: Introduction to CP Violation (C Jarlskog); CP-Violation in the K 0 -K 0 -System (K Kleinknecht); The Quark Mixing Matrix, Charm Decays and B Decays (S Stone); The Question of CP Noninvariance - As Seen through the Eyes of Neutral Beauty (I I Bigi et al.); In Search of CP Noninvariance in Heavy Quark Systems (L-L Chau); CP Violation at High Energy e + e - Colliders (J Bernabéu & M B Gavela); CP Violation in the Standard Model with Four Families (A Datta & E A Paschos); CP Effects When Neutrinos are their Own Antiparticles (B Kayser); On Spontaneous CP Violation Trigg

  7. Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration1

    Science.gov (United States)

    Gunes, Zeynep; Zucconi, Adriana; Cioce, Mario; Meola, Annalisa; Pezzanera, Monica; Acali, Stefano; Zampaglione, Immacolata; De Pratti, Valeria; Bova, Luca; Talamo, Fabio; Demartis, Anna; Monaci, Paolo; La Monica, Nicola; Ciliberto, Gennaro; Vitelli, Alessandra

    2011-01-01

    RON belongs to the c-MET family of receptor tyrosine kinases. As its well-known family member MET, RON and its ligand macrophage-stimulating protein have been implicated in the progression and metastasis of tumors and have been shown to be overexpressed in cancer. We generated and tested a large number of human monoclonal antibodies (mAbs) against human RON. Our screening yielded three high-affinity antibodies that efficiently block ligand-dependent intracellular AKT and MAPK signaling. This effect correlates with the strong reduction of ligand-activated migration of T47D breast cancer cell line. By cross-competition experiments, we showed that the antagonistic antibodies fall into three distinct epitope regions of the RON extracellular Sema domain. Notably, no inhibition of tumor growth was observed in different epithelial tumor xenografts in nude mice with any of the antibodies. These results suggest that distinct properties beside ligand antagonism are required for anti-RON mAbs to exert antitumor effects in vivo. PMID:21286376

  8. Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor Antagonists.

    Science.gov (United States)

    Cheng, Han; Lear-Rooney, Calli M; Johansen, Lisa; Varhegyi, Elizabeth; Chen, Zheng W; Olinger, Gene G; Rong, Lijun

    2015-10-01

    Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among the most lethal infectious threats to mankind. Infections by these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates with high mortality rates. Since there is currently no vaccine or antiviral therapy approved for humans, there is an urgent need to develop prophylactic and therapeutic options for use during filoviral outbreaks and bioterrorist attacks. One of the ideal targets against filoviral infection and diseases is at the entry step, which is mediated by the filoviral glycoprotein (GP). In this report, we screened a chemical library of small molecules and identified numerous inhibitors, which are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs, including histamine receptors, 5-HT (serotonin) receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These inhibitors can effectively block replication of both infectious EBOV and MARV, indicating a broad antiviral activity of the GPCR antagonists. The time-of-addition experiment and microscopic studies suggest that GPCR antagonists block filoviral entry at a step following the initial attachment but prior to viral/cell membrane fusion. These results strongly suggest that GPCRs play a critical role in filoviral entry and GPCR antagonists can be developed as an effective anti-EBOV/MARV therapy. Infection of Ebola virus and Marburg virus can cause severe illness in humans with a high mortality rate, and currently there is no FDA-approved vaccine or therapeutic treatment available. The 2013-2015 epidemic in West Africa underscores a lack of our understanding in the infection and pathogenesis of these viruses and the urgency of drug discovery and development. In this study, we have identified numerous inhibitors that are known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs. These inhibitors can effectively block replication of both infectious

  9. IL-1 Receptor Antagonist Chimeric Protein: Context-Specific and Inflammation-Restricted Activation

    NARCIS (Netherlands)

    Rider, P.; Carmi, Y.; Yossef, R.; Guttman, O.; Eini, H.; Azam, T.; Dinarello, C.A.; Lewis, E.C.

    2015-01-01

    Both IL-1alpha and IL-1beta are highly inflammatory cytokines mediating a wide spectrum of diseases. A recombinant form of the naturally occurring IL-1R antagonist (IL-1Ra), which blocks IL-1R1, is broadly used to treat autoimmune and autoinflammatory diseases; however, blocking IL-1 increases the

  10. CP violation in neutral B decays to non-CP-eigenstates

    International Nuclear Information System (INIS)

    Kayser, B.

    1992-01-01

    If CP violation comes from complex phases in the quark mixing matrix, then neutral B decays to CP eigenstates will exhibit large, cleanly-predicted CP-violating effects. The authors show that the same is true of neutral B decays to several types of ''near-CP-eigenstates.'' By experimentally studying the latter decays as well as those to the CP eigenstates, one will be able to obtain more definitive information on CP violation from a given number of B mesons

  11. Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

    Science.gov (United States)

    Sforna, Luigi; D'Adamo, Maria Cristina; Servettini, Ilenio; Guglielmi, Luca; Pessia, Mauro; Franciolini, Fabio

    2015-01-01

    Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current (IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation (IDRKs). PMID:25652918

  12. The Relative Potency of Inverse Opioid Agonists and a Neutral Opioid Antagonist in Precipitated Withdrawal and Antagonism of Analgesia and Toxicity

    OpenAIRE

    Sirohi, Sunil; Dighe, Shveta V.; Madia, Priyanka A.; Yoburn, Byron C.

    2009-01-01

    Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was exa...

  13. Giant CP stars

    International Nuclear Information System (INIS)

    Loden, L.O.; Sundman, A.

    1989-01-01

    This study is part of an investigation of the possibility of using chemically peculiar (CP) stars to map local galactic structure. Correct luminosities of these stars are therefore crucial. CP stars are generally regarded as main-sequence or near-main-sequence objects. However, some CP stars have been classified as giants. A selection of stars, classified in literature as CP giants, are compared to normal stars in the same effective temperature interval and to ordinary 'non giant' CP stars. There is no clear confirmation of a higher luminosity for 'CP giants', than for CP stars in general. In addition, CP characteristics seem to be individual properties not repeated in a component star or other cluster members. (author). 50 refs., 5 tabs., 3 figs

  14. CpG + CpNpG Analysis of Protein-Coding Sequences from Tomato

    DEFF Research Database (Denmark)

    Hobolth, Asger; Nielsen, Rasmus; Wang, Ying

    2006-01-01

    We develop codon-based models for simultaneously inferring the mutational effects of CpG and CpNpG methylation in coding regions. In a data set of 369 tomato genes, we show that there is very little effect of CpNpG methylation but a strong effect of CpG methylation affecting almost all genes. We...... further show that the CpNpG and CpG effects are largely uncorrelated. Our results suggest different roles of CpG and CpNpG methylation, with CpNpG methylation possibly playing a specialized role in defense against transposons and RNA viruses....

  15. Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists

    DEFF Research Database (Denmark)

    Ebert, B; Thorkildsen, C; Andersen, S

    1998-01-01

    Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors in the development and maintainance of neuropathic pain. In neuropathic pain, there is generally involved a presumed opioid-insensitive component, which apparently can be blocked by NMDA receptor antagonists. However...... for the NMDA receptor antagonism of these compounds and its relevance for clinical pain treatment; an overview of structure-activity relationships for the relevant opioids as noncompetitive NMDA receptor antagonists also is given. It is concluded that although the finding that some opioids are weak...

  16. Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells

    International Nuclear Information System (INIS)

    Wu, Xiaoqin; Zhao, Bin; Cheng, Yahui; Yang, Yang; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Zhang, Lei; Lv, Xiongwen; Li, Jun

    2015-01-01

    Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G 0 /G 1 cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells. - Highlights: • MeCP2 plays a key role in the proliferation of human HCC cells. • Melittin reduces MeCP2 expression in vitro. • Melittin induces G 0 /G 1 cell cycle arrest in SMMC-7721 cells. • MeCP2 modulates the Shh signaling pathway in SMMC-7721 cells. • Melittin blocks the Shh signaling pathway in SMMC-7721 cells.

  17. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  18. Cytosine methylation at CpCpG sites triggers accumulation of non-CpG methylation in gene bodies

    OpenAIRE

    Zabet, NR; Catoni, Marco; Prischi, F; Paszkowski, Jerzy Waclaw

    2017-01-01

    Methylation of cytosine is an epigenetic mark involved in the regulation of transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly in CpGs but in plants non-CpG methylation (in the CpHpG or CpHpH contexts, where H is A, C or T) is also present and is associated with the transcriptional silencing of transposable elements. In addition, CpG methylation is found in coding regions of active genes. In the absence of the demethylas...

  19. Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks

    Science.gov (United States)

    Schäffer, Lauge; Brissette, Renee E.; Spetzler, Jane C.; Pillutla, Renuka C.; Østergaard, Søren; Lennick, Michael; Brandt, Jakob; Fletcher, Paul W.; Danielsen, Gillian M.; Hsiao, Ku-Chuan; Andersen, Asser S.; Dedova, Olga; Ribel, Ulla; Hoeg-Jensen, Thomas; Hansen, Per Hertz; Blume, Arthur J.; Markussen, Jan; Goldstein, Neil I.

    2003-01-01

    Insulin is thought to elicit its effects by crosslinking the two extracellular α-subunits of its receptor, thereby inducing a conformational change in the receptor, which activates the intracellular tyrosine kinase signaling cascade. Previously we identified a series of peptides binding to two discrete hotspots on the insulin receptor. Here we show that covalent linkage of such peptides into homodimers or heterodimers results in insulin agonists or antagonists, depending on how the peptides are linked. An optimized agonist has been shown, both in vitro and in vivo, to have a potency close to that of insulin itself. The ability to construct such peptide derivatives may offer a path for developing agonists or antagonists for treatment of a wide variety of diseases. PMID:12684539

  20. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: wangmw@mail.shcnc.ac.cn [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  1. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    International Nuclear Information System (INIS)

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-01

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K i = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  2. CP violation

    International Nuclear Information System (INIS)

    Gronau, M.

    1995-01-01

    We review the present status of the Standard Model of CP violation, which is based on a complex phase in the Cabibbo-Kobayashi-Maskawa (CKM) matrix. So far CP violation has been observed only in K 0 -K 0 mixing, consistent with a sizable phase. The implications of future CP nonconserving measusrements in K and B decays are discussed within the model. Direct CP violation in K→2π may be observed in the near future, however this would not be a powerful test of the model. B decays provide a wide variety of CP asymmetry measurements, which can serve as precise tests of the Standard Model in cases where the asymmetry is cleanly related to phases of CKM matrix elements. Some of the most promising cases are discussed. ((orig.))

  3. Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells

    Science.gov (United States)

    Aguirre-Alvarado, Charmina; Segura-Cabrera, Aldo; Velázquez-Quesada, Inés; Hernández-Esquivel, Miguel A.; García-Pérez, Carlos A.; Guerrero-Rodríguez, Sandra L.; Ruiz, Angel J.; Rodríguez-Moreno, Andrea; Pérez-Tapia, Sonia M.; Velasco-Velázquez, Marco A.

    2016-01-01

    CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 and 11,421 molecules. Drugs that performed best in docking were examined in molecular dynamics simulations, identifying etoposide as a potential CD44 antagonist. Ligand competition and cell adhesion assays in MDA-MB-231 cells demonstrated that etoposide decreased cell binding to HA as effectively as a blocking antibody. Etoposide-treated MDA-MB-231 cells developed an epithelial morphology; increased their expression of E-cadherin; and reduced their levels of EMT-associated genes and cell migration. By gene expression analysis, etoposide reverted an EMT signature similarly to CD44 knockdown, whereas other topoisomerase II (TOP2) inhibitors did not. Moreover, etoposide decreased the proportion of CD44+/CD24− cells, lowered chemoresistance, and blocked mammosphere formation. Our data indicate that etoposide blocks CD44 activation, impairing key cellular functions that drive malignancy, thus rendering it a candidate for further translational studies and a potential lead compound in the development of new CD44 antagonists. PMID:27009862

  4. Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds.

    Science.gov (United States)

    Macfarlane, D E; Manzel, L

    1998-02-01

    Phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune responses. We report that quinacrine, chloroquine, and structurally related compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231 murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI 231. They also inhibit IL-6 synthesis and thymidine uptake by human unfractionated PBMC induced by CpG-ODN. The compounds did not inhibit LPS-induced responses. Half-maximal inhibition required 10 nM quinacrine or 100 nM chloroquine. Inhibition was noncompetitive with respect to CpG-ODN. Quinine, quinidine, and primaquine were much less powerful. Quinacrine was effective even when added after the CpG-ODN. Near-toxic concentrations of ammonia plus bafilomycin A1 (used to inhibit vesicular acidification) did not reduce the efficacy of the quinacrine, but the effects of both quinacrine and chloroquine were enhanced by inhibition of the multidrug resistance efflux pump by verapamil. Agents that bind to DNA, including propidium iodide, Hoechst dye 33258, and coralyne chloride did not inhibit CpG-ODN effect, nor did 4-bromophenacyl bromide, an inhibitor of phospholipase A2. Examination of the structure-activity relationship of seventy 4-aminoquinoline and 9-aminoacridine analogues reveals that increased activity was conferred by bulky hydrophobic substituents on positions 2 and 6 of the quinoline nucleus. No correlation was found between published antimalarial activity and ability to block CpG-ODN-induced effects. These results are discussed in the light of the ability of quinacrine and chloroquine to induce remission of rheumatoid arthritis and lupus erythematosus.

  5. Antibodies to the extracellular pore loop of TRPM8 act as antagonists of channel activation.

    Directory of Open Access Journals (Sweden)

    Silke Miller

    Full Text Available The mammalian transient receptor potential melastatin channel 8 (TRPM8 is highly expressed in trigeminal and dorsal root ganglia. TRPM8 is activated by cold temperature or compounds that cause a cooling sensation, such as menthol or icilin. TRPM8 may play a role in cold hypersensitivity and hyperalgesia in various pain syndromes. Therefore, TRPM8 antagonists are pursued as therapeutics. In this study we explored the feasibility of blocking TRPM8 activation with antibodies. We report the functional characterization of a rabbit polyclonal antibody, ACC-049, directed against the third extracellular loop near the pore region of the human TRPM8 channel. ACC-049 acted as a full antagonist at recombinantly expressed human and rodent TRPM8 channels in cell based agonist-induced 45Ca2+ uptake assays. Further, several poly-and monoclonal antibodies that recognize the same region also blocked icilin activation of not only recombinantly expressed TRPM8, but also endogenous TRPM8 expressed in rat dorsal root ganglion neurons revealing the feasibility of generating monoclonal antibody antagonists. We conclude that antagonist antibodies are valuable tools to investigate TRPM8 function and may ultimately pave the way for development of therapeutic antibodies.

  6. Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiaoqin; Zhao, Bin; Cheng, Yahui; Yang, Yang; Huang, Cheng; Meng, Xiaoming; Wu, Baoming; Zhang, Lei; Lv, Xiongwen; Li, Jun, E-mail: xqwu01@foxmail.com

    2015-10-01

    Hepatocellular carcinoma (HCC) has a high mortality rate worldwide and still remains to be a noticeable public health problem. Therefore, new remedies are urgently needed. Melittin, a major component of bee venom, is known to suppress cell growth in various cancers including HCC. However, the mechanism of the anticancer effect of melittin on HCC has not been fully elucidated. It has been reported that Methyl-CpG binding protein 2 (MeCP2) plays a key role in tumor proliferation, apoptosis, migration and invasion. In the present study, we found the high expression of MeCP2 in human HCC tissues and in the SMMC-7721 cell line. MeCP2 silencing inhibited cell proliferation, while over-expression of MeCP2 promoted cell growth in SMMC-7721 cells. It indicates that MeCP2 may be an attractive target for human HCC. We further found that melittin could inhibit cell proliferation by reducing MeCP2 expression in vitro. Interestingly, the inhibitory effect of melittin on cell proliferation was due to a delay in G{sub 0}/G{sub 1} cell cycle progression, without influencing cell apoptosis. Next, we investigated the potential molecular mechanisms and found that MeCP2 could modulate Shh signaling in SMMC-7721 cells. Further study indicates that melittin may induce the demethylation of PTCH1 promoter, resulting in the increased expression of PTCH1. Furthermore, the expression of Shh and GLI1 was significantly lowered upon treatment of melittin. These results suggest that melittin can block Shh signaling in vitro. In short, these results indicate that melittin inhibits cell proliferation by down-regulating MeCP2 through Shh signaling in SMMC-7721 cells. - Highlights: • MeCP2 plays a key role in the proliferation of human HCC cells. • Melittin reduces MeCP2 expression in vitro. • Melittin induces G{sub 0}/G{sub 1} cell cycle arrest in SMMC-7721 cells. • MeCP2 modulates the Shh signaling pathway in SMMC-7721 cells. • Melittin blocks the Shh signaling pathway in SMMC-7721 cells.

  7. Non-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancer

    DEFF Research Database (Denmark)

    Oster, Bodil; Linnet, Lene; Christensen, Lise Lotte

    2012-01-01

    Gene silencing by DNA hypermethylation of CpG islands is a well-characterized phenomenon in cancer. The effect of hypomethylation in particular of non-CpG island genes is much less well described. By genome-wide screening, we identified 105 genes in microsatellite stable (MSS) colorectal adenocar......Gene silencing by DNA hypermethylation of CpG islands is a well-characterized phenomenon in cancer. The effect of hypomethylation in particular of non-CpG island genes is much less well described. By genome-wide screening, we identified 105 genes in microsatellite stable (MSS) colorectal...... of non-CpG island-associated promoters deregulate gene expression nearly as frequent as do CpG-island hypermethylation. The hypomethylation of SRPX2 is focal and not part of a large block. Furthermore, it often translates to an increased expression level, which may be modulated by miR-149....

  8. CP Violation course

    CERN Multimedia

    CERN. Geneva HR-RFA

    2006-01-01

    The lecture introduces the concepts and phenomena of matter-antimatter symmetry violation, so-called "CP" violation. The lecture is organized in four courses, the first being devoted to a historical overview and an introduction into fundamental discrete symmetries. The second course introduces the most compelling CP-violating phenomena, and presents the first experimental discovery of CP violation in the neutral kaon system. The third course discusses how CP violation is beautifully incorporated into the Standard Model of particle interactions, and how modern B-meson "factories" provide precise tests of this picture. Finally, the fourth and last course introduces CP violation and the genesis of our matter world.

  9. β-TrCP1 Is a Vacillatory Regulator of Wnt Signaling.

    Science.gov (United States)

    Long, Marcus John; Lin, Hong-Yu; Parvez, Saba; Zhao, Yi; Poganik, Jesse Richard; Huang, Paul; Aye, Yimon

    2017-08-17

    Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the β-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that Nrf2/AR strongly inhibits β-catenin/Wnt. The magnitude and mechanism of this negative regulation are dependent on the direct interaction between β-catenin N terminus and β-TrCP1 (an antagonist of both Nrf2 and β-catenin), and independent of binding between Nrf2 and β-TrCP1. Intriguingly, β-catenin positively regulates AR. Because AR is a negative regulator of Wnt regardless of β-catenin N terminus, this switch of function is likely sufficient to establish a new Wnt/AR equilibrium during tumorigenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effects of the noncompetitive N-methyl-d-aspartate receptor antagonists ketamine and MK-801 on pain-stimulated and pain-depressed behaviour in rats.

    Science.gov (United States)

    Hillhouse, T M; Negus, S S

    2016-09-01

    Pain is a significant public health concern, and current pharmacological treatments have problematic side effects and limited effectiveness. N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have emerged as one class of candidate treatments for pain because of the significant contribution of glutamate signalling in nociceptive processing. This study compared effects of the NMDA receptor antagonists ketamine and MK-801 in assays of pain-stimulated and pain-depressed behaviour in rats. The nonsteroidal anti-inflammatory drug ketoprofen was examined for comparison as a positive control. Intraperitoneal injection of dilute acid served as an acute visceral noxious stimulus to stimulate a stretching response or depress intracranial self-stimulation (ICSS) in male Sprague-Dawley rats. Ketamine (1.0-10.0 mg/kg) blocked acid-stimulated stretching but failed to block acid-induced depression of ICSS, whereas MK-801 (0.01-0.1 mg/kg) blocked both acid-stimulated stretching and acid-induced depression of ICSS. These doses of ketamine and MK-801 did not alter control ICSS in the absence of the noxious stimulus; however, higher doses of ketamine (10 mg/kg) and MK-801 (0.32 mg/kg) depressed all behaviour. Ketoprofen (1.0 mg/kg) blocked both acid-induced stimulation of stretching and depression of ICSS without altering control ICSS. These results support further consideration of NMDA receptor antagonists as analgesics; however, some NMDA receptor antagonists are more efficacious at attenuating pain-depressed behaviours. NMDA receptor antagonists produce dissociable effects on pain-depressed behaviour. Provides evidence that pain-depressed behaviours should be considered and evaluated when determining the antinociceptive effects of NMDA receptor antagonists. © 2016 European Pain Federation - EFIC®

  11. LHCb : Measuring $CP$ violation with $\\Delta A_{CP}$ at LHCb

    CERN Multimedia

    Pearce, A

    2014-01-01

    Measurements are presented of direct $CP$ violation in $D^{0}$ meson decays in LHCb, using the $\\Delta A_{CP}$ technique, and a proposal is outlined to make similar measurements in the decays of the charmed baryon $\\Lambda_{c}^{+}$. The motivations for use of the $\\Delta A_{CP}$ method are discussed, along with the current results and future prospects.

  12. Thermoresponsive Poly(2-Oxazoline) Molecular Brushes by Living Ionic Polymerization: Modulation of the Cloud Point by Random and Block Copolymer Pendant Chains

    KAUST Repository

    Zhang, Ning

    2012-08-10

    Molecular brushes (MBs) of poly(2-oxazoline)s were prepared by living anionic polymerization of 2-isopropenyl-2-oxazoline to form the backbone and living cationic ring-opening polymerization of 2-n-propyl-2-oxazoline and 2-methyl-2-oxazoline to form random and block copolymers. Their aqueous solutions displayed a distinct thermoresponsive behavior as a function of the side-chain composition and sequence. The cloud point (CP) of MBs with random copolymer side chains is a linear function of the hydrophilic monomer content and can be modulated in a wide range. For MBs with block copolymer side chains, it was found that the block sequence had a strong and surprising effect on the CP. While MBs with a distal hydrophobic block had a CP at 70 °C, MBs with hydrophilic outer blocks already precipitated at 32 °C. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. CP violation in B decay

    OpenAIRE

    Yamamoto, Hitoshi

    2001-01-01

    We review the physics of CP violation in B decays. After introducing the CKM matrix and how it causes CP violation, we cover three types of CP violation that can occur in B decays: CP violation in mixing, CP violation by mixing-decay interference, and CP violation in decay.

  14. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2008-01-01

    Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  15. Double dissociation of spike timing-dependent potentiation and depression by subunit-preferring NMDA receptor antagonists in mouse barrel cortex.

    Science.gov (United States)

    Banerjee, Abhishek; Meredith, Rhiannon M; Rodríguez-Moreno, Antonio; Mierau, Susanna B; Auberson, Yves P; Paulsen, Ole

    2009-12-01

    Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation (t-LTP) requires postsynaptic NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4-to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit-containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit-preferring antagonist blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead. These data demonstrate an NMDA receptor subunit-dependent double dissociation of t-LTD and t-LTP mechanisms at layer 4-to-layer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

  16. The effects of the selective 5-HT(2C) receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats.

    Science.gov (United States)

    Strong, Paul V; Greenwood, Benjamin N; Fleshner, Monika

    2009-05-01

    Rats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites. Blocking 5-HT(2C) receptors in the face of an increase in serotonin can alleviate anxiety behaviors in some animal models. However, specific 5-HT receptor subtypes involved in learned helplessness remain unknown. The current experiments tested the hypothesis that 5-HT(2C) receptor activation is necessary and sufficient for the expression of learned helplessness. The selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) administered i.p. to adult male Fischer 344 rats prior to shuttle box behavioral testing, but not before stress, blocked stress-induced deficits in escape learning but had no effect on the exaggerated shock-elicited freezing. The selective 5-HT(2C) receptor agonist CP-809101 was sufficient to produce learned helplessness-like behaviors in the absence of prior stress and these effects were blocked by pretreatment with SB 242084. Results implicate the 5-HT(2C) receptor subtype in mediating the shuttle box escape deficits produced by exposure to uncontrollable stress and suggest that different postsynaptic 5-HT receptor subtypes underlie the different learned helplessness behaviors.

  17. CP violation and modular symmetries

    International Nuclear Information System (INIS)

    Dent, Thomas

    2001-01-01

    We reconsider the origin of CP violation in fundamental theory. Existing string models of spontaneous CP violation make ambiguous predictions, due to the arbitrariness of CP transformation and the apparent noninvariance of the results under duality. We find a modular CP invariance condition, applicable to any predictive model of spontaneous CP violation, which circumvents these problems; it strongly constrains CP violation by heterotic string moduli. The dilaton is also evaluated as a source of CP violation, but is likely experimentally excluded. We consider the prospects for explaining CP violation in strongly coupled strings and brane worlds

  18. CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

    Science.gov (United States)

    He, Xingxing; Kong, Xinjuan; Yan, Junwei; Yan, Jingjun; Zhang, Yunan; Wu, Qian; Chang, Ying; Shang, Haitao; Dou, Qian; Song, Yuhu; Liu, Fang

    2015-03-01

    Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.

  19. The comparison of antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide (CP) and sulfated CP.

    Science.gov (United States)

    Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

    2015-02-01

    Codonopsis pilosula polysaccharide (CP) was extracted, purified and modified by chlorosulfonic acid-pyridine method to obtain a sulfated CP (sCP). Their antioxidative activities in vitro were compared through the free radical-scavenging test. The results demonstrated that the scavenging capabilities of sCP were significantly stronger than those of CP. In vivo test, the mice hepatic injury model was prepared by BCG/LPS method, then administrated respectively with sCP and CP at three dosages, the biochemical indexes in serum, antioxidative indexes in liver homogenate and histopathological change in liver of the mice were compared. The results showed that in high (200mg/kg) and middle (150mg/kg) dosages of sCP groups, the contents of ALT, AST and TNF-α in serum and MDA in liver homogenate were significantly lower than those in the model group and numerically lower than those in the CP groups, the activities of SOD and GSH-Px in liver homogenate were significantly higher than those in the model group and numerically higher than those in the CP groups. In the model group there were obvious pathological changes in the liver, while in the sCP groups were near normal. These results indicate that sCP and CP possess antioxidative activity in vitro and in vivo, the activity of sCP is stronger than that of CP and sulfation modification can enhance the antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons

    Science.gov (United States)

    Sampathkumar, Charanya; Wu, Yuan-Ju; Vadhvani, Mayur; Trimbuch, Thorsten; Eickholt, Britta; Rosenmund, Christian

    2016-01-01

    Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. DOI: http://dx.doi.org/10.7554/eLife.19374.001 PMID:27782879

  1. Calcium antagonistic effects of Chinese crude drugs: Preliminary investigation and evaluation by 45Ca

    International Nuclear Information System (INIS)

    Liu Ning; Yang Yuanyou; Mo Shangwu; Liao Jiali; Jin Jiannan

    2005-01-01

    Coronary and other diseases in cardiac or brain blood vessels are considered to be due to the excessive influx of Ca 2+ into cytoplasm. If Ca 2+ channels in cell membrane are blocked by medicines or other substances with considerable calcium antagonistic effects, these diseases might be cured or controlled. The influence of some Chinese crude drugs, including Crocus sativus, Carthamus tinctorius, Ginkgo biloba and Bulbus allii macrostemi on Ca 2+ influx in isolated rat aortas was investigated by using 45 Ca as a radioactive tracer, and their calcium antagonistic effects were evaluated. It can be noted that Ca 2+ uptake in isolated rat aorta rings in normal physiological status was not markedly altered by these drugs, whereas the Ca 2+ influxes induced by norepinephrine of 1.2 μmol/L and KCl of 100 mmol/L were significantly inhibited by Crocus, Carthamus and Bulbus in a concentration-dependent manner, but not by Ginkgo. The results show that extracellular Ca 2+ influx through receptor-operated Ca 2+ channels and potential-dependent Ca 2+ channels can be blocked by Crocus, Carthamus and Bulbus. This implies that these Chinese crude drugs have obvious calcium antagonistic effects

  2. CP-Recursion in Danish

    DEFF Research Database (Denmark)

    Nyvad, Anne Mette; Christensen, Ken Ramshøj; Vikner, Sten

    2017-01-01

    Based on data from extraction, embedded V2, and complementizer stacking, this paper proposes a cP/CP-analysis of CP-recursion in Danish. Because extraction can be shown to be possible from relative clauses, wh-islands, and adverbial clauses, and given that long extraction is successive......-cyclic, an extra specifier position has to be available as an escape hatch. Consequently, such extractions require a CP-recursion analysis, as has been argued for embedded V2 and for complementizer stacking. Given that CP-recursion in embedded V2 clauses does not allow extraction, whereas other types of CP......-recursion do, we suggest that embedded V2 is fundamentally different, in that main clause V2 and embedded V2 involve a CP (“big CP”), whereas all other clausal projections above IP are instances of cP (“little cP”). The topmost “little” c° has an occurrence feature that enables extraction but bars spell...

  3. Synthesis and oxidation of CpIrIII compounds: functionalization of a Cp methyl group.

    Science.gov (United States)

    Park-Gehrke, Lisa S; Freudenthal, John; Kaminsky, Werner; Dipasquale, Antonio G; Mayer, James M

    2009-03-21

    [CpIrCl(2)](2) () and new CpIr(III)(L-L)X complexes (L-L = N-O or C-N chelating ligands; X = Cl, I, Me) have been prepared and their reactivity with two-electron chemical oxidants explored. Reaction of with PhI(OAc)(2) in wet solvents yields a new chloro-bridged dimer in which each of the Cp ligands has been singly acetoxylated to form [Cp(OAc)Ir(III)Cl(2)](2) () (Cp(OAc) = eta(5)-C(5)Me(4)CH(2)OAc). Complex and related carboxy- and alkoxy-functionalized Cp(OR) complexes can also be prepared from plus (PhIO)(n) and ROH. [Cp(OAc)Ir(III)Cl(2)](2) () and the methoxy analogue [Cp(OMe)Ir(III)Cl(2)](2) () have been structurally characterized. Treatment of [CpIrCl(2)](2) () with 2-phenylpyridine yields CpIr(III)(ppy)Cl () (ppy = cyclometallated 2-phenylpyridyl) which is readily converted to its iodide and methyl analogues CpIr(III)(ppy)I and CpIr(III)(ppy)Me (). CpIr(III) complexes were also prepared with N-O chelating ligands derived from anthranilic acid (2-aminobenzoic acid) and alpha-aminoisobutyric acid (H(2)NCMe(2)COOH), ligands chosen to be relatively oxidation resistant. These complexes and were reacted with potential two-electron oxidants including PhI(OAc)(2), hexachlorocyclohexadienone (C(6)Cl(6)O), N-fluoro-2,4,6-trimethylpyridinium (Me(3)pyF(+)), [Me(3)O]BF(4) and MeOTf (OTf = triflate, CF(3)SO(3)). Iridium(V) complexes were not observed or implicated in these reactions, despite the similarity of the potential products to known CpIr(V) species. The carbon electrophiles [Me(3)O]BF(4) and MeOTf appear to react preferentially at the N-O ligands, to give methyl esters in some cases. Overall, the results indicate that Cp is not inert under oxidizing conditions and is therefore not a good supporting ligand for oxidizing organometallic complexes.

  4. CP violation and modular symmetries

    OpenAIRE

    Dent, Thomas

    2001-01-01

    We reconsider the origin of CP violation in fundamental theory. Existing string models of spontaneous CP violation make ambiguous predictions, due to the arbitrariness of CP transformation and the apparent non-invariance of the results under duality. We find an unambiguous modular CP invariance condition, applicable to predictive models of spontaneous CP violation, which circumvents these problems; it strongly constrains CP violation by heterotic string moduli. The dilaton is also evaluated a...

  5. CP violation in B decays

    International Nuclear Information System (INIS)

    Kayser, B.

    1990-01-01

    The study of CP-violating effects in B decays will be a good test of whether CP violation is caused by the known weak interaction. If this is its origin, then large, cleanly-predicted CP-violating effects are expected in certain neutral B decays to hadronic CP eigenstates. The phenomenology of CP violation in the B system is reviewed, and the genesis of these large effects is explained. In this it is shown that large, cleanly-predicted effects are also expected in some decays to states which are not CP eigenstates. The combined study of the latter decays and those to CP eigenstates may make it possible to obtain a statistically-significant CP-violating signal with fewer B mesons that would otherwise be required

  6. A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

    Science.gov (United States)

    David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

    2014-11-01

    Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

  7. The structure of completely positive matrices according to their CP-rank and CP-plus-rank

    NARCIS (Netherlands)

    Dickinson, Peter James Clair; Bomze, Immanuel M.; Still, Georg J.

    2015-01-01

    We study the topological properties of the cp-rank operator $\\mathrm{cp}(A)$ and the related cp-plus-rank operator $\\mathrm{cp}^+(A)$ (which is introduced in this paper) in the set $\\mathcal{S}^n$ of symmetric $n\\times n$-matrices. For the set of completely positive matrices, $\\mathcal{CP}^n$, we

  8. CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

    Science.gov (United States)

    Zhang, Yang; Li, Xiang-Xiang; Ma, Yuan; Xu, Jie; Zhao, Li-Na; Qian, Xue-Feng; Zhang, Xian-Feng; Shi, Jin-Fang; Han, Qing-Zhen

    2017-12-04

    Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

  9. CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.

    Science.gov (United States)

    He, Xing-Xing; Zhang, Yu-Nan; Yan, Jun-Wei; Yan, Jing-Jun; Wu, Qian; Song, Yu-Hu

    2016-01-01

    The tumor suppressor p53 is one of the most frequently mutated genes in hepatocellular carcinoma (HCC). Previous studies demonstrated that CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in tumor cells. However, the research on the application of CP-31398 to liver cancer has not been reported. Here, we investigated the effects of CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In tumor xenografts developed by PLC/PRF/5 cells, the inhibition of tumor growth by CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that CP-31398 inhibited the growth of p53-mutated liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that CP-31398 blocked the growth of xenografts tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.

  10. Continuous vs. blocks of physiotherapy for motor development in children with cerebral palsy and similar syndromes: A prospective randomized study.

    Science.gov (United States)

    Brunner, Anne-Louise; Rutz, Erich; Juenemann, Stephanie; Brunner, Reinald

    2014-12-01

    To determine whether physiotherapy is more effective when applied in blocks or continuously in children with cerebral palsy (CP). A prospective randomized cross-over design study compared the effect of regular physiotherapy (baseline) with blocks of physiotherapy alternating with no physiotherapy over one year. Thirty-nine institutionalized children with CP and clinically similar syndromes (6-16 years old, Gross Motor Function Classification Scale II-IV) were included. During the first scholastic year, group A received regular physiotherapy, group B blocks of physiotherapy and vice versa in the second year. The Gross Motor Function Measure 66 (GMFM-66) was the outcome measure. Thirteen children in each group completed the study. GMFM-66 improved (p Physiotherapy may be more effective when provided regularly rather than in blocks.

  11. Trimethylsilylcyclopentadienyl (cp{sup '}) uranium chemistry. Synthetic and structural studies of Cp{sup '}{sub 4}U and Cp{sup '}{sub 3}UX (X = Cl, I, Me)

    Energy Technology Data Exchange (ETDEWEB)

    Windorff, Cory J.; MacDonald, Matthew R.; Ziller, Joseph W.; Evans, William J. [Department of Chemistry, University of California, Irvine, CA (United States)

    2017-12-13

    Cp{sup '}{sub 4}U (Cp{sup '} = C{sub 5}H{sub 4}SiMe{sub 3}) was synthesized from: (a) KCp{sup '} and [Cp{sup '}{sub 3}U(THF)][BPh{sub 4}]; (b) Cp{sup '}{sub 3}U and Cp{sup '}{sub 2}Pb; and (c) [K(2.2.2-cryptand)][Cp{sup '}{sub 4}U] and AgBPh{sub 4}. The compound was identified by X-ray crystallography as a rare example of a structurally-characterized tetrakis(cyclopentadienyl)U{sup IV} complex. For comparison, the corresponding Th complex, Cp{sup '}{sub 4}Th, was isolated from the direct combination of ThBr{sub 4}(THF){sub 4} with excess KCp{sup '}. During the preparation of Cp{sup '}{sub 3}UMe, the precursor of the [Cp{sup '}{sub 3}U(THF)][BPh{sub 4}] reagent used above, it was discovered that the reaction of Cp{sup '}{sub 3}UCl and MeLi gives a mixture of Cp{sup '}{sub 3}UMe and Cp{sup '}{sub 3}UCl that can co-crystallize better than Cp{sup '}{sub 3}UMe in pure form. The Cp'{sub 3}UMe/Cp{sup '}{sub 3}UCl mixture forms single crystals suitable for X-ray crystallography and provides a new way to characterize the oil, Cp{sup '}{sub 3}UMe. Cp{sup '}{sub 3}UCl and Cp{sup '}{sub 3}UI were also crystallographically characterized for comparison with the Cp{sup '}{sub 3}UMe/Cp{sup '}{sub 3}UCl crystals. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. CP violation

    Indian Academy of Sciences (India)

    We have just entered a period during which we expect considerable progress toward understanding CP violation. Here we review what we have learnt so far, and what is to be expected in the near future. To do this we cover the foundation of CP violation at a level which can be understood by physicists who are not working ...

  13. Phenomenology of CP violation

    International Nuclear Information System (INIS)

    Ecker, G.

    1987-01-01

    A short survey of the theoretical status of CP violation is presented. The Standart Model is confronted with the present experimental situation. Possible future tests of our notions of CP violation are discussed, concentrating on rare K decays. Other promising reactions such as B decays are briefly reviewed. Among alternative models of CP violation, multi-Higgs extensions of the Standart Model, left-right symmetric gauge theories and minimal SUSY models are discussed. Finally, the relevance of generalized CP invariance is emphasized. 64 refs., 7 figs. (Author)

  14. CP violation

    CERN Multimedia

    CERN. Geneva

    1999-01-01

    In the first two lectures, CP violation in the K system is pedagogically reviewed: its manifestations in the neutral K meson systems, in rare K meson decays and in decays of charged K mesons, and results from classical and current experiments, are discussed. In the third lecture, CP Violation in the B system and the forthcoming experimental tests will be discussed.

  15. In vitro H1-receptor antagonist activity of methanolic extract of tuber of Stephania glabra

    Directory of Open Access Journals (Sweden)

    Nisar Ahmad Khan

    2010-06-01

    Full Text Available In the present study, methanolic extract of tuber of Stephania glabra was evaluated for H1-bloker activity by employing in vitro screening models of guinea pig ileum and goat tracheal chain preparation. Goat isolated trachea and guinea pig ileum contracted to histamine in a dose-dependent manner while chlorpheniramine blocked this effect. The methanolic extract produced significant dose-dependent H1-receptor antagonist activity by blocking histamine-induced contraction.

  16. Is CP violation maximal

    International Nuclear Information System (INIS)

    Gronau, M.

    1984-01-01

    Two ambiguities are noted in the definition of the concept of maximal CP violation. The phase convention ambiguity is overcome by introducing a CP violating phase in the quark mixing matrix U which is invariant under rephasing transformations. The second ambiguity, related to the parametrization of U, is resolved by finding a single empirically viable definition of maximal CP violation when assuming that U does not single out one generation. Considerable improvement in the calculation of nonleptonic weak amplitudes is required to test the conjecture of maximal CP violation. 21 references

  17. CP violation in gauge theories

    International Nuclear Information System (INIS)

    Escobar, C.O.

    Some aspects of CP violation in gauge theories are reviewed. The topics covered include a discussion of the Kobayashi-Maskawa six-quarks model, models of soft- CP violation (extended Higgs sector), the strong CP problem and finally some speculations relating CP violation and magnetic charges in non-abelian gauge theories. (Author) [pt

  18. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    Science.gov (United States)

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  19. CP-even and CP-odd transverse polarization of the electron in muon decay

    International Nuclear Information System (INIS)

    Kuznetsov, A.

    1981-01-01

    A model of the weak interaction which contains intermediate vector bosons of the most general form and which admits CP violation in muon decay is used to calculate the CP-even and CP-odd transverse polarization of the μ-decay electrons with inclusion of radiative corrections. It is shown that these corrections are important only at the beginning of the spectrum, and their contribution reduces the observed effects of the transverse polarization. The transverse polarization grows appreciably at electron energies close to the maximum energy and at small emission angles. It is expedient to search for the CP-even and CP-odd transverse polarization of the electrons at energies E/sub e/ = 0.975E/sup max//sub e/ and emission angles theta = 25--35 0

  20. Measuring $CP$ violation with $\\Delta A_{CP}$ at LHCb

    CERN Document Server

    Pearce, Alex

    2014-01-01

    The control of systematic uncertainties is a key component of many analyses performed at the Large Hadron Collider, and will only become more important as more data are taken during Run II. Many of the CP measurements performed using the LHCb detector have statistical precisions below the per cent level, and so particular care must be taken in this area. One technique for dealing with the various production and detection asymmetries which can mask the physics asymmetry of interest, and increase the measurement’s systematic uncertainty, is $\\Delta A_{CP}$ . The application of $\\Delta A_{CP}$ in three separate LHCb analyses of $D^{0}$ and $\\Lambda_{b}^{0}$ decays will be discussed, along with prospects for applying the technique to $\\Lambda_{c}^{+}$ decays.

  1. CP violation

    International Nuclear Information System (INIS)

    Quinn, H.

    1995-12-01

    In this talk the author briefly reviews the cosmological importance of CP violation and the status of calculations of baryogenisis in the context of the Standard Model. The author then turns to a discussion of Standard Model Predictions for CP violation in B decays, stressing the importance of multiple measurements to overconstrain the model parameters and thus search for indications of beyond-Standard-Model physics

  2. On the determination of CP-even and CP-odd components of a mixed CP Higgs boson at e+e- linear colliders

    International Nuclear Information System (INIS)

    Dova, Maria Teresa; Ferrari, Sergio

    2005-01-01

    We present a method to investigate the CP quantum numbers of the Higgs boson in the process e + e - ->Zφ at a future e + e - linear collider (LC), where φ, a generic Higgs boson, is a mixture of CP-even and CP-odd states. The procedure consists of a comparison of the data with predictions obtained from Monte Carlo simulations corresponding to the productions of scalar and pseudoscalar Higgs and the interference term which constitutes a distinctive signal of CP violation. We present estimates of the sensitivity of the method from Monte Carlo studies using hypothetical data samples with a full LC detector simulation taking into account the background signals

  3. Modeling the building blocks of biodiversity.

    Directory of Open Access Journals (Sweden)

    Lucas N Joppa

    Full Text Available BACKGROUND: Networks of single interaction types, such as plant-pollinator mutualisms, are biodiversity's "building blocks". Yet, the structure of mutualistic and antagonistic networks differs, leaving no unified modeling framework across biodiversity's component pieces. METHODS/PRINCIPAL FINDINGS: We use a one-dimensional "niche model" to predict antagonistic and mutualistic species interactions, finding that accuracy decreases with the size of the network. We show that properties of the modeled network structure closely approximate empirical properties even where individual interactions are poorly predicted. Further, some aspects of the structure of the niche space were consistently different between network classes. CONCLUSIONS/SIGNIFICANCE: These novel results reveal fundamental differences between the ability to predict ecologically important features of the overall structure of a network and the ability to predict pair-wise species interactions.

  4. CP Violation

    International Nuclear Information System (INIS)

    Aleksan, R.

    1993-06-01

    The violation of the CP symmetry is a phenomenon, the origin of which is not yet well established and deserves a particular attention since it may be a fundamental property of Nature with very important consequences for the evolution of the universe. We propose in these lectures to have an overview of this phenomenon as we understand it so far. To this end, and after introducing the discrete space-time symmetries, we discuss the observation of the violation of the CP symmetry in the neutral kaon decays. We then derive the general formalism for any neutral system made of a particle and its antiparticle and discuss how CP violation is introduced. We show how this phenomenon is generated in the Standard Model of the electroweak interactions and what are the predictions that can be made. In particular we shall concentrate on the expected effects in the decays of mesons involving the b quark. We review the various possibilities for observing these effects, calculate their magnitudes and show how the consistency of the theory can be tested. Finally, we outline the experimental prospects for studying CP non conservation at an asymmetric B Factory to either verify the Standard Model mechanism or provide evidence for new physics. (author)

  5. CP-even and CP-odd transverse polarization of the electron in the muon decay

    International Nuclear Information System (INIS)

    Kuznetsov, A.V.

    1981-01-01

    In the most general weak interaction model with intermediate vector bosons, allowing CP breaking in the muon decay, CP- even and CP-odd transverse polarization of the μ-decay electrons is calculated taking into account the radiative corrections. It is shown that such corrections are essential only at the beginning of the spectrum reducing the observed transverse polarization effects. When the electron energy is close to its maximum and the emission angles are small, the transverse polarization considerably grows. Search for CP-even and CP-odd transverse polarization of the electrons should be carried out at energies Esub(e) approximately equal to O.975 Esub(e)sup(max) and emission angles THETA approximately equal to 25+35 deg [ru

  6. CP-violation and instantons

    International Nuclear Information System (INIS)

    Han, C.G.

    1980-01-01

    Effects of Yang-Mills instantons on CP-violating strong interactions are studied. Using simplified models of CP-noninvariant weak interactions, we calculate the induced strong CP-violation. Even in the simple examples studied, the CP-violating phase of a vacuum-to-vacuum transition amplitude differs in general from the phase of the determinant of the quark mass matrix multiplied by the topological charge of the background Yang-Mills field. Then several CP-violating phenomena such as eta → 2π decay and neutron electric dipole moment induced by instantons are studied. The result of our explicit calculation of eta → 2π decay strength verifies the current algebraic method used by Crewther et al. We also present a calculation of the instanton contribution, in the dilute gas approximation for instanton gas, to the electric dipole moment of a free quark without using 't Hooft's effective Lagrangian

  7. Leptonic CP violation theory

    DEFF Research Database (Denmark)

    Hagedorn, C.

    2017-01-01

    I summarize the status of theoretical predictions for the yet to be measured leptonic CP phases, the Dirac phase δ and the two Majorana phases α and β. I discuss different approaches based on: (a) a flavor symmetry without and with corrections, (b) different types of sum rules and (c) flavor and CP...... symmetries. I show their predictive power with examples. In addition, I present scenarios in which low and high energy CP phases are connected so that predictions for the CP phases α, β and δ become correlated to the sign of the baryon asymmetry YB of the Universe that is generated via leptogenesis....

  8. Measurement of CP-Violating Asymmetries in B0 Decays to CP Eigenstates

    Energy Technology Data Exchange (ETDEWEB)

    MacFarlane, David B

    2001-02-26

    We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23 million {Upsilon}(4S) {yields} B{bar B} decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events where one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2{beta}, is derived from the decay time distributions in such events. The result is sin2{beta} = 0.34 {+-} 0.20 (stat) {+-} 0.05 (syst).

  9. Measurement of CP-violating asymmetries in B0 decays to CP eigenstates.

    Science.gov (United States)

    Aubert, B; Boutigny, D; De Bonis, I; Gaillard, J M; Jeremie, A; Karyotakis, Y; Lees, J P; Robbe, P; Tisserand, V; Palano, A; Chen, G P; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Reinertsen, P L; Stugu, B; Abbott, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Clark, A R; Dardin, S; Day, C; Dow, S F; Elioff, T; Fan, Q; Gaponenko, I; Gill, M S; Goozen, F R; Gowdy, S J; Gritsan, A; Groysman, Y; Jacobsen, R G; Jared, R C; Kadel, R W; Kadyk, J; Karcher, A; Kerth, L T; Kipnis, I; Kluth, S; Kolomensky, Y G; Kral, J F; Lafever, R; LeClerc, C; Levi, M E; Lewis, S A; Lionberger, C; Liu, T; Long, M; Lynch, G; Marino, M; Marks, K; Meyer, A B; Mokhtarani, A; Momayezi, M; Nyman, M; Oddone, P J; Ohnemus, J; Oshatz, D; Patton, S; Perazzo, A; Peters, C; Pope, W; Pripstein, M; Quarrie, D R; Rasson, J E; Roe, N A; Romosan, A; Ronan, M T; Shelkov, V G; Stone, R; Telnov, A V; von der Lippe, H; Weber, T; Wenzel, W A; Zisman, M S; Bright-Thomas, P G; Harrison, T J; Hawkes, C M; Kirk, A; Knowles, D J; O'Neale, S W; Watson, A T; Watson, N K; Deppermann, T; Koch, H; Krug, J; Kunze, M; Lewandowski, B; Peters, K; Schmuecker, H; Steinke, M; Andress, J C; Barlow, N R; Bhimji, W; Chevalier, N; Clark, P J; Cottingham, W N; De Groot, N; Dyce, N; Foster, B; Mass, A; McFall, J D; Wallom, D; Wilson, F F; Abe, K; Hearty, C; Mattison, T S; McKenna, J A; Thiessen, D; Camanzi, B; Jolly, S; McKemey, A K; Tinslay, J; Blinov, V E; Bukin, A D; Bukin, D A; Buzykaev, A R; Dubrovin, M S; Golubev, V B; Ivanchenko, V N; Kolachev, G M; Korol, A A; Kravchenko, E A; Onuchin, A P; Salnikov, A A; Serednyakov, S I; Skovpen, Y I; Telnov, V I; Yushkov, A N; Lankford, A J; Mandelkern, M; McMahon, S; Stoker, D P; Ahsan, A; Buchanan, C; Chun, S; MacFarlane, D B; Prell, S; Rahatlou, S; Raven, G; Sharma, V; Burke, S; Campagnari, C; Dahmes, B; Hale, D; Hart, P A; Kuznetsova, N; Kyre, S; Levy, S L; Long, O; Lu, A; Richman, J D; Verkerke, W; Witherell, M; Yellin, S; Beringer, J; Dorfan, D E; Eisner, A M; Frey, A; Grillo, A A; Grothe, M; Heusch, C A; Johnson, R P; Kroeger, W; Lockman, W S; Pulliam, T; Sadrozinski, H; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Spencer, E N; Turri, M; Walkowiak, W; Williams, D C; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hanson, J E; Hitlin, D G; Metzler, S; Oyang, J; Porter, F C; Ryd, A; Samuel, A; Weaver, M; Yang, S; Zhu, R Y; Devmal, S; Geld, T L; Jayatilleke, S; Jayatilleke, S M; Mancinelli, G; Meadows, B T; Sokoloff, M D; Bloom, P; Fahey, S; Ford, W T; Gaede, F; van Hoek, W C; Johnson, D R; Michael, A K; Nauenberg, U; Olivas, A; Park, H; Rankin, P; Roy, J; Sen, S; Smith, J G; Wagner, D L; Blouw, J; Harton, J L; Krishnamurthy, M; Soffer, A; Toki, W H; Warner, D W; Wilson, R J; Zhang, J; Brandt, T; Brose, J; Colberg, T; Dahlinger, G; Dickopp, M; Dubitzky, R S; Eckstein, P; Futterschneider, H; Krause, R; Maly, E; Müller-Pfefferkorn, R; Otto, S; Schubert, K R; Schwierz, R; Spaan, B; Wilden, L; Behr, L; Bernard, D; Bonneaud, G R; Brochard, F; Cohen-Tanugi, J; Ferrag, S; Fouque, G; Gastaldi, F; Matricon, P; Mora de Freitas, P; Renard, C; Roussot, E; T'Jampens, S; Thiebaux, C; Vasileiadis, G; Verderi, M; Anjomshoaa, A; Bernet, R; Di Lodovico, F; Khan, A; Muheim, F; Playfer, S; Swain, J E; Falbo, M; Bozzi, C; Dittongo, S; Folegani, M; Piemontese, L; Treadwell, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Falciai, D; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Xie, Y; Zallo, A; Bagnasco, S; Buzzo, A; Contri, R; Crosetti, G; Lo Vetere, M; Macri, M; Monge, M R; Pallavicini, M; Passaggio, S; Pastore, F C; Patrignani, C; Pia, M G; Robutti, E; Santroni, A; Morii, M; Bartoldus, R; Dignan, T; Hamilton, R; Mallik, U; Cochran, J; Crawley, H B; Fischer, P A; Lamsa, J; McKay, R; Meyer, W T; Rosenberg, E I; Albert, J N; Beigbeder, C; Benkebil, M; Breton, D; Cizeron, R; Du, S; Grosdidier, G; Hast, C; Höcker, A; LePeltier, V; Lutz, A M; Plaszczynski, S; Schune, M H; Trincaz-Duvoid, S; Truong, K; Valassi, A; Wormser, G; Bionta, R M; Brigljević, V; Brooks, A; Fackler, O; Fujino, D; Lange, D J; Mugge, M; O'Connor, T G; Pedrotti, B; Shi, X; van Bibber, K; Wenaus, T J; Wright, D M; Wuest, C R; Yamamoto, B; Carroll, M; Fry, J R; Gabathuler, E; Gamet, R; George, M; Kay, M; Payne, D J; Sloane, R J; Touramanis, C; Aspinwall, M L; Bowerman, D A; Dauncey, P D; Egede, U; Eschrich, I; Gunawardane, N J; Martin, R; Nash, J A; Price, D R; Sanders, P; Smith, D; Azzopardi, D E; Back, J J; Dixon, P; Harrison, P F; Newman-Coburn, D; Potter, R J; Shorthouse, H W; Strother, P; Vidal, P B; Williams, M I; Cowan, G; George, S; Green, M G; Kurup, A; Marker, C E; McGrath, P; McMahon, T R; Salvatore, F; Scott, I; Vaitsas, G; Brown, D; Davis, C L; Ford, K; Li, Y; Pavlovich, J; Allison, J; Barlow, R J; Boyd, J T; Fullwood, J; Jackson, F; Lafferty, G D; Savvas, N; Simopoulos, E T; Thompson, R J; Weatherall, J H; Bard, R; Farbin, A; Jawahery, A; Lillard, V; Olsen, J; Roberts, D A; Schieck, J R; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Lin, C S; Staengle, H; Willocq, S; Wittlin, J; Brau, B; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Britton, D I; Milek, M; Patel, P M; Trischuk, J; Lanni, F; Palombo, F; Bauer, J M; Booke, M; Cremaldi, L; Eschenberg, V; Kroeger, R; Reep, M; Reidy, J; Sanders, D A; Summers, D J; Beaulieu, M; Martin, J P; Nief, J Y; Seitz, R; Taras, P; Zacek, V; Nicholson, H; Sutton, C S; Cavallo, N; Cartaro, C; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Paolucci, P; Piccolo, D; Sciacca, C; LoSecco, J M; Alsmiller, J R; Gabriel, T A; Handler, T; Heck, J; Brau, J E; Frey, R; Iwasaki, M; Sinev, N B; Strom, D; Borsato, E; Colecchia, F; Dal Corso, F; Galeazzi, F; Margoni, M; Marzolla, M; Michelon, G; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Torassa, E; Voci, C; Bailly, P; Benayoun, M; Briand, H; Chauveau, J; David, P; De La Vaissière, C; Del Buono, L; Genat, J F; Hamon, O; Le Diberder, F; Lebbolo, H; Leruste, P; Lory, J; Martin, L; Roos, L; Stark, J; Versillé, S; Zhang, B; Manfredi, P F; Ratti, L; Re, V; Speziali, V; Frank, E D; Gladney, L; Guo, Q H; Panetta, J H; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Bosi, F; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Martinez-Vidal, F; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Sandrelli, F; Simi, G; Triggiani, G; Walsh, J; Hairre, M; Judd, D; Paick, K; Turnbull, L; Wagoner, D E; Albert, J; Bula, C; Fernholz, R; Lu, C; McDonald, K T; Miftakov, V; Sands, B; Schaffner, S F; Smith, A J; Tumanov, A; Varnes, E W; Bronzini, F; Buccheri, A; Bulfon, C; Cavoto, G; del Re, D; Faccini, R; Ferrarotto, F; Ferroni, F; Fratini, K; Lamanna, E; Leonardi, E; Mazzoni, M A; Morganti, S; Piredda, G; Safai Tehrani, F; Serra, M; Voena, C; Waldi, R; Jacques, P F; Kalelkar, M; Plano, R J; Adye, T; Claxton, B; Franek, B; Galagedera, S; Geddes, N I; Gopal, G P; Lidbury, J; Xella, S M; Aleksan, R; Besson, P; Bourgeois, P; De Domenico, G; Emery, S; Gaidot, A; Ganzhur, S F; Gosset, L; Hamel de Monchenault, G; Kozanecki, W; Langer, M; London, G W; Mayer, B; Serfass, B; Vasseur, G; Yeche, C; Zito, M; Copty, N; Purohit, M V; Singh, H; Yumiceva, F X; Adam, I; Anthony, P L; Aston, D; Baird, K; Bartelt, J; Becla, J; Bell, R; Bloom, E; Boeheim, C T; Boyarski, A M; Boyce, R F; Bulos, F; Burgess, W; Byers, B; Calderini, G; Claus, R; Convery, M R; Coombes, R; Cottrell, L; Coupal, D P; Coward, D H; Craddock, W W; DeStaebler, H; Dorfan, J; Doser, M; Dunwoodie, W; Ecklund, S; Fieguth, T H; Field, R C; Freytag, D R; Glanzman, T; Godfrey, G L; Grosso, P; Haller, G; Hanushevsky, A; Harris, J; Hasan, A; Hewett, J L; Himel, T; Huffer, M E; Innes, W R; Jessop, C P; Kawahara, H; Keller, L; Kelsey, M H; Kim, P; Klaisner, L A; Kocian, M L; Krebs, H J; Kunz, P F; Langenegger, U; Langeveld, W; Leith, D W; Louie, S K; Luitz, S; Luth, V; Lynch, H L; MacDonald, J; Manzin, G; Mariske, H; McCulloch, M; McShurley, D; Menke, S; Messner, R; Metcalfe, S; Moffeit, K C; Mount, R; Muller, D R; Nelson, D; Nordby, M; O'Grady, C P; O'Neill, F G; Oxoby, G; Pavel, T; Perl, J; Petrak, S; Putallaz, G; Quinn, H; Raines, P E; Ratcliff, B N; Reif, R; Robertson, S H; Rochester, L S; Roodman, A; Russell, J J; Sapozhnikov, L; Saxton, O H; Schietinger, T; Schindler, R H; Schwiening, J; Seeman, J T; Serbo, V V; Skarpass, K; Snyder, A; Soha, A; Spanier, S M; Stahl, A; Stelzer, J; Su, D; Sullivan, M K; Talby, M; Tanaka, H A; Va'vra, J; Wagner, S R; Weinstein, A J; White, J L; Wienands, U; Wisniewski, W J; Young, C C; Zioulas, G; Burchat, P R; Cheng, C H; Kirkby, D; Meyer, T I; Roat, C; De Silva, A; Henderson, R; Berridge, S; Bugg, W; Cohn, H; Hart, E; Weidemann, A W; Benninger, T; Izen, J M; Kitayama, I; Lou, X C; Turcotte, M; Bianchi, F; Bona, M; Di Girolamo, B; Gamba, D; Smol, A; Zanin, D; Bosisio, L; Della Ricca, G; Lanceri, L; Pompili, A; Poropat, P; Vuagnin, G; Panvini, R S; Brown, C M; Kowalewski, R; Roney, J M; Band, H R; Charles, E; Dasu, S; Elmer, P; Hu, H; Johnson, J R; Nielsen, J; Orejudos, W; Pan, Y; Prepost, R; Scott, I J; von Wimmersperg-Toeller, J H; Wu, S L; Yu, Z; Zobernig, H; Kordich, T M; Moore, T B; Neal, H

    2001-03-19

    We present measurements of time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurement uses a data sample of 23x10(6) Upsilon(4S)-->BbarB decays collected by the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we find events in which one neutral B meson is fully reconstructed in a CP eigenstate containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay time distributions in such events. The result is sin2beta = 0.34+/-0.20 (stat)+/-0.05 (syst).

  10. Exploring CP Violation in the MSSM

    CERN Document Server

    Arbey, A.; Godbole, R.M.; Mahmoudi, F.

    2015-01-01

    We explore the prospects for observing CP violation in the minimal supersymmetric extension of the Standard Model (MSSM) with six CP-violating parameters, three gaugino mass phases and three phases in trilinear soft supersymmetry-breaking parameters, using the CPsuperH code combined with a geometric approach to maximize CP-violating observables subject to the experimental upper bounds on electric dipole moments. We also implement CP-conserving constraints from Higgs physics, flavour physics and the upper limits on the cosmological dark matter density and spin-independent scattering. We study possible values of observables within the constrained MSSM (CMSSM), the non-universal Higgs model (NUHM), the CPX scenario and a variant of the phenomenological MSSM (pMSSM). We find values of the CP-violating asymmetry A_CP in b -> s gamma decay that may be as large as 3%, so future measurements of A_CP may provide independent information about CP violation in the MSSM. We find that CP-violating MSSM contributions to the...

  11. Deviation from bimaximal mixing and leptonic CP phases in S4 family symmetry and generalized CP

    International Nuclear Information System (INIS)

    Li, Cai-Chang; Ding, Gui-Jun

    2015-01-01

    The lepton flavor mixing matrix having one row or one column in common with the bimaximal mixing up to permutations is still compatible with the present neutrino oscillation data. We provide a thorough exploration of generating such a mixing matrix from S 4 family symmetry and generalized CP symmetry H CP . Supposing that S 4 ⋊H CP is broken down to Z 2 ST 2 SU ×H CP ν in the neutrino sector and Z 4 TST 2 U ⋊H CP l in the charged lepton sector, one column of the PMNS matrix would be of the form (1/2,1/√2,1/2) T up to permutations, both Dirac CP phase and Majorana CP phases are trivial to accommodate the observed lepton mixing angles. The phenomenological implications of the remnant symmetry K 4 (TST 2 ,T 2 U) ×H CP ν in the neutrino sector and Z 2 SU ×H CP l in the charged lepton sector are studied. One row of PMNS matrix is determined to be (1/2,1/2,−i/√2), and all the three leptonic CP phases can only be trivial to fit the measured values of the mixing angles. Two models based on S 4 family symmetry and generalized CP are constructed to implement these model independent predictions enforced by remnant symmetry. The correct mass hierarchy among the charged leptons is achieved. The vacuum alignment and higher order corrections are discussed.

  12. A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

    DEFF Research Database (Denmark)

    Royer, J F; Schratl, P; Lorenz, S

    2007-01-01

    developed small molecule antagonist of CRTH2, Cay10471, on eosinophil function with respect to recruitment, respiratory burst and degranulation. METHODS: Chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils were determined using microBoyden chambers. Eosinophil release...... from bone marrow was investigated in the in situ perfused guinea pig hind limb preparation. Respiratory burst and degranulation were measured by flow cytometry. RESULTS: Cay10471 bound with high affinity to recombinant human and guinea pig CRTH2, but not DP, receptors. The antagonist prevented the PGD......(2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

  13. Leptogenesis and residual CP symmetry

    International Nuclear Information System (INIS)

    Chen, Peng; Ding, Gui-Jun; King, Stephen F.

    2016-01-01

    We discuss flavour dependent leptogenesis in the framework of lepton flavour models based on discrete flavour and CP symmetries applied to the type-I seesaw model. Working in the flavour basis, we analyse the case of two general residual CP symmetries in the neutrino sector, which corresponds to all possible semi-direct models based on a preserved Z 2 in the neutrino sector, together with a CP symmetry, which constrains the PMNS matrix up to a single free parameter which may be fixed by the reactor angle. We systematically study and classify this case for all possible residual CP symmetries, and show that the R-matrix is tightly constrained up to a single free parameter, with only certain forms being consistent with successful leptogenesis, leading to possible connections between leptogenesis and PMNS parameters. The formalism is completely general in the sense that the two residual CP symmetries could result from any high energy discrete flavour theory which respects any CP symmetry. As a simple example, we apply the formalism to a high energy S 4 flavour symmetry with a generalized CP symmetry, broken to two residual CP symmetries in the neutrino sector, recovering familiar results for PMNS predictions, together with new results for flavour dependent leptogenesis.

  14. Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt

    Science.gov (United States)

    Chen, Yi-Cun; Zhu, Wei; Zhong, Shu-Ping; Zheng, Fu-Chun; Gao, Fen-Fei; Zhang, Yan-Mei; Xu, Han; Zheng, Yan-Shan; Shi, Gang-Gang

    2015-01-01

    BACKGROUND AND PURPOSE Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups. The objective of this study was to investigate the bioactivity of these novel calcium antagonists, especially the vasodilation activity and cardiac side-effects. The possible working mechanisms of these haloperidol derivatives were also explored. EXPERIMENTAL APPROACH Novel calcium antagonists were synthesized by amination. Compounds were screened for their activity of vasodilation on isolated thoracic aortic ring of rats. Their cardiac side effects were explored. The patch-clamp, confocal laser microscopy and the computer-fitting molecular docking experiments were employed to investigate the possible working mechanisms of these calcium antagonists. RESULTS The novel calcium antagonists, X1, X2 and X3 showed stronger vasodilation effect and less cardiac side effect than that of classical calcium antagonists. They blocked L-type calcium channels with an potent effect order of X1 > X2 > X3. Consistently, X1, X2 and X3 interacted with different regions of Ca2+-CaM-CaV1.2 with an affinity order of X1 > X2 > X3. CONCLUSIONS The new halopedidol derivatives X1, X2 and X3 are novel calcium antagonists with stronger vasodilation effect and less cardiac side effect. They could have wide clinical application. PMID:26544729

  15. DIVA vaccine properties of the live chimeric pestivirus strain CP7_E2gif.

    Science.gov (United States)

    von Rosen, Tanya; Rangelova, Desislava; Nielsen, Jens; Rasmussen, Thomas Bruun; Uttenthal, Åse

    2014-06-04

    Live modified vaccines to protect against classical swine fever virus (CSFV), based on chimeric pestiviruses, have been developed to enable serological Differentiation of Infected from Vaccinated Animals (DIVA). In this context, the chimeric virus CP7_E2gif vaccine candidate is unique as it does not include any CSFV components. In the present study, the DIVA vaccine properties of CP7_E2gif were evaluated in comparison to the conventional live attenuated Riemser C-strain vaccine. Sera and tonsil samples obtained from pigs immunised with these two vaccines were analysed. No viral RNA was found in serum after vaccination with CP7_E2gif, whereas some serum samples from C-strain vaccinated animals were positive. In both vaccinated groups, individual viral RNA-positive tonsil samples were detected in animals euthanised between 7 and 21 days post vaccination. Furthermore, serum samples from these animals, together with archival samples from pigs vaccinated with CP7_E2gif and subsequently CSFV challenged, were analysed for specific antibodies using ELISAs and for homologous neutralising antibodies. In animals vaccinated with CP7_E2gif, neutralising antibodies were detected from day 10. However, the sera remained negative for anti-CSFV E2-specific antibodies whereas pigs vaccinated with C-strain seroconverted against CSFV by 14 days after vaccination, as determined by a CSFV-E2 specific blocking ELISA. One week after subsequent CSFV challenge, a strong anti-CSFV E2 reaction was detected in CP7_E2gif vaccinated pigs and anti-E(rns) antibodies were detected from 10 days after infection. In conclusion, CP7_E2gif has the potential to be used as a DIVA vaccine in combination with detection of anti-CSFV E2-specific antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Study on Ca2+ antagonistic effect and mechanism of Chinese herbal drugs using 45Ca

    International Nuclear Information System (INIS)

    Yang Yuanyou; Liu Ning; Mo Shangwu; Qiu Mingfeng; Jin Jiannan; Liao Jiali

    2002-01-01

    The Ca 2+ antagonistic effect and mechanism of Chinese herbal drugs are studied by using 45 Ca. The results indicate that potential-dependent Ca 2+ channel (PDC) and receptor-operated Ca 2+ channel (ROC) in cell membranes of smooth muscle can be blocked by several Chinese herbal drugs, including as Crocus sativus L., Carthamus L., Di-ao-xin-xue-kang (DAXXG) and Ginkgo biloba L. leaves. Among them Crocus sativus L. has the strongest antagonistic effect on Ca 2+ channel, while Ginkgo biloba L. leaves has no obvious effect. The whole prescription and the other functional drugs have significant effect on ROC and PDC. The compositions extracted by hexane have the strongest antagonistic. The wrinkled giant hyssop have five active compositions and Pei-lan have two active compositions

  17. CP violating scalar Dark Matter

    Science.gov (United States)

    Cordero-Cid, A.; Hernández-Sánchez, J.; Keus, V.; King, S. F.; Moretti, S.; Rojas, D.; Sokołowska, D.

    2016-12-01

    We study an extension of the Standard Model (SM) in which two copies of the SM scalar SU(2) doublet which do not acquire a Vacuum Expectation Value (VEV), and hence are inert, are added to the scalar sector. We allow for CP-violation in the inert sector, where the lightest inert state is protected from decaying to SM particles through the conservation of a Z 2 symmetry. The lightest neutral particle from the inert sector, which has a mixed CP-charge due to CP-violation, is hence a Dark Matter (DM) candidate. We discuss the new regions of DM relic density opened up by CP-violation, and compare our results to the CP-conserving limit and the Inert Doublet Model (IDM). We constrain the parameter space of the CP-violating model using recent results from the Large Hadron Collider (LHC) and DM direct and indirect detection experiments.

  18. Synthesis of [18F]-labelled nebivolol as a β1-adrenergic receptor antagonist for PET imaging agent

    International Nuclear Information System (INIS)

    Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae; Chang, Dong Jo

    2017-01-01

    Selective β 1 -agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β 1 -antagonists including nebivolol have high binding affinity on β 1 -adrenergic receptor, not β 2 -receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β 1 -blockers in clinically used β 1 - blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β 1 -blocker. Nebivolol is C 2 -symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of 18 F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for 18 F-aromatic substitution, was synthesized in moderate yield which was readily subjected to 18 F-aromatic substitution to give 18 F-labelled nebivolol

  19. V2 and cP/CP

    DEFF Research Database (Denmark)

    Vikner, Sten; Christensen, Ken Ramshøj; Nyvad, Anne Mette

    2017-01-01

    As in Nyvad et al. (2017), we will explore a particular derivation of (embedded) V2, in terms of a cP/CP-distinction, which may be seen as a version of the CP-recursion analysis (de Haan & Weerman 1986; Vikner 1995 and many others). e idea is that because embedded V2 clauses do not allow extraction......, whereas other types of CP-recursion clauses do (Christensen et al. 2013a; 2013b; Christensen & Nyvad 2014), CP-recursion in embedded V2 is assumed to be fundamentally di erent from other kinds of CP-recursion, in that main clause V2 and embedded V2 involve a CP (“big CP”), whereas other clausal...... projections above IP are instances of cP (“little cP”)....

  20. CP invariance: a point of view

    International Nuclear Information System (INIS)

    Mohan, Gyan

    1983-01-01

    That the longlived component L of K 0 has both CP = +1 and CP = -1 modes of decay is often cited as evidence of violation of CP invariance. The careful ones find the compelling evidence to be the non-dilution of the regeneration interference pattern when the incident K 0 beam is mixed even substantially with anti-K 0 . However the two phenomena comprehensively imply that L has a CP = +1 component Lsub(+) and CP = -1 component Lsub(-) and that the longlived component of both K 0 and anti-K 0 are one and the same L. This does not demand abandoning CP invariance. It does imply that anti-K 0 is not the CP conjugate of K 0 . (author)

  1. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    International Nuclear Information System (INIS)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    2007-01-01

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

  2. Is CP a gauge symmetry?

    International Nuclear Information System (INIS)

    Choi, K.; Kaplan, D.B.; Nelson, A.E.

    1993-01-01

    Conventional solutions to the strong CP problem all require the existence of global symmetries. However, quantum gravity may destroy global symmetries, making it hard to understand why the electric dipole moment of the neutron (EDMN) is so small. We suggest here that CP is actually a discrete gauge symmetry, and is therefore not violated by quantum gravity. We show that four-dimensional CP can arise as a discrete gauge symmetry in theories with dimensional compactification, if the original number of Minkowski dimensions equals 8k+1, 8k+2 or 8k+3, and if there are certain restrictions on the gauge group; these conditions are met by superstrings. CP may then be broken spontaneously below 10 9 GeV, explaining the observed CP violation in the kaon system without inducing a large EDMN. We discuss the phenomenology of such models, as well as the peculiar properties of cosmic 'SP strings' which could be produced at the compactification scale. Such strings have the curious property that a particle carried around the string is turned into its CP conjugate. A single CP string renders four-dimensional space-time nonorientable. (orig.)

  3. CP-violations in B decays

    Indian Academy of Sciences (India)

    Recent results on CP-violation measurements in decays from energy asymmetric -factory experiments are reported. Thanks to large accumulated data samples, CP-violations in decays in mixing-decay interference and direct CP-violation are now firmly established. The measurements of three angles of the unitarity ...

  4. Beautiful CP violation

    International Nuclear Information System (INIS)

    Dunietz, I.

    1997-01-01

    CP violation is observed to date only in K 0 decays and is parameterizable by a single quantity ε. Because it is one of the least understood phenomena in the Standard Model and holds a clue to baryogenesis, it must be investigated further. Highly specialized searches in K 0 decays are possible. Effects in B decays are much larger. In addition to the traditional B d → J/ψK S , π + π - asymmetries, CP violation could be searched for in already existing inclusive B data samples. The rapid B s --anti B s oscillations cancel in untagged B s data samples, which therefore allow feasibility studies for the observation of CP violation and the extraction of CKM elements with present vertex detectors. The favored method for the extraction of the CKM angle γ is shown to be unfeasible and a solution is presented involving striking direct CP violation in charged B decays. Novel methods for determining the B s mixing parameter Δm are described without the traditional requirement of flavor-specific final states

  5. Unilateral cervical plexus block for prosthetic laryngoplasty in the standing horse.

    Science.gov (United States)

    Campoy, L; Morris, T B; Ducharme, N G; Gleed, R D; Martin-Flores, M

    2018-04-20

    Locoregional anaesthetic techniques can facilitate certain surgeries being performed under standing procedural sedation. The second and third spinal cervical nerves (C2, C3) are part of the cervical plexus and provide sensory innervation to the peri-laryngeal structures in people; block of these nerves might permit laryngeal lateralisation surgery in horses. To describe the anatomical basis for an ultrasound-guided cervical plexus block in horses. To compare this block with conventional local anaesthetic tissue infiltration in horses undergoing standing prosthetic laryngoplasty. Cadaveric study followed by a double-blinded prospective clinical trial. A fresh equine cadaver was dissected to characterise the distribution of C2 and C3 to the perilaryngeal structures on the left side. A second cadaver was utilised to correlate ultrasound images with the previously identified structures; a tissue marker was injected to confirm the feasibility of an ultrasound-guided approach to the cervical plexus. In the clinical study, horses were assigned to two groups, CP (n = 17; cervical plexus block) and INF (n = 17; conventional tissue infiltration). Data collection and analyses included time to completion of surgical procedure, sedation time, surgical field conditions and surgeon's perception of block quality. We confirmed that C2 and C3 provided innervation to the perilaryngeal structures. The nerve root of C2 was identified ultrasonographically located between the longus capitis and the cleidomastoideus muscles, caudal to the parotid gland. The CP group was deemed to provide better (Pblock is a viable alternative to tissue infiltration and it improves the surgical field conditions. © 2018 EVJ Ltd.

  6. Some ideas for learning CP-theories

    OpenAIRE

    Fierens, Daan

    2008-01-01

    Causal Probabilistic logic (CP-logic) is a language for describing complex probabilistic processes. In this talk we consider the problem of learning CP-theories from data. We briefly discuss three possible approaches. First, we review the existing algorithm by Meert et al. Second, we show how simple CP-theories can be learned by using the learning algorithm for Logical Bayesian Networks and converting the result into a CP-theory. Third, we argue that for learning more complex CP-theories, an ...

  7. A search for CP violation in hyperon decays by the hyper-CP experiment at Fermilab

    International Nuclear Information System (INIS)

    Holmstrom, T.

    2002-01-01

    The Hyper-CP collaboration is performing a precision search for CP violation in hyperon decays, these decays are sensitive to sources of CP violation to which neutral kaon decays are not. The measured CP observable is proportional to the difference between the product of the Ξ and Λ decay α parameters and that of the CP-conjugate decays. About 2.5 billion fully-reconstructed Ξ - → Λπ - → pπ - π - and Ξ-bar + → Λ-barπ + → p-barπ + π + decays were taken in 2 fixed-target runs at Fermilab, allowing a statistical sensitivity of about 2.10 -4 in the CP asymmetry. These 2 runs gave us the largest sample of Ξ and Ω ever collected. An initial study has been done on a fraction of the data and we have obtained: A ΞΛ equals (-7±12(statistical)±6.2(systematic))*10 -4 . Other preliminary results are also presented in this series of slides

  8. Analysis list: Cp190 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Cp190 Cell line,Embryo,Larvae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/...target/Cp190.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Cp190.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/dm3/target/Cp190.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cp190.Cell_l...ine.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cp190.Embryo.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/dm3/colo/Cp190.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/

  9. Testing New Indirect CP Violation

    International Nuclear Information System (INIS)

    Grossman, Yuval; Nir, Yosef; Perez, Gilad

    2009-01-01

    If new CP violating physics contributes to neutral meson mixing, but its contribution to CP violation in decay amplitudes is negligible, then there is a model independent relation between four (generally independent) observables related to the mixing: the mass splitting (x), the width splitting (y), the CP violation in mixing (1-|q/p|), and the CP violation in the interference of decays with and without mixing (φ). For the four neutral meson systems, this relation can be written in a simple approximate form: ytanφ≅x(1-|q/p|). In the K system, all four observables have been measured and obey the relation to excellent accuracy. For the B s and D systems, new predictions are provided. The success or failure of these relations will probe the physics that is responsible for the CP violation.

  10. GaussianCpG: a Gaussian model for detection of CpG island in human genome sequences.

    Science.gov (United States)

    Yu, Ning; Guo, Xuan; Zelikovsky, Alexander; Pan, Yi

    2017-05-24

    As crucial markers in identifying biological elements and processes in mammalian genomes, CpG islands (CGI) play important roles in DNA methylation, gene regulation, epigenetic inheritance, gene mutation, chromosome inactivation and nuclesome retention. The generally accepted criteria of CGI rely on: (a) %G+C content is ≥ 50%, (b) the ratio of the observed CpG content and the expected CpG content is ≥ 0.6, and (c) the general length of CGI is greater than 200 nucleotides. Most existing computational methods for the prediction of CpG island are programmed on these rules. However, many experimentally verified CpG islands deviate from these artificial criteria. Experiments indicate that in many cases %G+C is human genome. We analyze the energy distribution over genomic primary structure for each CpG site and adopt the parameters from statistics of Human genome. The evaluation results show that the new model can predict CpG islands efficiently by balancing both sensitivity and specificity over known human CGI data sets. Compared with other models, GaussianCpG can achieve better performance in CGI detection. Our Gaussian model aims to simplify the complex interaction between nucleotides. The model is computed not by the linear statistical method but by the Gaussian energy distribution and accumulation. The parameters of Gaussian function are not arbitrarily designated but deliberately chosen by optimizing the biological statistics. By using the pseudopotential analysis on CpG islands, the novel model is validated on both the real and artificial data sets.

  11. CP -symmetry of order 4 and its consequences

    International Nuclear Information System (INIS)

    Ivanov, Igor P.

    2017-01-01

    Extended Higgs sectors offer rich opportunities for various forms of CP -violation. Here, we describe a new form of CP-conservation and discuss its consequences. We give a concrete example of a three-Higgs-doublet model dubbed CP4-3HDM with a CP -symmetry of order 4 and no other other accidental symmetries. If the vacuum conserves this symmetry, the model is CP -conserving with pairwise mass-degenerate extra neutral Higgs bosons. These fields cannot be classified as CP -even or CP -odd but they can be combined into complex physical fields which are CP -half-odd, that is, they pick up the i factor upon CP transformation. These CP -half-odd scalars can be Yukawa-coupled to the fermion bilinears in a CP -conserving way. We discuss fundamental and phenomenological features of the model, and stress a peculiar clash between the CP -symmetry and any convention for the particle-antiparticle assignment. (paper)

  12. CP violation in b-hadrons

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00341004

    2016-01-01

    Latest LHCb measurements of $CP$ violation in b-hadrons are presented based on $pp$ collision data collected in 2011 and 2012 at centre-of-mass energies of $\\sqrt{s}=7$ $\\rm TeV$ and $8\\ \\rm TeV$ respectively. The total integrated luminosity collected is 3.0 fb$^{-1}$. Results include recent measurements of $CP$ violation in $B_d$ and $B_s$ mixing, along with those of quantifying the effects of $b\\to c\\bar{c} s$ loop pollution. Standard Model $CP$ violation tests in loop transitions are discussed with results consistent with expectations. New decays of b-baryons are presented and preliminary studies of $CP$ violation are performed.

  13. MeCP2 silencing of LncRNA H19 controls hepatic stellate cell proliferation by targeting IGF1R

    International Nuclear Information System (INIS)

    Yang, Jing-Jing; Liu, Li-Ping; Tao, Hui; Hu, Wei; Shi, Peng; Deng, Zi-Yu; Li, Jun

    2016-01-01

    Highlights: • H19 plays a key role in HSCs proliferation and fibrosis. • MeCP2/H19 axis involvement in HSCs activation and fibrosis. • MeCP2 negative controls H19 expression in activated HSCs. • Identification of IGF1R as new target of H19 in HSC. - Abstract: Methyl-CpG-binding protein 2 (MeCP2) plays a key role in liver fibrosis. However, the potential mechanism of MeCP2 in liver fibrosis remains unclear. Early reports suggest that LncRNA H19 is important epigenetic regulator with critical roles in cell proliferation, but its role in hepatic fibrosis remains elusive. Sprague-Dawley rats liver fibrosis was generated by 12-weeks treatment with CCl 4 intraperitoneal injection. HSC-T6 cells were used in vitro study. The expression levels of MeCP2, H19, IGF1R, α-SMA, and Col1A1 were estimated by Western blotting, qRT-PCR and Immunohistochemistry. HSC-T6 cells were transfected with MeCP2-siRNA, pEGF-C1-MeCP2, pEX-3-H19, and H19-siRNA. Finally, cell proliferation ability was assessed by the MTT assay. Here, we found that H19 was significantly down-regulated in HSCs and fibrosis tissues, and an opposite pattern is observed for MeCP2 and IGF1R. Silencing of MeCP2 blocked HSCs proliferation. Knockdown of MeCP2 elevated H19 expression in activated HSCs, and over-expression of MeCP2 inhibited H19 expression in activated HSCs. Moreover, we investigated the effect of H19 on IGF1R expression. Overexpression of H19 in HSCs repressed the expression of IGF1R, and an opposite pattern is observed for H19 silenced. In addition, we reported that overexpression of H19 inhibited the TGF-β1-induced proliferation of HSCs. Furthermore, MeCP2 negative regulation of H19 by targeting the protein IGF1R. Taken together, these results demonstrated that MeCP2 silencing of H19 can alter the IGF1R overexpression, thus contributing to HSCs proliferation. These data could suggest the development of combination therapies that target the MeCP2.

  14. Medicinal chemistry of small molecule CCR5 antagonists for blocking HIV-1 entry: a review of structural evolution.

    Science.gov (United States)

    Tian, Ye; Zhang, Dujuan; Zhan, Peng; Liu, Xinyong

    2014-01-01

    CCR5, a member of G protein-coupled receptors superfamily, plays an important role in the HIV-1 entry process. Antagonism of this receptor finally leads to the inhibition of R5 strains of HIV entry into the human cells. The identification of CCR5 antagonists as antiviral agents will provide more option for HAART. Now, more than a decade after the first small molecule CCR5 inhibitor was discovered, great achievements have been made. In this article, we will give a brief introduction of several series of small molecule CCR5 antagonists, focused on their appealing structure evolution, essential SAR information and thereof the enlightenment of strategies on CCR5 inhibitors design.

  15. Structural and Electrochemical Consequences of [Cp*] Ligand Protonation.

    Science.gov (United States)

    Peng, Yun; Ramos-Garcés, Mario V; Lionetti, Davide; Blakemore, James D

    2017-09-05

    There are few examples of the isolation of analogous metal complexes bearing [η 5 -Cp*] and [η 4 -Cp*H] (Cp* = pentamethylcyclopentadienyl) complexes within the same metal/ligand framework, despite the relevance of such structures to catalytic applications. Recently, protonation of Cp*Rh(bpy) (bpy = 2,2'-bipyridyl) has been shown to yield a complex bearing the uncommon [η 4 -Cp*H] ligand, rather than generating a [Rh III -H] complex. We now report the purification and isolation of this protonated species, as well as characterization of analogous complexes of 1,10-phenanthroline (phen). Specifically, reaction of Cp*Rh(bpy) or Cp*Rh(phen) with 1 equiv of Et 3 NH + Br - affords rhodium compounds bearing endo-η 4 -pentamethylcyclopentadiene (η 4 -Cp*H) as a ligand. NMR spectroscopy and single-crystal X-ray diffraction studies confirm protonation of the Cp* ligand, rather than formation of metal hydride complexes. Analysis of new structural data and electronic spectra suggests that phen is significantly reduced in Cp*Rh(phen), similar to the case of Cp*Rh(bpy). Backbonding interactions with olefinic motifs are activated by formation of [η 4 -Cp*H]; protonation of [Cp*] stabilizes the low-valent metal center and results in loss of reduced character on the diimine ligands. In accord with these changes in electronic structure, electrochemical studies reveal a distinct manifold of redox processes that are accessible in the [Cp*H] complexes in comparison with their [Cp*] analogues; these processes suggest new applications in catalysis for the complexes bearing endo-η 4 -Cp*H.

  16. Exploring CP violation in the MSSM.

    Science.gov (United States)

    Arbey, Alexandre; Ellis, John; Godbole, Rohini M; Mahmoudi, Farvah

    We explore the prospects for observing CP violation in the minimal supersymmetric extension of the Standard Model (MSSM) with six CP-violating parameters, three gaugino mass phases and three phases in trilinear soft supersymmetry-breaking parameters, using the CPsuperH code combined with a geometric approach to maximise CP-violating observables subject to the experimental upper bounds on electric dipole moments. We also implement CP-conserving constraints from Higgs physics, flavour physics and the upper limits on the cosmological dark matter density and spin-independent scattering. We study possible values of observables within the constrained MSSM (CMSSM), the non-universal Higgs model (NUHM), the CPX scenario and a variant of the phenomenological MSSM (pMSSM). We find values of the CP-violating asymmetry [Formula: see text] in [Formula: see text] decay that may be as large as 3 %, so future measurements of [Formula: see text] may provide independent information about CP violation in the MSSM. We find that CP-violating MSSM contributions to the [Formula: see text] meson mass mixing term [Formula: see text] are in general below the present upper limit, which is dominated by theoretical uncertainties. If these could be reduced, [Formula: see text] could also provide an interesting and complementary constraint on the six CP-violating MSSM phases, enabling them all to be determined experimentally, in principle. We also find that CP violation in the [Formula: see text] and [Formula: see text] couplings can be quite large, and so may offer interesting prospects for future [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] colliders.

  17. CP violation in atoms

    International Nuclear Information System (INIS)

    Barr, S.M.

    1992-01-01

    Electric dipole moments of large atoms are an excellent tool to search for CP violation beyond the Standard Model. These tell us about the electron EDM but also about CP-violating electron-nucleon dimension-6 operators that arise from Higgs-exchange. Rapid strides are being made in searches for atomic EDMs. Limits on the electron EDM approaching the values which would be expected from Higgs-exchange mediated CP violation have been achieved. It is pointed out that in this same kind of model if tan β is large the effects in atoms of the dimension-6 e - n operators may outweigh the effect of the electron EDM. (author) 21 refs

  18. CpG island mapping by epigenome prediction.

    Directory of Open Access Journals (Sweden)

    Christoph Bock

    2007-06-01

    Full Text Available CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1 reliance on arbitrary threshold parameters that bear little biological justification, (2 failure to account for widespread heterogeneity among CpG islands, and (3 apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to

  19. CpG island mapping by epigenome prediction.

    Science.gov (United States)

    Bock, Christoph; Walter, Jörn; Paulsen, Martina; Lengauer, Thomas

    2007-06-01

    CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1) reliance on arbitrary threshold parameters that bear little biological justification, (2) failure to account for widespread heterogeneity among CpG islands, and (3) apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of "CpG island strength" that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted "bona fide" CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to their characteristic

  20. Did the CP audits promote the enterprises' CP? A case study in Beijing.

    Science.gov (United States)

    Yu, Gang; Huang, Jun; Chen, Qing

    2002-03-09

    Seven enterprises that have had recent Cleaner Production (CP) audits in Beijing were interviewed to identify whether these enterprises implemented the audit recommendations. If enterprises did implement the recommendations, their reasons and the results were analyzed. Finally, some suggestions on how to promote enterprise-wide CP were given.

  1. CP violation and the top quark

    International Nuclear Information System (INIS)

    Atwood, D.

    1994-02-01

    We consider signals of CP violation in semi-leptonic decay of the top quark. We show that the transverse polarization asymmetries of the τ-lepton in the decay t → brv is extremely sensitive CP violation. As an illustration we consider CP phases arising from the charged Higgs exchange in the Weinberg three Higgs doublet model. Qualitatively, the polarization asymmetries are enhanced over rate or energy asymmetries by a factor of O(m t /m r ) ∼ 100 with a corresponding increase in sensitivity to CP violating parameters. We also examine τ polarization in b decays via b → cvr and find that may also be very effective in constraining CP violating effects such as those that arise from an extended Higgs sector

  2. CP violation without elementary scalar fields

    International Nuclear Information System (INIS)

    Eichten, E.; Lane, K.; Preskill, J.

    1980-04-01

    Dynamically broken gauge theories of electroweak interactions provide a natural mechanism for generating CP violation. Even if all vacuum angles are unobservable, strong CP violation is not automatically avoided. In the absence of strong CP violation, the neutron electric dipole moment is expected to be of order 10 -24 e cm

  3. Baculovirus resistance in codling moth (Cydia pomonella L.) caused by early block of virus replication.

    Science.gov (United States)

    Asser-Kaiser, Sabine; Radtke, Pit; El-Salamouny, Said; Winstanley, Doreen; Jehle, Johannes A

    2011-02-20

    An up to 10,000-fold resistance against the biocontrol agent Cydia pomonella granulovirus (CpGV) was observed in field populations of codling moth, C. pomonella, in Europe. Following different experimental approaches, a modified peritrophic membrane, a modified midgut receptor, or a change of the innate immune response could be excluded as possible resistance mechanisms. When CpGV replication was traced by quantitative PCR in different tissues of susceptible and resistant insects after oral and intra-hemocoelic infection, no virus replication could be detected in any of the tissues of resistant insects, suggesting a systemic block prior to viral DNA replication. This conclusion was corroborated by fluorescence microscopy using a modified CpGV (bacCpGV(hsp-eGFP)) carrying enhanced green fluorescent gene (eGFP), which showed that infection in resistant insects did not spread. In conclusion, the different lines of evidence indicate that CpGV can enter but not replicate in the cells of resistant codling moth larvae. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. B decays and models for CP violation

    International Nuclear Information System (INIS)

    He, Xiao Gang

    1995-12-01

    The decay modes B to π π,υK S , K - D, πK and ηK are promising channels to study the unitarity triangle of the CP violating Cabibbo-Kobayashi-Maskawa (CKM) matrix. The consequences of these measurements in the Weinberg model are discussed. It is shown that measurements of CP violation in B decay can be used to distinguish Standard Model from Weinberg model and that the following different mechanisms for CP violation can be distinguished: 1) CP is violated in the CKM sector only; 2) CP is violated spontaneously in the Higgs sector only; and 3) CP is violated in both the CKM and Higgs sectors. 27 refs., 4 figs

  5. Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate

    NARCIS (Netherlands)

    Gerlag, Daniëlle M.; Hollis, Sally; Layton, Mark; Vencovský, Jiří; Szekanecz, Zoltán; Braddock, Martin; Tak, Paul P.; Oparanov, Boycho; Stoilov, Rumen; Yaneva, Tanya; Batalov, Anastas; Arteaga, Edgardo Tobias; Escalante, William Otero; Velez, Patricia; Restrepo, Jose Molina; Augustinova, Sevda; Blahova, Anna; Dvorak, Zdenek; Novosad, Libor; Rosa, Jan; Stehlikova, Helena; Vitek, Petr; Balazs, Tibor; Seregely, Katalin; Szombati, Istvan; Tarjan, Katalin; Csengei, Gabor; Galeazzi, Mauro; Saleniece, Sarmite; Saulite-Kandevica, Daina; Coleiro, Bernard; Badurski, Janusz; Brzosko, Marek; Chudzik, Dariusz; Gruszecka-Marczynska, Katarzyna; Hensel, Joanna; Pokrzywnicka-Gajek, Ines; Korpanty-Danda, Joanna; Sochocka-Bykowska, Malgorzata; Tlustochowicz, Witold; Stopinska-Polaszewska, Maria; Gluszko, Piotr; Nedelcovici, Corina; Radulescu, Florin; Gavrila, Mirea; Tanasescu, Coman; Korshunov, Nikolay; Matsievskaia, Galina; Damjanov, Nemanja; Dimic, Aleksandar

    2010-01-01

    To investigate both the preclinical effects of blocking the chemokine receptor CCR5 and the clinical effects of this approach on the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease. Preclinical evaluations of AZD5672, a small-molecule antagonist of CCR5, were

  6. Superweak-like models of CP violation

    International Nuclear Information System (INIS)

    Lavoura, L.

    1992-01-01

    I put forward a two-Higgs-doublet model in which CP violation is mediated only by the neutral Higgs bosons, via the mechanism of scalar-pseudoscalar mixing. In this model there is no CP violation in the exchange of either W bosons or of charged Higgs bosons. The model is therefore an approximate realization of the superweak theory of CP violation. It has only two basic CP-violating quantities. I point out that other models of this kind, but with more than two Higgs doublets, may also be built

  7. Present status of CP violation

    International Nuclear Information System (INIS)

    Ng, J.N.

    1989-06-01

    A review of the status of CP violation in kaons is given. Status of our knowledge of quark mixing angles in the standard six quark model is presented. The role Β d o - Βd o transition plays in this study is examined. A comparison of the estimates of CP violation effects from models beyond the standard one is given. Other experiments that have the capability of testing different CP violation models are also discussed. (Author) 35 refs., 6 figs., tab

  8. AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists.

    Science.gov (United States)

    Moody, Terry W; Tashakkori, Nicole; Mantey, Samuel A; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T

    2017-01-01

    While peptide antagonists for the gastrin-releasing peptide receptor (BB 2 R), neuromedin B receptor (BB 1 R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB 1 R, BB 2 R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB 1 R, BB 2 R, and BRS-3 with similar affinity ( K i = 1.4-10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca 2+ in human lung cancer cells transfected with BB 1 R, BB 2 R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

  9. Constraints on the CP-Violating MSSM

    CERN Document Server

    Arbey, A; Godbole, R M; Mahmoudi, F

    2016-01-01

    We discuss the prospects for observing CP violation in the MSSM with six CP-violating phases, using a geometric approach to maximise CP-violating observables subject to the experimental upper bounds on electric dipole moments. We consider constraints from Higgs physics, flavour physics, the dark matter relic density and spin-independent scattering cross section with matter.

  10. Synthesis of [{sup 18}F]-labelled nebivolol as a β{sub 1}-adrenergic receptor antagonist for PET imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taek Soo; Park, Jeong Hoon; Lee, Jun Young; Yang, Seung Dae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongeup (Korea, Republic of); Chang, Dong Jo [College of pharmacy, Sunchon National University, Suncheon (Korea, Republic of)

    2017-02-15

    Selective β{sub 1}-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective β{sub 1}-antagonists including nebivolol have high binding affinity on β{sub 1}-adrenergic receptor, not β{sub 2}-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective β{sub 1}-blockers in clinically used β{sub 1}- blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective β{sub 1}-blocker. Nebivolol is C{sub 2}-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of {sup 18}F. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for {sup 18}F-aromatic substitution, was synthesized in moderate yield which was readily subjected to {sup 18}F-aromatic substitution to give {sup 18}F-labelled nebivolol.

  11. Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening

    Science.gov (United States)

    Diao, Yanyan; Jiang, Jing; Zhang, Shoude; Li, Shiliang; Shan, Lei; Huang, Jin; Zhang, Weidong; Li, Honglin

    2018-04-01

    Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast two-hybrid (Y2H) assay, six natural products were identified as FXR antagonists which blocked the CDCA-induced SRC-1 association. The IC50 values of compounds 2a, a diterpene bearing polycyclic skeleton, and 3a, named daphneone with chain scaffold, are as low as 1.29 μM and 1.79 μM, respectively. Compared to the control compound guggulsterone (IC50 = 6.47 μM), compounds 2a and 3a displayed 5-fold and 3-fold higher antagonistic activities against FXR, respectively. Remarkably, the two representative compounds shared low topological similarities with other reported FXR antagonists. According to the putative binding poses, the molecular basis of these antagonists against FXR was also elucidated in this report.

  12. Highlights of CP 2000

    CERN Document Server

    Ellis, John R.

    2001-01-01

    Various developing topics in CP violation are reviewed. There are many theoretical reasons to hope that the CKM paradigm may be incomplete. It is surely too soon to be claiming new physics in \\epsilon^\\prime/\\epsilon or in D^0-\\bar D^0 mixing, but rare K decays offer interesting places to search for new physics. It is probably also premature to see a clash between global CKM fits and current estimates of sin \\beta and \\gamma, where much more precise data will soon be available. There are interesting possibilities to look for CP violation in neutrino oscillations and in Higgs physics. Rapid progress can be expected now that CP violation is moving to the top of the particle physics agenda.

  13. The CpG island searcher: a new WWW resource.

    Science.gov (United States)

    Takai, Daiya; Jones, Peter A

    2003-01-01

    Clusters of CpG dinucleotides in GC rich regions of the genome called "CpG islands" frequently occur in the 5' ends of genes. Methylation of CpG islands plays a role in transcriptional silencing in higher organisms in certain situations. We have established a CpG-island-extraction algorithm, which we previously developed [Takai and Jones, 2002], on a web site which has a simple user interface to identify CpG islands from submitted sequences of up to 50kb. The web site determines the locations of CpG islands using parameters (lower limit of %GC, ObsCpG/ExpCpG, length) set by the user, to display the value of parameters on each CpG island, and provides a graphical map of CpG dinucleotide distribution and borders of CpG islands. A command-line version of the CpG islands searcher has also been developed for larger sequences. The CpG Island Searcher was applied to the latest sequence and mapping information of human chromosomes 20, 21 and 22, and a total of 2345 CpG islands were extracted and 534 (23%) of them contained first coding exons and 650 (28%) contained other exons. The CpG Island Searcher is available on the World Wide Web at http://www.cpgislands.com or http://www.uscnorris.com/cpgislands/cpg.cgi.

  14. CP violation in K decays

    International Nuclear Information System (INIS)

    Gilman, F.J.

    1989-05-01

    Recent theoretical and experimental progress on the manifestation of CP violation in K decays, and toward understanding whether CP violation originates in a phase, or phases, in the weak mixing matrix of quarks is reviewed. 23 refs., 10 figs

  15. 60 years controlled nuclear fission: CP-1

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    On December 2, 1942, the Chicago Pile 1 (CP-1) went critical for the first time. In this way, the scientists and engineers involved in the project under the leadership of Enrico Fermi succeeded in demonstrating that a self-sustaining nuclear reaction with nuclear fission processes was technically feasible. Only four years after the discovery and proof of nuclear fission by Otto Hahn, Fritz Strassmann, and Lise Meitner, the experiment consisting of graphite blocks as the moderator and uranium dioxide pellets as the fuel, as well as instrumentation and control devices, had been set up in the former squash court of the field and track stadium of the University of Chicago. Precisely at 3.36 a.m. Chicago time, after control rods had been withdrawn, the instruments showed the chain reaction by the neutron flux they indicated. An important cornerstone in the use of nuclear power had thus been laid. (orig.)

  16. CP violation conditions in N-Higgs-doublet potentials

    International Nuclear Information System (INIS)

    Nishi, C. C.

    2006-01-01

    Conditions for CP violation in the scalar potential sector of general N-Higgs-doublet models are analyzed from a group theoretical perspective. For the simplest two-Higgs-doublet model potential, a minimum set of conditions for explicit and spontaneous CP violation is presented. The conditions can be given a clear geometrical interpretation in terms of quantities in the adjoint representation of the basis transformation group for the two doublets. Such conditions depend on CP-odd pseudoscalar invariants. When the potential is CP invariant, the explicit procedure to reach the real CP-basis and the explicit CP transformation can also be obtained. The procedure to find the real basis and the conditions for CP violation are then extended to general N-Higgs-doublet model potentials. The analysis becomes more involved and only a formal procedure to reach the real basis is found. Necessary conditions for CP invariance can still be formulated in terms of group invariants: the CP-odd generalized pseudoscalars. The problem can be completely solved for three Higgs-doublets

  17. Higgs boson searches in CP-conserving and CP-violating MSSM scenarios with the DELPHI detector

    International Nuclear Information System (INIS)

    Abdallah, J.; Antilogus, P.; Augustin, J.E.

    2008-01-01

    This paper presents the final interpretation of the results from DELPHI on the searches for Higgs bosons in the minimal supersymmetric extension of the Standard Model (MSSM). A few representative scenarios are considered, that include CP conservation and explicit CP violation in the Higgs sector. The experimental results encompass the searches for neutral Higgs bosons at LEP1 and LEP2 in final states as expected in the MSSM, as well as LEP2 searches for charged Higgs bosons and for neutral Higgs bosons decaying into hadrons independent of the quark flavour. The data reveal no significant excess with respect to background expectations. The results are translated into excluded regions of the parameter space in the various scenarios. In the CP-conserving case, these lead to limits on the masses of the lightest scalar and pseudoscalar Higgs bosons, h and A, and on tan β. The dependence of these limits on the top quark mass is discussed. Allowing for CP violation reduces the experimental sensitivity to Higgs bosons. It is shown that this effect depends strongly on the values of the parameters responsible for CP violation in the Higgs sector. (orig.)

  18. Strong CP, flavor, and twisted split fermions

    International Nuclear Information System (INIS)

    Harnik, Roni; Perez, Gilad; Schwartz, Matthew D.; Shirman, Yuri

    2005-01-01

    We present a natural solution to the strong CP problem in the context of split fermions. By assuming CP is spontaneously broken in the bulk, a weak CKM phase is created in the standard model due to a twisting in flavor space of the bulk fermion wavefunctions. But the strong CP phase remains zero, being essentially protected by parity in the bulk and CP on the branes. As always in models of spontaneous CP breaking, radiative corrections to theta bar from the standard model are tiny, but even higher dimension operators are not that dangerous. The twisting phenomenon was recently shown to be generic, and not to interfere with the way that split fermions naturally weaves small numbers into the standard model. It follows that out approach to strong CP is compatible with flavor, and we sketch a comprehensive model. We also look at deconstructed version of this setup which provides a viable 4D model of spontaneous CP breaking which is not in the Nelson-Barr class. (author)

  19. Novel activities by ebolavirus and marburgvirus interferon antagonists revealed using a standardized in vitro reporter system.

    Science.gov (United States)

    Guito, Jonathan C; Albariño, César G; Chakrabarti, Ayan K; Towner, Jonathan S

    2017-01-15

    Filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (IFN) responses early in infection. Filoviral protein VP35 is implicated as the major IFN induction antagonist, while Ebola virus (EBOV) VP24 or Marburg virus (MARV) VP40 are known to block downstream IFN signaling. Despite progress elucidating EBOV and MARV antagonist function, those for most other filoviruses, including Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV), Bundibugyo (BDBV) and Ravn (RAVV) viruses, remain largely neglected. Thus, using standardized vectors and reporter assays, we characterized activities by each IFN antagonist from all known ebolavirus and marburgvirus species side-by-side. We uncover noncanonical suppression of IFN induction by ebolavirus VP24, differing potencies by MARV and RAVV proteins, and intriguingly, weaker antagonism by VP24 of RESTV. These underlying molecular explanations for differential virulence in humans could guide future investigations of more-neglected filoviruses as well as treatment and vaccine studies. Published by Elsevier Inc.

  20. B decays and models for CP violation

    International Nuclear Information System (INIS)

    He, X.

    1996-01-01

    The decay modes B to ππ, ψK S , K - D, πK, and ηK are promising channels to study the unitarity triangle of the CP-violating Cabibbo-Kobayashi-Maskawa (CKM) matrix. In this paper I study the consequences of these measurements in the Weinberg model. I show that using the same set of measurements, the following different mechanisms for CP violation can be distinguished: (1) CP is violated in the CKM sector only; (2) CP is violated spontaneously in the Higgs sector only; and (3) CP is violated in both the CKM and Higgs sectors. copyright 1996 The American Physical Society

  1. CP violation in ATLAS

    International Nuclear Information System (INIS)

    Saavedra, A.F.

    1995-01-01

    Full text: In the standard model CP violation is generated by a non trivial complex phase in the CKM matrix. The Standard Model does not predict the elements of the CKM matrix, they need to be experimentally measured. This will show if all the CP violation phenomena can be accounted by the complex phase or there are other contributing mechanisms which lie beyond the scope of Standard Model. It is of interest to overconstraint the so called unitary triangle by measuring each angle (α, β and γ) from the CP asymmetry that occurs in different decay modes. During the initial low luminosity period of the LHC a large effort will be concentrated in studying B physics, especially CP violation in the B 0 - B-bar 0 system, with the ATLAS detector. The features of the detector which are important for CP studies are: sharp trigger from the muon spectrometer (muons will be identify down to p T ≅ 5GeV, be able to distinguish electrons from hadrons (down to p T ≅ 1 GeV) with the Straw Tracker and Transition detector and high resolution of tracks, secondary vertices with the Semiconductor Tracker (resolution of 10-90 μm. For some decays modes ATLAS is expected to obtain larger sample of events than the B-factories that are being proposed. It has been calculated that the systematic error σ sin (2 α) = 0.06 and σ sin ( 2 β) = 0.027 which is comparable with other future experiments

  2. Flavour Physics and CP Violation

    CERN Document Server

    Fleischer, Robert

    2006-01-01

    The starting point of these lectures is an introduction to the weak interactions of quarks and the Standard-Model description of CP violation, where the central role is played by the Cabibbo-Kobayashi-Maskawa matrix and the corresponding unitarity triangles. Since the B-meson system will govern the stage of (quark) flavour physics and CP violation in this decade, it will be our main focus. We shall classify B-meson decays, introduce the theoretical tools to deal with them, investigate the requirements for non-vanishing CP-violating asymmetries, and discuss the main strategies to explore CP violation and the preferred avenues for physics beyond the Standard Model to enter. This formalism is then applied to discuss the status of important B-factory benchmark modes, where we focus on puzzling patterns in the data that may indicate new-physics effects, as well as the prospects for B-decay studies at the LHC.

  3. Dopamine transporter-dependent and -independent striatal binding of the benztropine analog JHW 007, a cocaine antagonist with low abuse liability

    Science.gov (United States)

    The benztropine analog JHW 007 displays high affinity for the dopamine transporter (DAT), but unlike typical DAT ligands, has relatively low abuse liability and blocks effects of cocaine,including its self-administration. To determine sites responsible for the cocaine-antagonist effects of JHW 007, ...

  4. CP trajectory diagram--a tool for a pictorial representation of CP and matter effects in neutrino oscillations

    International Nuclear Information System (INIS)

    Minakata, Hisakazu; Nunokawa, Hiroshi

    2003-01-01

    We introduce a 'CP trajectory diagram in bi-probability space' as a powerful tool for a pictorial representation of the genuine CP and the matter effects in neutrino oscillations. The existence of correlated ambiguity in the determination of CP-violating phase δ and the sign of Δm 13 2 is uncovered. The principles of tuning the beam energy for a given baseline distance are proposed to resolve the ambiguity and to maximize the CP-odd effect. We finally point out, quite contrary to what is usually believed, that the ambiguity may be resolved with ∼50% chance in the super-JHF experiment despite its relatively short baseline of 300 km

  5. Theory prospective on leptonic CP violation

    International Nuclear Information System (INIS)

    Petcov, S.T.

    2016-01-01

    The phenomenology of 3-neutrino mixing, the current status of our knowledge about the 3-neutrino mixing parameters, including the absolute neutrino mass scale, and of the Dirac and Majorana CP violation in the lepton sector are reviewed. The problems of CP violation in neutrino oscillations and of determining the nature – Dirac or Majorana – of massive neutrinos are discussed. The seesaw mechanism of neutrino mass generation and the related leptogenesis scenario of generation of the baryon asymmetry of the Universe are considered. The results showing that the CP violation necessary for the generation of the baryon asymmetry of the Universe in leptogenesis can be due exclusively to the Dirac and/or Majorana CP-violating phase(s) in the neutrino mixing matrix U are briefly reviewed. The discrete symmetry approach to understanding the observed pattern of neutrino mixing and the related predictions for the leptonic Dirac CP violation are also reviewed.

  6. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases.

    Directory of Open Access Journals (Sweden)

    Julia Arand

    2012-06-01

    Full Text Available The enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood. Here, we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of selected single copy genes and repetitive elements (LINE1, B1, IAP-LTR-retrotransposons, and major satellites. The analysis unambiguously identifies a substantial amount of regional incomplete methylation maintenance, i.e. hemimethylated CpG positions, with variant degrees among cell types. Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively catalysed by Dnmt3a and Dnmt3b. This sequence position-, cell type-, and region-dependent non-CpG methylation is strongly linked to neighboring CpG methylation and requires the presence of Dnmt3L. The generation of a comprehensive data set of 146,000 CpG dyads was used to apply and develop parameter estimated hidden Markov models (HMM to calculate the relative contribution of DNA methyltransferases (Dnmts for de novo and maintenance DNA methylation. The comparative modelling included wild-type ESCs and mutant ESCs deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM analysis identifies a considerable de novo methylation activity for Dnmt1 at certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b contribute de novo function. However, both enzymes are also essential to maintain symmetrical CpG methylation at distinct repetitive and single copy sequences in ESCs.

  7. Soft CP violation in K-meson systems

    International Nuclear Information System (INIS)

    Montero, J.C.; Nishi, C.C.; Pleitez, V.; Ravinez, O.; Rodriguez, M.C.

    2006-01-01

    We consider a model with soft CP violation which accommodates the CP violation in the neutral kaons even if we assume that the Cabibbo-Kobayashi-Maskawa mixing matrix is real and the sources of CP violation are three complex vacuum expectation values and a trilinear coupling in the scalar potential. We show that for some reasonable values of the masses and other parameters the model allows us to explain all the observed CP violation processes in the K 0 -K 0 system

  8. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    Science.gov (United States)

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  9. Risk Factors for Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) Acquisition Among Contacts of Newly Diagnosed CP-CRE Patients.

    Science.gov (United States)

    Schwartz-Neiderman, Anat; Braun, Tali; Fallach, Noga; Schwartz, David; Carmeli, Yehuda; Schechner, Vered

    2016-10-01

    OBJECTIVE Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are extremely drug-resistant pathogens. Screening of contacts of newly identified CP-CRE patients is an important step to limit further transmission. We aimed to determine the risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient. METHODS A matched case-control study was performed in a tertiary care hospital in Israel. The study population was comprised of patients who underwent rectal screening for CP-CRE following close contact with a newly identified CP-CRE index patient. Cases were defined as positive tests for CP-CRE. For each case patient, 2 matched controls were randomly selected from the pool of contacts who tested negative for CP-CRE following exposure to the same index case. Bivariate and multivariate analyses were conducted using conditional logistic regression. RESULTS In total, 53 positive contacts were identified in 40 unique investigations (896 tests performed on 735 contacts) between October 6, 2008, and June 7, 2012. bla KPC was the only carbapenemase identified. In multivariate analysis, risk factors for CP-CRE acquisition among contacts were (1) contact with an index patient for ≥3 days (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.0-48.9), (2) mechanical ventilation (OR, 4.1; 95% CI, 1.4-11.9), and (3) carriage or infection with another multidrug-resistant organism (MDRO; OR, 2.6; 95% CI, 1.0-7.1). Among patients who received antibiotics, cephalosporins were associated with a lower risk of acquisition. CONCLUSIONS Patient characteristics (ventilation and carriage of another MDRO) as well as duration of contact are risk factors for CP-CRE acquisition among contacts. The role of cephalosporins requires further study. Infect Control Hosp Epidemiol 2016;1-7.

  10. MeCP2 regulates ethanol sensitivity and intake.

    Science.gov (United States)

    Repunte-Canonigo, Vez; Chen, Jihuan; Lefebvre, Celine; Kawamura, Tomoya; Kreifeldt, Max; Basson, Oan; Roberts, Amanda J; Sanna, Pietro Paolo

    2014-09-01

    We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  11. CP and other gauge symmetries in string theory

    International Nuclear Information System (INIS)

    Dine, M.; Leigh, R.G.; MacIntire, D.A.

    1992-01-01

    We argue that CP is a gauge symmetry in string theory. As a consequence, CP cannot be explicitly broken either perturbatively or nonperturbatively; there can be no nonperturbative CP-violating parameters. String theory is thus an example of a theory where all θ angles arise due to spontaneous CP violation, and are in principle calculable

  12. NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

    Science.gov (United States)

    Moore, N A; Blackman, A; Awere, S; Leander, J D

    1993-06-11

    In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

  13. Invariant approach to CP in unbroken Δ(27

    Directory of Open Access Journals (Sweden)

    Gustavo C. Branco

    2015-10-01

    Full Text Available The invariant approach is a powerful method for studying CP violation for specific Lagrangians. The method is particularly useful for dealing with discrete family symmetries. We focus on the CP properties of unbroken Δ(27 invariant Lagrangians with Yukawa-like terms, which proves to be a rich framework, with distinct aspects of CP, making it an ideal group to investigate with the invariant approach. We classify Lagrangians depending on the number of fields transforming as irreducible triplet representations of Δ(27. For each case, we construct CP-odd weak basis invariants and use them to discuss the respective CP properties. We find that CP violation is sensitive to the number and type of Δ(27 representations.

  14. CP determination and tests for CP or P violation by the V1V2 decay mode

    International Nuclear Information System (INIS)

    Nelson, C.A.

    1984-01-01

    A decay mode such as phiphi, UPSILONUPSILON, K/sup asterisk+/K/sup asterisk-/, or D/sup asterisk+/D/sup asterisk-/ can be used to distinguish between a neutral spin-0 technipion and a neutral spin-0 Higgs particle. By this generalization of phiphi parity test, the CP eigenvalue γ/sub C/P can be determined for an X particle of any spin J which decays CP invariantly into VV, or VV-bar, where each vector meson either decays into two spin-0 bosons, or is ω. The absence in a VV, or VV-bar, decay channel of sin2phi and sinphi terms in the azimuthal distribution is due to CP invariance and/or P invariance. For a V 1 V 2 decay channel without a V 1 bold-arrow-left-rightV 2 exchange property, and in a mode like K/sup asterisk+/K /sup asterisk0/, such terms would imply that P is violated. For a V 1 V 2 mode such as phiω where each vector meson is its own antiparticle, such terms would imply that both P and CP are violated; when CP invariance holds, the γ/sub C/P(-)/sup J/ eigenvalue of X can be determined provided certain amplitudes do not accidentally vanish

  15. CP violation

    International Nuclear Information System (INIS)

    Gilman, F.J.

    1989-12-01

    Predictions for CP violation in the three generation Standard Model are reviewed based on what is known about the Cabibbo-Kobayashi-Maskawa matrix. Application to the K and B meson systems are emphasized. 43 refs., 13 figs

  16. 75 FR 35125 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to the Foreign...

    Science.gov (United States)

    2010-06-21

    ... California CP 22000, Mexico; Calle Granito No. 2025, Seccion El Dorado, Fraccionamiento Playas de Tijuana, Tijuana, Baja California, Mexico; Calle Granito No. 602, Seccion El Dorado, Fraccionamiento Playas de... blocked pursuant to the Kingpin Act. 1. Carrillo Rodriguez, Luis Miguel, c/o VUELA PERU S.A.C., Lima, Peru...

  17. AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Terry W. Moody

    2017-07-01

    Full Text Available While peptide antagonists for the gastrin-releasing peptide receptor (BB2R, neuromedin B receptor (BB1R, and bombesin (BB receptor subtype-3 (BRS-3 exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM. AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

  18. AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

    Science.gov (United States)

    Moody, Terry W.; Tashakkori, Nicole; Mantey, Samuel A.; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T.

    2017-01-01

    While peptide antagonists for the gastrin-releasing peptide receptor (BB2R), neuromedin B receptor (BB1R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists. PMID:28785244

  19. Arsenic-Rich Polyarsenides Stabilized by Cp*Fe Fragments.

    Science.gov (United States)

    Schmidt, Monika; Konieczny, David; Peresypkina, Eugenia V; Virovets, Alexander V; Balázs, Gabor; Bodensteiner, Michael; Riedlberger, Felix; Krauss, Hannes; Scheer, Manfred

    2017-06-12

    The redox chemistry of [Cp*Fe(η 5 -As 5 )] (1, Cp*=η 5 -C 5 Me 5 ) has been investigated by cyclic voltammetry, revealing a redox behavior similar to that of its lighter congener [Cp*Fe(η 5 -P 5 )]. However, the subsequent chemical reduction of 1 by KH led to the formation of a mixture of novel As n scaffolds with n up to 18 that are stabilized only by [Cp*Fe] fragments. These include the arsenic-poor triple-decker complex [K(dme) 2 ][{Cp*Fe(μ,η 2:2 -As 2 )} 2 ] (2) and the arsenic-rich complexes [K(dme) 3 ] 2 [(Cp*Fe) 2 (μ,η 4:4 -As 10 )] (3), [K(dme) 2 ] 2 [(Cp*Fe) 2 (μ,η 2:2:2:2 -As 14 )] (4), and [K(dme) 3 ] 2 [(Cp*Fe) 4 (μ 4 ,η 4:3:3:2:2:1:1 -As 18 )] (5). Compound 4 and the polyarsenide complex 5 are the largest anionic As n ligand complexes reported thus far. Complexes 2-5 were characterized by single-crystal X-ray diffraction, 1 H NMR spectroscopy, EPR spectroscopy (2), and mass spectrometry. Furthermore, DFT calculations showed that the intermediate [Cp*Fe(η 5 -As 5 )] - , which is presumably formed first, undergoes fast dimerization to the dianion [(Cp*Fe) 2 (μ,η 4:4 -As 10 )] 2- . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist

    International Nuclear Information System (INIS)

    Fielding, S.; Wilker, J.C.; Chernack, J.; Ramirez, V.; Wilmot, C.A.; Martin, L.L.; Payack, J.F.; Cornfeldt, M.L.; Rudolphi, K.A.; Rush, D.K.

    1990-01-01

    8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia

  1. Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes.

    Directory of Open Access Journals (Sweden)

    Robby M Zachariah

    Full Text Available Rett Syndrome (RTT is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the relevant isoform for RTT. However, due to the unavailability of MeCP2 isoform-specific antibodies, the endogenous expression pattern of MeCP2E1 is unknown. To gain insight into the expression of MeCP2E1 in brain, we have developed an anti-MeCP2E1 antibody and validated its specificity in cells exogenously expressing individual MeCP2 isoforms. This antibody does not show any cross-reactivity with MeCP2E2 and detects endogenous MeCP2E1 in mice brain, with no signal in Mecp2(tm1.1Bird y/- null mice. Additionally, we show the endogenous MeCP2E1 expression throughout different brain regions in adult mice, and demonstrate its highest expression in the brain cortex. Our results also indicate that MeCP2E1 is highly expressed in primary neurons, as compared to primary astrocytes. This is the first report of the endogenous MeCP2E1 expression at the protein levels, providing novel avenues for understanding different aspects of MeCP2 function.

  2. CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist

    DEFF Research Database (Denmark)

    Hasbak, P; Sams, A; Schifter, S

    2001-01-01

    . The partial porcine mRNA sequences shared 82 - 92% nucleotide identity with human sequences. 3. The human peptides alphaCGRP, betaCGRP, AM and amylin induced relaxation with pEC(50) values of 8.1, 8.1, 6.7 and 6.1 M respectively. 4. The antagonistic properties of a novel non-peptide CGRP antagonist 'Compound...... 1' (WO98/11128), betaCGRP(8 - 37) and the proposed AM receptor antagonist AM(22 - 52) were compared to the well-known CGRP(1) receptor antagonist alphaCGRP(8 - 37). 5. The alphaCGRP(8 - 37) and betaCGRP(8 - 37) induced concentration-dependent (10(-7) - 10(-5) M) rightward shift of both the alpha......(-6) M) had no significant antagonistic effect. 7. In conclusion, the building blocks forming CGRP and AM receptors were present in the porcine LAD, whereas those of the amylin receptor were not. alphaCGRP, betaCGRP, AM and amylin mediated vasorelaxation via the CGRP receptors. No functional response...

  3. Report of the CP-violation working group

    International Nuclear Information System (INIS)

    Hoffman, C.M.

    1982-01-01

    The CP-Violation Working Group met twice during the workshop. A nice summary of our present knowledge of CP-violation was presented in the talk by Prof. James W. Cronin. In the final paragraph of his talk, Prof. Cronin argues that higher precision experiments studying CP-violation at LAMPF II will be extremely important no matter what additional knowledge we acquire in the time before LAMPF II is constructed. The crucial issue at present is to uncover the underlying mechanism responsible for CP-violation. The Working Group heard several talks aimed at reviewing the theoretical status of CP-violation and the directions that future experimental efforts might take. These talks included: Kaon Experiments at KEK, T. Yamazaki, University of Tokyo; Mechanisms for CP Violation, P. Herczeg, Los Alamos; and The Experimental Status of eta 00 Experiments, J.W. Cronin, Univ. of Chicago. There were also extended discussions on which experiments appear to be the most important and how to best perform these measurements. A summary of these discussions is given

  4. Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.

    Science.gov (United States)

    Araque, A; Ferreira, W; Lucas, S; Buño, W

    1992-01-31

    The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex.

  5. Flavour Physics and CP Violation

    CERN Document Server

    Fleischer, Robert

    2005-01-01

    The starting point of these lectures is an introduction to the weak interactions of quarks and the Standard-Model description of CP violation, where the key element is the Cabibbo--Kobayashi--Maskawa matrix and the corresponding unitarity triangles. Since the B-meson system will govern the stage of (quark) flavour physics and CP violation in this decade, it will be -- after a brief look at the kaon system -- our main focus. We shall classify B-meson decays, introduce the theoretical tools to deal with them, explore the requirements for non-vanishing CP-violating asymmetries, and discuss B^0_q--B^0_q_bar mixing (q={d,s}). We will then turn to B-factory benchmark modes, discuss the physics potential of B^0_s mesons, which is particularly promising for B-decay experiments at hadron colliders, and emphasize the importance of studies of rare decays, which are absent at the tree level in the Standard Model, complement nicely the studies of CP violation, and provide interesting probes for new physics.

  6. CP violation in the K and B systems

    International Nuclear Information System (INIS)

    Kayser, B.

    1997-01-01

    Although CP violation was discovered more than thirty years ago, its origin is still unknown. In these lectures, we describe the CP-violation effects which have been seen in K decays, and explain how CP violation can be caused by the Standard Model weak interaction. The hypothesis that this interaction is indeed the origin of CP violation will be incisively tested by future experiments on B and K decays. We explain what quantities these experiments will try to determine, and how they will be able to determine them in a theoretically clean way. To clarify the physics of the K system, we give a phase-convention-free description of CP violation in this system. We conclude by briefly exploring whether electric dipole moments actually violate CP even if CPT invariance is not assumed. (author)

  7. CP violation in the K and B systems

    International Nuclear Information System (INIS)

    Kayser, B.

    1996-11-01

    Although CP violation was discovered more than thirty years ago, its origin is still unknown. In these lectures, we describe the CP- violating effects which have been seen in K decays, and explain how CP violation can be caused by the Standard Model weak interaction. The hypothesis that this interaction is indeed the origin of CP violation will be incisively tested by future experiments on B and K decays. We explain what quantities these experiments will try to determine, and how they will be able to determine them in a theoretically clean way. To clarify the physics of the K system, we give a phase-convention-free description of CP violation in this system. We conclude by briefly exploring whether electric dipole moments actually violate CP even if CPT invariance is not assumed

  8. Effects of NMDA receptor antagonists on probability discounting depend on the order of probability presentation.

    Science.gov (United States)

    Yates, Justin R; Breitenstein, Kerry A; Gunkel, Benjamin T; Hughes, Mallory N; Johnson, Anthony B; Rogers, Katherine K; Shape, Sara M

    Risky decision making can be measured using a probability-discounting procedure, in which animals choose between a small, certain reinforcer and a large, uncertain reinforcer. Recent evidence has identified glutamate as a mediator of risky decision making, as blocking the N-methyl-d-aspartate (NMDA) receptor with MK-801 increases preference for a large, uncertain reinforcer. Because the order in which probabilities associated with the large reinforcer can modulate the effects of drugs on choice, the current study determined if NMDA receptor ligands alter probability discounting using ascending and descending schedules. Sixteen rats were trained in a probability-discounting procedure in which the odds against obtaining the large reinforcer increased (n=8) or decreased (n=8) across blocks of trials. Following behavioral training, rats received treatments of the NMDA receptor ligands MK-801 (uncompetitive antagonist; 0, 0.003, 0.01, or 0.03mg/kg), ketamine (uncompetitive antagonist; 0, 1.0, 5.0, or 10.0mg/kg), and ifenprodil (NR2B-selective non-competitive antagonist; 0, 1.0, 3.0, or 10.0mg/kg). Results showed discounting was steeper (indicating increased risk aversion) for rats on an ascending schedule relative to rats on the descending schedule. Furthermore, the effects of MK-801, ketamine, and ifenprodil on discounting were dependent on the schedule used. Specifically, the highest dose of each drug decreased risk taking in rats in the descending schedule, but only MK-801 (0.03mg/kg) increased risk taking in rats on an ascending schedule. These results show that probability presentation order modulates the effects of NMDA receptor ligands on risky decision making. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. CP nonconservation in dynamically broken gauge theories

    International Nuclear Information System (INIS)

    Lane, K.

    1981-01-01

    The recent proposal of Eichten, Lane, and Preskill for CP nonconservation in electroweak gauge theories with dynamical symmetry breaking is reviewed. Through the alignment of the vacuum with the explicit chiral symmetry breaking Hamiltonian, these theories provide a natural way to understand the dynamical origin of CP nonconservation. Special attention is paid to the problem of strong CP violation. Even through all vacuum angles are zero, this problem is not automatically avoided. In the absence of strong CP violation, the neutron electric dipole moment is expected to be 10 -24 -10 -26 e-cm. A new class of models is proposed in which both strong CP violation and large /ΔS/ = 2 effects may be avoided. In these models, /ΔC/ = 2 processes such as D/sup o/ D/sup -o/ mixing may be large enough to observe

  10. Higgs boson searches in CP-conserving and CP-violating MSSM scenarios with the DELPHI detector

    CERN Document Server

    Abdallah, J.; Adam, W.; Adzic, P.; Albrecht, T.; Alemany-Fernandez, R.; Allmendinger, T.; Allport, P.P.; Amaldi, U.; Amapane, N.; Amato, Sandra F.; Anashkin, E.; Andreazza, A.; Andringa, Sofia; Anjos, N.; Antilogus, Pierre; Apel, W-D.; Arnoud, Y.; Ask, S.; Asman, B.; Augustin, Jean-Eudes; Augustinus, A.; Baillon, P.; Ballestrero, A.; Bambade, P.; Barbier, R.; Bardin, D.; Barker, G.J.; Baroncelli, Antonio; Battaglia, Marco; Baubillier, M.; Becks, K-H.; Begalli, M.; Behrmann, A.; Ben-Haim, Eli; Benekos, N.; Benvenuti, A.; Berat, C.; Berggren, Mikael; Berntzon, L.; Bertrand, D.; Besancon, Marc; Besson, N.; Bloch, Daniel; Blom, M.; Bluj, Michal; Bonesini, Maurizio; Boonekamp, M.; Booth, PSL; Borisov, G.; Botner, Olga; Bouquet, B.; Bowcock, T.J.V.; Boyko, I.; Bracko, Marko; Brenner, R.; Brodet, E.; Bruckman, P.; Brunet, J.M.; Buschbeck, B.; Buschmann, P.; Calvi, M.; Camporesi, Tiziano; Canale, V.; Carena, F.; Castro, Nuno Filipe; Cavallo, F.; Chapkin, M.; Charpentier, Ph.; Checchia, Paolo; Chierici, R.; Chliapnikov, P.; Chudoba, J.; Chung, Suh-Urk; Cieslik, K.; Collins, P.; Contri, Roberto; Cosme, G.; Cossutti, Fabio; Costa, M.J.; Crennell, D.; Cuevas, Javier; D'Hondt, J.; Dalmau, J.; da Silva, T.; Da Silva, W.; Della Ricca, Giuseppe; De Angelis, Alessandro; De Boer, W.; De Clercq, C.; De Lotto, Barbara; De Maria, N.; De Min, A.; de Paula, L.; Di Ciaccio, L.; Di Simone, A.; Doroba, K.; Eigen, G.; Ekelof, Tord; Ellert, Mattias; Elsing, M.; Espirito Santo, Maria Catarina; Fanourakis, George K.; Feindt, Michael; Fernandez, J.; Ferrer, Antonio; Ferro, F.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fulda-Quenzer, F.; Fuster, J.; Gandelman, Miriam; Garcia, C.; Gavillet, Philippe; Gazis, Evangelos; Gomez-Ceballos, G.; Goncalves, P.; Graziani, E.; Grosdidier, G.; Grzelak, K.; Guy, J.; Haag, C.; Hallgren, A.; Hamacher, Klaus; Hamilton, K.; Haug, S.; Hauler, F.; Hedberg, Vincent; Hennecke, M.; Herr, H.; Hoffman, J.; Holmgren, S-O.; Holt, P.J.; Houlden, M.A.; Jackson, John Neil; Jarlskog, Goran; Jarry, P.; Jeans, D.; Johansson, Erik Karl; Johansson, P.D.; Jonsson, P.; Joram, C.; Jungermann, L.; Kapusta, Frederic; Katsanevas, S.; Katsoufis, E.; Kernel, Gabrijel; Kerzel, U.; King, B.T.; Kjaer, N.J.; Kluit, Peter; Kokkinias, P.; Kourkoumelis, C.; Kouznetsov, O.; Krumstein, Z.; Kucharczyk, M.; Lamsa, J.; Leder, G.; Ledroit, F.; Leinonen, L.; Leitner, R.; Lemonne, Jacques; Lepeltier, V.; Lesiak, T.; Liebig, W.; Liko, D.; Lipniacka, A.; Lopes, J.H.; Lopez, J.M.; Loukas, D.; Lutz, Pierre; Lyons, Louis; MacNaughton, J.; Malek, A.; Maltezos, S.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J-C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Mazzucato, F.; Mazzucato, M.; Nulty, R.Mc; Meroni, C.; Migliore, E.; Mitaroff, W.; Mjoernmark, U.; Moa, T.; Moch, M.; Monge, R.; Montenegro, J.; Moraes, D.; Moreno, S.; Morettini, P.; Muller, Ulrich; Muenich, K.; Mulders, M.; Mundim Filho, Luiz Martins; Murray, W.; Muryn, B.; Myatt, G.; Myklebust, T.; Nassiakou, M.; Navarria, F.; Nawrocki, K.; Nicolaidou, R.; Oblakowska-Mucha, A.; Obraztsov, V.; Olshevski, A.; Onofre, A.; Orava, R.; Osterberg, K.; Ouraou, A.; Oyanguren, A.; Paganoni, M.; Paiano, S.; Palacios, J.P.; Palka, Henryk; Papadopoulou, Th.D.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Peralta, L.; Perepelitsa, V.; Perrotta, Andrea; Petrolini, Alessandro; Piedra, Jonatan; Pieri, L.; Pierre, Francois; Pimenta, M.; Piotto, E.; Poireau, V.; Pol, M.E.; Polok, G.; Pozdniakov, V.; Pukhaeva, N.; Pullia, A.; Rames, J.; Read, A.; Rebecchi, P.; Rehn, J.; Reid, D.; Reinhardt, R.; Renton, Peter; Richard, F.; Ridky, Jan; Rivero, M.; Rodriguez, D.; Romero, A.; Ronchese, Paolo; Roudeau, P.; Rovelli, T.; Ruhlmann, Vanina; Ryabtchikov, D.; Sadovsky, A.; Salmi, L.; Salt, J.; Sander, C.; Savoy-Navarro, A.; Schwickerath, U.; Segar, A.; Sekulin, R.; Siebel, Martin; Sisakian, A.; Smadja, G.; Smirnova, O.; Sokolov, Andrei Valerevich; Sopczak, A.; Sosnowski, R.; Spassov, T.; Stanitzki, M.; Stocchi, A.; Strauss, J.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Szumlak, T.; Tabarelli de Fatis, T.; Taffard, A.C.; Tegenfeldt, F.; Timmermans, Jan; Tkatchev, L.; Tobin, M.; Todorovova, S.; Tome, B.; Tonazzo, A.; Tortosa, P.; Travnicek, Petr; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, Clara; Turluer, M-L.; Tyapkin, I.A.; Tyapkin, P.; Tzamarias, S.; Uvarov, V.; Valenti, Giovanni; Van Dam, P.; Van Eldik, J.; van Remortel, N.; Van Vulpen, I.; Vegni, G.; Veloso, Filipe; Venus, W.; Verdier, Patrice; Verzi, V.; Vilanova, D.; Vitale, Lorenzo; Vrba, V.; Wahlen, H.; Washbrook, A.J.; Weiser, C.; Wicke, D.; Wickens, J.; Wilkinson, G.; Winter, M.; Witek, M.; Yushchenko, O.; Zalewska, A.; Zalewski, P.; Zavrtanik, Danilo; Zhuravlov, V.; Zimine, N.I.; Zintchenko, Alexandre

    2008-01-01

    This paper presents the final interpretation of the results from DELPHI on the searches for Higgs bosons in the Minimal Supersymmetric extension of the Standard Model (MSSM). A few representative scenarios are considered, that include CP conservation and explicit CP violation in the Higgs sector. The experimental results encompass the searches for neutral Higgs bosons at LEP1 and LEP2 in final states as expected in the MSSM, as well as LEP2 searches for charged Higgs bosons and for neutral Higgs bosons decaying into hadrons independent of the quark flavour. The data reveal no significant excess with respect to background expectations. The results are translated into excluded regions of the parameter space in the various scenarios. In the CP-conserving case, these lead to limits on the masses of the lightest scalar and pseudoscalar Higgs bosons, h and A, and on tan(beta). The dependence of these limits on the top quark mass is discussed. Allowing for CP violation reduces the experimental sensitivity to Higgs b...

  11. Synthesis of cyclopentadienyl capped polyethylene and subsequent block copolymer formation via hetero Diels-Alder (HDA) chemistry.

    Science.gov (United States)

    Espinosa, Edgar; Glassner, Mathias; Boisson, Christophe; Barner-Kowollik, Christopher; D'Agosto, Franck

    2011-09-15

    In the current contribution it is demonstrated - for the first time - that poly(ethylene) (M(n) = 1,400 as well as 2,800 g  ·  mol(-1) , PDI = 1.2) can be readily equipped with highly reactive cyclopentadienyl (Cp) end groups. The Cp terminal poly(ethylene) can subsequently be reacted in an efficient hetero Diels-Alder (HDA) reaction with macromolecules (poly(isobornyl acrylate) (M(n) = 4,600 g  ·  mol(-1) , PDI = 1.10) and poly(styrene) (M(n) = 6,300 g  ·  mol(-1) , PDI = 1.13) featuring strongly electron withdrawing thiocarbonyl thio end groups, prepared via reversible addition fragmentation chain transfer (RAFT) polymerization employing benzylpyridin-2-yldithioformate (BPDF) as transfer agent. The resulting block copolymers have been analyzed via high-temperature size exclusion chromatography (SEC) as well as nuclear magnetic resonance (NMR) spectroscopy. The current system allows for the removal of the excess of the non-poly(ethylene) containing segment via filtration of the poly(ethylene)-containing block copolymer. However, the reaction temperatures need to be judiciously selected. Characterization of the generated block copolymers at elevated temperatures can lead - depending on the block copolymer type - to the occurrence of retro Diels-Alder processes. The present study thus demonstrates that RAFT-HDA ligation can be effectively employed for the generation of block copolymers containing poly(ethylene) segments. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. A novel BLyS antagonist peptide designed based on the 3-D complex structure of BCMA and BLyS

    International Nuclear Information System (INIS)

    Sun Jian; Feng Jiannan; Li Yan; Shen Beifen

    2006-01-01

    B lymphocyte stimulator (BLyS) is a member of tumor necrosis factor (TNF) family. Because of its roles in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome (SS), BLyS antagonists have been tested to treat SLE- and RA-like symptoms in mice and obtained optimistic results. So far, reported BLyS antagonists were mostly decoyed BLyS receptors or anti-BLyS antibodies. In this study, a novel BLyS antagonist peptide, PT, was designed based on the modeling 3-D complex structure of BCMA and BLyS. The interaction mode of PT with BLyS was analyzed theoretically. The results of competitive ELISA demonstrated that PT could inhibit the binding of BCMA-Fc and anti-BLyS antibody to BLyS in vitro. In addition, PT could partly block the proliferating activity of BLyS on mice splenocytes. The BLyS antagonizing activity of PT was significant (p < 0.05). This study highlights the possibility of using BLyS antagonist peptide to neutralize BLyS activity. Further optimization of PT with computer-guided molecular design method to enhance its biopotency may be useful in developing new BLyS antagonists to treat BLyS-related autoimmune diseases

  13. The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects

    Science.gov (United States)

    Schwandt, Melanie L; Cortes, Carlos R; Kwako, Laura E; George, David T; Momenan, Reza; Sinha, Rajita; Grigoriadis, Dimitri E; Pich, Emilio Merlo; Leggio, Lorenzo; Heilig, Markus

    2016-01-01

    Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21–65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse. PMID:27109623

  14. CP violation in the baryon sector

    CERN Document Server

    Smith, Eluned Anne

    2017-01-01

    The study of CP violation in the baryon sector is still a relatively new field and offers the possibility to make many CP measurements which could complement those performed in the meson sector. This is especially true of late given the large number of baryons currently being produced at the LHC. Such measurements could help further over-constrain the CKM unitary triangle, as well as furthering our understand of baryongenesis. These proceedings will give an overview of the current state of the search for CP violation in the baryon sector.

  15. CP violation in CMS expected performance

    CERN Document Server

    Stefanescu, J

    1999-01-01

    The CMS experiment can contribute significantly to the measurement of the CP violation asymmetries. A recent evaluation of the expected precision on the CP violation parameter sin 2 beta in the channel B /sub d//sup 0/ to J/ psi $9 K/sub s//sup 0/ has been performed using a simulation of the CMS tracker including full pattern recognition. CMS has also studied the possibility to observe CP violation in the decay channel B/sub s//sup 0/ to J/ psi phi . The $9 results of these studies are reviewed. (7 refs).

  16. Testing CP in K/sub μ/3 decays

    International Nuclear Information System (INIS)

    Leurer, M.

    1989-01-01

    K factories will open the way for high-precision CP tests in K/sub μ/ 3 decays. The standard model does not predict CP breaking in this process. We consider here the effects of nonstandard interactions mediated by vector and scalar particles and by leptoquarks. We show that, for the only experimentally measurable quantity, vector particles alone never induce CP violation, and give a general expression for the CP breaking induced by scalars and leptoquarks

  17. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

    Science.gov (United States)

    Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I; Lluís, Carme; Cortés, Antoni; Volkow, Nora D; Schiffmann, Serge N; Ferré, Sergi; Casadó, Vicent

    2015-07-07

    Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

  18. Search for CP-violation in the charm sector at LHCb

    International Nuclear Information System (INIS)

    Coombes, M.P.

    2014-01-01

    Results of searches for CP-violation in charm hadrons and measurements of CP-violating and D 0 mixing parameters are presented for LHCb data accumulated during 2010 and 2011. A time-integrated CP-violating asymmetry in two-body D 0 decays constitutes the first evidence of CP violation in the decay of charm hadrons. No CP violation has been found in D + → K - K + π + decays. Concerning mixing and time-dependent CP asymmetries in D 0 decays, results are compatible with the absence of CP-violation

  19. Topics in CP violation

    Science.gov (United States)

    Quinn, H. R.

    1993-02-01

    Given the varied backgrounds of the members of this audience this talk will be a grab bag of topics related to the general theme of CP Violation. I do not have time to dwell in detail on any of them. First, for the astronomers and astrophysicists among you, I want to begin by reviewing the experimental status of evidence for CP violation in particle processes. There is only one system where this has been observed, and that is in the decays of neutral K mesons.

  20. Topics in CP violation

    International Nuclear Information System (INIS)

    Quinn, H.R.

    1993-02-01

    Given the varied backgrounds of the members of this audience this talk will be a grab bag of topics related to the general theme of CP Violation. I do not have time to dwell in detail on any of them. First, for the astronomers and astrophysicists among you, I want to begin by reviewing the experimental status of evidence for CP violation in particle processes. There is only one system where this has been observed, and that is in the decays of neutral K mesons

  1. Flavour physics and CP violation

    Indian Academy of Sciences (India)

    It is well known that the study of flavour physics and CP violation is very important to critically test the Standard Model and to look for possible signature of new physics beyond it. The observation of CP violation in kaon system in 1964 has ignited a lot of experimental and theoretical efforts to understand its origin and to look ...

  2. The Physiological Functions and Structural Determinants of Catalytic Bias in the [FeFe]-Hydrogenases CpI and CpII of Clostridium pasteurianum Strain W5

    Directory of Open Access Journals (Sweden)

    Jesse B. Therien

    2017-07-01

    Full Text Available The first generation of biochemical studies of complex, iron-sulfur-cluster-containing [FeFe]-hydrogenases and Mo-nitrogenase were carried out on enzymes purified from Clostridium pasteurianum (strain W5. Previous studies suggested that two distinct [FeFe]-hydrogenases are expressed differentially under nitrogen-fixing and non-nitrogen-fixing conditions. As a result, the first characterized [FeFe]-hydrogenase (CpI is presumed to have a primary role in central metabolism, recycling reduced electron carriers that accumulate during fermentation via proton reduction. A role for capturing reducing equivalents released as hydrogen during nitrogen fixation has been proposed for the second hydrogenase, CpII. Biochemical characterization of CpI and CpII indicated CpI has extremely high hydrogen production activity in comparison to CpII, while CpII has elevated hydrogen oxidation activity in comparison to CpI when assayed under the same conditions. This suggests that these enzymes have evolved a catalytic bias to support their respective physiological functions. Using the published genome of C. pasteurianum (strain W5 hydrogenase sequences were identified, including the already known [NiFe]-hydrogenase, CpI, and CpII sequences, and a third hydrogenase, CpIII was identified in the genome as well. Quantitative real-time PCR experiments were performed in order to analyze transcript abundance of the hydrogenases under diazotrophic and non-diazotrophic growth conditions. There is a markedly reduced level of CpI gene expression together with concomitant increases in CpII gene expression under nitrogen-fixing conditions. Structure-based analyses of the CpI and CpII sequences reveal variations in their catalytic sites that may contribute to their alternative physiological roles. This work demonstrates that the physiological roles of CpI and CpII are to evolve and to consume hydrogen, respectively, in concurrence with their catalytic activities in vitro, with Cp

  3. The Physiological Functions and Structural Determinants of Catalytic Bias in the [FeFe]-Hydrogenases CpI and CpII of Clostridium pasteurianum Strain W5

    Science.gov (United States)

    Therien, Jesse B.; Artz, Jacob H.; Poudel, Saroj; Hamilton, Trinity L.; Liu, Zhenfeng; Noone, Seth M.; Adams, Michael W. W.; King, Paul W.; Bryant, Donald A.; Boyd, Eric S.; Peters, John W.

    2017-01-01

    The first generation of biochemical studies of complex, iron-sulfur-cluster-containing [FeFe]-hydrogenases and Mo-nitrogenase were carried out on enzymes purified from Clostridium pasteurianum (strain W5). Previous studies suggested that two distinct [FeFe]-hydrogenases are expressed differentially under nitrogen-fixing and non-nitrogen-fixing conditions. As a result, the first characterized [FeFe]-hydrogenase (CpI) is presumed to have a primary role in central metabolism, recycling reduced electron carriers that accumulate during fermentation via proton reduction. A role for capturing reducing equivalents released as hydrogen during nitrogen fixation has been proposed for the second hydrogenase, CpII. Biochemical characterization of CpI and CpII indicated CpI has extremely high hydrogen production activity in comparison to CpII, while CpII has elevated hydrogen oxidation activity in comparison to CpI when assayed under the same conditions. This suggests that these enzymes have evolved a catalytic bias to support their respective physiological functions. Using the published genome of C. pasteurianum (strain W5) hydrogenase sequences were identified, including the already known [NiFe]-hydrogenase, CpI, and CpII sequences, and a third hydrogenase, CpIII was identified in the genome as well. Quantitative real-time PCR experiments were performed in order to analyze transcript abundance of the hydrogenases under diazotrophic and non-diazotrophic growth conditions. There is a markedly reduced level of CpI gene expression together with concomitant increases in CpII gene expression under nitrogen-fixing conditions. Structure-based analyses of the CpI and CpII sequences reveal variations in their catalytic sites that may contribute to their alternative physiological roles. This work demonstrates that the physiological roles of CpI and CpII are to evolve and to consume hydrogen, respectively, in concurrence with their catalytic activities in vitro, with CpII capturing excess

  4. Measurement of the direct $CP$-violating parameter $A_{CP}$ in the decay $D^+ \\to K^-\\pi^+\\pi^+$

    CERN Document Server

    Abazov, Victor Mukhamedovich; Acharya, Bannanje Sripath; Adams, Mark Raymond; Adams, Todd; Agnew, James P; Alexeev, Guennadi D; Alkhazov, Georgiy D; Alton, Andrew K; Askew, Andrew Warren; Atkins, Scott; Augsten, Kamil; Avila, Carlos A; Badaud, Frederique; Bagby, Linda F; Baldin, Boris; Bandurin, Dmitry V; Banerjee, Sunanda; Barberis, Emanuela; Baringer, Philip S; Bartlett, JFrederick; Bassler, Ursula Rita; Bazterra, Victor; Bean, Alice L; Begalli, Marcia; Bellantoni, Leo; Beri, Suman B; Bernardi, Gregorio; Bernhard, Ralf Patrick; Bertram, Iain A; Besancon, Marc; Beuselinck, Raymond; Bhat, Pushpalatha C; Bhatia, Sudeep; Bhatnagar, Vipin; Blazey, Gerald Charles; Blessing, Susan K; Bloom, Kenneth A; Boehnlein, Amber S; Boline, Daniel Dooley; Boos, Edward E; Borissov, Guennadi; Borysova, Maryna; Brandt, Andrew; Brandt, Oleg; Brock, Raymond L; Bross, Alan D; Brown, Duncan Paul; Bu, Xue-Bing; Buehler, Marc; Buescher, Volker; Bunichev, Viacheslav Yevgenyevich; Burdin, Sergey; Buszello, Claus Peter; Camacho-Perez, Enrique; Casey, Brendan Cameron Kieran; Castilla-Valdez, Heriberto; Caughron, Seth Aaron; Chakrabarti, Subhendu; Chan, Kwok Ming Leo; Chandra, Avdhesh; Chapon, Emilien; Chen, Guo; Cho, Sung-Woong; Choi, Suyong; Choudhary, Brajesh C; Cihangir, Selcuk; Claes, Daniel R; Clutter, Justace Randall; Cooke, Michael P; Cooper, William Edward; Corcoran, Marjorie D; Couderc, Fabrice; Cousinou, Marie-Claude; Cutts, David; Das, Amitabha; Davies, Gavin John; de Jong, Sijbrand Jan; De La Cruz-Burelo, Eduard; Deliot, Frederic; Demina, Regina; Denisov, Dmitri S; Denisov, Sergei P; Desai, Satish Vijay; Deterre, Cecile; DeVaughan, Kayle Otis; Diehl, HThomas; Diesburg, Michael; Ding, Pengfei; Dominguez, DAaron M; Dubey, Abhinav Kumar; Dudko, Lev V; Duperrin, Arnaud; Dutt, Suneel; Eads, Michael T; Edmunds, Daniel L; Ellison, John A; Elvira, VDaniel; Enari, Yuji; Evans, Harold G; Evdokimov, Valeri N; Faure, Alexandre; Feng, Lei; Ferbel, Thomas; Fiedler, Frank; Filthaut, Frank; Fisher, Wade Cameron; Fisk, HEugene; Fortner, Michael R; Fox, Harald; Fuess, Stuart C; Garbincius, Peter H; Garcia-Bellido, Aran; Garcia-Gonzalez, Jose Andres; Gavrilov, Vladimir B; Geng, Weigang; Gerber, Cecilia Elena; Gershtein, Yuri S; Ginther, George E; Gogota, Olga; Golovanov, Georgy Anatolievich; Grannis, Paul D; Greder, Sebastien; Greenlee, Herbert B; Grenier, Gerald Jean; Gris, Phillipe Luc; Grivaz, Jean-Francois; Grohsjean, Alexander; Gruenendahl, Stefan; Gruenewald, Martin Werner; Guillemin, Thibault; Gutierrez, Gaston R; Gutierrez, Phillip; Haley, Joseph Glenn Biddle; Han, Liang; Harder, Kristian; Harel, Amnon; Hauptman, John Michael; Hays, Jonathan M; Head, Tim; Hebbeker, Thomas; Hedin, David R; Hegab, Hatim; Heinson, Ann; Heintz, Ulrich; Hensel, Carsten; Heredia-De La Cruz, Ivan; Herner, Kenneth Richard; Hesketh, Gavin G; Hildreth, Michael D; Hirosky, Robert James; Hoang, Trang; Hobbs, John D; Hoeneisen, Bruce; Hogan, Julie; Hohlfeld, Mark; Holzbauer, Jenny Lyn; Howley, Ian James; Hubacek, Zdenek; Hynek, Vlastislav; Iashvili, Ia; Ilchenko, Yuriy; Illingworth, Robert A; Ito, Albert S; Jabeen, Shabnam; Jaffre, Michel J; Jayasinghe, Ayesh; Jeong, Min-Soo; Jesik, Richard L; Jiang, Peng; Johns, Kenneth Arthur; Johnson, Emily; Johnson, Marvin E; Jonckheere, Alan M; Jonsson, Per Martin; Joshi, Jyoti; Jung, Andreas Werner; Juste, Aurelio; Kajfasz, Eric; Karmanov, Dmitriy Y; Katsanos, Ioannis; Kaur, Manbir; Kehoe, Robert Leo Patrick; Kermiche, Smain; Khalatyan, Norayr; Khanov, Alexander; Kharchilava, Avto; Kharzheev, Yuri N; Kiselevich, Ivan Lvovich; Kohli, Jatinder M; Kozelov, Alexander V; Kraus, James Alexander; Kumar, Ashish; Kupco, Alexander; Kurca, Tibor; Kuzmin, Valentin Alexandrovich; Lammers, Sabine Wedam; Lebrun, Patrice; Lee, Hyeon-Seung; Lee, Seh-Wook; Lee, William M; Lei, Xiaowen; Lellouch, Jeremie; Li, Dikai; Li, Hengne; Li, Liang; Li, Qi-Zhong; Lim, Jeong Ku; Lincoln, Donald W; Linnemann, James Thomas; Lipaev, Vladimir V; Lipton, Ronald J; Liu, Huanzhao; Liu, Yanwen; Lobodenko, Alexandre; Lokajicek, Milos; Lopes de Sa, Rafael; Luna-Garcia, Rene; Lyon, Adam Leonard; Maciel, Arthur KA; Madar, Romain; Magana-Villalba, Ricardo; Malik, Sudhir; Malyshev, Vladimir L; Mansour, Jason; Martinez-Ortega, Jorge; McCarthy, Robert L; Mcgivern, Carrie Lynne; Meijer, Melvin M; Melnitchouk, Alexander S; Menezes, Diego D; Mercadante, Pedro Galli; Merkin, Mikhail M; Meyer, Arnd; Meyer, Jorg Manfred; Miconi, Florian; Mondal, Naba K; Mulhearn, Michael James; Nagy, Elemer; Narain, Meenakshi; Nayyar, Ruchika; Neal, Homer A; Negret, Juan Pablo; Neustroev, Petr V; Nguyen, Huong Thi; Nunnemann, Thomas P; Hernandez Orduna, Jose de Jesus; Osman, Nicolas Ahmed; Osta, Jyotsna; Pal, Arnab; Parashar, Neeti; Parihar, Vivek; Park, Sung Keun; Partridge, Richard A; Parua, Nirmalya; Patwa, Abid; Penning, Bjoern; Perfilov, Maxim Anatolyevich; Peters, Reinhild Yvonne Fatima; Petridis, Konstantinos; Petrillo, Gianluca; Petroff, Pierre; Pleier, Marc-Andre; Podstavkov, Vladimir M; Popov, Alexey V; Prewitt, Michelle; Price, Darren; Prokopenko, Nikolay N; Qian, Jianming; Quadt, Arnulf; Quinn, Breese; Ratoff, Peter N; Razumov, Ivan A; Ripp-Baudot, Isabelle; Rizatdinova, Flera; Rominsky, Mandy Kathleen; Ross, Anthony; Royon, Christophe; Rubinov, Paul Michael; Ruchti, Randal C; Sajot, Gerard; Sanchez-Hernandez, Alberto; Sanders, Michiel P; Santos, Angelo Souza; Savage, David G; Savitskyi, Mykola; Sawyer, HLee; Scanlon, Timothy P; Schamberger, RDean; Scheglov, Yury A; Schellman, Heidi M; Schwanenberger, Christian; Schwienhorst, Reinhard H; Sekaric, Jadranka; Severini, Horst; Shabalina, Elizaveta K; Shary, Viacheslav V; Shaw, Savanna; Shchukin, Andrey A; Simak, Vladislav J; Skubic, Patrick Louis; Slattery, Paul F; Smirnov, Dmitri V; Snow, Gregory R; Snow, Joel Mark; Snyder, Scott Stuart; Soldner-Rembold, Stefan; Sonnenschein, Lars; Soustruznik, Karel; Stark, Jan; Stoyanova, Dina A; Strauss, Michael G; Suter, Louise; Svoisky, Peter V; Titov, Maxim; Tokmenin, Valeriy V; Tsai, Yun-Tse; Tsybychev, Dmitri; Tuchming, Boris; Tully, Christopher George T; Uvarov, Lev; Uvarov, Sergey L; Uzunyan, Sergey A; Van Kooten, Richard J; van Leeuwen, Willem M; Varelas, Nikos; Varnes, Erich W; Vasilyev, Igor A; Verkheev, Alexander Yurievich; Vertogradov, Leonid S; Verzocchi, Marco; Vesterinen, Mika; Vilanova, Didier; Vokac, Petr; Wahl, Horst D; Wang, Michael HLS; Warchol, Jadwiga; Watts, Gordon Thomas; Wayne, Mitchell R; Weichert, Jonas; Welty-Rieger, Leah Christine; Williams, Mark Richard James; Wilson, Graham Wallace; Wobisch, Markus; Wood, Darien Robert; Wyatt, Terence R; Xie, Yunhe; Yamada, Ryuji; Yang, Siqi; Yasuda, Takahiro; Yatsunenko, Yuriy A; Ye, Wanyu; Ye, Zhenyu; Yin, Hang; Yip, Kin; Youn, Sungwoo; Yu, Jiaming; Zennamo, Joseph; Zhao, Tianqi Gilbert; Zhou, Bing; Zhu, Junjie; Zielinski, Marek; Zieminska, Daria; Zivkovic, Lidija

    2014-12-11

    We measure the direct CP-violating parameter A_CP for the decay of the charged charm meson, D+ -> K-pi+pi+ (and charge conjugate), using the full 10.4 fb-1 sample of ppbar collisions at sqrt(s) = 1.96 TeV collected by the D0 detector at the Fermilab Tevatron collider. We extract the raw reconstructed charge asymmetry by fitting the invariant mass distributions for the sum and difference of charge-specific samples. This quantity is then corrected for detector-related asymmetries using data-driven methods and for possible physics asymmetries (from B -> D processes) using input from Monte Carlo simulation. We measure A_CP = [-0.16 +- 0.15 (stat.) +- 0.09 (syst.)]%, which is consistent with zero, as expected from the standard model prediction of CP conservation, and is the most precise measurement of this quantity to date

  5. Evidence for non-CpG methylation in mammals

    DEFF Research Database (Denmark)

    Yan, Jie; Zierath, Juleen R; Barres, Romain

    2011-01-01

    In mammals, the existence of cytosine methylation on non-CpG sequences is controversial. Here, we adapted a LuminoMetric-based Assay (LUMA) to determine global non-CpG methylation levels in rodent and human tissues. We observed that......In mammals, the existence of cytosine methylation on non-CpG sequences is controversial. Here, we adapted a LuminoMetric-based Assay (LUMA) to determine global non-CpG methylation levels in rodent and human tissues. We observed that...

  6. Characterization of muscarinic receptor subtypes in primary cultures of cerebellar granule cells using specific muscarinic receptor antagonists

    International Nuclear Information System (INIS)

    McLeskey, S.W.

    1989-01-01

    In cerebellar granule cell cultures, two muscarinic receptor mediated responses were observed: inhibition of adenylate cyclase (M-AC) and stimulation of phosphoinositide hydrolysis (M-PI). These responses were antagonized by three purported specific muscarinic antagonists: pirenzipine and (-)QNX (specific for M-PI) and methoctramine (specific for M-AC). However, the specificity for the three antagonists in blocking these responses is not comparable to the specificity observed in binding studies on these cells or to that quoted in the literature. Two peaks of molecular sizes were found in these cells corresponding to the two molecular sizes of muscarinic receptive proteins reported in the literature. Muscarinic receptive proteins were alkylated with 3 H-propylbenzilylcholine mustard followed by sodium dodecylsulfate polyacrylamide gel electrophoresis. Pirenzipine and (-)QNX were able to block alkylation of the high molecular size peak, which corresponds to the receptive protein m 3 reported in the literature. Methoctramine was able to block alkylation of a portion of the lower molecular size peak, possibly corresponding to the m 2 and/or m 4 receptive proteins reported in the literature. Studies attempting to show the presence of receptor reserve for either of the two biochemical responses present in these cells by alkylation of the receptive protein with nonradiolabeled propylbenzilylcholine mustard (PBCM) were confounded by specificity of this agent for the lower molecular weight peak of muscarinic receptive protein. Thus the muscarinic receptive proteins coupled to M-AC were alkylated preferentially over the ones coupled to M-PI

  7. Strong-Weak CP Hierarchy from Non-Renormalization Theorems

    Energy Technology Data Exchange (ETDEWEB)

    Hiller, Gudrun

    2002-01-28

    We point out that the hierarchy between the measured values of the CKM phase and the strong CP phase has a natural origin in supersymmetry with spontaneous CP violation and low energy supersymmetry breaking. The underlying reason is simple and elegant: in supersymmetry the strong CP phase is protected by an exact non-renormalization theorem while the CKM phase is not. We present explicit examples of models which exploit this fact and discuss corrections to the non-renormalization theorem in the presence of supersymmetry breaking. This framework for solving the strong CP problem has generic predictions for the superpartner spectrum, for CP and flavor violation, and predicts a preferred range of values for electric dipole moments.

  8. Testing non-standard CP violation in neutrino propagation

    International Nuclear Information System (INIS)

    Winter, Walter

    2009-01-01

    Non-standard physics which can be described by effective four fermion interactions may be an additional source of CP violation in the neutrino propagation. We discuss the detectability of such a CP violation at a neutrino factory. We assume the current baseline setup of the international design study of a neutrino factory (IDS-NF) for the simulation. We find that the CP violation from certain non-standard interactions is, in principle, detectable significantly below their current bounds - even if there is no CP violation in the standard oscillation framework. Therefore, a new physics effect might be mis-interpreted as the canonical Dirac CP violation, and a possibly even more exciting effect might be missed

  9. Finding CP-violating Higgses

    OpenAIRE

    Kalinowski, Jan

    1999-01-01

    In a general two-Higgs-doublet model with CP violation in the Higgs sector, the three neutral physical Higgs bosons have no definite CP properties. A new sum rule relating Yukawa and Higgs-Z couplings implies that a neutral Higgs boson cannot escape detection at an e^+e^- collider if it is kinematically accessible in Z+Higgs, $b\\bar b+$Higgs and $t\\bar t+$Higgs production, irrespective of the mixing angles and the masses of the other neutral Higgs bosons. The implications of the sum rules for...

  10. An Antiprogestin, CDB4124, Blocks Progesterone’s Attenuation of the Negative Effects of a Mild Stress on Sexual Behavior

    OpenAIRE

    Uphouse, Lynda; Hiegel, Cindy

    2012-01-01

    These experiments were designed to test the hypothesis that a progesterone receptor antagonist would block progesterone’s ability to reduce the negative effects of a 5 min restraint on female rat sexual behavior. Ovariectomized Fisher rats were injected with 10 μg estradiol benzoate. Two days later, rats were injected subcutaneously (sc) with the progesterone receptor antagonist, CDB4124 (17 α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione) (60 mg/kg), or v...

  11. Bangladesh Cerebral Palsy Register (BCPR): a pilot study to develop a national cerebral palsy (CP) register with surveillance of children for CP.

    Science.gov (United States)

    Khandaker, Gulam; Smithers-Sheedy, Hayley; Islam, Johurul; Alam, Monzurul; Jung, Jenny; Novak, Iona; Booy, Robert; Jones, Cheryl; Badawi, Nadia; Muhit, Mohammad

    2015-09-25

    The causes and pathogenesis of cerebral palsy (CP) are all poorly understood, particularly in low- and middle-income countries (LMIC). There are gaps in knowledge about CP in Bangladesh, especially in the spheres of epidemiological research, intervention and service utilization. In high-income countries CP registers have made substantial contributions to our understanding of CP. In this paper, we describe a pilot study protocol to develop, implement, and evaluate a CP population register in Bangladesh (i.e., Bangladesh Cerebral Palsy Register - BCPR) to facilitate studies on prevalence, severity, aetiology, associated impairments and risk factors for CP. The BCPR will utilise a modified version of the Australian Cerebral Palsy Register (ACPR) on a secured web-based platform hosted by the Cerebral Palsy Alliance Research Institute, Australia. A standard BCPR record form (i.e., data collection form) has been developed in consultation with local and international experts. Using this form, the BPCR will capture information about maternal health, birth history and the nature of disability in all children with CP aged CP will be identified by using the community based Key Informants Method (KIM). Data from the completed BPCR record together with details of assessment by a research physician will be entered into an online data repository. Once implemented, BCPR will be, to the best of our knowledge, the first formalised CP register from a LMIC. Establishment of the BCPR will enable estimates of prevalence; facilitate clinical surveillance and promote research to improve the care of individuals with CP in Bangladesh.

  12. CP violation searches in the charm sector at LHCb

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    LHCb has collected the world's largest sample of charmed hadrons, thus enabling measurements of direct and indirect CP violation parameters of D^0 mesons to be made with unprecedented precision. The difference in CP asymmetries between the singly Cabibbo-suppressed (SCS) D^0 -> K+K- and D^0 -> pi+pi- decays (Delta A_CP) has emerged as a powerful observable to search for direct CPV in the charm sector. By taking the difference between the two modes, most of the asymmetries induced by the detector or coming from the production mechanism are cancelled. The measurement of Delta A_CP done at LHCb is the most precise measurement of a time-integrated CP asymmetry in the charm sector from a single experiment, with a precision reaching the sub-permille level. Two independent measurements of Delta A_CP based on complementary data sets will be presented. Related 2-body searches and searches for direct CP violation in multi-body decays of the D^0 mesons will be discussed. Indirect CP violation in charm is measured throug...

  13. $CP$ violation in the B system at LHCb

    CERN Document Server

    AUTHOR|(CDS)2067431

    2014-01-01

    A selection of recent LHCb results on $CP$ violation in the $B$ system is presented. These include direct $CP$ violation measurements in $B^0 \\to \\phi K^*(892)^0$, $B_{(s)}^0 \\to K^\\pm\\pi^\\pm$, $B^\\pm \\to K^\\pm \\pi^+\\pi^-$, $B^\\pm \\to K^\\pm K^+K^-$ and $B^\\pm \\to \\phi K^\\pm$ decays; time-dependent $CP$ violation measurements in $B_s^0 \\to K^+K^-$ and $B^0 \\to \\pi^+\\pi^-$ decays; determination of the flavour-specific $CP$-violating asymmetry $a_{sl}^s$ in $B_s^0$ decays; and study of the mixing-induced $CP$ violation in $B_s^0 \\to J/\\psi K^+K^-$ and $B_s^0 \\to J/\\psi \\pi^+\\pi^-$ decays.

  14. Four-dimensional CP2 model on a lattice

    International Nuclear Information System (INIS)

    Bitar, K.M.; Raja, R.

    1983-01-01

    We investigate the phenomenon of dynamical generation of gauge interactions from CP/sup N/-1 models in four dimensions. We do this for the CP 2 model on a lattice. The phase diagram of a model that interpolates between CP 2 and U(1) gauge theory on a lattice is first mapped out. The potential between static charges in various regions of this diagram is also measured. Contrary to hopes based on the large-N behavior of similar models in two dimensions and on our phase diagram, we find that the potentials generated by CP 2 do not bear any resemblance to those of U(1). They are rather similar to the Higgs phase of an Abelian gauge theory in both phases displayed by CP 2

  15. Completing the Heterocubane Family [Cp*AlE]4 (E = O, S, Se, and Te) by Selective Oxygenation and Sulfuration of [Cp*Al]4: Density Functional Theory Calculations of [Cp*AlE]4 and Reactivity of [Cp*AlO]4 toward Hydrolysis.

    Science.gov (United States)

    Stelzer, Adrian C; Hrobárik, Peter; Braun, Thomas; Kaupp, Martin; Braun-Cula, Beatrice

    2016-05-16

    The subvalent aluminum compound [Cp*Al]4 (1) reacts with dioxygen, N2O, or sulfur to yield the heterocubane complexes [Cp*AlX]4 [X = O (2) and S (3)]. Treatment of [Cp*AlO]4 (2) with (tBuO)3SiOH gave [(tBuO)3SiOAlO]4 (6) and Cp*H. The structures and spectroscopic data of the Al clusters are supported by density functional theory (DFT) calculations, which also demonstrate the importance of noncovalent interactions (NCI) in oligomeric Al(I) complexes as well as in [Cp*AlS]4 and the heavier homologues of Se and Te. The computed (27)Al NMR shifts indicate a deshielding at the Al centers with increasing electronegativity of the chalcogen atom as well as significant spin-orbit shielding effects within the heavier heterocubane [Al4E4] cores. Further hydrolysis of 6 with an additional amount of silanol in the presence of water resulted in the formation of [Al4(OH)6(OH2)2(OSiOtBu3)6] (7), which shows a structural motif found in boehmite and diaspore.

  16. Toimintaterapeuttinen nukkekoti CP-vammaisille lapsille

    OpenAIRE

    Ruotsalainen, Ulla; Tokola, Eveliina

    2009-01-01

    Toiminnallisen opinnäytetyön tarkoitus oli suunnitella ja rakentaa toimintaterapeuttinen nukkekoti CP-vammaisille lapsille. Työn toimeksiantajana oli toimintaterapeutti Päivi Raitanen Terapiapajalta. Työn tavoitteena oli toteuttaa mukana kuljetettava ja lapsen pyörätuolin pöytälevylle sopiva nukkekoti, jolla leikkiminen tukee CP-vammaisen lapsen toimintaterapiaa. Yleisimpiä tavoitteita ovat muun muuassa hienomotoristen taitojen, leikkitaitojen, syy-seuraussuhteiden ja visuaalisen hahmott...

  17. Measurements of direct CP violation in charm decays at LHCb

    CERN Document Server

    INSPIRE-00257861

    2013-01-01

    Two searches for direct CP violation in D 0 ! h h + (where h = K or ) are presented using data corresponding to an integrated luminosity of 1.0 fb 1 collected in 2011 by LHCb in pp collisions at a centre-of-mass energy of 7 TeV. One analysis uses D 0 mesons produced via a D resonance and the other analysis uses D 0 mesons originating from semileptonic b - decays. In the rst case the avour is tagged by the charge of the accompanying pion and in the latter by the muon charge. The dierence of the CP -violating asymmetries ( A CP = A CP ( K K + ) A CP ( + )) in the two decay channels is measured to be A CP (muon tagged) = (0 : 49 0 : 30 (stat) 0 : 14 (syst))% ; A CP (pion tagged) = ( 0 : 35 0 : 15 (stat) 0 : 10 (syst))% ; A CP (LHCb) = ( 0 : 15 0 : 16)% : These results do not conrm evidence for CP violation in the charm sector

  18. Rapid relief of block by mecamylamine of neuronal nicotinic acetylcholine receptors of rat chromaffin cells in vitro: an electrophysiological and modeling study.

    Science.gov (United States)

    Giniatullin, R A; Sokolova, E M; Di Angelantonio, S; Skorinkin, A; Talantova, M V; Nistri, A

    2000-10-01

    The mechanism responsible for the blocking action of mecamylamine on neuronal nicotinic acetylcholine receptors (nAChRs) was studied on rat isolated chromaffin cells recorded under whole-cell patch clamp. Mecamylamine strongly depressed (IC(50) = 0.34 microM) inward currents elicited by short pulses of nicotine, an effect slowly reversible on wash. The mecamylamine block was voltage-dependent and promptly relieved by a protocol combining membrane depolarization with a nicotine pulse. Either depolarization or nicotine pulses were insufficient per se to elicit block relief. Block relief was transient; response depression returned in a use-dependent manner. Exposure to mecamylamine failed to block nAChRs if they were not activated by nicotine or if they were activated at positive membrane potentials. These data suggest that mecamylamine could not interact with receptors either at rest or at depolarized level. Other nicotinic antagonists like dihydro-beta-erythroidine or tubocurarine did not share this action of mecamylamine although proadifen partly mimicked it. Mecamylamine is suggested to penetrate and block open nAChRs that would subsequently close and trap this antagonist. Computer modeling indicated that the mechanism of mecamylamine blocking action could be described by assuming that 1) mecamylamine-blocked receptors possessed a much slower, voltage-dependent isomerization rate, 2) the rate constant for mecamylamine unbinding was large and poorly voltage dependent. Hence, channel reopening plus depolarization allowed mecamylamine escape and block relief. In the presence of mecamylamine, therefore, nAChRs acquire the new property of operating as coincidence detectors for concomitant changes in membrane potential and receptor occupancy.

  19. Val L. Fitch, the CP Violation, and Antimatter

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis Val L. Fitch, the CP Violation, and Antimatter Resources ) 'to verify a fundamental tenet of physics, known as CP [charge-parity] symmetry, by showing that two into two pi mesons. Cronin and Fitch had found an example of CP violation. The discovery's

  20. CP violation through particle mixing and the H-A lineshape

    International Nuclear Information System (INIS)

    Bernabeu, Jose; Binosi, Daniele; Papavassiliou, Joannis

    2006-01-01

    We consider the possibility of looking for CP-mixing effects in two-Higgs doublet models (and particularly in the MSSM) by studying the lineshape of the CP-even (H) and CP-odd (A) neutral scalars. In most cases H and A come quite degenerate in mass, and their s-channel production would lead to nearly overlapping resonances. CP-violating effects may connect these two Higgs bosons, giving origin to one-loop particle mixing, which, due to their mass proximity, can be resonantly enhanced. The corresponding transition amplitude contains then CP-even and CP-odd components; besides the signal of intereference between both amplitudes, leading to a CP-odd asymmetry, we propose to look for the mixing probability itself, a quantity which, although CP-even, can originate only from a CP-odd amplitude. We show that, in general, the effect of such a mixing probability cannot be mimicked by (or be re-absorbed into) a simple redefinition of the H and A masses in the context of a CP-conserving model. Specifically, the effects of the CP-mixing are such that, either the mass-splitting of the H and A bosons cannot be accounted for in the absence of CP-mixing, and/or the detailed energy dependence of the produced lineshape is clearly different from the one obtained by redefining the masses, but not allowing any mixing. This analysis suggests that the detailed study of the lineshape of this Higgs system may provide valuable information on the CP nature of the underlying theory

  1. Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda; Werge, Thomas

    2006-01-01

    Several clinical studies have shown that alterations in the cannabinoid system in the brain may be associated with schizophrenia. Although evidence points towards an antipsychotic potential for cannabinoid antagonists, experimental studies have shown inconsistent behavioural effects of cannabinoi...

  2. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  3. CP violation outside the standard model phenomenology for pedestrians

    International Nuclear Information System (INIS)

    Lipkin, H.J.

    1993-01-01

    So far the only experimental evidence for CP violation is the 1964 discovery of K L →2π where the two mass eigenstates produced by neutral meson mixing both decay into the same CP eigenstate. This result is described by two parameters ε and ε'. Today ε ∼ its 1964 value, ε' data are still inconclusive and there is no new evidence for CP violation. One might expect to observe similar phenomena in other systems and also direct CP violation as charge asymmetries between decays of charge conjugate hadrons H ± → f ± . Why is it so hard to find CP violation? How can B Physics help? Does CP lead beyond the standard model? The author presents a pedestrian symmetry approach which exhibits the difficulties and future possibilities of these two types of CP-violation experiments, neutral meson mixing and direct charge asymmetry: what may work, what doesn't work and why

  4. Search for neutral Higgs bosons in CP-conserving and CP-violating MSSM scenarios

    CERN Document Server

    Abbiendi, G.; Akesson, P.F.; Alexander, G.; Allison, John; Amaral, P.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Azuelos, G.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brigliadori, L.; Brown, Robert M.; Buesser, K.; Burckhart, H.J.; Campana, S.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Feld, L.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Hoffman, Kara Dion; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krieger, P.; von Krogh, J.; Kruger, K.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Layter, J.G.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Masetti, G.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Moed, S.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

    2004-01-01

    This report summarizes the final results from the OPAL collaboration on searches for neutral Higgs bosons predicted by the Minimal Supersymmetric Standard Model (MSSM). CP-conserving and for the first time at LEP CP-violating scenarios are studied. New scenarios are also included, which aim to set the stage for Higgs searches at future colliders. The results are based on the data collected with the OPAL detector at e+e- centre-of-mass energies up to 209 GeV. The data are consistent with the prediction of the Standard Model with no Higgs boson produced. Model-independent limits are derived for the cross-section of a number of events topologies motivated by prediction of the MSSM. Limits on Higgs boson masses and other MSSM parameters are obtained for a number of representative MSSM benchmark scenarios. For example, in the CP-conserving scenario mh-max where the MSSM parameters are adjusted to predict the largest range of values for mh at each tan beta, and for a top quark mass of 174.3 GeV, the domain 0.784.5 ...

  5. Synthesis and Electronic Structure of Dissymmetrical, Naphthalene-Bridged Sandwich Complexes [Cp ' Fe(mu-C10H8)MCp*](x) (x=0,+1; M = Fe, Ru; Cp ' = eta(5)-C5H2-1,2,4-tBu(3); Cp* = eta(5)-C5Me5)

    NARCIS (Netherlands)

    Malberg, J.; Lupton, E.; Schnöckelborg, E.M.; de Bruin, B.; de Sutter, J.; Meyer, K.; Hartl, F.; Wolf, R.

    2013-01-01

    The dissymmetrical naphthalene-bridged complexes [Cp'Fe(mu-C10H8)FeCp*] (3; Cp* = eta(5)-C5Me5, Cp' = eta(5)-C5H2-1,2,4-tBu(3)) and [Cp'Fe(mu-C10H8)RuCp*] (4) were synthesized via a one-pot procedure from FeCl2(thf)(1.5), Cp'K, KC10H8, and [Cp*FeCl(tmeda)] (tmeda =

  6. Baryogenesis and standard model CP violation

    International Nuclear Information System (INIS)

    Huet, P.

    1994-08-01

    The standard model possesses a natural source of CP violation contained in the phase of the CKM matrix. Whether the latter participated to the making of the matter-antimatter asymmetry of the observable universe is a fundamental question which has been addressed only recently. The generation of a CP observable occurs through interference of quantum paths along which a sequence of flavor mixings and chirality flips take place. The coherence of this phenomenon in the primeval plasma is limited by the fast quark-gluon interactions. At the electroweak era, this phenomenon of decoherence forbids a successful baryogenesis based on the sole CP violation of the CKM matrix

  7. CP asymmetries in the supersymmetric trilepton signal at the LHC

    International Nuclear Information System (INIS)

    Bornhauser, S.; Drees, M.; Dreiner, H.; Eboli, O.J.P.; Kim, J.S.; Kittel, O.

    2012-01-01

    In the CP-violating Minimal Supersymmetric Standard Model, we study the production of a neutralino-chargino pair at the LHC. For their decays into three leptons, we analyze CP asymmetries which are sensitive to the CP phases of the neutralino and chargino sector. We present analytical formulas for the entire production and decay process, and identify the CP-violating contributions in the spin correlation terms. This allows us to define the optimal CP asymmetries. We present a detailed numerical analysis of the cross sections, branching ratios, and the CP observables. For light neutralinos, charginos, and squarks, the asymmetries can reach several 10%. We estimate the discovery potential for the LHC to observe CP violation in the trilepton channel. (orig.)

  8. Flavor and CP invariant composite Higgs models

    International Nuclear Information System (INIS)

    Redi, Michele; Weiler, Andreas

    2011-09-01

    The flavor protection in composite Higgs models with partial compositeness is known to be insufficient. We explore the possibility to alleviate the tension with CP odd observables by assuming that flavor or CP are symmetries of the composite sector, broken by the coupling to Standard Model fields. One realization is that the composite sector has a flavor symmetry SU(3) or SU(3) U x SU(3) D which allows us to realize Minimal Flavor Violation. We show how to avoid the previously problematic tension between a flavor symmetric composite sector and electro-weak precision tests. Some of the light quarks are substantially or even fully composite with striking signals at the LHC. We discuss the constraints from recent dijet mass measurements and give an outlook on the discovery potential. We also present a different protection mechanism where we separate the generation of flavor hierarchies and the origin of CP violation. This can eliminate or safely reduce unwanted CP violating effects, realizing effectively ''Minimal CP Violation'' and is compatible with a dynamical generation of flavor at low scales. (orig.)

  9. Limits from LEP Data on CP-Violating Nonminimal Higgs Sectors

    International Nuclear Information System (INIS)

    Gunion, J.F.; Grzadkowski, B.; Kalinowski, J.; Haber, H.E.; Kalinowski, J.

    1997-01-01

    We derive a sum rule which shows how to extend limits from LEP data on the masses of the lightest CP-even and CP-odd Higgs bosons of a CP-conserving two-Higgs doublet model to any two Higgs bosons of a general CP-violating two-Higgs-doublet model. We generalize the analysis to a Higgs sector consisting of an arbitrary number of Higgs doublets and singlets, giving explicit limits for the CP-conserving and CP-violating two-doublet plus one-singlet Higgs sectors. copyright 1997 The American Physical Society

  10. Two C3H Type Zinc Finger Protein Genes, CpCZF1 and CpCZF2, from Chimonanthus praecox Affect Stamen Development in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Huamin Liu

    2017-08-01

    Full Text Available Wintersweet (Chimonanthus praecox is a popular garden plant because of its flowering time, sweet fragrance, and ornamental value. However, research into the molecular mechanism that regulates flower development in wintersweet is still limited. In this study, we sought to investigate the molecular characteristics, expression patterns, and potential functions of two C3H-type zinc finger (CZF protein genes, CpCZF1 and CpCZF2, which were isolated from the wintersweet flowers based on the flower developmental transcriptome database. CpCZF1 and CpCZF2 were more highly expressed in flower organs than in vegetative tissues, and during the flower development, their expression profiles were associated with flower primordial differentiation, especially that of petal and stamen primordial differentiation. Overexpression of either CpCZF1 or CpCZF2 caused alterations on stamens in transgenic Arabidopsis. The expression levels of the stamen identity-related genes, such as AGAMOUS (AG, PISTILLATA (PI, SEPALLATA1 (SEP1, SEPALLATA2 (SEP2, SEPALLATA3 (SEP3, APETALA1 (AP1, APETALA2 (AP2, and boundary gene RABBIT EAR (RBE were significantly up-regulated in CpCZF1 overexpression lines. Additionally, the transcripts of AG, PI, APETALA3 SEP1-3, AP1, and RBE were markedly increased in CpCZF2 overexpressed plant inflorescences. Moreover, CpCZF1 and CpCZF2 could interact with each other by using yeast two-hybrid and bimolecular fluorescence complementation assays. Our results suggest that CpCZF1 and CpCZF2 may be involved in the regulation of stamen development and cause the formation of abnormal flowers in transgenic Arabidopsis plants.

  11. Ultra-Fast RAFT-HDA Click Conjugation: An Efficient Route to High Molecular Weight Block Copolymers.

    Science.gov (United States)

    Inglis, Andrew J; Stenzel, Martina H; Barner-Kowollik, Christopher

    2009-11-02

    The use of the reversible addition fragmentation chain transfer-hetero Diels-Alder (RAFT-HDA) click reaction for the modular construction of block copolymers is extended to the generation of high molecular weight materials. Cyclopentadienyl end-functionalized polystyrene (PS-Cp) prepared via both atom transfer radical polymerization (ATRP) and the RAFT process are conjugated to poly(isobornyl acrylate) (PiBoA) (also prepared via RAFT polymerization) to achieve well-defined block copolymers with molecular weights ranging from 34 000 to over 100 000 g · mol(-1) and with small polydispersities (PDI HDA click chemistry can provide access to high molecular weight block copolymers in a simple and straight-forward fashion. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Astrocyte-specific regulation of hMeCP2 expression in Drosophila

    Directory of Open Access Journals (Sweden)

    David L. Hess-Homeier

    2014-10-01

    Full Text Available Alterations in the expression of Methyl-CpG-binding protein 2 (MeCP2 either by mutations or gene duplication leads to a wide spectrum of neurodevelopmental disorders including Rett Syndrome and MeCP2 duplication disorder. Common features of Rett Syndrome (RTT, MeCP2 duplication disorder, and neuropsychiatric disorders indicate that even moderate changes in MeCP2 protein levels result in functional and structural cell abnormalities. In this study, we investigated two areas of MeCP2 pathophysiology using Drosophila as a model system: the effects of MeCP2 glial gain-of-function activity on circuits controlling sleep behavior, and the cell-type specific regulation of MeCP2 expression. In this study, we first examined the effects of elevated MeCP2 levels on microcircuits by expressing human MeCP2 (hMeCP2 in astrocytes and distinct subsets of amine neurons including dopamine and octopamine (OA neurons. Depending on the cell-type, hMeCP2 expression reduced sleep levels, altered daytime/nighttime sleep patterns, and generated sleep maintenance deficits. Second, we identified a 498 base pair region of the MeCP2e2 isoform that is targeted for regulation in distinct subsets of astrocytes. Levels of the full-length hMeCP2e2 and mutant RTT R106W protein decreased in astrocytes in a temporally and spatially regulated manner. In contrast, expression of the deletion Δ166 hMeCP2 protein was not altered in the entire astrocyte population. qPCR experiments revealed a reduction in full-length hMeCP2e2 transcript levels suggesting transgenic hMeCP2 expression is regulated at the transcriptional level. Given the phenotypic complexities that are caused by alterations in MeCP2 levels, our results provide insight into distinct cellular mechanisms that control MeCP2 expression and link microcircuit abnormalities with defined behavioral deficits.

  13. A model for the origin and mechanisms of CP violation

    International Nuclear Information System (INIS)

    Wu, Y.

    1995-01-01

    In this talk I will show that the two-Higgs doublet model with vacuum CP violation and approximate global U(1) family symmetries may provide one of the simplest and attractive models for understanding the origin and mechanisms of CP violation. It is shown that the mechanism of spontaneous symmetry breaking provides not only a mechanism for generating masses of the bosons and fermions, but also a mechanism for creating CP-phases of the bosons and fermions, so that CP violation occurs, after spontaneous symmetry breaking, in all possible ways from a single CP phase of the vacuum and is generally classified into four types of CP-violating mechanism. A new type of CP-violating mechanism in the charged Higgs boson interactions of the fermions is emphasized and can provide a consistent description for both established and reported CP-, P-, and T-violating phenomena. Of particular importance is the new source of CP violation for charged Higgs boson interactions that lead to the value of ε'/ε as large as 10 -3 independent of the CKM phase. copyright 1995 American Institute of Physics

  14. Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

    KAUST Repository

    Takahashi, Yuta; Wu, Jun; Suzuki, Keiichiro; Martinez-Redondo, Paloma; Li, Mo; Liao, Hsin-Kai; Wu, Min-Zu; Herná ndez-Bení tez, Reyna; Hishida, Tomoaki; Shokhirev, Maxim Nikolaievich; Esteban, Concepcion Rodriguez; Sancho-Martinez, Ignacio; Belmonte, Juan Carlos Izpisua

    2017-01-01

    that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation

  15. Origin of CP-violation through quark mass matrix

    International Nuclear Information System (INIS)

    Kang, K.

    1990-01-01

    After a brief review of the CP violation models, we trace the origin of CP-phases from the phases of a class of quark mass matrices compatible with the calculability condition. The case of three generations corresponding to the standard milliweak CP model is discussed explicitly for the generic case of Fritzsch-type mass matrices. (orig.)

  16. Constructing co-Higgs bundles on CP^2

    OpenAIRE

    Rayan, Steven

    2013-01-01

    On a complex manifold, a co-Higgs bundle is a holomorphic vector bundle with an endomorphism twisted by the tangent bundle. The notion of generalized holomorphic bundle in Hitchin's generalized geometry coincides with that of co-Higgs bundle when the generalized complex manifold is ordinary complex. Schwarzenberger's rank-2 vector bundle on the projective plane, constructed from a line bundle on the double cover CP^1 \\times CP^1 \\to CP^2, is naturally a co-Higgs bundle, with the twisted endom...

  17. Registration of 'CP 09-2392' Sugarcane

    Science.gov (United States)

    CP 09-2392’ (Reg. No.____; PI _____) sugarcane, a complex hybrid of Saccharum spp, was developed through cooperative research conducted by the USDA-ARS, the University of Florida, and the Florida Sugar Cane League, Inc., and was released to growers in June 2016. ‘CP 09-2392’ was selected from a cro...

  18. CP properties of symmetry-constrained two-Higgs-doublet models

    CERN Document Server

    Ferreira, P M; Nachtmann, O; Silva, Joao P

    2010-01-01

    The two-Higgs-doublet model can be constrained by imposing Higgs-family symmetries and/or generalized CP symmetries. It is known that there are only six independent classes of such symmetry-constrained models. We study the CP properties of all cases in the bilinear formalism. An exact symmetry implies CP conservation. We show that soft breaking of the symmetry can lead to spontaneous CP violation (CPV) in three of the classes.

  19. Frequency Constrained ShiftCP Modeling of Neuroimaging Data

    DEFF Research Database (Denmark)

    Mørup, Morten; Hansen, Lars Kai; Madsen, Kristoffer H.

    2011-01-01

    The shift invariant multi-linear model based on the CandeComp/PARAFAC (CP) model denoted ShiftCP has proven useful for the modeling of latency changes in trial based neuroimaging data[17]. In order to facilitate component interpretation we presently extend the shiftCP model such that the extracted...... components can be constrained to pertain to predefined frequency ranges such as alpha, beta and gamma activity. To infer the number of components in the model we propose to apply automatic relevance determination by imposing priors that define the range of variation of each component of the shiftCP model...

  20. Aspects of soft and spontaneous CP violation

    International Nuclear Information System (INIS)

    Frampton, P.H.; Harada, M.

    1999-01-01

    We study four different models for CP violation: the standard Kobayashi-Maskawa (KM) model, the aspon model of spontaneous breaking, and two models of soft breaking. In all except the standard model, the strong CP problem is addressed and solved. Testable predictions for the area of the unitarity triangle and for (ε ' /ε) K are emphasized. The issue of CP violation may well become the first place where the standard model of particle theory is shown definitively to be deficient. There are two reasons for expecting this to happen: (1) the strong CP problem is still not understood in the unadorned standard model and (2) the KM mechanism, although unquestionably present, may not provide the full explanation of ε K and (ε ' /ε) K . copyright 1999 The American Physical Society

  1. Postcountershock myocardial damage after pretreatment with adrenergic and calcium channel antagonists in halothane-anesthetized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Gaba, D.M.; Metz, S.; Maze, M.

    1985-05-01

    Transthoracic electric countershock can cause necrotic myocardial lesions in humans as well as experimental animals. The authors investigated the effect on postcountershock myocardial damage of pretreatment with prazosin, an alpha-1 antagonist; L-metoprolol, a beta-1 antagonist, and verapamil, a calcium channel-blocking agent. Twenty dogs were anesthetized with halothane and given two transthoracic countershocks of 295 delivered joules each after drug or vehicle treatment. Myocardial injury was quantitated 24 h following countershock by measuring the uptake of technetium-99m pyrophosphate in the myocardium. Elevated technetium-99m pyrophosphate uptake occurred in visible lesions in most dogs regardless of drug treatment. For each of four parameters of myocardial damage there was no statistically significant difference between control animals and those treated with prazosin, metoprolol, or verapamil. These data suggest that adrenergic or calcium channel-mediated mechanisms are not involved in the pathogenesis of postcountershock myocardial damage.

  2. Thermoresponsive Poly(2-Oxazoline) Molecular Brushes by Living Ionic Polymerization: Modulation of the Cloud Point by Random and Block Copolymer Pendant Chains

    KAUST Repository

    Zhang, Ning; Luxenhofer, Robert; Jordan, Rainer

    2012-01-01

    random and block copolymers. Their aqueous solutions displayed a distinct thermoresponsive behavior as a function of the side-chain composition and sequence. The cloud point (CP) of MBs with random copolymer side chains is a linear function

  3. Masses, flavor mix and CP violation

    International Nuclear Information System (INIS)

    Chaussard, L.

    2004-06-01

    The author describes the relationships between masses, mixing of flavors and CP violation. This document is divided into 4 chapters: 1) fermions' masses, 2) mixing of flavors and CP violation, 3) beauty physics and 4) neutrino physics. In chapter 1 an attempt is made to explain what is behind the concepts of lepton mass and quark mass. As for neutrinos, the only neutral fermion, Dirac's and Majorana's views are exposed as well as their consequences. Fermion flavors are mixed in the process of mass generation and this mix is responsible for the breaking of CP and T symmetries. In chapter 2 the author shows how the analysis of particle oscillations from neutral mesons (K 0 , D 0 , B d 0 and B s 0 ) and from neutrinos can shed light on CP violation. Chapter 3 is dedicated to the contribution of beauty physics to the determination of the unitary triangle, through the oscillations of beauty mesons. In chapter 4 the author reviews the experimental results obtained recently concerning neutrino mass and neutrino oscillations and draws some perspectives on future neutrino experiments. (A.C.)

  4. Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

    KAUST Repository

    Takahashi, Yuta

    2017-05-05

    CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.

  5. Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands.

    Directory of Open Access Journals (Sweden)

    Carlos Bueno

    Full Text Available Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others suggest that MeCP2 post-transcriptional processing generates multiple molecular forms linked to cell signaling, but so far they have not been properly analyzed in relation to Rett syndrome experimental models. The purpose of this study is to advance understanding of multiple MeCP2 immunoreactive bands in control neural cells and p.T158M MeCP2e1 mutant cells. We have generated stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Application of N- and C- terminal MeCP2 antibodies, and also, RFP antibody minimized concerns about nonspecific cross-reactivity, since they react with the same antigen at different epitopes. We report the existence of multiple MeCP2 immunoreactive bands in control cells, stable wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Also, MeCP2 immunoreactive bands differences were found between wild-type and p.T158M MeCP2e1-RFP mutant expressing cells. Slower migration phosphorylated band around 70kDa disappeared in p.T158M MeCP2e1-RFP mutant expressing cells. These data suggest that threonine 158 could represent an important phosphorylation site potentially involved in protein function. Our results clearly indicate that MeCP2 antibodies have no cross-reactivity with similar epitopes on others proteins, supporting the

  6. The NK-1 Receptor Antagonist L-732,138 Induces Apoptosis and Counteracts Substance P-Related Mitogenesis in Human Melanoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Miguel Muñoz

    2010-04-01

    Full Text Available It has been recently demonstrated that substance P (SP and neurokinin-1 (NK-1 receptor antagonists induce cell proliferation and cell inhibition in human melanoma cells, respectively. However, the antitumor action of the NK-1 receptor antagonist L-732,138 on such cells is unknown. The aim of this study was to demonstrate an antitumor action of L-732,138 against three human melanoma cell lines (COLO 858, MEL HO, COLO 679. We found that L-732,138 elicits cell growth inhibition in a concentration dependent manner in the melanoma cells studied. Moreover, L-732,138 blocks SP mitogen stimulation. The specific antitumor action of L-732,138 occurred through the NK-1 receptor and melanoma cell death was by apoptosis. These findings indicate that the NK-1 receptor antagonist L-732,138 could be a new antitumor agent in the treatment of human melanoma.

  7. The NK-1 Receptor Antagonist L-732,138 Induces Apoptosis and Counteracts Substance P-Related Mitogenesis in Human Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Miguel, E-mail: mmunoz@cica.es; Rosso, Marisa; González-Ortega, Ana [Research Laboratory on Neuropeptides, Virgen del Rocío University Hospital, Sevilla (Spain); Coveñas, Rafael [Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Laboratory 14), Salamanca (Spain)

    2010-04-20

    It has been recently demonstrated that substance P (SP) and neurokinin-1 (NK-1) receptor antagonists induce cell proliferation and cell inhibition in human melanoma cells, respectively. However, the antitumor action of the NK-1 receptor antagonist L-732,138 on such cells is unknown. The aim of this study was to demonstrate an antitumor action of L-732,138 against three human melanoma cell lines (COLO 858, MEL HO, COLO 679). We found that L-732,138 elicits cell growth inhibition in a concentration dependent manner in the melanoma cells studied. Moreover, L-732,138 blocks SP mitogen stimulation. The specific antitumor action of L-732,138 occurred through the NK-1 receptor and melanoma cell death was by apoptosis. These findings indicate that the NK-1 receptor antagonist L-732,138 could be a new antitumor agent in the treatment of human melanoma.

  8. CP Violation in Single Top Quark Production

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Weigang [Michigan State Univ., East Lansing, MI (United States)

    2012-01-01

    We present a search for CP violation in single top quark production with the DØ experiment at the Tevatron proton-antiproton collider. CP violation in the top electroweak interaction results in different single top quark production cross sections for top and antitop quarks. We perform the search in the single top quark final state using 5.4 fb-1 of data, in the s-channel, t-channel, and for both combined. At this time, we do not see an observable CP asymmetry.

  9. [Regulatory B cells activated by CpG-ODN combined with anti-CD40 monoclonal antibody inhibit CD4(+)T cell proliferation].

    Science.gov (United States)

    Wang, Keng; Tao, Lei; Su, Jianbing; Zhang, Yueyang; Zou, Binhua; Wang, Yiyuan; Li, Xiaojuan

    2016-09-01

    Objective To observe the immunosuppressive function of regulatory B cells (Bregs) in vitro after activated by CpG oligodeoxynucleotide (CpG-ODN) and anti-CD40 mAb. Methods Mice splenic CD5(+)CD1d(high)B cells and CD5(-)CD1d(low)B cells were sorted by flow cytometry. These B cells were first stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours, and then co-cultured with purified CD4(+)T cells. The interleukin 10 (IL-10) expression in the activated Bregs and other B cell subset, as well as the proliferation and interferon γ (IFN-γ) expression in the CD4(+) T cells activated by anti-CD3 mAb plus anti-CD28 mAb were determined by flow cytometry. Results CD5(+)CD1d(high) B cells activated by CpG-ODN plus anti-CD40 mAb blocked the up-regulated CD4(+)T proliferation and significantly reduced the IFN-γ level. At the same time, activated CD5(-)CD1d(low)B cells showed no inhibitory effect on CD4(+)T cells. Further study revealed that IL-10 expression in the CD5(+)CD1d(high) B cells were much higher than that in the CD5(-)CD1d(low)B cells after stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours. Conclusion CD5(+)CD1d(high) B cells activated by CpG-ODN combined with anti-CD40 mAb have immune inhibitory effects on CD4(+)T cell activation in vitro , which possibly due to IL-10 secretion.

  10. Carbon adaptation influence the antagonistic ability of ...

    African Journals Online (AJOL)

    Jane

    2011-10-24

    Oct 24, 2011 ... INTRODUCTION. The use of antagonistic bacteria to control soil-borne ... plant was used to evaluate the antifungal activities of antagonistic bacteria. ..... antagonistic bacteria and cloning of its phenazine carboxylic acid genes.

  11. Benchmark test of CP-PACS for lattice QCD

    International Nuclear Information System (INIS)

    Yoshie, Tomoteru

    1996-01-01

    The CP-PACS is a massively parallel computer dedicated for calculations in computational physics and will be in operation in the spring of 1996 at Center for Computational Physics, University of Tsukuba. In this paper, we describe the architecture of the CP-PACS and report the results of the estimate of the performance of the CP-PACS for typical lattice QCD calculations. (author)

  12. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    Science.gov (United States)

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  13. Worm Algorithm for CP(N-1) Model

    CERN Document Server

    Rindlisbacher, Tobias

    2017-01-01

    The CP(N-1) model in 2D is an interesting toy model for 4D QCD as it possesses confinement, asymptotic freedom and a non-trivial vacuum structure. Due to the lower dimensionality and the absence of fermions, the computational cost for simulating 2D CP(N-1) on the lattice is much lower than that for simulating 4D QCD. However, to our knowledge, no efficient algorithm for simulating the lattice CP(N-1) model has been tested so far, which also works at finite density. To this end we propose a new type of worm algorithm which is appropriate to simulate the lattice CP(N-1) model in a dual, flux-variables based representation, in which the introduction of a chemical potential does not give rise to any complications. In addition to the usual worm moves where a defect is just moved from one lattice site to the next, our algorithm additionally allows for worm-type moves in the internal variable space of single links, which accelerates the Monte Carlo evolution. We use our algorithm to compare the two popular CP(N-1) l...

  14. Flavor and CP invariant composite Higgs models

    Energy Technology Data Exchange (ETDEWEB)

    Redi, Michele [CERN - European Organization for Nuclear Research, Geneva (Switzerland). Theory Div.; INFN, Firenze (Italy); Weiler, Andreas [CERN - European Organization for Nuclear Research, Geneva (Switzerland). Theory Div.; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-09-15

    The flavor protection in composite Higgs models with partial compositeness is known to be insufficient. We explore the possibility to alleviate the tension with CP odd observables by assuming that flavor or CP are symmetries of the composite sector, broken by the coupling to Standard Model fields. One realization is that the composite sector has a flavor symmetry SU(3) or SU(3){sub U} x SU(3){sub D} which allows us to realize Minimal Flavor Violation. We show how to avoid the previously problematic tension between a flavor symmetric composite sector and electro-weak precision tests. Some of the light quarks are substantially or even fully composite with striking signals at the LHC. We discuss the constraints from recent dijet mass measurements and give an outlook on the discovery potential. We also present a different protection mechanism where we separate the generation of flavor hierarchies and the origin of CP violation. This can eliminate or safely reduce unwanted CP violating effects, realizing effectively ''Minimal CP Violation'' and is compatible with a dynamical generation of flavor at low scales. (orig.)

  15. CP-violation and Todd effects at lep-II

    International Nuclear Information System (INIS)

    Bilal, A.; Masso, E.; Rujula, A. de

    1991-01-01

    LEP-II will be a tool study CP-violation in processes involving vector bosons, and will test in particular the CP properties of the coupling of photons and Z's to W-pairs. While it is difficult to observe truly CP-odd effects, it is easy to measure T-odd ones. The latter can originate from CP-violation, or from radiative corrections involving the absorptive part of the scattering amplitude. T-odd effects are interesting in themselves, in that they accurately test the standard model and are sensitive to its unmeasured ingredients, such as the WW→WW scattering amplitude of the masses of the top quark and the elementary scalar. The prediction of the standard T-odd effects is a necessary stepping stone in the search for an honest-to-goodness violation of CP in the pure gauge sector. We thoroughly analyse the T-odd observables in the e + e - →W + W - process within the standard model, as well as the extra effects to be expected if the γW + W - and/or ZW + W - vertices were to violate CP in a non-standard fashion. (orig.)

  16. A CP violating mixing matrix compatible with neutral flavour conservation and spontaneous CP violation

    International Nuclear Information System (INIS)

    Ecker, G.; Grimus, W.; Neufeld, H.

    1987-01-01

    A specific ansatz for the Yukawa couplings of a four-generation SU(2) L x U(I) model with two Higgs doublets is discussed which leads to neutral flavour conservation, spontaneous CP violation and to a genuinely complex mixing matrix. W exchange conserves CP in the limit m t' = m t only. The decay rate for t → b is reduced by a factor two compared to the Standard Model with three generations. The phenomenological implications for K 0 -K-bar 0 and B 0 -B-bar 0 are investigated. (Author)

  17. The seesaw path to leptonic CP violation

    CERN Document Server

    Caputo, A.; Kekic, M.; López-Pavón, J.; Salvado, J.

    2017-04-24

    Future experiments such as SHiP and high-intensity $e^+ e^-$ colliders will have a superb sensitivity to heavy Majorana neutrinos with masses below $M_Z$. We show that the measurement of the mixing to electrons and muons of one such state could imply the discovery of leptonic CP violation in the context of seesaw models. We quantify in the minimal model the CP discovery potential of these future experiments, and demonstrate that a 5$\\sigma$ CL discovery of leptonic CP violation would be possible in a very significant fraction of parameter space.

  18. Leptogenesis and low energy CP-violation in neutrino physics

    International Nuclear Information System (INIS)

    Pascoli, S.; Petcov, S.T.; Riotto, A.

    2007-01-01

    Taking into account the recent progress in the understanding of the lepton flavor effects in leptogenesis, we investigate in detail the possibility that the CP-violation necessary for the generation of the baryon asymmetry of the Universe is due exclusively to the Dirac and/or Majorana CP-violating phases in the PMNS neutrino mixing matrix U, and thus is directly related to the low energy CP-violation in the lepton sector (e.g., in neutrino oscillations, etc.). We first derive the conditions of CP-invariance of the neutrino Yukawa couplings λ in the see-saw Lagrangian, and of the complex orthogonal matrix R in the 'orthogonal' parametrization of λ. We show, e.g. that under certain conditions (i) real R and specific CP-conserving values of the Majorana and Dirac phases can imply CP-violation, and (ii) purely imaginary R does not necessarily imply breaking of CP-symmetry. We study in detail the case of hierarchical heavy Majorana neutrino mass spectrum, presenting results for three possible types of light neutrino mass spectrum: (i) normal hierarchical, (ii) inverted hierarchical, and (iii) quasi-degenerate. Results in the alternative case of quasi-degenerate in mass heavy Majorana neutrinos, are also derived. The minimal supersymmetric extension of the standard theory with right-handed Majorana neutrinos and see-saw mechanism of neutrino mass generation is discussed as well. We illustrate the possible correlations between the baryon asymmetry of the Universe and (i) the rephasing invariant J CP controlling the magnitude of CP-violation in neutrino oscillations, or (ii) the effective Majorana mass in neutrinoless double beta decay, in the cases when the only source of CP-violation is respectively the Dirac or the Majorana phases in the neutrino mixing matrix

  19. CP violation in the lepton sector with Majorana neutrinos

    International Nuclear Information System (INIS)

    Aguila, F. del

    1995-01-01

    We study CP violation in the lepton sector in extended models with right-handed neutrinos, without and with left-right symmetry, and with arbitrary mass terms. We find the conditions which must be satisfied by the neutrino and charged lepton mass matrices for CP conservation. These constraints, which are independent of the choice of weak basis, are proven to be also sufficient in simple cases. This invariant formulation makes apparent the necessary requirements for CP violation, as well as the size of CP violating effects. As an example, we show that CP violation can be much larger in left-right symmetric models than in models with only additional right-handed neutrinos, i.e., without right-handed currents. (orig.)

  20. James Cronin, CP Violation, and the Pierre Auger Observatory

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis James Cronin, CP Violation and the Pierre Auger Observatory matter over antimatter."1 "The experiment uncovered the CP [charge-parity] violation, or a with Additional Information Additional information about James Cronin and the charge-parity (CP

  1. CPLEAR et BABAR, all aspects of CP violation; CPLEAR et BABAR la violation de CP dans tous ses etats

    Energy Technology Data Exchange (ETDEWEB)

    Yeche, Ch

    2003-06-01

    This report of French 'Habilitation a diriger les recherches' summarizes my scientific activity from 1993 to 2003. During this decade, my research work was related to two particle physics experiments: CPLEAR and BABAR. The first one, CPLEAR, has recorded data from 1988 to 1995 on the low energy anti-proton ring (LEAR) at CERN. This experiment was devoted to the study of T, CPT et CP discrete symmetries. The second experiment, BABAR, has been running since 1999, on the PEP-II B factory at SLAC. This experiment searches for CP violation and tests the Standard Model through the measurements of the angles and the sides of the Unitarity Triangle. My research work is divided in five main topics: Study of CP and CPT violation in K{sup 0} {yields} {pi}{sup +} {pi}{sup -} decays; Performance optimization of the particle identification detector (DIRC) of the BABAR experiment; B meson tagging in BABAR experiment; {delta}m{sub d} measurement and Search for CP and T violation in mixing with dilepton events; Search for CP violation in B{sup 0} {yields} {rho}{sup {+-}} {pi}{sup {+-}} and B{sup 0} {yields} {pi}{sup {+-}} K{sup {+-}} decays. (author)

  2. Intracerebroventricular Infusion of the (Pro)renin Receptor Antagonist PRO20 Attenuates Deoxycorticosterone Acetate-Salt–Induced Hypertension

    Science.gov (United States)

    Li, Wencheng; Sullivan, Michelle N.; Zhang, Sheng; Worker, Caleb J.; Xiong, Zhenggang; Speth, Robert C.; Feng, Yumei

    2016-01-01

    We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT1 receptor–dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension. PMID:25421983

  3. Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension.

    Science.gov (United States)

    Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng; Worker, Caleb J; Xiong, Zhenggang; Speth, Robert C; Feng, Yumei

    2015-02-01

    We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT(1) receptor-dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension. © 2014 American Heart Association, Inc.

  4. CP110 exhibits novel regulatory activities during centriole assembly in Drosophila

    Science.gov (United States)

    Franz, Anna; Roque, Hélio; Saurya, Saroj; Dobbelaere, Jeroen

    2013-01-01

    CP110 is a conserved centriole protein implicated in the regulation of cell division, centriole duplication, and centriole length and in the suppression of ciliogenesis. Surprisingly, we report that mutant flies lacking CP110 (CP110Δ) were viable and fertile and had no obvious defects in cell division, centriole duplication, or cilia formation. We show that CP110 has at least three functions in flies. First, it subtly influences centriole length by counteracting the centriole-elongating activity of several centriole duplication proteins. Specifically, we report that centrioles are ∼10% longer than normal in CP110Δ mutants and ∼20% shorter when CP110 is overexpressed. Second, CP110 ensures that the centriolar microtubules do not extend beyond the distal end of the centriole, as some centriolar microtubules can be more than 50 times longer than the centriole in the absence of CP110. Finally, and unexpectedly, CP110 suppresses centriole overduplication induced by the overexpression of centriole duplication proteins. These studies identify novel and surprising functions for CP110 in vivo in flies. PMID:24297749

  5. Spontaneous CP violation on the lattice

    CERN Document Server

    Laine, Mikko

    2000-01-01

    At finite temperatures around the electroweak phase transition, the thermodynamics of the MSSM can be described by a three-dimensional two Higgs doublet effective theory. This effective theory has a phase where CP is spontaneously violated. We study spontaneous CP violation with non-perturbative lattice simulations, and analyse whether one could end up in this phase for any physical MSSM parameter values.

  6. Investigation of Inclusive CP Asymmetries in B$^{0}$ Decays

    CERN Document Server

    Barate, R; Ghez, P; Goy, C; Lees, J P; Merle, E; Minard, M N; Pietrzyk, B; Bravo, S; Casado, M P; Chmeissani, M; Crespo, J M; Fernández, E; Fernández-Bosman, M; Garrido, L; Graugès-Pous, E; Martínez, M; Merino, G; Miquel, R; Mir, L M; Pacheco, A; Ruiz, H; Colaleo, A; Creanza, D; De Palma, M; Iaselli, Giuseppe; Maggi, G; Maggi, M; Nuzzo, S; Ranieri, A; Raso, G; Ruggieri, F; Selvaggi, G; Silvestris, L; Tempesta, P; Tricomi, A; Zito, G; Huang, X; Lin, J; Ouyang, Q; Wang, T; Xie, Y; Xu, R; Xue, S; Zhang, J; Zhang, L; Zhao, W; Abbaneo, D; Boix, G; Buchmüller, O L; Cattaneo, M; Cerutti, F; Dissertori, G; Drevermann, H; Forty, Roger W; Frank, M; Greening, T C; Hansen, J B; Harvey, J; Janot, P; Jost, B; Lehraus, Ivan; Mato, P; Minten, Adolf G; Moutoussi, A; Ranjard, F; Rolandi, Luigi; Schlatter, W D; Schmitt, M; Schneider, O; Spagnolo, P; Tejessy, W; Teubert, F; Tournefier, E; Wright, A E; Ajaltouni, Ziad J; Badaud, F; Chazelle, G; Deschamps, O; Falvard, A; Gay, P; Guicheney, C; Henrard, P; Jousset, J; Michel, B; Monteil, S; Montret, J C; Pallin, D; Perret, P; Podlyski, F; Hansen, J D; Hansen, J R; Hansen, P H; Nilsson, B S; Petersen, B; Wäänänen, A; Daskalakis, G; Kyriakis, A; Markou, C; Simopoulou, Errietta; Vayaki, Anna; Blondel, A; Bonneaud, G R; Brient, J C; Rougé, A; Rumpf, M; Swynghedauw, M; Verderi, M; Videau, H L; Focardi, E; Parrini, G; Zachariadou, K; Antonelli, A; Antonelli, M; Bencivenni, G; Bologna, G; Bossi, F; Campana, P; Capon, G; Chiarella, V; Laurelli, P; Mannocchi, G; Murtas, F; Murtas, G P; Passalacqua, L; Pepé-Altarelli, M; Halley, A W; Lynch, J G; Negus, P; O'Shea, V; Raine, C; Teixeira-Dias, P; Thompson, A S; Cavanaugh, R J; Dhamotharan, S; Geweniger, C; Hanke, P; Hansper, G; Hepp, V; Kluge, E E; Putzer, A; Sommer, J; Tittel, K; Werner, S; Wunsch, M; Beuselinck, R; Binnie, David M; Cameron, W; Dornan, Peter J; Girone, M; Marinelli, N; Sedgbeer, J K; Thompson, J C; Thomson, E; Ghete, V M; Girtler, P; Kneringer, E; Kuhn, D; Rudolph, G; Bowdery, C K; Buck, P G; Finch, A J; Foster, F; Hughes, G; Jones, R W L; Robertson, N A; Giehl, I; Jakobs, K; Kleinknecht, K; Quast, G; Renk, B; Rohne, E; Sander, H G; Wachsmuth, H W; Zeitnitz, C; Bonissent, A; Carr, J; Coyle, P; Leroy, O; Payre, P; Rousseau, D; Talby, M; Aleppo, M; Ragusa, F; Dietl, H; Ganis, G; Heister, A; Hüttmann, K; Lütjens, G; Mannert, C; Männer, W; Moser, H G; Schael, S; Settles, Ronald; Stenzel, H; Wiedenmann, W; Wolf, G; Azzurri, P; Boucrot, J; Callot, O; Chen, S; Cordier, A; Davier, M; Duflot, L; Grivaz, J F; Heusse, P; Jacholkowska, A; Le Diberder, F R; Lefrançois, J; Lutz, A M; Schune, M H; Veillet, J J; Videau, I; Yuan, C; Zerwas, D; Bagliesi, G; Boccali, T; Calderini, G; Ciulli, V; Foà, L; Giassi, A; Ligabue, F; Messineo, A; Palla, Fabrizio; Rizzo, G; Sanguinetti, G; Sciabà, A; Sguazzoni, G; Tenchini, Roberto; Venturi, A; Verdini, P G; Blair, G A; Cowan, G D; Green, M G; Medcalf, T; Strong, J A; Von Wimmersperg-Töller, J H; Clifft, R W; Edgecock, T R; Norton, P R; Tomalin, I R; Bloch-Devaux, B; Colas, P; Emery, S; Kozanecki, Witold; Lançon, E; Lemaire, M C; Locci, E; Pérez, P; Rander, J; Renardy, J F; Roussarie, A; Schuller, J P; Schwindling, J; Trabelsi, A; Vallage, B; Black, S N; Dann, J H; Johnson, R P; Kim, H Y; Konstantinidis, N P; Litke, A M; McNeil, M A; Taylor, G; Booth, C N; Cartwright, S L; Combley, F; Lehto, M H; Thompson, L F; Affholderbach, K; Böhrer, A; Brandt, S; Grupen, Claus; Misiejuk, A; Prange, G; Sieler, U; Giannini, G; Gobbo, B; Rothberg, J E; Wasserbaech, S R; Armstrong, S R; Cranmer, K; Elmer, P; Ferguson, D P S; Gao, Y; González, S; Hayes, O J; Hu, H; Jin, S; Kile, J; McNamara, P A; Nielsen, J; Orejudos, W; Pan, Y B; Saadi, Y; Scott, I J; Walsh, J; Wu Sau Lan; Wu, X; Zobernig, G

    2001-01-01

    A search for CP violating effects in the mixing of neutral B mesons is performed using a sample of 4.1 million hadronic Z decays collected with the ALEPH detector from 1991 to 1995. By studying time-dependent asymmetries in flavour-tagged samples of semileptonic and fully inclusive b-hadron decays, two measurements of the semileptonic asymmetry a_cp are extracted. No evidence for CP violation is observed, and the combined value a_cp = -0.013 +- 0.026 is obtained.

  7. CP-odd Phase Correlations and Electric Dipole Moments

    CERN Document Server

    Olive, Keith A; Ritz, A; Santoso, Y; Olive, Keith A.; Pospelov, Maxim; Ritz, Adam; Santoso, Yudi

    2005-01-01

    We revisit the constraints imposed by electric dipole moments (EDMs) of nucleons and heavy atoms on new CP-violating sources within supersymmetric theories. We point out that certain two-loop renormalization group corrections induce significant mixing between the basis-invariant CP-odd phases. In the framework of the constrained minimal supersymmetric standard model (CMSSM), the CP-odd invariant related to the soft trilinear A-phase at the GUT scale, theta_A, induces non-trivial and distinct CP-odd phases for the three gaugino masses at the weak scale. The latter give one-loop contributions to EDMs enhanced by tan beta, and can provide the dominant contribution to the electron EDM induced by theta_A. We perform a detailed analysis of the EDM constraints within the CMSSM, exhibiting the reach, in terms of sparticle spectra, which may be obtained assuming generic phases, as well as the limits on the CP-odd phases for some specific parameter points where detailed phenomenological studies are available. We also i...

  8. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  9. Light Higgs boson in THDM with explicit CP violation

    International Nuclear Information System (INIS)

    Akhmetzyanova, Eh.N.; Dolgopolov, M.V.; Smirnov, I.A.; Dubinin, M.N.

    2005-01-01

    The effective Lagrangian of the two-doublet Higgs sector with complex parameters is considered in the case of Minimal Supersymmetric Model with explicit CP violation. Light Higgs boson decay widths are calculated for the scenario with maximal mixing of CP even and CP odd states [ru

  10. A brief introduction to the strong CP problem

    International Nuclear Information System (INIS)

    Wu, Dan-di; Melbourne Univ., Parkville

    1991-09-01

    The present status of the strong CP problem is briefly reviewed in a heuristic way. A crisis in EDMN calculation is explained. The equation of vacuum alignment obtained by the author and collaborators last year put a constraint on strong CP parameters. Thus the strong CP will be forced to vanish in one of the three scenarios characterized by axion, zero quark mass, and vanishing quark condensate. 12 refs

  11. A Cp-theory problem book compactness in function spaces

    CERN Document Server

    Tkachuk, Vladimir V

    2015-01-01

    This third volume in Vladimir Tkachuk's series on Cp-theory problems applies all modern methods of Cp-theory to study compactness-like properties in function spaces and introduces the reader to the theory of compact spaces widely used in Functional Analysis. The text is designed to bring a dedicated reader from basic topological principles to the frontiers of modern research covering a wide variety of topics in Cp-theory and general topology at the professional level.  The first volume, Topological and Function Spaces © 2011, provided an introduction from scratch to Cp-theory and general topology, preparing the reader for a professional understanding of Cp-theory in the last section of its main text. The second volume, Special Features of Function Spaces © 2014, continued from the first, giving reasonably complete coverage of Cp-theory, systematically introducing each of the major topics and providing 500 carefully selected problems and exercises with complete solutions. This third volume is self-contained...

  12. Systematic CpT (ApG) Depletion and CpG Excess Are Unique Genomic Signatures of Large DNA Viruses Infecting Invertebrates

    Science.gov (United States)

    Upadhyay, Mohita; Sharma, Neha; Vivekanandan, Perumal

    2014-01-01

    Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates (n = 105; viruses infecting mammals = 99; viruses infecting aves = 6; viruses infecting reptiles = 1) and invertebrates (n = 88; viruses infecting insects = 84; viruses infecting crustaceans = 4). We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. PMID:25369195

  13. CP violation in B and D decays

    International Nuclear Information System (INIS)

    Bigi, I.I.

    1986-06-01

    Non-leptonic B decays offer the best opportunity to discover the violation of CP invariance outside the neutral K system. Employing the Standard Model one predicts - with reasonable confidence - CP asymmetries of up to 205 (or even more in some cases). The branching ratios for the individual exclusive modes of interest are not expected to exceed the 10 -3 level in most cases; the identification of such decays poses non-trivial problems. It is shown that by summing intelligently over appropriate classes of decays one can greatly enhance statistics without jeopardizing the signal. Data that contain 10 6 produced B mesons would allow meaningful searches for CP violation. It is noted that ''New Physics'' could lead to CP asymmetries in D 0 decays of order 1%. Due to higher branching ratios one can search for such effects in samples of 10 6 produced D mesons. 7 refs

  14. GLP-1 receptor antagonist as a potential probe for pancreatic β-cell imaging

    International Nuclear Information System (INIS)

    Mukai, Eri; Toyoda, Kentaro; Kimura, Hiroyuki; Kawashima, Hidekazu; Fujimoto, Hiroyuki; Ueda, Masashi; Temma, Takashi; Hirao, Konomu; Nagakawa, Kenji; Saji, Hideo; Inagaki, Nobuya

    2009-01-01

    We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic β-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [ 125 I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [ 125 I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120 min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [ 125 I]BH-exendin(9-39) injection into transgenic mice with pancreatic β-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic β-cell imaging.

  15. Inhibition of the superantigenic activities of Staphylococcal enterotoxin A by an aptamer antagonist.

    Science.gov (United States)

    Wang, Kaiyu; Wu, Dong; Chen, Zhuang; Zhang, Xianhui; Yang, Xiangyue; Yang, Chaoyong James; Lan, Xiaopeng

    2016-09-01

    Staphylococcal enterotoxin A (SEA) is an important component of Staphylococcus aureus pathogenesis. SEA induces T lymphocytes activation and proliferation, resulting in the release of a large number of inflammatory cytokines. Blocking the toxic cascade triggered by SEA may be an effective strategy for the treatment of SEA-induced diseases. Through a systematic evolution of ligands by exponential enrichment process, we obtained an aptamer (S3) that could bind SEA with both high affinity and specificity, with a Kd value 36.93 ± 7.29 nM (n = 3). This aptamer antagonist effectively inhibited SEA-mediated human peripheral blood mononuclear cells proliferation and inflammatory cytokines (IFN-γ, TNF-α, IL-2 and IL-6) secretion. Moreover, PEGylated S3 significantly reduced mortality in murine lethal toxic shock models established by lipopolysaccharide-potentiated SEA. Therefore, this novel aptamer antagonist has the potential to become a new strategy for treating S. aureus infections and SEA-induced diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. CP-violating profile of the electroweak bubble wall

    Energy Technology Data Exchange (ETDEWEB)

    Funakubo, Koichi [Saga Univ. (Japan). Dept. of Physics; Kakuto, Akira; Otsuki, Shoichiro; Takenaga, Kazunori; Toyoda, Fumihiko

    1995-11-01

    In any scenario of the electroweak baryogenesis, the profile of the CP violating bubble wall, created at the first-order phase transition, plays an essential role. We attempt to determine it by solving the equations of motion for the scalars in the two-Higgs-doublet model at the transition temperature. According to the parameters in the potential, we found three solutions. Two of them smoothly connect the CP-violating broken phase and the symmetric phase, while the other connects CP-conserving vacua but violates CP in the intermediate region. We also estimate the chiral charge flux, which will be turned into the baryon density in the symmetric phase by the sphaleron process. (author).

  17. LHC experimental sensitivity to CP violating gtt couplings

    CERN Document Server

    Sjölin, J

    2003-01-01

    The level of CP violation in pp to tt+X induced by the standard model is known to be below the experimental sensitivity by many orders of magnitude. However, in some effective theories, it is plausible that new CP violating physics could reveal itself as additional non- renormalizable terms in the Lagrangian. Since these should respect the symmetries of the low-energy gauge interaction, violate CP and generate the correct event topology, the set of allowed terms is highly restricted. This analysis gives an estimate of the expected experimental sensitivity to the lowest order effective CP violating gtt interaction term beyond the standard model using simulated data from the ATLAS detector at the LHC. (36 refs).

  18. CP violating observables in e$^{-}$e$^{+}$ --> W$^{-}$W$^{+}$

    CERN Document Server

    Chang, D; Phillips, I

    1993-01-01

    We consider various integrated lepton charge-energy asymmetries and azimuthal asymmetries as tests of CP violation in the process $e^-e^+ \\to W^-W^+$. These asymmetries are sensitive to different linear combinations of the CP violating form factors in the three gauge boson $W^-W^+$ production vertex, and can distinguish dispersive and absorptive parts of the form factors. It makes use of purely hadronic and purely leptonic modes of $W$'s decays as well as the mixed modes. The techniques of using the kinematics of jets or missing momentum to construct CP--odd observables are also employed. These CP violating observables are illustrated in the generalized Left-Right Model and the Charged Higgs Model.

  19. Sigma decomposition: the CP-odd Lagrangian

    Energy Technology Data Exchange (ETDEWEB)

    Hierro, I.M. [Dipartimento di Fisica “G. Galilei”, Università di Padova and INFN, Sezione di Padova,Via Marzolo 8, I-35131 Padua (Italy); Merlo, L. [Instituto de Física Teórica, IFT-UAM/CSIC, Universidad Autónoma de Madrid,Cantoblanco, 28049, Madrid (Spain); Rigolin, S. [Dipartimento di Fisica “G. Galilei”, Università di Padova and INFN, Sezione di Padova,Via Marzolo 8, I-35131 Padua (Italy)

    2016-04-04

    In Alonso et al., http://dx.doi.org/10.1007/JHEP12(2014)034, the CP-even sector of the effective chiral Lagrangian for a generic composite Higgs model with a symmetric coset has been constructed, up to four momenta. In this paper, the CP-odd couplings are studied within the same context. If only the Standard Model bosonic sources of custodial symmetry breaking are considered, then at most six independent operators form a basis. One of them is the weak-θ term linked to non-perturbative sources of CP violation, while the others describe CP-odd perturbative couplings between the Standard Model gauge bosons and an Higgs-like scalar belonging to the Goldstone boson sector. The procedure is then applied to three distinct exemplifying frameworks: the original SU(5)/SO(5) Georgi-Kaplan model, the minimal custodial-preserving SO(5)/SO(4) model and the minimal SU(3)/(SU(2)×U(1)) model, which intrinsically breaks custodial symmetry. Moreover, the projection of the high-energy electroweak effective theory to the low-energy chiral effective Lagrangian for a dynamical Higgs is performed, uncovering strong relations between the operator coefficients and pinpointing the differences with the elementary Higgs scenario.

  20. CpGislandEVO: A Database and Genome Browser for Comparative Evolutionary Genomics of CpG Islands

    Directory of Open Access Journals (Sweden)

    Guillermo Barturen

    2013-01-01

    Full Text Available Hypomethylated, CpG-rich DNA segments (CpG islands, CGIs are epigenome markers involved in key biological processes. Aberrant methylation is implicated in the appearance of several disorders as cancer, immunodeficiency, or centromere instability. Furthermore, methylation differences at promoter regions between human and chimpanzee strongly associate with genes involved in neurological/psychological disorders and cancers. Therefore, the evolutionary comparative analyses of CGIs can provide insights on the functional role of these epigenome markers in both health and disease. Given the lack of specific tools, we developed CpGislandEVO. Briefly, we first compile a database of statistically significant CGIs for the best assembled mammalian genome sequences available to date. Second, by means of a coupled browser front-end, we focus on the CGIs overlapping orthologous genes extracted from OrthoDB, thus ensuring the comparison between CGIs located on truly homologous genome segments. This allows comparing the main compositional features between homologous CGIs. Finally, to facilitate nucleotide comparisons, we lifted genome coordinates between assemblies from different species, which enables the analysis of sequence divergence by direct count of nucleotide substitutions and indels occurring between homologous CGIs. The resulting CpGislandEVO database, linking together CGIs and single-cytosine DNA methylation data from several mammalian species, is freely available at our website.

  1. Addressing the strong CP problem with quark mass ratios

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Cruz, J.L.; Saldana-Salazar, U.J. [Benemerita Univ. Autonoma de Puebla (Mexico). Facultad de Ciencias Fisico-Matematicas; Hollik, W.G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2016-05-15

    The strong CP problem is one of many puzzles in the theoretical description of elementary particles physics that still lacks an explanation. Solutions to that problem usually comprise new symmetries or fields or both. The main problem seems to be how to achieve small CP in the strong interactions despite large CP violation in weak interactions. Observation of CP violation is exclusively through the Higgs-Yukawa interactions. In this letter, we show that with minimal assumptions on the structure of mass (Yukawa) matrices the strong CP problem does not exist in the Standard Model and no extension to solve this is needed. However, to solve the flavor puzzle, models based on minimal SU(3) flavor groups leading to the proposed flavor matrices are favored.

  2. Addressing the strong CP problem with quark mass ratios

    International Nuclear Information System (INIS)

    Diaz-Cruz, J.L.; Saldana-Salazar, U.J.

    2016-05-01

    The strong CP problem is one of many puzzles in the theoretical description of elementary particles physics that still lacks an explanation. Solutions to that problem usually comprise new symmetries or fields or both. The main problem seems to be how to achieve small CP in the strong interactions despite large CP violation in weak interactions. Observation of CP violation is exclusively through the Higgs-Yukawa interactions. In this letter, we show that with minimal assumptions on the structure of mass (Yukawa) matrices the strong CP problem does not exist in the Standard Model and no extension to solve this is needed. However, to solve the flavor puzzle, models based on minimal SU(3) flavor groups leading to the proposed flavor matrices are favored.

  3. Neutrino mixing and lepton CP-phase in neutrino oscillations

    International Nuclear Information System (INIS)

    Ryzhikh, D.A.; Ter-Martirosyan, K.A.

    2001-01-01

    One studied oscillations of the Dirac neutrinos belonging to three generations in vacuum with regard to the effect of the lepton CP-breaking phase on them in the matrix of lepton mixing (analogue of the quark CP-phase). In the general form one obtained formulae for probabilities of transition of neutrino of one kind to another at oscillations depending on three angles of mixing and on CP-phase. It was pointed that when measuring oscillation average probabilities of transition of neutrino of one kind to another one might in principle, restore the value of lepton CP-phase. Manifestation of CP-phase in the form of deviation of the values of probabilities of direct neutrino transition from reverse one is the effect practically escaping observation [ru

  4. CP violation and supersymmetry-breaking in superstring models

    International Nuclear Information System (INIS)

    Dent, T.E.

    2000-09-01

    In this thesis I discuss aspects of the phenomenology of heterotic string, theory, using low-energy effective supergravity models. I investigate the origin of CP violation, the implications for low-energy physics of the modular invariance of the theory, supersymmetry-breaking via gaugino condensation in a hidden sector, and the interplay between these topics. I review the theory of CP violation and the problem of CP violation in supersymmetry phenomenology. In a scenario where the origin of CP violation lies in the compactification of the extra dimensions of string theory, I present simple models which include a duality symmetry acting on the compactification modulus and on observable fields. I show how the structure of the theory affects CP-violating observables, and discuss the effect of such a symmetry on low-energy physics in general. I present a detailed investigation of supersymmetry-breaking by gaugino condensation in supergravity, in particular as applied to the stabilisation of string moduli. For hidden sectors with or without matter I calculate corrections to the usual formulae for the scalar potential and soft supersymmetry-breaking terms. I discuss the phenomenological implications of these corrections and show that they may affect the value of the compactification modulus. and consequently the prospects for predictions of CP violation in string models. (author)

  5. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8

    DEFF Research Database (Denmark)

    Lüttichau, H R; Gerstoft, J; Schwartz, T W

    2001-01-01

    The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted...... as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist on the murine CCR8 as well as the human CCR8. MC148 was found to bind and block responses through the human CCR8 with high affinity, but surprisingly MC148 was unable to bind and block responses through the murine CCR8. Because...

  6. arXiv Flavour Physics and CP Violation

    CERN Document Server

    Kamenik, J.F.

    2016-01-01

    These notes represent a summary of three lectures on flavour and CP violation, given at the CERNs European School of High Energy Physics in 2014. They cover flavour physics within the standard model, phenomenology of CP violation in meson mixing and decays, as well as constraints of flavour observableson physics beyond the standard model. In preparing the lectures (and consequently this summary) I drew heavily from several existing excellent and exhaustive sets of lecture notes and reviews on flavour physics and CP violation [1]. The reader is encouraged to consult those as well as the original literature for a more detailed study.

  7. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    John Gatfield

    Full Text Available Two endothelin receptor antagonists (ERAs, bosentan and ambrisentan, are currently approved for the treatment of pulmonary arterial hypertension (PAH, a devastating disease involving an activated endothelin system and aberrant contraction and proliferation of pulmonary arterial smooth muscle cells (PASMC. The novel ERA macitentan has recently concluded testing in a Phase III morbidity/mortality clinical trial in PAH patients. Since the association and dissociation rates of G protein-coupled receptor antagonists can influence their pharmacological activity in vivo, we used human PASMC to characterize inhibitory potency and receptor inhibition kinetics of macitentan, ambrisentan and bosentan using calcium release and inositol-1-phosphate (IP(1 assays. In calcium release assays macitentan, ambrisentan and bosentan were highly potent ERAs with K(b values of 0.14 nM, 0.12 nM and 1.1 nM, respectively. Macitentan, but not ambrisentan and bosentan, displayed slow apparent receptor association kinetics as evidenced by increased antagonistic potency upon prolongation of antagonist pre-incubation times. In compound washout experiments, macitentan displayed a significantly lower receptor dissociation rate and longer receptor occupancy half-life (ROt(1/2 compared to bosentan and ambrisentan (ROt(1/2:17 minutes versus 70 seconds and 40 seconds, respectively. Because of its lower dissociation rate macitentan behaved as an insurmountable antagonist in calcium release and IP(1 assays, and unlike bosentan and ambrisentan it blocked endothelin receptor activation across a wide range of endothelin-1 (ET-1 concentrations. However, prolongation of the ET-1 stimulation time beyond ROt(1/2 rendered macitentan a surmountable antagonist, revealing its competitive binding mode. Bosentan and ambrisentan behaved as surmountable antagonists irrespective of the assay duration and they lacked inhibitory activity at high ET-1 concentrations. Thus, macitentan is a competitive

  8. CP Violation and B Physics

    International Nuclear Information System (INIS)

    Quinn, Helen R

    2001-01-01

    These lectures provide a basic overview of topics related to the study of CP Violation in B decays. In the first lecture, I review the basics of discrete symmetries in field theories, the quantum mechanics of neutral but flavor-non-trivial mesons, and the classification of three types of CP violation [1]. The actual second lecture which I gave will be separately published as it is my Dirac award lecture and is focused on the separate topic of strong CP Violation. In Lecture 2 here, I cover the Standard Model predictions for neutral B decays, and in particular discuss some channels of interest for CP Violation studies. Lecture 3 reviews the various tools and techniques used to deal with the hadronic physics effects. In Lecture 4, I briefly review the present and planned experiments that can study B decays. I cannot teach all the details of this subject in this short course, so my approach is instead to try to give students a grasp of the relevant concepts and an overview of the available tools. The level of these lectures is introductory. I will provide some references to more detailed treatments and current literature, but this is not a review article so I do not attempt to give complete references to all related literature. By now there are some excellent textbooks that cover this subject in great detail [1]. I refer students to these for more details and for more complete references to the original literature

  9. B physics and CP violation

    International Nuclear Information System (INIS)

    Quinn, H.

    2002-01-01

    These lectures provide a basic overview of topics related to the study of CP Violation in B decays. In the first lecture, I review the basics of discrete symmetries in field theories, the quantum mechanics of neutral but flavor-non-trivial mesons, and the classification of three types of CP violation. The actual second lecture which I gave will be separately published as it is my Dirac award lecture and is focussed on the separate topic of strong CP Violation. In Lecture 2 here, I cover the Standard Model predictions for neutral B decays, and in particular discuss some channels of interest for CP Violation studies. Lecture 3 reviews the various tools and techniques used to deal with the hadronic physics effects. In Lecture 4, I briefly review the present and planned experiments that can study B decays. I cannot teach all the details of this subject in this short course, so my approach is instead to try to give students a grasp of the relevant concepts and an overview of the available tools. The level of these lectures is introductory. I will provide some references to more detailed treatments and current literature, but this is not a review article so I do not attempt to give complete references to all related literature. By now there are some excellent textbooks that cover this subject in great detail. I refer students to these for more details and for more complete references to the original literature. (author)

  10. Measurement of the Branching Fractions and CP Asymmetries of B{sup -} --> D{sup 0}{sub (CP)}K{sup -} Decays with the BABAR Detector

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B

    2004-08-17

    The authors have reconstructed B{sup -} --> D{sup 0}K{sup -} decays with D{sup 0} mesons decaying to non-CP (K{sup -}{pi}{sup +}), CD-even (K{sup -}K{sup +}, {pi}{sup -}{pi}{sup +}) and CP-odd (K{sup 0}{sub s}{pi}{sup 0}) eigenstates. They have measured the CP asymmetries A{sub CP{sup +}} = 0.40 {+-} 0.15(stat) {+-} 0.08(syst), A{sup CP{sup -}} = 0.21 {+-} 0.17(stat) {+-} 0.07(syst), and the double ratio of branching fractions R{sub +} = 0.87 {+-} 0.14(stat) {+-} 0.06(syst), R{sub -} = 0.80 {+-} 0.14(stat) {+-} 0.08(syst). These results improve the previous existing measurements from BABAR. All results presented in this document are preliminary.

  11. CP violation in KL → π0e+e-

    International Nuclear Information System (INIS)

    Littenberg, L.S.

    1989-01-01

    It's been appreciated for many years that the decays K L → π 0 ell bar ell are CP violating to lowest order in the Standard Model, and that the component of direct CP violation in these decays is likely to be comparable to that of the CP violation due to state mixing (ε). This is to be contrasted with the case of K 0 → ππ wherein the latter contribution is predicted to be hundreds of times larger than the former. This paper investigates this CP violation further. 19 refs., 2 figs

  12. CP violation in τ → ντ + 3π

    International Nuclear Information System (INIS)

    Tsai, Y.S.

    1998-01-01

    In the Standard Model no CP violation can occur in decay processes involving leptons either as a parent or a daughter because these processes involve one W exchange and thus, even if the CP violating complex coupling exists in these decays, its effect will not show up when the amplitude is squared. The author needs two diagrams to interfere with each other to see the CP violating effects. Here, he discusses ways to find CP violation in the decay of τ ± → ν τ + 3π from unpolarized as well as polarized τ ±

  13. Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

    Directory of Open Access Journals (Sweden)

    Zoltán Oláh

    2007-06-01

    Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

  14. On the determination of the CP of the Higgs boson

    Energy Technology Data Exchange (ETDEWEB)

    Skjold, A.

    1995-12-31

    While the Higgs particle of the Standard Models is a Cp-even scalar particle, extended models may contain Higgs particles that are odd under CP, and also models invoking Higgs-like particles which are not eigenstates of CP may be considered. In the context of Higgs production via the Bjorken process and Higgs decay to tour fermions distributions that are sensitive to the CP parity are discussed. The author also discuss observables which may demonstrate presence of CP violation and identify a phase shift {delta} which is a measure of the strength of CP violation in the Higgs-vector-vector coupling, and which can be measured directly in the relevant distribution. In the case of Higgs production via the Bjorken process at a future e{sup +}e{sup -}collider, Monte Carlo data on the expected efficiency is presented, and it is concluded that it is relatively easy to determine whether the produced particle is even or odd under CP. However, observation of any CP violation would require a very large amount of data. It is argued that the analogous prospects at LEP2 or at a future hadron collider like the LHC seem to be less promising. 63 refs.

  15. On the determination of the CP of the Higgs boson

    Energy Technology Data Exchange (ETDEWEB)

    Skjold, A

    1996-12-31

    While the Higgs particle of the Standard Models is a Cp-even scalar particle, extended models may contain Higgs particles that are odd under CP, and also models invoking Higgs-like particles which are not eigenstates of CP may be considered. In the context of Higgs production via the Bjorken process and Higgs decay to tour fermions distributions that are sensitive to the CP parity are discussed. The author also discuss observables which may demonstrate presence of CP violation and identify a phase shift {delta} which is a measure of the strength of CP violation in the Higgs-vector-vector coupling, and which can be measured directly in the relevant distribution. In the case of Higgs production via the Bjorken process at a future e{sup +}e{sup -}collider, Monte Carlo data on the expected efficiency is presented, and it is concluded that it is relatively easy to determine whether the produced particle is even or odd under CP. However, observation of any CP violation would require a very large amount of data. It is argued that the analogous prospects at LEP2 or at a future hadron collider like the LHC seem to be less promising. 63 refs.

  16. On the determination of the CP of the Higgs boson

    International Nuclear Information System (INIS)

    Skjold, A.

    1995-01-01

    While the Higgs particle of the Standard Models is a Cp-even scalar particle, extended models may contain Higgs particles that are odd under CP, and also models invoking Higgs-like particles which are not eigenstates of CP may be considered. In the context of Higgs production via the Bjorken process and Higgs decay to tour fermions distributions that are sensitive to the CP parity are discussed. The author also discuss observables which may demonstrate presence of CP violation and identify a phase shift δ which is a measure of the strength of CP violation in the Higgs-vector-vector coupling, and which can be measured directly in the relevant distribution. In the case of Higgs production via the Bjorken process at a future e + e - collider, Monte Carlo data on the expected efficiency is presented, and it is concluded that it is relatively easy to determine whether the produced particle is even or odd under CP. However, observation of any CP violation would require a very large amount of data. It is argued that the analogous prospects at LEP2 or at a future hadron collider like the LHC seem to be less promising. 63 refs

  17. CpG traffic lights are markers of regulatory regions in humans

    KAUST Repository

    Khamis, Abdullah M.; Lioznova, Anna V.; Artemov, Artem V.; Ramensky, Vasily; Bajic, Vladimir B.; Medvedeva, Yulia A.

    2016-01-01

    DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

  18. CpG traffic lights are markers of regulatory regions in humans

    KAUST Repository

    Khamis, Abdullah M.

    2016-12-29

    DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

  19. On the energy crisis in noncommutative CP(1) model

    International Nuclear Information System (INIS)

    Sourrouille, Lucas

    2010-01-01

    We study the CP(1) system in (2+1)-dimensional noncommutative space with and without Chern-Simons term. Using the Seiberg-Witten map we convert the noncommutative CP(1) system to an action written in terms of the commutative fields. We find that this system presents the same infinite size instanton solution as the commutative Chern-Simons-CP(1) model without a potential term. Based on this result we argue that the BPS equations are compatible with the full variational equations of motion, rejecting the hypothesis of an 'energy crisis'. In addition we examine the noncommutative CP(1) system with a Chern-Simons interaction. In this case we find that when the theory is transformed by the Seiberg-Witten map it also presents the same instanton solution as the commutative Chern-Simons-CP(1) model.

  20. The possibility of leptonic CP-violation measurement with JUNO

    Science.gov (United States)

    Smirnov, M. V.; Hu, Zh. J.; Li, S. J.; Ling, J. J.

    2018-06-01

    The existence of CP-violation in the leptonic sector is one of the most important issues for modern science. Neutrino physics is a key to the solution of this problem. JUNO (under construction) is the near future of neutrino physics. However CP-violation is not a priority for the current scientific program. We estimate the capability of δCP measurement, assuming a combination of the JUNO detector and a superconductive cyclotron as the antineutrino source. This method of measuring CP-violation is an alternative to conventional beam experiments. A significance level of 3σ can be reached for 22% of the δCP range. The accuracy of measurement lies between 8o and 22o. It is shown that the dominant influence on the result is the uncertainty in the mixing angle Θ23.

  1. Implications of maximal Jarlskog invariant and maximal CP violation

    International Nuclear Information System (INIS)

    Rodriguez-Jauregui, E.; Universidad Nacional Autonoma de Mexico

    2001-04-01

    We argue here why CP violating phase Φ in the quark mixing matrix is maximal, that is, Φ=90 . In the Standard Model CP violation is related to the Jarlskog invariant J, which can be obtained from non commuting Hermitian mass matrices. In this article we derive the conditions to have Hermitian mass matrices which give maximal Jarlskog invariant J and maximal CP violating phase Φ. We find that all squared moduli of the quark mixing elements have a singular point when the CP violation phase Φ takes the value Φ=90 . This special feature of the Jarlskog invariant J and the quark mixing matrix is a clear and precise indication that CP violating Phase Φ is maximal in order to let nature treat democratically all of the quark mixing matrix moduli. (orig.)

  2. Introduction to heavy meson decays and CP asymmetries

    International Nuclear Information System (INIS)

    Ligeti, Zoltan

    2003-01-01

    These lectures are intended to provide an introduction to heavy meson decays and CP violation. The first lecture contains a brief review of the standard model and how the CKM matrix and CP violation arise, mixing and CP violation in neutral meson systems, and explanation of the cleanliness of the sin 2β measurement. The second lecture deals with the heavy quark limit, some applications of heavy quark symmetry and the operator product expansion for exclusive and inclusive semileptonic B decays. The third lecture concerns with theoretically clean CP violation measurements that may become possible in the future, and some developments toward a better understanding of nonleptonic B decays. The conclusions include a subjective best buy list for the near future

  3. Rephasing-invariant CP violating parameters with Majorana neutrinos

    International Nuclear Information System (INIS)

    Nieves, Jose F.; Pal, Palash B.

    2001-06-01

    We analyze the dependence of the squared amplitudes on the rephasing-invariant CP-violating parameters of the lepton sector, involving Majorana neutrinos, for various lepton- conserving and lepton-violating processes. We analyze the conditions under which the CP-violating effects in such processes vanish, in terms of the minimal set of rephasing invariants, giving special attention to the dependence on the extra CP-violating parameters that are due to the Majorana nature of the neutrinos. (author)

  4. Neutrinos as a probe of CP-violation and leptogenesis

    Indian Academy of Sciences (India)

    Establishing CP-violation in the lepton sector is one of the most challenging future tasks in neutrino physics. The lepton mixing matrix contains one Dirac phase and, if neutrinos are Majorana particles, two additional CP-violating phases. I will review the main theoretical aspects of CP-violation in the lepton sector. Then, I will ...

  5. A bottom-up approach to the strong CP problem

    Science.gov (United States)

    Diaz-Cruz, J. L.; Hollik, W. G.; Saldana-Salazar, U. J.

    2018-05-01

    The strong CP problem is one of many puzzles in the theoretical description of elementary particle physics that still lacks an explanation. While top-down solutions to that problem usually comprise new symmetries or fields or both, we want to present a rather bottom-up perspective. The main problem seems to be how to achieve small CP violation in the strong interactions despite the large CP violation in weak interactions. In this paper, we show that with minimal assumptions on the structure of mass (Yukawa) matrices, they do not contribute to the strong CP problem and thus we can provide a pathway to a solution of the strong CP problem within the structures of the Standard Model and no extension at the electroweak scale is needed. However, to address the flavor puzzle, models based on minimal SU(3) flavor groups leading to the proposed flavor matrices are favored. Though we refrain from an explicit UV completion of the Standard Model, we provide a simple requirement for such models not to show a strong CP problem by construction.

  6. Status of the CP-PACS Project

    International Nuclear Information System (INIS)

    Ukawa, A.

    1995-01-01

    The CP-PACS Project, which started in April 1992, is a five-year plan to develop a massively parallel computer for carrying out research in computational physics with primary emphasis on lattice QCD. This article describes the architectural design of the CP-PACS computer, the entire computing system including the front end and mass storage, and results of benchmarks for the expected performance for lattice QCD applications. ((orig.))

  7. First evidence for direct CP violation

    International Nuclear Information System (INIS)

    Schaffer, A.C.

    1988-06-01

    The double ratio R of the relative decay rates of the short-and long-lived neutral kaons into two charged and two neutral pions was measured to be 0.980 ± 0.004 ± 0.005. The deviation of R from unity implies CP violation in the transition of the CP-odd K 2 into two pions with ε , / ε = (3.3 ± 1.1) X 10 -3

  8. CP symmetry violation. The search for its origin

    International Nuclear Information System (INIS)

    Cronin, J.W.

    1981-01-01

    The present experimental situation on detection of CP symmetry violation is presented. Interference between decays of long-lived (Ksub(L)sup(0)) and short-lived (Ksub(S)sup(0)) mesons into two charged pions serves a direct demonstration of the fact that the effect is caused by CP symmetry breaking. The time distribution of decays into π + π - when the 4-10 GeV Ksub(L) meson beam passes through a carbon regenerator is given as an example of the measurement accuracy. The measurements of the charge asymmetry in half-lepton channels of Ksub(L)→π +- l +- ν decay where l is an electron or a muon are discussed. It is noted that the presence of the charge asymmetry serves an indication of CP invariance violation and permits to carry out experimental differentiation between the matter and antimatter. Different theoretical assumptions on the nature of CP invariance violation are discussed. A list of experiments on search for CP, T and C invariance violation carried out in different laboratories of the world is given [ru

  9. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels

    2015-01-01

    to the local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

  10. A violation of CP symmetry in B meson decays

    International Nuclear Information System (INIS)

    Karyotakis, Y.; Monchenault, G.H. de

    2002-01-01

    This article reviews the issue of CP-violation and reports the most recent results about the observation of large CP asymmetries in the decay of neutral B-mesons. Some of the CP asymmetries in the neutral B-meson decay are expected to be large. CP-violation always involves quantum mechanical interference. This occurs for instance when there are 2 paths for a particle to decay into a given final state. The interference between the mixing-induced amplitude (B 0 → B-bar 0 → f) and the decay amplitude (B 0 → f) to a CP eigenstate f leads to a time dependent CP asymmetry that can be interpreted in terms of the angles of the unitary triangle (sin(2β)). The experimental challenge comes from the fact that B decays to some CP eigenstates have very small branching ratios and low efficiencies for complete reconstruction of the final state. It is therefore necessary to produce a very large number of B-mesons to perform a CP-measurement. To make the measurement possible, a new type of e + e - collider, called asymmetric B-factory has been designed. 2 asymmetric B-factories are operating in the world: PEP2 (Stanford, Usa) fitted with the Babar detector and KEK-B (Japan) which hosts Belle detector. The measurements given by Babar and Belle are in good agreement and can be combined. The average value is sin(2β) = 0.78 ± 0.08 and this value is in excellent agreement with the standard model predictions based on available experimental data. (A.C.)

  11. Reaction of (CP(2)asterisk-lnH)(2) (ln=Y, La) and CP(2)asterisk-Y(2-C(6)H(4)CH(2)NMe(2)) with esters and amides and molecular-structure of [CP(2)asterisk-Y(mu- ocme=chc(oet)o)](2)

    NARCIS (Netherlands)

    Deelman, B.J; Wierda, F.; Meetsma, A.; Teuben, J.H

    1995-01-01

    The activation of esters and amides by (Cp(2)*LnH)(2) [Ln = Y (1a), Ln = La (1b), Cp*=C(5)Me] and Cp(2)*Y(2-C(6)H(4)CH(2)NMe(2)) (2) is described. Compounds 1a and 1b react with ethyl acetate to form Cp(2)*YOEt (3a) and Cp(2)*LaOEt (30). With 1a and ethyl benzoate a 1:1 mixture of 3a and

  12. The seesaw path to leptonic CP violation

    Energy Technology Data Exchange (ETDEWEB)

    Caputo, A.; Hernandez, P. [Universidad de Valencia and CSIC, Edificio Institutos Investigacion, Instituto de Fisica Corpuscular, Paterna (Spain); CERN, Theoretical Physics Department, Geneva (Switzerland); Kekic, M.; Salvado, J. [Universidad de Valencia and CSIC, Edificio Institutos Investigacion, Instituto de Fisica Corpuscular, Paterna (Spain); Lopez-Pavon, J. [CERN, Theoretical Physics Department, Geneva (Switzerland)

    2017-04-15

    Future experiments such as SHiP and high-intensity e{sup +}e{sup -} colliders will have a superb sensitivity to heavy Majorana neutrinos with masses below M{sub Z}. We show that the measurement of the mixing to electrons and muons of one such state could establish the existence of CP violating phases in the neutrino mixing matrix, in the context of low-scale seesaw models. We quantify in the minimal model the CP reach of these future experiments, and demonstrate that CP violating phases in the mixing matrix could be established at 5σ CL in a very significant fraction of parameter space. (orig.)

  13. Quark mixing and CP violation

    International Nuclear Information System (INIS)

    Paschos, E.A.

    1992-01-01

    These lectures present a pedagogical introduction to the topics quark mixing and CP violation. They explain how the mixing matrix comes about and reviews the values of constraints for its elements. The second chapter reviews the CP transformation properties of amplitudes and defines the quantities which are measured in the experiments. Then it reviews the theory of CP violation in the standard model. In addition to the phase and the angles introduced through the flavor matrix, numerical predictions also depend (a) on hadronic matrix elements of weak current operators and (b) the short distance expansion of effective Hamiltonians computed by methods of Quantum Chromodynamics (QCD). I also review these topics and present predictions for (ε'/ε) which are shown to be consistent with the experiments. Last but not least, the article is divided into sections which are as self-contained as possible. The article assumes a general knowledge of the electroweak theory. For guidance, the interested reader will find a table of contents at the end of the text. (author). 29 refs, 5 figs, 1 tab

  14. CP violation experiment at Fermilab

    International Nuclear Information System (INIS)

    Hsiung, Yee B.

    1990-07-01

    The E731 experiment at Fermilab has searched for ''direct'' CP violation in K 0 → ππ, which is parametrized by var-epsilon '/var-epsilon. For the first time, in 20% of the data set, all four modes of the K L,S → π + π - (π 0 π 0 ) were collected simultaneously, providing a great check on the systematic uncertainty. The result is Re(var-epsilon '/var-epsilon) = -0.0004 ± 0.0014 (stat) ± 0.0006(syst), which provides no evidence for ''direct'' CP violation. The CPT symmetry has also been tested by measuring the phase difference Δφ = φ 00 - φ ± between the two CP violating parameters η 00 and η ± . We fine Δφ = -0.3 degrees ± 2.4 degree(stat) ± 1.2 degree(syst). Using this together with the world average φ ± , we fine that the phase of the K 0 -bar K 0 mixing parameter var-epsilon is 44.5 degree ± 1.5 degree. Both of these results agree well with the predictions of CPT symmetry. 17 refs., 10 figs

  15. 77 FR 37098 - Proposed Collection; Comment Request for Form 8038-CP

    Science.gov (United States)

    2012-06-20

    ... 8038-CP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 8038-CP, Return for Credit Payments to Issuers of Qualified Bonds. DATES: Written comments should... Issuers of Qualified Bonds. OMB Number: 1545-2142. Form Number: Form 8038-CP. Abstract: Form 8038-CP...

  16. Search for CP violation in baryon decays at LHCb

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    The phenomenon of CP violation has been observed in the K- and B-meson systems, but not yet with any baryonic particle. We report on searches for CP violation in baryon decays at LHCb using Run I data. We find evidence for CP violation in Lambda0b -> p pi- pi+ pi- decays with a statistical significance corresponding to 3.3 standard deviations, including systematic uncertainties. This represents the first evidence of CP violation in the baryon sector. An overview of other recent results of baryon decays will be presented, along with some highlights of the charmless B-decay programme.

  17. The impact of intragenic CpG content on gene expression.

    Science.gov (United States)

    Bauer, Asli Petra; Leikam, Doris; Krinner, Simone; Notka, Frank; Ludwig, Christine; Längst, Gernot; Wagner, Ralf

    2010-07-01

    The development of vaccine components or recombinant therapeutics critically depends on sustained expression of the corresponding transgene. This study aimed to determine the contribution of intragenic CpG content to expression efficiency in transiently and stably transfected mammalian cells. Based upon a humanized version of green fluorescent protein (GFP) containing 60 CpGs within its coding sequence, a CpG-depleted variant of the GFP reporter was established by carefully modulating the codon usage. Interestingly, GFP reporter activity and detectable protein amounts in stably transfected CHO and 293 cells were significantly decreased upon CpG depletion and independent from promoter usage (CMV, EF1 alpha). The reduction in protein expression associated with CpG depletion was likewise observed for other unrelated reporter genes and was clearly reflected by a decline in mRNA copy numbers rather than translational efficiency. Moreover, decreased mRNA levels were neither due to nuclear export restrictions nor alternative splicing or mRNA instability. Rather, the intragenic CpG content influenced de novo transcriptional activity thus implying a common transcription-based mechanism of gene regulation via CpGs. Increased high CpG transcription correlated with changed nucleosomal positions in vitro albeit histone density at the two genes did not change in vivo as monitored by ChIP.

  18. A Cp-theory problem book special features of function spaces

    CERN Document Server

    Tkachuk, Vladimir V

    2014-01-01

    The books in Vladimir Tkachuk’s A Cp-Theory Problem Book series will be the ‘go to’ texts for basic reference to Cp-theory. This second volume, Special Features of Function Spaces, gives a reasonably complete coverage of Cp-theory, systematically introducing each of the major topics and providing  500 carefully selected problems and exercises with complete solutions. Bonus results and open problems are also given. The text is designed to bring a dedicated reader from basic topological principles to the frontiers of modern research covering a wide variety of topics in Cp-theory and general topology at the professional level. The first volume, Topological and Function Spaces © 2011, provided an introduction from scratch to Cp-theory and general topology, preparing the reader for a professional understanding of Cp-theory in the last section of its main text. This second volume continues from the first, and can be used as a textbook for courses in both Cp-theory and general topology as well as a referenc...

  19. CpG Oligodeoxynucleotides as a Future Vaccine for Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Kunio Sano

    2005-01-01

    Full Text Available An astounding feature of the DNA sequences termed CpG motifs is the induction of immune and inflammatory responses in a senseless manner. CpG motifs exist abundantly in microbes and evoke innate immunity that constitutes the first line of defense against microbial infections in vertebrates. CpG motifs that essentially work in an antigen-nonspecific fashion, however, turn into novel immunomodulators that can manipulate acquired immunity in an antigen-specific manner if oligodeoxynucleotides containing CpG motifs (CpG ODNs are directly conjugated to the antigen. CpG ODNs with potent polyclonal Th1-inducing ability show promise for application in immunotherapy whereby neutralization of dominant allergy-prone Th2 cells is achieved by inducing allergen-specific Th1 cells. The underlying mechanisms include an unexpected enhancement of dendritic cell function as a linker between innate and acquired immunity. In the foreseeable future the mainstream therapeutic role of corticosteroids in anti-inflammatory therapy for allergic diseases could possibly be replaced by immunotherapy using CpG ODN-conjugated antigens.

  20. Is CP violation observable in long baseline neutrino oscillation experiments?

    International Nuclear Information System (INIS)

    Tanimoto, M.

    1997-01-01

    We have studied CP violation originating from the phase of the neutrino-mixing matrix in the long baseline neutrino oscillation experiments. The direct measurement of CP violation is the difference of the transition probabilities between CP-conjugate channels. In those experiments, the CP-violating effect is not suppressed if the highest neutrino mass scale is taken to be 1 endash 5 eV, which is appropriate for the cosmological hot dark matter. Assuming the hierarchy for the neutrino masses, the upper bounds of CP violation have been calculated for three cases, in which mixings are constrained by the recent short baseline ones. The calculated upper bounds are larger than 10 -2 , which will be observable in the long baseline accelerator experiments. The matter effect, which is not CP invariant, has been also estimated in those experiments. copyright 1997 The American Physical Society

  1. Naloxone : actions of an antagonist

    NARCIS (Netherlands)

    Dorp, Eveline Louise Arianna van

    2009-01-01

    The opioid antagonist naloxone has a special place in pharmacology – it has no intrinsic action of its own, but it is able to save lives in the case of life threatening side-effects caused by other drugs. Naloxone is an antagonist for all opioid receptors, but most specifically for the μ-opioid

  2. Higgs pair production in the MSSM with explicit CP violation

    International Nuclear Information System (INIS)

    Demir, D.A.

    1999-07-01

    In the minimal supersymmetric standard model with explicit CP violation, associated production of the lightest Higgs boson with heavier ones is analyzed. Due to explicit CP violation, the Higgs bosons are no longer CP eigenstates so that both of the heavy Higgs bosons contribute to the process. While the radiative corrections in the Higgs sector turn out to be quite important, the vertex radiative corrections remain small as in the CP conserving theory. (author)

  3. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice.

    Science.gov (United States)

    Ailanen, Liisa; Vähätalo, Laura H; Salomäki-Myftari, Henriikka; Mäkelä, Satu; Orpana, Wendy; Ruohonen, Suvi T; Savontaus, Eriika

    2018-01-01

    Neuropeptide Y (NPY) plays an important role in the regulation of energy homeostasis in the level of central and sympathetic nervous systems (SNSs). Genetic silencing of peripheral Y 2 -receptors have anti-obesity effects, but it is not known whether pharmacological blocking of peripheral Y 2 -receptors would similarly benefit energy homeostasis. The effects of a peripherally administered Y 2 -receptor antagonist were studied in healthy and energy-rich conditions with or without excess NPY. Genetically obese mice overexpressing NPY in brain noradrenergic nerves and SNS (OE-NPY DβH ) represented the situation of elevated NPY levels, while wildtype (WT) mice represented the normal NPY levels. Specific Y 2 -receptor antagonist, BIIE0246, was administered (1.3 mg/kg/day, i.p.) for 2 or 4.5 weeks to OE-NPY DβH and WT mice feeding on chow or Western diet. Treatment with Y 2 -receptor antagonist increased body weight gain in both genotypes on chow diet and caused metabolic disturbances (e.g., hyperinsulinemia and hypercholesterolemia), especially in WT mice. During energy surplus (i.e., on Western diet), blocking of Y 2 -receptors induced obesity in WT mice, whereas OE-NPY DβH mice showed reduced fat mass gain, hepatic glycogen and serum cholesterol levels relative to body adiposity. Thus, it can be concluded that with normal NPY levels, peripheral Y 2 -receptor antagonist has no potential for treating obesity, but oppositely may even induce metabolic disorders. However, when energy-rich diet is combined with elevated NPY levels, e.g., stress combined with an unhealthy diet, Y 2 -receptor antagonism has beneficial effects on metabolic status.

  4. On the strong CP problem

    Energy Technology Data Exchange (ETDEWEB)

    Dowrick, N.J. (Dept. of Physics, Oxford (United Kingdom)); McDougall, N.A. (National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan))

    1992-07-09

    We show that two well-known solutions to the strong CP problem, the axion and a massless quark, may be understood in terms of the mechanism recently proposed by Samuel where long-range interactions between topological charges may be responsible for the removal of CP violation. We explain how the axion and a QCD meson (identified as the {eta}' if all quarks are massless) suppress fluctuations in global topological charge by almost identical dynamical although the masses, couplings and relevant length scales are very different. Furthermore, we elucidate the precise origin of the {eta}' mass. (orig.).

  5. Higgs-production at LHC. Observables for the measurements of CP properties; Produktion von Higgsbosonen am LHC. Observablen zur Bestimmung ihrer CP-Quantenzahlen

    Energy Technology Data Exchange (ETDEWEB)

    Ziethe, J.

    2007-05-22

    In this work we calculated observables which can be used to determine the CP parity of the Higgs boson. We considered the neutral Higgs bosons of the MSSM as well as CP-indefinite Higgs bosons. The calculation have been made for an application at LHC. For Higgs production we considered gluon fusion (in NLO) and b-quark annihilation (in LO) and for the Higgs decay studied the decay in tau lepton or top quark. We find that the angle between the charged particles of the tau (or top) decay are a good observable to determine CP properties of the intermediate Higgs bosons. For CP indefinite Higgs bosons we considered triplet-correlation-observables. (orig.)

  6. Measurements of the B0 bar B0 CP asymmetry

    International Nuclear Information System (INIS)

    Lueth, V.

    1993-01-01

    A figure of merit for a measurement of CP violation is the error on the intrinsic asymmetry A CP . The observed asymmetry A obs will always be smaller than A CP due to a number of effects that dilute the measurement. If one defines A obs =DA CP , where D represents the product of all dilution factors, then the error on A CP , δA CP is related to the number of produced B 0 or bar B 0 , N prod , needed to obtain a given error on δA CP by N prod =1/((δA CP ) 2 D 2 εBr). To determine the figure of merit for a particular decay mode one must determine the number of reconstructed events N obs and calculate the corresponding dilution factor D. N obs depends on the luminosity and production cross section, on the branching ratio of the B 0 or bar B 0 into the specific final state under study, Br, and on ε, the reconstruction efficiency for both the combination of the signal CP state and any tagging signal. The production rate N prod , the dilution factor D, and the efficiency ε, differ substantially in magnitude as a function of energy and detector layout. The detection efficiency and dilution factor can both be written as a product of several factors that can be estimated for a particular experiment. These factors depend critically on the decay mode under study, the tagging method, the detector configuration, and more generally on the production process, backgrounds, and detector performance. Furthermore, the present knowledge of these quantities varies largely, as well as ones ability to ultimately measure the dilution factor which relates the experimentally observed asymmetry to the true CP asymmetry

  7. CPLEAR et BABAR, all aspects of CP violation

    International Nuclear Information System (INIS)

    Yeche, Ch.

    2003-06-01

    This report of French 'Habilitation a diriger les recherches' summarizes my scientific activity from 1993 to 2003. During this decade, my research work was related to two particle physics experiments: CPLEAR and BABAR. The first one, CPLEAR, has recorded data from 1988 to 1995 on the low energy anti-proton ring (LEAR) at CERN. This experiment was devoted to the study of T, CPT et CP discrete symmetries. The second experiment, BABAR, has been running since 1999, on the PEP-II B factory at SLAC. This experiment searches for CP violation and tests the Standard Model through the measurements of the angles and the sides of the Unitarity Triangle. My research work is divided in five main topics: Study of CP and CPT violation in K 0 → π + π - decays; Performance optimization of the particle identification detector (DIRC) of the BABAR experiment; B meson tagging in BABAR experiment; Δm d measurement and Search for CP and T violation in mixing with dilepton events; Search for CP violation in B 0 → ρ ± π ± and B 0 → π ± K ± decays. (author)

  8. CP-odd phase correlations and electric dipole moments

    International Nuclear Information System (INIS)

    Olive, Keith A.; Pospelov, Maxim; Ritz, Adam; Santoso, Yudi

    2005-01-01

    We revisit the constraints imposed by electric dipole moments (EDMs) of nucleons and heavy atoms on new CP-violating sources within supersymmetric theories. We point out that certain two-loop renormalization group corrections induce significant mixing between the basis-invariant CP-odd phases. In the framework of the constrained minimal supersymmetric standard model, the CP-odd invariant related to the soft trilinear A-phase at the grand unified theory (GUT) scale, θ A , induces nontrivial and distinct CP-odd phases for the three gaugino masses at the weak scale. The latter give one-loop contributions to EDMs enhanced by tanβ, and can provide the dominant contribution to the electron EDM induced by θ A . We perform a detailed analysis of the EDM constraints within the constrained minimal supersymmetric standard model, exhibiting the reach, in terms of sparticle spectra, which may be obtained assuming generic phases, as well as the limits on the CP-odd phases for some specific parameter points where detailed phenomenological studies are available. We also illustrate how this reach will expand with results from the next generation of experiments which are currently in development

  9. CP violation in multibody decays of beauty baryons

    Energy Technology Data Exchange (ETDEWEB)

    Durieux, Gauthier

    2016-08-15

    Beauty baryons are being observed in large numbers in the LHCb detector. The rich kinematic distributions of their multibody decays are therefore becoming accessible and provide us with new opportunities to search for CP violation. We analyse the angular distributions of some three- and four-body decays of spin-1/2 baryons using the Jacob-Wick helicity formalism. The asymmetries that provide access to small differences of CP-odd phases between decay amplitudes of identical CP-even phases are notably discussed. The understanding gained on processes featuring specific resonant intermediate states allows us to establish which asymmetries are relevant for what purpose. It is for instance shown that some CP-odd angular asymmetries measured by the LHCb collaboration in the Λ{sub b}→Λφ→pπ K{sup +}K{sup -} decay are expected to vanish identically.

  10. Heavy quarks and CP: Moriond 1985

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1985-03-01

    The presentations at the Fifth Moriond Workshop on Heavy Quarks, Flavor Mixing, and CP Violation (La Plagne, France, January 13-19, 1985) are summarized. The following topics are reviewed. What's New (beyond the top, top quarks, bottom quarks, charm quarks, strange quarks, and others); why is all this being done (strong interactions and hadron structure, and electroweak properties); and what next (facilities and can one see CP violation in the B-anti B system). 64 refs., 10 figs

  11. Status in CP violation

    International Nuclear Information System (INIS)

    Fayard, L.

    1989-11-01

    Twenty-five years after the discovery of CP violation in the neutral Kaon system, we still dont know exactly the origin and the components of that weak non invariance. The two more precise experiments give slightly different answers concerning the direct way of CP violation NA 31 gives ε prime/ε incompatible with the Superweak Model (for which ε prime=0) and in agreement with Standard Model predictions compatible with both. Again, one needs new and precise results in order to conclude about ε prime. E731 and NA31 are actually working on their new data samples. Longer term ideas are also being discussed, looking for new experiments able to give ε prime/ε with a precision. Concerning CPT invariance the situation seems to be more clear

  12. CP violation in K- and B-meson decays

    CERN Multimedia

    2000-01-01

    These lectures will describe CP violation in K- and B-meson decays and will include the following topics:i) Grand view of the field including CKM matrix and the unitarily triangle ii) General aspects of the theoretical framework iii) Fundamentals of particle-antiparticle mixing iv) Fundamentals of CP violation v) Standard analysis of the unitarily triangle vi) The ratio e'/e including most recent developments vii) CP Violation in rare K- decays viii) Violation in B-Decays (asymmetries and other strategies) ix) A brief look beyond the Standard Model

  13. SU(4) x U(1) gauge theory. II. CP nonconservation

    International Nuclear Information System (INIS)

    Deshpande, N.G.; Hwa, R.C.; Mannheim, P.D.

    1979-01-01

    We exploit the higher symmetry inherent in an SU(4) x U(1) gauge theory to construct a spontaneously broken theory of CP nonconservation. Higgs multiplets in the adjoint representation of SU(4) contain both even and odd CP fields; thus, requiring the simultaneous nonvanishing of the vacuum expectation values of these fields leads to CP noninvariance of the vacuum. We find that all the CP-nonconserving effects are mediated in our theory by the superheavy gauge bosons of the broken SU(4) x U(1) symmetry. In fact, the very existence of CP violation sets an upper limit on the masses of these bosons. In our model the dominant CP effect lies in the neutral kaon system and is found to arise through a direct (ΔS = 2) K 1 -K 2 transition. The model has all the features of a superweak theory, with a neutron electric dipole moment substantially smaller than 10 -24 e cm

  14. Histologic and inflammatory lamellar changes in horses with oligofructose-induced laminitis treated with a CXCR1/2 antagonist

    OpenAIRE

    Lima, Leonardo R. de; Mendes, Heloisa M.F.; Soriani, Frederico M.; Souza, Danielle G. de; Alves, Geraldo Eleno S.; Teixeira, Mauro M.; Faleiros, Rafael R.

    2016-01-01

    Abstract: With the hypothesis that blocking chemokine signaling can ameliorate acute laminitis, the aim was to evaluate the therapeutic effect of intravenous DF1681B, a selective antagonist for CXCR1 and CXCR2 (chemokine receptors), in an oligofructose equine laminitis model. To twelve mixed breed clinically healthy hoses with no previous history of hoof-related lameness was administered oligofructose (10g/kg given by nasogastric tube) and divided into two groups: treated (intravenous DF1681B...

  15. Phenomenology of CP violation from the Kobayashi-Maskawa model

    International Nuclear Information System (INIS)

    Wang, L.L.C.

    1980-01-01

    The CP violation consequences of the K-M model, which Kobayashi, Maskawa introduced in 1977 for the purpose of incorporating CP violation via the complexity in the mixing matrix of the quarks are discussed. Much of the talk is a review of current work on the subject. Some new results on the CP violation effects in exclusive and inclusive decays of bottom, charm and strange particles are also given

  16. Circadian cycle-dependent MeCP2 and brain chromatin changes.

    Directory of Open Access Journals (Sweden)

    Alexia Martínez de Paz

    Full Text Available Methyl CpG binding protein 2 (MeCP2 is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.

  17. Neutral D→KK^{*} Decays as Discovery Channels for Charm CP Violation.

    Science.gov (United States)

    Nierste, Ulrich; Schacht, Stefan

    2017-12-22

    We point out that the CP asymmetries in the decays D^{0}→K_{S}K^{*0} and D^{0}→K_{S}K[over ¯]^{*0} are potential discovery channels for charm CP violation in the standard model. We stress that no flavor tagging is necessary, the untagged CP asymmetry a_{CP}^{dir}(D[over (-)]→K_{S}K^{*0}) is essentially equal to the tagged one, so that the untagged measurement comes with a significant statistical gain. Depending on the relevant strong phase, |a_{CP}^{dir,untag}| can be as large as 0.003. The CP asymmetry is dominantly generated by exchange diagrams and does not require nonvanishing penguin amplitudes. While the CP asymmetry is smaller than in the case of D^{0}→K_{S}K_{S}, the experimental analysis is more efficient due to the prompt decay K^{*0}→K^{+}π^{-}. One may further search for favorable strong phases in the Dalitz plot in the vicinity of the K^{*0} peak.

  18. Flavour Physics and CP Violation : Expecting the LHC

    CERN Document Server

    Fleischer, Robert

    2008-01-01

    The starting point of these lectures is an introduction to the weak interactions of quarks and the Standard-Model description of CP violation, where the central role is played by the Cabibbo-Kobayashi-Maskawa matrix and the corresponding unitarity triangles. Since the B-meson system governs the stage of (quark) flavour physics and CP violation, it is our main focus: we shall classify B-meson decays, introduce the theoretical tools to deal with them, investigate the requirements for non-vanishing CP-violating asymmetries, and discuss the main strategies to explore CP violation and the preferred avenues for physics beyond the Standard Model to enter. This formalism allows us then to discuss important benchmark modes, where we will also address the question of how much space for new-physics effects in the B studies at the LHC is left by the recent experimental results from the B factories and the Tevatron.

  19. Measurement of the CP Content and CP Violating Asymmetries in Neutral B Decays to Two D Mesons with the BaBar Detector

    Energy Technology Data Exchange (ETDEWEB)

    Lillard, V.

    2005-04-25

    This dissertation presents a measurement of time-dependent CP-violating asymmetries and a measurement of the CP-odd parity fraction in the decay B{sup 0} {yields} D*{sup +} D*{sup -}. The measurements are derived from a data sample of 88 x 10{sup 6} B{bar B} pairs collected by the BABAR detector at the PEP-II asymmetric-energy B Factory located at the Stanford Linear Accelerator Center. A one-dimensional angular analysis of the decay products measures the CP-odd fraction to be 0.063 {+-} 0.055(stat) {+-} 0.009(syst), indicating that the D*{sup +}D*{sup -} final state is mostly CP-even. The time-dependent CP asymmetry parameters Im({lambda}{sub +}) and |{lambda}{sub +}| are determined from an analysis of the time-dependence of flavor-tagged B decays. One neutral B meson is fully reconstructed in a D*{sup +} D*{sup -} final state, while the other B is inclusively reconstructed in order to determine its flavor. The Standard Model predicts the CP asymmetry parameters Im({lambda}{sub +}) and |{lambda}{sub +}| to be sin2{beta} and 1, respectively, in the absence of penguin diagram contributions. They are determined to be 0.05 {+-} 0.29(stat) {+-} 0.10(syst) and 0.75 {+-} 0.19(stat) {+-} 0.02(syst), respectively, which corresponds to a 2.5 sigma deviation from Standard Model predictions with penguin contributions ignored.

  20. CP asymmetries in semiinclusive B0 decays

    Energy Technology Data Exchange (ETDEWEB)

    Dunietz, Isard

    1999-02-01

    It was recently pointed out that inclusive B^0(t) decays could show CP violation. The totally inclusive asymmetry is expected to be tiny [O(10^{-3})] because of large cancellations among the asymmetries in the charmless, single charm and double charm final states. Enriching particular final state configurations could significantly increase the CP-asymmetry and observability. Such studies can extract fundamental CKM (Cabibbo-Kobayashi-Maskawa) parameters, and (perhaps) even Delta m(B_s). A superb vertex detector could see CP violation with 10^5 (10^6) flavor-tagged B_s (B_d) mesons within the CKM model. Because the effects could be significantly larger due to new physics, they should be searched for in existing or soon available data samples.

  1. A time-dependent measurement of charm CP violation at LHCb

    CERN Multimedia

    Smith, M

    2014-01-01

    A time dependent analysis of CP violation in charm mesons is presented through the measurement of the observable $A_{\\Gamma}$. This observable involves precise measurements of the D0 lifetime as it decays to a CP eigenstate. The results presented are the most precise to date. No CP violation is observed.

  2. New physics effects on CP violation in B decays

    International Nuclear Information System (INIS)

    Nir, Y.

    1993-01-01

    The author reviews new physics effects on CP violation in B decays. In chapter 2 he introduces the formalism, and discusses the Standard Model picture of CP violation in B decays, with special emphasis on the cleanliness of the predictions. Chapter 3 gives a general discussion of new physics effects: he points out the ingredients in the analysis that are sensitive to new physics and deduces the type of new physics that is most likely to modify the Standard Model predictions. Explicit examples are given in chapter 4: a model with Z-mediated flavor changing neutral currents demonstrates in which ways the new physics will manifest itself in CP asymmetries in B decays; a supersymmetric model with open-quotes quark-squark alignmentclose quotes mechanism shows that supersymmetry may affect CP asymmetries in B decays, even though the minimal supersymmetric Standard Model does not; multi-scalar models may affect the asymmetries even in the absence of new CP violating phases; schemes for quark mass matrices will be crucially tested by the CP asymmetries. In chapter 5 he explains how, if deviations from the Standard Model predictions are measured, one will be able to learn detailed features of the New Physics that is responsible for that

  3. Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Heejin Lim

    2018-03-01

    Full Text Available The binding of the tumor necrosis factor α (TNFα to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel®, infliximab (Remicade®, adalimumab (Humira®, certolizumab-pegol (Cimzia®, and golimumab (Simponi®, are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.

  4. CRF receptor antagonist astressin-B reverses and prevents alopecia in CRF over-expressing mice.

    Directory of Open Access Journals (Sweden)

    Lixin Wang

    2011-02-01

    Full Text Available Corticotropin-releasing factor (CRF signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF₂ receptor antagonist, astressin₂-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.

  5. On the Nature of CP Pup

    Science.gov (United States)

    Mason, E.; Orio, M.; Mukai, K.; Bianchini, A.; deMartino, D.; diMille, F.; Williams, R. E.

    2013-01-01

    We present new X-ray and optical spectra of the old nova CP Pup (nova Pup 1942) obtained with Chandra and the CTIO 4m telescope. The X-ray spectrum reveals a multi-temperature optically thin plasma reaching a maximum temperature of 36+19 keV 16 absorbed by local complex neutral material. The time resolved optical spectroscopy confirms the presence of the 1.47 hr period, with cycle-to-cycle amplitude changes, as well as of an additional long term modulation which is suggestive either of a longer pe- riod or of non-Keplerian velocities in the emission line regions. These new observational facts add further support to CP Pup as a magnetic cataclysmic variable (mCV). We compare the mCV and the non-mCV scenarios and while we cannot conclude whether CP Pup is a long period system, all observational evidences point at an intermediate polar (IP) type CV.

  6. Study of inclusive CP-asymmetries in B0 decays

    International Nuclear Information System (INIS)

    Huettmann, K.

    2000-01-01

    The object of the present thesis is the search for CP-violating effects in the mixing of neutral B mesons. For this the time-dependent CP asymmetry in the decay of completely inclusively reconstructed B 0 mesons was studied. The basis of the analysis were about 4.1 millions hadronic Z decays, which were token up in the years 1991-1995 with the ALEPH detector at the e + e - storage ring LEP at CERN. From the data b hadron decays were inclusively reconstructed by means of a search for secondary decay vertices. By a fit to the decay-time spectra od identified B 0 and anti B 0 decays the following value of the semileptonic asymmetry in the B d 0 - anti B d 0 system could be determined: a CP =0.016±0.034(stat.)±0.009(syst.). This value can be alternatively interpreted as a measurement of the CP-violating parameter Re ε B : Re εB/(1+ vertical stroke ε B vertical stroke 2 )=0.004±0.009(stat.)±0.002(syst.). Furthermore a combination of the results of this analysis with a further ALEPH measurement was performed. The value of a CP determined from this, which was obtained under regardment of the statistical correlation of both measurements as well as correlated systematic uncertainties, is: a CP =-0.013±0.026. The present result is compatible with the standard model prediction and yields no significant hint to CP violation in the B d 0 - anti B 0 d mixing. (orig.) [de

  7. Methods for detection of methyl-CpG dinucleotides

    Science.gov (United States)

    Dunn, John J.

    2012-09-11

    The invention provides methods for enriching methyl-CpG sequences from a DNA sample. The method makes use of conversion of cytosine residues to uracil under conditions in which methyl-cytosine residues are preserved. Additional methods of the invention enable to preservation of the context of me-CpG dinucleotides. The invention also provides a recombinant, full length and substantially pure McrA protein (rMcrA) for binding and isolation of DNA fragments containing the sequence 5'-C.sup.MeCpGG-3'. Methods for making and using the rMcrA protein, and derivatives thereof are provided.

  8. The Craterostigma plantagineum glycine-rich protein CpGRP1 interacts with a cell wall-associated protein kinase 1 (CpWAK1) and accumulates in leaf cell walls during dehydration.

    Science.gov (United States)

    Giarola, Valentino; Krey, Stephanie; von den Driesch, Barbara; Bartels, Dorothea

    2016-04-01

    Craterostigma plantagineum tolerates extreme desiccation. Leaves of this plant shrink and extensively fold during dehydration and expand again during rehydration, preserving their structural integrity. Genes were analysed that may participate in the reversible folding mechanism. Analysis of transcripts abundantly expressed in desiccated leaves identified a gene putatively coding for an apoplastic glycine-rich protein (CpGRP1). We studied the expression, regulation and subcellular localization of CpGRP1 and its ability to interact with a cell wall-associated protein kinase (CpWAK1) to understand the role of CpGRP1 in the cell wall during dehydration. The CpGRP1 protein accumulates in the apoplast of desiccated leaves. Analysis of the promoter revealed that the gene expression is mainly regulated at the transcriptional level, is independent of abscisic acid (ABA) and involves a drought-responsive cis-element (DRE). CpGRP1 interacts with CpWAK1 which is down-regulated in response to dehydration. Our data suggest a role of the CpGRP1-CpWAK1 complex in dehydration-induced morphological changes in the cell wall during dehydration in C. plantagineum. Cell wall pectins and dehydration-induced pectin modifications are predicted to be involved in the activity of the CpGRP1-CpWAK1 complex. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  9. p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice

    Directory of Open Access Journals (Sweden)

    Venkateshwar Madka

    2013-08-01

    Full Text Available The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group were fed control (AIN-76A or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001. A significant decrease in the bladder tumor weights (by 68.6–80.2%, P < .0001 in males and by 36.9–55.3%, P < .0001 in females was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.

  10. Theoretical Prediction on [5]Radialene Sandwich Complexes (CpM)2(C10H10) (Cp = η5-C5H5; M = Fe, Co, Ni): Geometry, Spin States, and Bonding.

    Science.gov (United States)

    Liu, Nan-Nan; Xue, Ying-Ying; Ding, Yi-Hong

    2017-02-09

    [5]Radialene, the missing link for synthesis of radialene family, has been finally obtained via the preparation and decomplexation of the [5]radialene-bis-Fe(CO) 3 complex. The stability of [5]radialene complex benefits from the coordination with Fe(CO) 3 by losing free 1,3-butadiene structures to avoid polymerization. In light of the similar coordination ability of half-sandwiches CpM(Cp = η 5 -C 5 H 5 ; M = Fe, Co, Ni), there is a great possibility that the sandwiched complexes of [5]radialene with CpM are available. Herein, we present the first theoretical prediction on the geometry, spin states and bonding of (CpM)(C 10 H 10 ) and (CpM) 2 (C 10 H 10 ). For M = Fe, Co, Ni, the ground states of (CpM)(C 10 H 10 ) and (CpM) 2 (C 10 H 10 ) are doublet and triplet, singlet and singlet, and doublet and triplet states, where each Fe, Co, and Ni adopts 17, 18, and 19 electron-configuration, respectively. In particular, (CpFe) 2 (C 10 H 10 ) and (CpNi) 2 (C 10 H 10 ) have considerable open-shell singlet features. Generally the trans isomers of (CpM) 2 (C 10 H 10 ) with two CpM fragments on the opposite sides of the [5]radialene plane are apparently more stable than the cis ones with CpM fragments on the same side. However, for the singlet and triplet isomers of (CpNi) 2 (C 10 H 10 ) (both cis and trans isomers), the energy differences are relatively small, indicating that these isomers all have the opportunity to exist. Besides, the easy Diels-Alder (DA) dimerization between the [3]dendralene-like fragments of (CpM)(C 10 H 10 ) suggests the great difficulty in isolating the (CpM)(C 10 H 10 ) monomer.

  11. CP violation with self-tagging Bd modes

    International Nuclear Information System (INIS)

    Dunietz, I.

    1991-01-01

    Gronau and Wyler (GW) extract the weak phase γ and remove the dependence on final state phases by measuring six charged B mesons rates, which are grouped into two trinangles. This note applies the GW method to self-tagging B d modes. Self-tagging eliminates the need for time-dependent measurements. Of interest are the six rates, Γ(B d →D 0 K *0 )=Γ(anti B d →anti D 0 anti K *0 ), Γ(B d →anti D 0 K *0 )=Γ(anti B d →D 0 anti K *0 ), Γ(B d →D 0 CP K *0 ) and Γ(anti B d →D 0 CP anti K *0 ), where D 0 CP denotes a CP eigenmode of a D 0 or anti D 0 . Here the K *0 must be seen in its K + π - mode, which tags the beauty flavour. An additional handle exists to resolve an ambiguity in vertical strokesin γvertical stroke, which accomplished by isospin symmetry from B u and B d data. Preliminary results of a feasibility study are given. (orig.)

  12. CP violation and ΔI=1/2 enhancement in K decays

    International Nuclear Information System (INIS)

    Choudhury, S.R.; Scadron, M.D.

    1996-01-01

    We study CP-conserving and CP-violating K 0 →ππ and K 0 →ππγ decays, using the same techniques which explain the ΔI=1/2 enhancement of the former to also explore CP violation of the latter transitions. If CP violation is driven by the WWγ vertex, we show that direct CP violation in K L →ππγ is scaled to the s→dγ E1 quark transition and the latter is suppressed by the GIM mechanism (compatible with recent experiments). In the same spirit, the dominant ΔI=1/2 enhancement of CP-conserving kaon weak decays can be scaled to an s→d quark transition which is enhanced by the GIM mechanism. copyright 1996 The American Physical Society

  13. Syntheses, structures and redox properties of some complexes containing the Os(dppe)Cp* fragment, including [{Os(dppe)Cp*}2(mu-C triple bondCC triple bond C)].

    Science.gov (United States)

    Bruce, Michael I; Costuas, Karine; Davin, Thomas; Halet, Jean-François; Kramarczuk, Kathy A; Low, Paul J; Nicholson, Brian K; Perkins, Gary J; Roberts, Rachel L; Skelton, Brian W; Smith, Mark E; White, Allan H

    2007-12-14

    The sequential conversion of [OsBr(cod)Cp*] (9) to [OsBr(dppe)Cp*] (10), [Os([=C=CH2)(dppe)Cp*]PF6 ([11]PF6), [Os(C triple bond CH)(dppe)Cp*] (12), [{Os(dppe)Cp*}2{mu-(=C=CH-CH=C=)}][PF6]2 ([13](PF6)2) and finally [{Os(dppe)Cp*}(2)(mu-C triple bond CC triple bond C)] (14) has been used to make the third member of the triad [{M(dppe)Cp*}2(mu-C triple bond CC triple bond C)] (M = Fe, Ru, Os). The molecular structures of []PF6, 12 and 14, together with those of the related osmium complexes [Os(NCMe)(dppe)Cp*]PF6 ([15]PF6) and [Os(C triple bond CPh)(dppe)Cp*] (16), have been determined by single-crystal X-ray diffraction studies. Comparison of the redox properties of 14 with those of its iron and ruthenium congeners shows that the first oxidation potential E1 varies as: Fe approximately Os < Ru. Whereas the Fe complex has been shown to undergo three sequential 1-electron oxidation processes within conventional electrochemical solvent windows, the Ru and Os compounds undergo no fewer than four sequential oxidation events giving rise to a five-membered series of redox related complexes [{M(dppe)Cp*}2(mu-C4)]n+ (n = 0, 1, 2, 3 and 4), the osmium derivatives being obtained at considerably lower potentials than the ruthenium analogues. These results are complimented by DFT and DT DFT calculations.

  14. Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line.

    Science.gov (United States)

    Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P

    2008-12-01

    Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

  15. Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

    Science.gov (United States)

    Cohen, C; Sanger, D J; Perrault, G

    1997-11-01

    The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

  16. Photodissociation dynamics of gaseous CpCo(CO)2 and ligand exchange reactions of CpCoH2 with C3H4, C3H6, and NH3.

    Science.gov (United States)

    Oana, Melania; Nakatsuka, Yumiko; Albert, Daniel R; Davis, H Floyd

    2012-05-31

    The photodissociation dynamics of CpCo(CO)(2) was studied in a molecular beam using photofragment translational energy spectroscopy with 157 nm photoionization detection of the metallic products. At 532 and 355 nm excitation, the dominant one-photon channel involved loss of a single CO ligand producing CpCoCO. The product angular distributions were isotropic, and a large fraction of excess energy appeared as product vibrational excitation. Production of CpCO + 2CO resulted from two-photon absorption processes. The two-photon dissociation of mixtures containing CpCo(CO)(2) and H(2) at the orifice of a pulsed nozzle was used to produce a novel 16-electron unsaturated species, CpCoH(2). Transition metal ligand exchange reactions, CpCoH(2) + L → CpCoL + H(2) (L = propyne, propene, or ammonia), were studied under single-collision conditions for the first time. In all cases, ligand exchange occurred via 18-electron association complexes with lifetimes comparable to their rotational periods. Although ligand exchange reactions were not detected from CpCoH(2) collisions with methane or propane (L = CH(4) or C(3)H(8)), a molecular beam containing CpCoCH(4) was produced by photolysis of mixtures containing CpCo(CO)(2) and CH(4).

  17. Discrete ambiguities in CP-violating asymmetries in B decays

    International Nuclear Information System (INIS)

    London, David

    1998-01-01

    The CP-angles α, β and γ can be extracted from CP-violating asymmetries in the B system, but only up to discrete ambiguities. These discrete ambiguities make it difficult to determine with certainty whether or not new physics is present. I show that, if the condition α+β+γ=π is imposed, there remains a twofold ambiguity in the CP-angle set (α,β,γ), and I discuss ways to cleanly resolve this final discrete ambiguity

  18. Measurement of Indirect CP Violation in Charm at LHCb

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00342046

    This thesis describes two pieces of work. The first is a study of the resolution of the LHCb vertex locator throughout Run 1. The second comprises analyses to measure the charm mixing and $CP$ violation observables $A_{\\Gamma}$ and $y_{CP}$. An estimate of the resolution of the LHCb vertex locator is required for use in the track fits. A method to measure the resolution with collision data has been developed and tested. The performance of the sub-detector throughout Run 1 of the LHC has been assessed. A significant degrading of the resolution has been seen. The effects of this on the track reconstruction has been examined with little change in the measured quantities being observed. The measurement of indirect $CP$ violation in neutral $D$ meson transitions has been measured through the observables $A_{\\Gamma}$ and $y_{CP}$, using $fb^{-1}$ of $pp$ collisions with a centre of mass energy $7 TeV$, collected by the LHCb detector in 2011. $A_{\\Gamma}$ describes the $CP$ asymmetry of the lifetime of the $D^0$ dec...

  19. FRET analysis of CP12 structural interplay by GAPDH and PRK.

    Science.gov (United States)

    Moparthi, Satish Babu; Thieulin-Pardo, Gabriel; de Torres, Juan; Ghenuche, Petru; Gontero, Brigitte; Wenger, Jérôme

    2015-03-13

    CP12 is an intrinsically disordered protein playing a key role in the regulation of the Benson-Calvin cycle. Due to the high intrinsic flexibility of CP12, it is essential to consider its structural modulation induced upon binding to the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) enzymes. Here, we report for the first time detailed structural modulation about the wild-type CP12 and its site-specific N-terminal and C-terminal disulfide bridge mutants upon interaction with GAPDH and PRK by Förster resonance energy transfer (FRET). Our results indicate an increase in CP12 compactness when the complex is formed with GAPDH or PRK. In addition, the distributions in FRET histograms show the elasticity and conformational flexibility of CP12 in all supra molecular complexes. Contrarily to previous beliefs, our FRET results importantly reveal that both N-terminal and C-terminal site-specific CP12 mutants are able to form the monomeric (GAPDH-CP12-PRK) complex. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 2,2'-Dithiobis(N-ethyl-spermine-5-carboxamide) is a high affinity, membrane-impermeant antagonist of the mammalian polyamine transport system.

    Science.gov (United States)

    Huber, M; Pelletier, J G; Torossian, K; Dionne, P; Gamache, I; Charest-Gaudreault, R; Audette, M; Poulin, R

    1996-11-01

    We have synthesized 2,2'-dithiobis(N-ethyl-spermine-5-carboxamide) (DESC), its thiol monomer (MESC), and the mixed MESC-cysteamine disulfide (DEASC) as potential inhibitors of polyamine transport in mammalian cells. DESC was the most potent antagonist of spermine transport in ZR-75-1 human breast cancer cells, with Ki values of 5. 0 +/- 0.7, 80 +/- 31, and 16 +/- 3 microM for DESC, MESC, and DEASC, respectively. DESC also strongly blocked putrescine and spermidine uptake in ZR-75-1 cells (Ki = 1.6 +/- 0.5 and 2.7 +/- 1.1 microM, respectively). While DESC and MESC were purely competitive inhibitors of putrescine transport, DEASC was a mixed competitive/noncompetitive antagonist. Remarkably, DESC was virtually impermeant in ZR-75-1 cells despite its low Ki toward polyamine transport. The marked difference in affinity between DESC and MESC was essentially due to the tail-to-tail juxtaposition of two spermine-like structures, suggesting that dimeric ligands of the polyamine transporter might simultaneously interact with more than one binding site. While DESC strongly decreased the initial rate of [3H]spermidine transport, even a 40-fold molar excess of antagonist could not completely abolish intracellular spermidine accumulation. Moreover, as little as 0.3 microM spermidine fully restored growth in ZR-75-1 cells treated with an inhibitor of polyamine biosynthesis in the presence of 50 microM DESC, thus emphasizing the importance of uptake of trace amounts of exogenous polyamines. Thus, reducing the exogenous supply of polyamines with a potent competitive inhibitor may be kinetically inadequate to block replenishment of the polyamine pool in polyamine-depleted tumor cells that display high transport capacity. These results demonstrate that polyamine analogues cross-linked into a dimeric structure such as DESC interact with high affinity with the mammalian polyamine carrier without being used as substrates. These novel properties provide a framework for the design of

  1. Evolving role of MeCP2 in Rett syndrome and autism.

    Science.gov (United States)

    LaSalle, Janine M; Yasui, Dag H

    2009-10-01

    Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2. Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome, the understanding of MeCP2 function has evolved. Although MeCP2 was predicted to be a global transcriptional repressor of methylated promoters, large-scale combined epigenomic approaches of MeCP2 binding, methylation and gene expression have demonstrated that MeCP2 binds preferentially to intergenic and intronic regions, and sparsely methylated promoters of active genes. This review compares the evolution of thought within two ‘classic’ epigenetic mechanisms of parental imprinting and X chromosome inactivation to that of the MeCP2 field, and considers the future relevance of integrated epigenomic databases to understanding autism and Rett syndrome.

  2. Synthesis and structural studies of Cp{sup *} rhodium and Cp{sup *} iridium complexes of picolinic hydrazine ligand

    Energy Technology Data Exchange (ETDEWEB)

    Palepu, Narasinga Rao; Kollipara, Mohan Rao [Centre for Advanced Studies in Chemistry, North-Eastern Hill University, Shillong (India); Kaminsky Werner [Dept. of Chemistry, University of Washington, Seattle (United States)

    2017-01-15

    A series of Cp{sup *}Rh and Cp{sup *}Ir complexes of picolinic hydrazine ligand are synthesized and characterized. Picolinic hydrazine has yielded only dinuclear complexes in the case of rhodium metal whereas both mono and dinuclear complexes with iridium metal. Iridium complexes are formed as quaternary salts by the migration of the N–H proton onto the adjacent amine group of the hydrazine after binding to the metal. Picolinic hydrazine acts as nitrogen and oxygen donor ligand in the form of bi and tetradentate bonding modes.

  3. Synthesis of Carboxylate Cp*Zr(IV) Species: Toward the Formation of Novel Metallocavitands.

    Science.gov (United States)

    Daigle, Maxime; Bi, Wenhua; Légaré, Marc-André; Morin, Jean-François; Fontaine, Frédéric-Georges

    2015-06-01

    With the intent of generating metallocavitands isostructural to species [(CpZr)3(μ(3)-O)(μ(2)-OH)3(κO,O,μ(2)-O2C(R))3](+), the reaction of Cp*2ZrCl2 and Cp*ZrCl3 with phenylcarboxylic acids was carried out. Depending on the reaction conditions, five new complexes were obtained, which consisted of Cp*2ZrCl(κ(2)-OOCPh) (1), (Cp*ZrCl(κ(2)-OOCPh))2(μ-κ(2)-OOCPh)2 (2), [(Cp*Zr(κ(2)-OOCPh))2(μ-κ(2)-OOCPh)2(μ(2)-OH)2]·Et2O (3·Et2O), [[Cp*ZrCl2](μ-Cl)(μ-OH)(μ-O2CC6H5)[Cp*Zr

  4. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    International Nuclear Information System (INIS)

    Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

    2011-01-01

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: ► Nicotine-induced StAR inhibition in two human adrenal cell models. ► Nicotine-induced single CpG site methylation in StAR promoter. ► Persistent StAR inhibition and single CpG methylation after nicotine termination. ► Single CpG methylation located at Pax6 binding motif regulates St

  5. A Chiang-type lagrangian in CP^2

    Science.gov (United States)

    Cannas da Silva, Ana

    2018-03-01

    We analyse a monotone lagrangian in CP^2 that is hamiltonian isotopic to the standard lagrangian RP^2, yet exhibits a distinguishing behaviour under reduction by one of the toric circle actions, namely it intersects transversally the reduction level set and it projects one-to-one onto a great circle in CP^1. This lagrangian thus provides an example of embedded composition fitting work of Wehrheim-Woodward and Weinstein.

  6. Constraints on Mixing and CP-Violation in the Neutral Charmed Meson System at LHCb

    CERN Document Server

    Alexander, Michael Thomas; Soler, P

    This thesis presents measurements of the charm sector mixing and CP-violation parameters yCP and AGamma, made using data collected in 2010 by the LHCb experiment at the LHC at a centre of mass energy of 7 TeV. yCP is defined as the difference from unity of the ratio of the effective lifetime of the D0 meson decaying to a CP-undefined final state to its lifetime when decaying to a CP-eigenstate. AGamma is the CP-asymmetry of the effective lifetimes of the D0 and D0bar when decaying to a CP-eigenstate. In the absence of CPV yCP will be consistent with the mixing parameter y, and AGamma will be consistent with zero. CP-violation in the charm sector is predicted to be very small in the SM, though first evidence for direct CP-violation in D0 decays has recently been observed by LHCb. Observation of significantly more CP-violation than is allowed in the SM would be a strong indication of new physics. The current world best measurements of yCP and AGamma show no evidence of CP-violation. The methods used to measure ...

  7. Neutrino mass matrix: Inverted hierarchy and CP violation

    International Nuclear Information System (INIS)

    Frigerio, Michele; Smirnov, Alexei Yu.

    2003-01-01

    We reconstruct the neutrino mass matrix in the flavor basis, in the case of an inverted mass hierarchy (ordering), using all available experimental data on neutrino masses and oscillations. We analyze the dependence of the matrix elements m αβ on the CP violating Dirac δ and Majorana ρ and σ phases, for different values of the absolute mass scale. We find that the present data admit various structures of the mass matrix: (i) hierarchical structures with a set of small (zero) elements; (ii) structures with equalities among various groups of elements: e-row and/or μτ-block elements, diagonal and/or off-diagonal elements; (iii) 'democratic' structure. We find the values of phases for which these structures are realized. The mass matrix elements can anticorrelate with flavor: inverted partial or complete flavor alignment is possible. For various structures of the mass matrix we identify the possible underlying symmetry. We find that the mass matrix can be reconstructed completely only in particular cases, provided that the absolute scale of the mass is measured. Generally, the freedom related to the Majorana phase σ will not be removed, thus admitting various types of mass matrix

  8. Coordination Chemistry of [E(Idipp)]2+ Ligands (E = Ge, Sn): Metal Germylidyne [Cp*(CO)2W≡Ge(Idipp)]+ and Metallotetrylene [Cp*(CO)3W–E(Idipp)]+ Cations

    KAUST Repository

    Lebedev, Yury; Das, Ujjal; Schnakenburg, Gregor; Filippou, Alexander C.

    2017-01-01

    The synthesis and full characterization of the NHC-stabilized tungstenochlorostannylene [Cp*(CO)3W–SnCl(Idipp)] (1Sn), the NHC-stabilized chlorogermylidyne complex [Cp*(CO)2W═GeCl(Idipp)] (2), the tungsten germylidyne complex salt [Cp*(CO)2W

  9. SM with two Higgs doublets: an example of CP-violation without Fermions

    International Nuclear Information System (INIS)

    Cvetic, G.

    1993-01-01

    Some CP-violation effects without fermions in the Standard Model are investigated with two Higgs doublets. First, the mass eigenstates of the physical neutral Higgses are calculated for small but nonzero CP-violation parameter ξ * , and then a ''forward-backward'' asymmetry A fb for the decay H → W + W - Z that would be a signal of CP-violation. The effects are in general small. However, A fb turns out to be a rather clean signal of CP-violation: neither the CP-conserving final state interactions nor the direct production background events contribute to Γ fb . The KM-type CP-violation effects that could in principle also contribute to A fb are negligible. 6 refs

  10. An efficient, block-by-block algorithm for inverting a block tridiagonal, nearly block Toeplitz matrix

    International Nuclear Information System (INIS)

    Reuter, Matthew G; Hill, Judith C

    2012-01-01

    We present an algorithm for computing any block of the inverse of a block tridiagonal, nearly block Toeplitz matrix (defined as a block tridiagonal matrix with a small number of deviations from the purely block Toeplitz structure). By exploiting both the block tridiagonal and the nearly block Toeplitz structures, this method scales independently of the total number of blocks in the matrix and linearly with the number of deviations. Numerical studies demonstrate this scaling and the advantages of our method over alternatives.

  11. CP-violating MSSM Higgs bosons in the light of LEP 2

    International Nuclear Information System (INIS)

    Carena, M.; Ellis, J.; Pilaftsis, A.; Wagner, C.E.M.

    2000-01-01

    In the MSSM, the CP parities of the neutral Higgs bosons may be mixed by radiative effects induced by explicit CP violation in the third generation of squarks. To allow for this possibility, we argue that the charged Higgs-boson mass and tanβ should be used to parametrize the MSSM Higgs sector. We introduce a new benchmark scenario of maximal CP violation appropriate for direct searches of CP-violating MSSM Higgs bosons. We show that the bounds established by LEP 2 on the MSSM Higgs sector may be substantially relaxed at low and intermediate values of tanβ in the presence of CP violation, and comment on possible Higgs boson signatures at LEP 2 within this framework.

  12. Why does CP violation matter to the universe?

    CERN Document Server

    Ellis, Jonathan Richard

    1999-01-01

    The seemingly obscure phenomenon of CP violation is increasingly being viewed as the key to a deeper understanding of both the behaviour of elementary particles and the big bang origin of the universe. Here, John Ellis of CERN explains how far and how deep the implications of CP violation extend. (0 refs).

  13. MeCP2 Rett mutations affect large scale chromatin organization

    DEFF Research Database (Denmark)

    Gupta, Noopur Agarwal; Becker, Annette; Jost, K Laurence

    2011-01-01

    Rett syndrome is a neurological, X chromosomal-linked disorder associated with mutations in the MECP2 gene. MeCP2 protein has been proposed to play a role in transcriptional regulation as well as in chromatin architecture. Since MeCP2 mutant cells exhibit surprisingly mild changes in gene...... expression, we have now explored the possibility that Rett mutations may affect the ability of MeCP2 to bind and organize chromatin. We found that all but one of the 21 missense MeCP2 mutants analyzed accumulated at heterochromatin and about half of them were significantly affected. Furthermore, two......-thirds of all mutants showed a significantly decreased ability to cluster heterochromatin. Three mutants containing different proline substitutions (P101H, P101R and P152R) were severely affected only in heterochromatin clustering and located far away from the DNA interface in the MeCP2 methyl-binding domain...

  14. Lectures on Flavor Physics and CP Violation

    CERN Document Server

    Grinstein, Benjamín

    2016-12-20

    These lectures on flavor physics are an introduction to the subject. First lec- ture: We discuss the meaning of flavor and the importance of flavor physics in restricting extensions of the Standard Model (SM) of Electroweak interactions. We explain the origin of the KM matrix and how its elements are determined. We discuss FCNC and the GIM mechanism, followed by how a principle of Minimal Flavor Violation leads to SM extensions that are safe as far as FCNC are concerned even if the new physics comes in at low, TeVish scales. This is illustrated by the example of B radiative decays ( b → sγ ). Second lecture: We then turn our attention to CP-violation. We start by presenting neutral meson mixing. Then we consider various CP-asymmetries, culminating in the theoretically clean interference between mixing and decay into CP eigenstates.

  15. On the measurement of leptonic CP violation

    International Nuclear Information System (INIS)

    Burguet Castell, J.; Gavela, M.B.; Gomez Cadenas, J.J.; Hernandez, P.; Mena, O.

    2001-01-01

    We show that the simultaneous determination of the leptonic CP-odd phase δ and the angle θ 13 from the subleading transitions ν e →ν μ and ν-bar e →ν-bar μ results generically, at fixed neutrino energy and baseline, in two degenerate solutions. In light of this, we refine a previous analysis of the sensitivity to leptonic CP violation at a neutrino factory, in the LMA-MSW scenario, by exploring the full range of δ and θ 13 . Furthermore, we take into account the expected uncertainties on the solar and atmospheric oscillation parameters and in the average Earth matter density along the neutrino path. An intermediate baseline of O(3000) km is still the best option to tackle CP violation, although a combination of two baselines turns out to be very important in resolving degeneracies

  16. Stacking reactions of the borole complex Cp*Rh(η5-C4H4BPh) with the dicationic fragments [Cp*M]2+ (M = Rh or Ir)

    International Nuclear Information System (INIS)

    Loginov, D.A.; Muratov, D.V.; Starikova, Z.A.; Petrovskij, P.V.; Kudinov, A.R.

    2006-01-01

    The reaction of the (borole)rhodium iodide complex [(η-C 4 H 4 BPh)RhI] 4 with Cp*Li afforded the sandwich compound Cp*Rh(η-C 4 H 4 BPh) (1). The reactions of compound 1 with the solvated complexes [Cp*M(MeNO 2 ) 3 ] 2+ (BF 4 - ) 2 gave triple-decker cationic complexes with the central borole ligand [Cp*Rh(μ-η 5 :η 5 -C 4 H 4 BPh)MCp*] 2+ (BF 4 - ) 2 (M = Rh or Ir). The structure of complex 1 was established by X-ray diffraction [ru

  17. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.

    Science.gov (United States)

    Knych, Heather K; Stanley, Scott D

    2014-01-01

    To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. Randomized crossover design. Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  18. Measurement of $CP$ asymmetry in $D^0\\rightarrow K^-K^+$ decays

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Archilli, Flavio; d'Argent, Philippe; Arnau Romeu, Joan; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Babuschkin, Igor; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Baszczyk, Mateusz; Batozskaya, Varvara; Batsukh, Baasansuren; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bezshyiko, Iaroslava; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bitadze, Alexander; Bizzeti, Andrea; Blake, Thomas; Blanc, Frederic; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Boettcher, Thomas; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Bossu, Francesco; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel; Campora Perez, Daniel Hugo; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chobanova, Veronika; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Costa Sobral, Cayo Mar; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Da Cunha Marinho, Franciole; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Serio, Marilisa; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Déléage, Nicolas; Easo, Sajan; Ebert, Marcus; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Fernandez Prieto, Antonio; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fini, Rosa Anna; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Franco Lima, Vinicius; Frank, Markus; Frei, Christoph; Fu, Jinlin; Furfaro, Emiliano; Färber, Christian; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garcia Martin, Luis Miguel; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gizdov, Konstantin; Gligorov, V.V.; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gorelov, Igor Vladimirovich; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Gruberg Cazon, Barak Raimond; Grünberg, Oliver; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Göbel, Carla; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; Hatch, Mark; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hombach, Christoph; Hopchev, P H; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jiang, Feng; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Kariuki, James Mwangi; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Koliiev, Serhii; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozachuk, Anastasiia; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Leflat, Alexander; Lefrançois, Jacques; Lefèvre, Regis; Lemaitre, Florian; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Maltsev, Timofei; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Mogini, Andrea; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Mulder, Mick; Mussini, Manuel; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Oldeman, Rudolf; Onderwater, Gerco; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Pais, Preema Rennee; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Pastore, Alessandra; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petrov, Aleksandr; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Pomery, Gabriela Johanna; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Poslavskii, Stanislav; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Remon Alepuz, Clara; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vicente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Rollings, Alexandra Paige; Romanovskiy, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rudolph, Matthew Scott; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sadykhov, Elnur; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schellenberg, Margarete; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubert, Konstantin; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Simone, Saverio; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefko, Pavol; Stefkova, Slavorima; Steinkamp, Olaf; Stemmle, Simon; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Eric; van Tilburg, Jeroen; Tilley, Matthew James; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Toriello, Francis; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tully, Alison; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valassi, Andrea; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Venkateswaran, Aravindhan; Vernet, Maxime; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voneki, Balazs; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Vázquez Sierra, Carlos; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Wark, Heather Mckenzie; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zarebski, Kristian Alexander; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhang, Yu; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhu, Xianglei; Zhukov, Valery; Zucchelli, Stefano

    2017-04-10

    A measurement of the time-integrated $CP$ asymmetry in the Cabibbo-suppressed decay $D^0\\rightarrow K^-K^+$ is performed using pp collision data, corresponding to an integrated luminosity of 3fb$^-1$, collected with the LHCb detector at centre-of-mass energies of 7 and 8 TeV. The flavour of the charm meson at production is determined from the charge of the pion in $D^{*+}\\rightarrow D^0 \\pi^+$ and $D^{*-}\\rightarrow \\bar{D^0} \\pi^-$ decays. The time-integrated $CP$ asymmetry $A_{CP}(K^-K^+)$ is obtained assuming negligible $CP$ violation in charm mixing and in Cabibbo-favoured $D^0\\rightarrow K^-\\pi^+$, $D^+\\rightarrow K^-\\pi^+\\pi^+$ and $D^+\\rightarrow \\bar{K^0}\\pi^+$ decays used as calibration channels. It is found to be $A_{CP}(K^-K^+)=(0.14\\pm0.15(stat)\\pm0.10(syst))\\%$. A combination of this result with previous LHCb measurements yields $A_{CP}(K^-K^+)=(0.04\\pm0.12(stat)\\pm0.10(syst))\\%$, $A_{CP}(\\pi^-\\pi^+)=(0.07\\pm0.14(stat)\\pm0.11(syst))\\%$. These are the most precise measurements from a single experi...

  19. Synthesis, properties, and crystal structure of complex Cp2Yb(DAD)

    International Nuclear Information System (INIS)

    Trifonov, A.A.; Kirillov, E.N.; Bochkarev, M.N.; Shumani, G.; Myule, S.

    1999-01-01

    Diazadiene complex of trivalent ytterbium Cp 2 Yb(DAD) (1) (DAD = Bu 1 -N CH-CH = N-Bu 1 ) was obtained by three routes: the oxidation of Cp 2 Yb(THF) 2 by diazadiene in tetrahydrofuran (THF), the reaction of Cp 2 YbCl with DAD 2- Na 2 + (2:1), and the reaction of Cp 2 YbCl(THF) with DAD - K + in the 1:1 ratio. Complex 1 was characterized by microanalysis, IR spectroscopy, magnetochemistry, and X-ray structural analysis [ru

  20. Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening

    Directory of Open Access Journals (Sweden)

    Xing Wang

    2016-03-01

    Full Text Available Endothelin-1 receptors (ETAR and ETBR act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand- and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 μM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA.

  1. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  2. Neutrino mass textures with maximal CP violation

    International Nuclear Information System (INIS)

    Aizawa, Ichiro; Kitabayashi, Teruyuki; Yasue, Masaki

    2005-01-01

    We show three types of neutrino mass textures, which give maximal CP violation as well as maximal atmospheric neutrino mixing. These textures are described by six real mass parameters: one specified by two complex flavor neutrino masses and two constrained ones and the others specified by three complex flavor neutrino masses. In each texture, we calculate mixing angles and masses, which are consistent with observed data, as well as Majorana CP phases

  3. Penguins and cp violation in β decays

    International Nuclear Information System (INIS)

    He, X.C.

    1996-11-01

    The measurement of the ε-parameter in the K 0 - K-bar 0 meson system is the only direct evidence for CP violation in the laboratory. The Standard Model (SM) of three generations with the source for CP violation arising from the phases in the Cabibbo-Kobayashi-Maskawa (CKM) matrix is consistent with the experiment. An unique feature of this model is that the CKM matrix is a 3 x 3 unitary matrix. (author)

  4. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    Science.gov (United States)

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  5. Synthesis and reactivity of dimolybdathiaborane cluster [(Cp Mo ...

    Indian Academy of Sciences (India)

    Cluster 2 has a bicapped octahedral geometry with the {Fe(CO)3} fragment occupying one of the ... thesis and characterization of [(Cp. ∗ ... Infrared spectra were obtained on a Nicolet 6700 FT-. IR spectrometer. Microanalyses for C, H, and N were performed on .... tains signals attributable to the one type of Cp. ∗ ligand.

  6. Searches for CP violation in two-body charm decays

    CERN Document Server

    INSPIRE-00160626

    2015-10-16

    The LHCb experiment recorded data corresponding to an integrated luminosity of 3.0 $fb^{-1}$ during its first run of data taking. These data yield the largest samples of charmed hadrons in the world and are used to search for CP violation in the $D^0$ system. Among the many measurements performed at LHCb, a measurement of the direct CP asymmetry in $D^0 \\rightarrow K_S^0 K_S^0$ decays is presented and is found to be $A_{CP}(D^0 \\rightarrow K_S^0 K_S^0) = (-2.9 \\pm 5.2 \\pm 2.2)\\, \\%, $ where the first uncertainty is statistical and the second systematic. This represents a significant improvement in precision over the previous measurement of this parameter. Measurements of the parameter $A^\\Gamma$, defined as the CP asymmetry of the $D^0$ effective lifetime when decaying to a CP eigenstate, are also presented. Using semi-leptonic b-hadron decays to tag the flavour of the $D^0$ meson at production with the $K^+K^-$ and $\\pi^+\\pi^-$ final states yields $A^\\Gamma(K^+K^-) = (-0.134 \\pm 0.077^{+0.026}_{-0.034})\\, \\%...

  7. submitter Time-dependent CP violation in charm mesons

    CERN Document Server

    Inguglia, Gianluca

    CP violation is a well established phenomenon for B and K mesons, but for D0 mesons, bound states made up of a quark-antiquark pair containing a charm quark, a conclusive answer to the question whether there is CP vio- lation or not, has yet to be determined. I show here the phenomenology of time-dependent CP asymmetries in charm decays, and discuss the implica- tions of experimental tests aimed at the measurement of CP violation in the interference between mixing and decays of charm mesons, in particular when studying the decay channels D0 ! h+h (h = K; ). The decay channels considered can also be used to constrain quantities that are poorly measured or still to be investigated, such as MIX and c;eff , provided that the e ects of penguin pollution are ignored. I considered correlated production of D0 mesons at the SuperB experiment and its planned asymmetric run at the charm threshold and performed a study of simulated events, nding that a boost factor = 0:28 would not be su cient to produce competitive re- ...

  8. Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

    Science.gov (United States)

    Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

    2017-10-01

    Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

  9. Small molecule antagonists of integrin receptors.

    Science.gov (United States)

    Perdih, A; Dolenc, M Sollner

    2010-01-01

    The complex and widespread family of integrin receptors is involved in numerous physiological processes, such as tissue remodeling, angiogenesis, development of the immune response and homeostasis. In addition, their key role has been elucidated in important pathological disorders such as cancer, cardiovascular diseases, osteoporosis, autoimmune and inflammatory diseases and in the pathogenesis of infectious diseases, making them highly important targets for modern drug design campaigns. In this review we seek to present a concise overview of the small molecule antagonists of this diverse and highly complex receptor family. Integrin antagonists are classified according to the targeted integrin receptor and are discussed in four sections. First we present the fibrinogen alpha(IIb)beta3 and the vitronectin alpha (V)beta(3) receptor antagonists. The remaining selective integrin antagonists are examined in the third section. The final section is dedicated to molecules with dual or multiple integrin activity. In addition, the use of antibodies and peptidomimetic approaches to modulate the integrin receptors are discussed, as well providing the reader with an overall appreciation of the field.

  10. Antiallergic effects of H1-receptor antagonists.

    Science.gov (United States)

    Baroody, F M; Naclerio, R M

    2000-01-01

    The primary mechanism of antihistamine action in the treatment of allergic diseases is believed to be competitive antagonism of histamine binding to cellular receptors (specifically, the H1-receptors), which are present on nerve endings, smooth muscles, and glandular cells. This notion is supported by the fact that structurally unrelated drugs antagonize the H1-receptor and provide clinical benefit. However, H1-receptor antagonism may not be their sole mechanism of action in treating allergic rhinitis. On the basis of in vitro and animal experiments, drugs classified as H1-receptor antagonists have long been recognized to have additional pharmacological properties. Most first-generation H1-antihistamines have anticholinergic, sedative, local anaesthetic, and anti-5-HT effects, which might favourably affect the symptoms of the allergic response but also contribute to side-effects. These additional properties are not uniformly distributed among drugs classified as H1-receptor antagonists. Azatadine, for example, inhibits in vitro IgE-mediated histamine and leukotriene (LT) release from mast cells and basophils. In human challenge models, terfenadine, azatadine, and loratadine reduce IgE-mediated histamine release. Cetirizine reduces eosinophilic infiltration at the site of antigen challenge in the skin, but not the nose. In a nasal antigen challenge model, cetirizine pretreatment did not affect the levels of histamine and prostaglandin D2 recovered in postchallenge lavages, whereas the levels of albumin, N-tosyl-L-arginine methyl ester (TAME) esterase activity, and LTs were reduced. Terfenadine, cetirizine, and loratadine blocked allergen-induced hyperresponsiveness to methacholine. In view of the complexity of the pathophysiology of allergy, a number of H1 antagonists with additional properties are currently under development for allergic diseases. Mizolastine, a new H1-receptor antagonist, has been shown to have additional actions that should help reduce the

  11. A Geometric Approach to CP Violation: Applications to the MCPMFV SUSY Model

    CERN Document Server

    Ellis, John; Pilaftsis, Apostolos

    2010-01-01

    We analyze the constraints imposed by experimental upper limits on electric dipole moments (EDMs) within the Maximally CP- and Minimally Flavour-Violating (MCPMFV) version of the MSSM. Since the MCPMFV scenario has 6 non-standard CP-violating phases, in addition to the CP-odd QCD vacuum phase \\theta_QCD, cancellations may occur among the CP-violating contributions to the three measured EDMs, those of the Thallium, neutron and Mercury, leaving open the possibility of relatively large values of the other CP-violating observables. We develop a novel geometric method that uses the small-phase approximation as a starting point, takes the existing EDM constraints into account, and enables us to find maximal values of other CP-violating observables, such as the EDMs of the Deuteron and muon, the CP-violating asymmetry in b --> s \\gamma decay, and the B_s mixing phase. We apply this geometric method to provide upper limits on these observables within specific benchmark supersymmetric scenarios, including extensions t...

  12. CP violation in the two-doublet Higgs sector of the MSSM

    International Nuclear Information System (INIS)

    Akhmetzyanova, Eh.N.; Dolgopolov, M.V.; Dubinin, M.N.

    2006-01-01

    Models with extended two-doublet Higgs sector are discussed in view of using their particular features to find out which sources of CP violation could take place in nature. It is considered the effective two-Higgs-doublet potential with complex parameters, when the CP invariance is broken both explicitly and spontaneously. For case of the two-doublet Higgs sector of the minimal supersymmetric model, when CP invariance is violated by the interactions of Higgs fields with the third generation of scalar quarks, the Higgs bosons mass spectrum in the case of maximal CP mixing is calculated which is significantly different from CP-conserving case. The phenomenological consequences for the Higgs mass spectrum in the decoupling regime and for the strong mixing case are considered [ru

  13. The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

    International Nuclear Information System (INIS)

    Cherukuri, Durga Prasad; Chen, Xiao B.O.; Goulet, Anne-Christine; Young, Robert N.; Han, Yongxin; Heimark, Ronald L.; Regan, John W.; Meuillet, Emmanuelle; Nelson, Mark A.

    2007-01-01

    Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein-coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant-negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer

  14. Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

    Science.gov (United States)

    Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  15. Isospin analysis of CP asymmetries in B decays

    International Nuclear Information System (INIS)

    Gronau, M.; London, D.

    1990-09-01

    There is some theoretical uncertainty in the predictions for CP violating hadronic asymmetries in neutral B decays to CP eigenstates due to the existence of penguin diagrams. Using isospin relatins, we show that it is possible to remove this uncertainty for the decays B d 0 → ππ, up to a 4-fold ambiguity. (orig.)

  16. 5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

    Directory of Open Access Journals (Sweden)

    Tiong Cheng Sia

    2013-08-01

    Full Text Available Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit ? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT. In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10µM and SDZ-205-557 (1-10µM in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.

  17. Kobayashi-Maskawa type of hard-CP-violation model with three-generation Majorana neutrinos

    International Nuclear Information System (INIS)

    Cheng, H.

    1986-01-01

    Within the framework of the Kobayashi-Maskawa (KM) type of hard CP-violation model with three-generation Majorana neutrinos, we point out that on-shell CP-violation phenomena (i.e., CP-violating effects taking place in on-shell processes), which are characteristic of Majorana neutrinos, can only occur in total-lepton-number-conserving reactions, and are unobservably small. Off-shell CP-nonconserving effects which arise from gauge bosons are undetectable, but those which are mediated by Higgs bosons could be seen in certain rare decays. It is emphasized that CP-odd effects intrinsic to Majorana behavior depend not only on the two CP-violating Majorana phases but also on the KM phase. We then demonstrate why the KM model, which has rich implications in the hadronic sector, leads to no observable CP-violating effects in leptonic processes (except in neutrino oscillations) directly related to the CP-odd KM phase

  18. Effects of glutamate and α2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats

    International Nuclear Information System (INIS)

    Alam, Mesbah; Danysz, Wojciech; Schmidt, Werner Juergen; Dekundy, Andrzej

    2009-01-01

    Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic α9/α10 and 5-HT 3 receptor antagonist), idazoxan (α 2 -adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle instead of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone + saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.

  19. Cationic Protic Imidazolylidene NHC Complexes of Cp*IrCl+ and Cp*RhCl+ with a Pyridyl Tether Formed at Ambient Temperature

    Directory of Open Access Journals (Sweden)

    Douglas B. Grotjahn

    2018-02-01

    Full Text Available Protic NHC (PNHC complexes with N1H, N2-alkyl/aryl imidazolylidene ligands are relatively rare, and routes for their synthesis differ from what is used to make non-protic analogs. Prior work from our group and others showed that in the presence of a tethering ligand (phosphine or in one case, pyridine, CpM and Cp*M (M = Ir, Ru PNHC complexes could be made by heating. Here, we find that the use of ionizing agents to activate [Cp*MIIICl(μ-Cl]2 (M = Ir, Rh allows for what we believe is unprecedented ambient temperature formation of PNHC complexes from neutral imidazoles; the product complexes are able to perform transfer hydrogenation.

  20. Gonadotrophin releasing hormone antagonist in IVF/ICSI

    Directory of Open Access Journals (Sweden)

    M S Kamath

    2008-01-01

    Full Text Available Objective : To study the efficacy of gonadotrophin releasing hormone (GnRH antagonist in In-vitro-fertilization/Intracytoplasmic sperm injection (IVF/ICSI cycles. Type of Study : Observational study. Setting: Reproductive Medicine Unit, Christian Medical College Hospital, Vellore, Tamil Nadu. Materials and Methods: GnRH antagonists were introduced into our practice in November 2005. Fifty-two women undergoing the antagonist protocol were studied and information gathered regarding patient profile, treatment parameters (total gonadotrophin dosage, duration of treatment, and oocyte yield, and outcomes in terms of embryological parameters (cleavage rates, implantation rates and clinical pregnancy. These parameters were compared with 121 women undergoing the standard long protocol. The costs between the two groups were also compared. Main Outcome : Clinical pregnancy rate. Results : The clinical pregnancy rate per embryo transfer in the antagonist group was 31.7% which was comparable to the clinical pregnancy rate in women undergoing the standard long protocol (30.63%. The costs between the two groups were comparable. Conclusions : GnRH antagonist protocol was found to be effective and comparable to the standard long protocol regimen. In addition it was simple, convenient, and patient friendly.

  1. Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis.

    Science.gov (United States)

    Silva, Mara Thais de Oliveira; Bezerra, Francisco Silvestre Brilhante; de Pinho, Rodrigo Barros; Begnini, Karine Rech; Seixas, Fabiana Kommling; Collares, Tiago; Portela, Ricardo Dias; Azevedo, Vasco; Dellagostin, Odir; Borsuk, Sibele

    2018-01-02

    Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Correction: Graillot, B.; et al. Progressive Adaptation of a CpGV Isolate to Codling Moth Populations Resistant to CpGV-M. Viruses 2014, 6, 5135–5144

    Directory of Open Access Journals (Sweden)

    Benoît Graillot

    2015-12-01

    Full Text Available In our article “Progressive Adaptation of a CpGV Isolate to Codling Moth Populations Resistant to CpGV-M.” (Viruses 2014, 6, 5135–5144; doi:10.3390/v6125135 [1] we obtained resistance values of the codling moth, Cydia pomonella, RGV laboratory colony [2], when challenged with Cydia pomonella Granulovirus, Mexican Isolate (CpGV-M, that were lower than those previously published [2]. Careful analysis of both the RGV colony and the CpGV-M virus stock used led to the realization that a low level contamination of this virus stock with CpGV-R5 occurred. We have made new tests with a verified stock, and the results are now in agreement with those previously published.

  3. A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex.

    Science.gov (United States)

    Sheardown, M J

    1988-04-13

    L(+)-AP4 (2-amino-4-phosphonobutyrate) depolarized slices of rat cerebral cortex, when applied following a 2 min priming application of quisqualate. This response diminishes with time and is not seen after NMDA application. A new selective non-N-methyl-D-aspartate (NMDA) antagonist, 6-cyano-7-nitro-2,3-dihydroxyquinoxaline (FG 9065), inhibits the L(+)-AP4 depolarization. It is argued that the response is mediated indirectly by postsynaptic quisqualate receptors.

  4. Quaternionic potentials and CP-violation

    International Nuclear Information System (INIS)

    Nishi, Celso Chikahiro

    2000-01-01

    Full text follows: In the formulation of Quantum Mechanics by using a non-commutative ring of quaternions, we attempt to solve the Schroedinger equation with quaternionic potentials. Decay processes can easily be modeled by including complex imaginary potentials. Although, it could be explained as a transition between states under action of a perturbation. Purely imaginary quaternionic potentials can be used to describe CP-violation effects. The neutral kaon system, K 0 - K-bar 0 or K L - K S , represents an example of CP-violation phenomenon. The inclusion of quaternionic potentials imply a reformulation of the whole quantum theory. The use of a quaternionic algebra in discussing the Schroedinger equation leads to the lost of time reversal invariance (T), closely connected to CP violation by the well-known CPT theorem. In particular, we study the Schroedinger equation in presence of a quaternionic potential barrier given in terms of V, real potential acting in the region of width a, and jW, purely quaternionic potential acting in the region of width b. Different cases, |W|/V and b/a, are discussed in view of possible deviations of standard Quantum Mechanics. The complex linear Schroedinger equation is solved for stationary states. The explicit solution contains complex and quaternionic transmission/reflection coefficients. A wave packet treatment needs to make a more realistic and physical description. We briefly discuss possible interpretations and remaining questions. (author)

  5. A General Cp*CoIII -Catalyzed Intramolecular C-H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids.

    Science.gov (United States)

    Lerchen, Andreas; Knecht, Tobias; Koy, Maximilian; Daniliuc, Constantin G; Glorius, Frank

    2017-09-07

    Herein, we report a Cp*Co III -catalyzed C-H activation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine, and tylophora alkaloids. This particular C-H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. History of the 'geste antagoniste' sign in cervical dystonia.

    Science.gov (United States)

    Poisson, A; Krack, P; Thobois, S; Loiraud, C; Serra, G; Vial, C; Broussolle, E

    2012-08-01

    The geste antagoniste is a voluntary maneuver that temporarily reduces the severity of dystonic posture or movements. It is a classical feature of focal and particularly cervical dystonia. However, the precise historical aspects of geste antagoniste still remain obscure. The goals of this review were (1) to clarify the origin of the geste antagoniste sign; (2) to identify the factors that led to its diffusion in the international literature; (3) to follow the evolution of that term across the twentieth century. We used medical and neurological French, German and English literature of the late nineteenth and early twentieth centuries, and the PubMed database by entering the terms geste antagoniste, antagonistic gesture and sensory trick. The geste antagoniste sign is a legacy of the Paris Neurological School of the end of the nineteenth century. The term was introduced by Meige and Feindel in their 1902 book on tics, written in the vein of their master, Brissaud, who first described this sign in 1893. The almost immediate translations of this book by Giese into German and Kinnier Wilson into English contributed to the rapid spreading of the term geste antagoniste, which is still in use worldwide today. The term antagonistic gesture is the translation proposed by Kinnier Wilson, which also led to the use of the term geste antagonistique. The geste antagoniste sign has long been considered a solid argument for the psychogenic origins of dystonia until the 1980s when Marsden made strong arguments for its organic nature.

  7. Search for Direct CP Violation in Quasi-2-Body Charmless B Decays

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2004-02-12

    We have searched for direct CP violation in quasi-two-body charmless B decays observed in a sample of about 45 million B mesons collected with the BABAR detector at the PEP-II collider. We measure the following charge asymmetries in decay: {Alpha}{sub CP}(B{sup {+-}} {yields} {eta}{prime}K{sup {+-}}) = -0.11 {+-} 0.02, {Alpha}{sub CP}(B{sup {+-}} {yields} {omega}{pi}{sup {+-}}) = 0.01{sub -0.31}{sup +0.29} {+-} 0.03, {Alpha}{sub CP}(B{sup {+-}} {yields} {phi}K{sup {+-}}) = -0.05 {+-} 0.20 {+-} 0.03, {Alpha}{sub CP}(B{sup {+-}} {yields} {phi}K*{sup {+-}}) = -0.43{sub -0.30}{sup +0.36} {+-} 0.06, and {Alpha}{sub CP}(B{sup 0}/{bar B}{sup 0} {yields} {phi}K*{sup 0}/{bar K}*{sup 0}) = 0.00 {+-} 0.27 {+-} 0.03.

  8. Methyl CpG–binding proteins induce large-scale chromatin reorganization during terminal differentiation

    Science.gov (United States)

    Brero, Alessandro; Easwaran, Hariharan P.; Nowak, Danny; Grunewald, Ingrid; Cremer, Thomas; Leonhardt, Heinrich; Cardoso, M. Cristina

    2005-01-01

    Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG–binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG–binding domain (MBD) only. Similar to MeCP2, another methyl CpG–binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation. PMID:15939760

  9. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  10. CP violation in the lepton sector and implications for leptogenesis

    DEFF Research Database (Denmark)

    Hagedorn, C.; Mohapatra, R. N.; Molinaro, E.

    2018-01-01

    We review the current status of the data on neutrino masses and lepton mixing and the prospects for measuring the CP-violating phases in the lepton sector. The possible connection between low energy CP violation encoded in the Dirac and Majorana phases of the Pontecorvo-Maki-Nakagawa-Sakata mixing...... matrix and successful leptogenesis is emphasized in the context of seesaw extensions of the Standard Model with a flavor symmetry Gf (and CP symmetry)....

  11. Reverse pupillary block associated with pigment dispersion syndrome after in-the-bag intraocular lens implantation.

    Science.gov (United States)

    Itagaki, Hideo; Kunikata, Toshio; Hiratsuka, Kentaro; Saito, Junichiro; Oshika, Tetsuro

    2013-12-01

    A 61-year-old man with high myopia who had received a systemic α1A-adrenoceptor antagonist had phacoemulsification and in-the-bag intraocular lens implantation in the right eye. One day postoperatively, marked pigment dispersion in the anterior chamber, posterior bowing of the iris, and iridodonesis were noted associated with a subsequent elevation in intraocular pressure (IOP). Pharmacological pupil dilation was effective in reducing pigment dispersion and IOP, and laser peripheral iridotomy was performed to alleviate posterior bowing of the iris. We hypothesize that dynamic changes in the aqueous humor flow by cataract surgery and latent flaccidity of the iris due to the systemic α1A-adrenoceptor antagonist caused reverse pupillary block. High myopia may be another risk factor for this complication. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  12. Magnesium sulphate as an adjuvant to bupivacaine in ultrasound-guided transversus abdominis plane block in patients scheduled for total abdominal hysterectomy under subarachnoid block

    Directory of Open Access Journals (Sweden)

    Shelly Rana

    2016-01-01

    Full Text Available Background and Aims: Transversus abdominis plane (TAP block has proven to be an effective component of multimodal analgesic regimens for a variety of abdominal procedures. Magnesium sulphate (MgSO4 N-methyl-D-aspartate receptor antagonist has the potential to be an ideal adjuvant in TAP block. We studied the efficacy of MgSO4as an adjuvant to bupivacaine in TAP block in patients scheduled for total abdominal hysterectomy (TAH under subarachnoid block (SAB. Methods: Sixty-five women belonging to American Society of Anesthesiologists physical status 1 or 2, aged between 35 and 70 years, scheduled for TAH under SAB were recruited. Patients in Group B (n = 32 received 18 mL 0.25% bupivacaine (45 mg with 2 mL normal saline (NS, whereas those in Group BM (n = 33 received 18 mL 0.25% bupivacaine (45 mg with 1.5 mL (150 mg MgSO4and 0.5 mL NS in the ultrasound (USG-guided TAP block performed on each side after the completion of the surgery under SAB. They were evaluated for pain at 0, 2, 4, 6, 12 and 24 h, time to first rescue analgesic and duration of postoperative analgesia were noted. Results: The post-operative visual analogue scale (VAS scores were lower in Group BM at 4, 6 and 12 h (P < 0.05. Mean duration of analgesia was significantly prolonged in Group BM with lesser requirement of rescue analgesic (P < 0.05 up to 12 h. Conclusion: MgSO4 (150 mg as an adjuvant to bupivacaine in USG-guided TAP block reduces post-operative pain scores, prolongs the duration of analgesia and decreases demands for rescue analgesics.

  13. LHCb CP violation

    CERN Document Server

    Vesterinen, Mika

    2016-01-01

    The study of $CP$ violation in the beauty hadron sector is a promising approach to search for the effects of physics beyond the Standard Model. Several recent measurements in this area from the LHCb experiment are reported in these proceedings. These are based on the Run-I dataset of 3~fb$^{-1}$ of data collected at proton-proton centre of mass energies of 7 and 8~TeV.

  14. Isolation, identification and antagonistic activity evaluation of actinomycetes in barks of nine trees

    Directory of Open Access Journals (Sweden)

    Wang Dong-sheng

    2017-01-01

    Full Text Available Actinomycetes are important producers of novel bioactive compounds. New sources need to be explored for isolating previously unknown bioactive compound-producing actinomycetes. Here we evaluated the potential of bark as a natural source of novel bioactive actinomycete species. Bark samples were collected from nine tree species at different elevations (1600-3400 ma.s.l. on Qin Mountain, Shaanxi Province, China. Actinomycetes were cultivated, enumerated and isolated using serial dilution and spread-plate techniques. The antimicrobial activity of actinomycete isolates was analyzed using an agar block method against 15 typical bacterial and fungal species and plant pathogens. The dominant isolates were identified by 16S rRNA-based sequence analysis. Results showed that actinomycete counts in bark samples of Quercus liaotungensis Koidz. was the highest among all trees species tested. The numbers of actinomycete species in bark samples were highest in Q. aliena var. acutiserrata and Spiraea alpina Pall. Antagonistic activity wasdetected in approximately 54% of the actinomycete isolates. Of these, 20 isolates (25% showed broad-spectrum antagonistic activity against ≥5 of the microorganisms tested. In conclusion, the bark on coniferous and broadleaf trees possesses a high diversity of actinomycetes and serves as a natural source of bioactive compound-producing actinomycetes.

  15. Instantons, CP-violation and axions

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, S. R.

    1980-07-01

    Some specific aspects of the developments in pseudoparticle solutions of Gauge theories are discussed. The general features of the Lagrangian are described. The concepts of instantons, confinement, O-vacua and CP nonconservation are explained.

  16. CP violation in the standard model and beyond

    International Nuclear Information System (INIS)

    Buras, A.J.

    1984-01-01

    The present status of CP violation in the standard six quark model is reviewed and a combined analysis with B-meson decays is presented. The theoretical uncertainties in the analysis are discussed and the resulting KM weak mixing angles, the phase delta and the ratio epsilon'/epsilon are given as functions of Tsub(B), GAMMA(b -> u)/GAMMA(b -> c), msub(t) and the B parameter. For certain ranges of the values of these parameters the standard model is not capable in reproducing the experimental values for epsilon' and epsilon parameters. Anticipating possible difficulties we discuss various alternatives to the standard explanation of CP violation such as horizontal interactions, left-right symmetric models and supersymmetry. CP violation outside the kaon system is also briefly discussed. (orig.)

  17. First Observation of CP Violation in B[over ¯]^{0}→D_{CP}^{(*)}h^{0} Decays by a Combined Time-Dependent Analysis of BABAR and Belle Data.

    Science.gov (United States)

    Abdesselam, A; Adachi, I; Adametz, A; Adye, T; Ahmed, H; Aihara, H; Akar, S; Alam, M S; Albert, J; Al Said, S; Andreassen, R; Angelini, C; Anulli, F; Arinstein, K; Arnaud, N; Asner, D M; Aston, D; Aulchenko, V; Aushev, T; Ayad, R; Babu, V; Badhrees, I; Bahinipati, S; Bakich, A M; Band, H R; Banerjee, Sw; Barberio, E; Bard, D J; Barlow, R J; Batignani, G; Beaulieu, A; Bellis, M; Ben-Haim, E; Bernard, D; Bernlochner, F U; Bettarini, S; Bettoni, D; Bevan, A J; Bhardwaj, V; Bhuyan, B; Bianchi, F; Biasini, M; Biswal, J; Blinov, V E; Bloom, P C; Bobrov, A; Bomben, M; Bondar, A; Bonneaud, G R; Bonvicini, G; Bozek, A; Bozzi, C; Bračko, M; Briand, H; Browder, T E; Brown, D N; Brown, D N; Bünger, C; Burchat, P R; Buzykaev, A R; Calabrese, R; Calcaterra, A; Calderini, G; Carpinelli, M; Cartaro, C; Casarosa, G; Cenci, R; Červenkov, D; Chang, P; Chao, D S; Chauveau, J; Cheaib, R; Chekelian, V; Chen, A; Chen, C; Cheng, C H; Cheon, B G; Chilikin, K; Chistov, R; Cho, K; Chobanova, V; Choi, H H F; Choi, S-K; Chrzaszcz, M; Cibinetto, G; Cinabro, D; Cochran, J; Coleman, J P; Contri, R; Convery, M R; Cowan, G; Cowan, R; Cremaldi, L; Dalseno, J; Dasu, S; Davier, M; Davis, C L; De Mori, F; De Nardo, G; Denig, A G; Derkach, D; de Sangro, R; Dey, B; Di Lodovico, F; Dingfelder, J; Dittrich, S; Doležal, Z; Dorfan, J; Drásal, Z; Drutskoy, A; Druzhinin, V P; Dubois-Felsmann, G P; Dunwoodie, W; Dutta, D; Ebert, M; Echenard, B; Eidelman, S; Eigen, G; Eisner, A M; Emery, S; Ernst, J A; Faccini, R; Farhat, H; Fast, J E; Feindt, M; Ferber, T; Ferrarotto, F; Ferroni, F; Field, R C; Filippi, A; Finocchiaro, G; Fioravanti, E; Flood, K T; Ford, W T; Forti, F; Franco Sevilla, M; Fritsch, M; Fry, J R; Fulsom, B G; Gabathuler, E; Gabyshev, N; Gamba, D; Garmash, A; Gary, J W; Garzia, I; Gaspero, M; Gaur, V; Gaz, A; Gershon, T J; Getzkow, D; Gillard, R; Li Gioi, L; Giorgi, M A; Glattauer, R; Godang, R; Goh, Y M; Goldenzweig, P; Golob, B; Golubev, V B; Gorodeisky, R; Gradl, W; Graham, M T; Grauges, E; Griessinger, K; Gritsan, A V; Grosdidier, G; Grünberg, O; Guttman, N; Haba, J; Hafner, A; Hamilton, B; Hara, T; Harrison, P F; Hast, C; Hayasaka, K; Hayashii, H; Hearty, C; He, X H; Hess, M; Hitlin, D G; Hong, T M; Honscheid, K; Hou, W-S; Hsiung, Y B; Huard, Z; Hutchcroft, D E; Iijima, T; Inguglia, G; Innes, W R; Ishikawa, A; Itoh, R; Iwasaki, Y; Izen, J M; Jaegle, I; Jawahery, A; Jessop, C P; Joffe, D; Joo, K K; Julius, T; Kang, K H; Kass, R; Kawasaki, T; Kerth, L T; Khan, A; Kiesling, C; Kim, D Y; Kim, J B; Kim, J H; Kim, K T; Kim, P; Kim, S H; Kim, Y J; King, G J; Kinoshita, K; Ko, B R; Koch, H; Kodyš, P; Kolomensky, Yu G; Korpar, S; Kovalskyi, D; Kowalewski, R; Kravchenko, E A; Križan, P; Krokovny, P; Kuhr, T; Kumar, R; Kuzmin, A; Kwon, Y-J; Lacker, H M; Lafferty, G D; Lanceri, L; Lange, D J; Lankford, A J; Latham, T E; Leddig, T; Le Diberder, F; Lee, D H; Lee, I S; Lee, M J; Lees, J P; Leith, D W G S; Leruste, Ph; Lewczuk, M J; Lewis, P; Libby, J; Lockman, W S; Long, O; Lopes Pegna, D; LoSecco, J M; Lou, X C; Lueck, T; Luitz, S; Lukin, P; Luppi, E; Lusiani, A; Luth, V; Lutz, A M; Lynch, G; MacFarlane, D B; Malaescu, B; Mallik, U; Manoni, E; Marchiori, G; Margoni, M; Martellotti, S; Martinez-Vidal, F; Masuda, M; Mattison, T S; Matvienko, D; McKenna, J A; Meadows, B T; Miyabayashi, K; Miyashita, T S; Miyata, H; Mizuk, R; Mohanty, G B; Moll, A; Monge, M R; Moon, H K; Morandin, M; Muller, D R; Mussa, R; Nakano, E; Nakazawa, H; Nakao, M; Nanut, T; Nayak, M; Neal, H; Neri, N; Nisar, N K; Nishida, S; Nugent, I M; Oberhof, B; Ocariz, J; Ogawa, S; Okuno, S; Olaiya, E O; Olsen, J; Ongmongkolkul, P; Onorato, G; Onuchin, A P; Onuki, Y; Ostrowicz, W; Oyanguren, A; Pakhlova, G; Pakhlov, P; Palano, A; Pal, B; Palombo, F; Pan, Y; Panduro Vazquez, W; Paoloni, E; Park, C W; Park, H; Passaggio, S; Patel, P M; Patrignani, C; Patteri, P; Payne, D J; Pedlar, T K; Peimer, D R; Peruzzi, I M; Pesántez, L; Pestotnik, R; Petrič, M; Piccolo, M; Piemontese, L; Piilonen, L E; Pilloni, A; Piredda, G; Playfer, S; Poireau, V; Porter, F C; Posocco, M; Prasad, V; Prell, S; Prepost, R; Puccio, E M T; Pulliam, T; Purohit, M V; Pushpawela, B G; Rama, M; Randle-Conde, A; Ratcliff, B N; Raven, G; Ribežl, E; Richman, J D; Ritchie, J L; Rizzo, G; Roberts, D A; Robertson, S H; Röhrken, M; Roney, J M; Roodman, A; Rossi, A; Rostomyan, A; Rotondo, M; Roudeau, P; Sacco, R; Sakai, Y; Sandilya, S; Santelj, L; Santoro, V; Sanuki, T; Sato, Y; Savinov, V; Schindler, R H; Schneider, O; Schnell, G; Schroeder, T; Schubert, K R; Schumm, B A; Schwanda, C; Schwartz, A J; Schwitters, R F; Sciacca, C; Seiden, A; Sekula, S J; Senyo, K; Seon, O; Serednyakov, S I; Sevior, M E; Shapkin, M; Shebalin, V; Shen, C P; Shibata, T-A; Shiu, J-G; Simard, M; Simi, G; Simon, F; Simonetto, F; Skovpen, Yu I; Smith, A J S; Smith, J G; Snyder, A; So, R Y; Sobie, R J; Soffer, A; Sohn, Y-S; Sokoloff, M D; Sokolov, A; Solodov, E P; Solovieva, E; Spaan, B; Spanier, S M; Starič, M; Stocchi, A; Stroili, R; Stugu, B; Su, D; Sullivan, M K; Sumihama, M; Sumisawa, K; Sumiyoshi, T; Summers, D J; Sun, L; Tamponi, U; Taras, P; Tasneem, N; Teramoto, Y; Tisserand, V; Todyshev, K Yu; Toki, W H; Touramanis, C; Trabelsi, K; Tsuboyama, T; Uchida, M; Uglov, T; Unno, Y; Uno, S; Usov, Y; Uwer, U; Vahsen, S E; Van Hulse, C; Vanhoefer, P; Varner, G; Vasseur, G; Va'vra, J; Verderi, M; Vinokurova, A; Vitale, L; Vorobyev, V; Voß, C; Wagner, M N; Wagner, S R; Waldi, R; Walsh, J J; Wang, C H; Wang, M-Z; Wang, P; Watanabe, Y; West, C A; Williams, K M; Wilson, F F; Wilson, J R; Wisniewski, W J; Won, E; Wormser, G; Wright, D M; Wu, S L; Wulsin, H W; Yamamoto, H; Yamaoka, J; Yashchenko, S; Yuan, C Z; Yusa, Y; Zallo, A; Zhang, C C; Zhang, Z P; Zhilich, V; Zhulanov, V; Zupanc, A

    2015-09-18

    We report a measurement of the time-dependent CP asymmetry of B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays, where the light neutral hadron h^{0} is a π^{0}, η, or ω meson, and the neutral D meson is reconstructed in the CP eigenstates K^{+}K^{-}, K_{S}^{0}π^{0}, or K_{S}^{0}ω. The measurement is performed combining the final data samples collected at the ϒ(4S) resonance by the BABAR and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6} BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6} BB[over ¯] pairs recorded by the Belle detector. We measure the CP asymmetry parameters -η_{f}S=+0.66±0.10(stat)±0.06(syst) and C=-0.02±0.07(stat)±0.03(syst). These results correspond to the first observation of CP violation in B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.

  18. Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Alvarado, M.; Biegon, A.

    2001-01-01

    The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.

  19. Flavour physics and CP violation

    CERN Document Server

    Nir, Y.

    2015-05-22

    We explain the many reasons for the interest in flavor physics. We describe flavor physics and the related CP violation within the Standard Model, and explain how the B-factories proved that the Kobayashi-Maskawa mechanism dominates the CP violation that is observed in meson decays. We explain the implications of flavor physics for new physics, with emphasis on the “new physics flavor puzzle”, and present the idea of minimal flavor violation as a possible solution. We explain why the values flavor parameters of the Standard Model are puzzling, present the Froggatt-Nielsen mechanism as a possible solution, and describe how measurements of neutrino parameters are interpreted in the context of this puzzle. We show that the recently discovered Higgs-like boson may provide new opportunities for making progress on the various flavor puzzles.

  20. CP nonconservation in decays of W and Z bosons

    International Nuclear Information System (INIS)

    Hou, W.; Deshpande, N.G.; Eilam, G.; Soni, A.

    1986-01-01

    The possibility of CP asymmetries in decays of W and Z bosons is examined. The asymmetries studied are the differences in the branching ratios of charge-conjugate modes such as W + →tb-bar vs W - →t-barb or Z→b-bars vs Z→bs-bar. In the standard model, with three generations, such effects are found to be vanishingly small. With four generations, flavor-changing transitions such as Z→bs-bar or b'b-bar may be observable, but the prospects for observing CP asymmetries appear discouraging. We also discuss the situation in some other models of CP nonconservation

  1. Ultrasonic green synthesis of an Ag/CP nanocomposite for enhanced photodegradation effectiveness.

    Science.gov (United States)

    Chang, Hai Ning; Hou, Suo Xia; Hao, Zeng Chuan; Cui, Guang Hua

    2018-01-01

    A nanoparticle of cobalt(II) coordination polymer (CP), [Co(L)(npht)] n (1) (H 2 npht=4-nitrophthalic acid, L=1,3-bis(5,6-dimethylbenzimidazol-1-ylmethyl)benzene) and its nanocomposite (Ag/CP 1) were obtained by the sonochemical approach and characterized by IR, elemental analysis, thermogravimetric analyses (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRPD). CP 1 shows a 1D double chain containing two different helical chains, which is further extended into a two-dimensional supramolecular framework by C-H⋯O hydrogen bonding interactions. The photoluminescence properties and photocatalytic properties of the nanoparticles of CP 1 and Ag/CP 1 on the degradation of methylene blue (MB) were investigated, Ag/CP 1 exhibited excellent photocatalytic activity under UV and visible light, which can be attributed to the strong interactions between Ag nanorods and CP 1, which lead to electron-hole pair separation between Ag nanorods and CP 1. In addition, the photocatalytic mechanism is also carried out by introducing t-butyl alcohol (TBA) as a widely used ·OH scavenger. The influence of ultrasound irradiation time and power on the morphology and size of the nanostructure CP 1 were studied. The results indicated that a decrease in time and an increase in power led to a decrease of particle size. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. CT-1-CP-induced ventricular electrical remodeling in mice.

    Science.gov (United States)

    Chen, Shu-fen; Wei, Tao-zhi; Rao, Li-ya; Xu, Ming-guang; Dong, Zhan-ling

    2015-02-01

    The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, PCP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, PCP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, PCP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious

  3. Soft CP violation and the global matter-antimatter symmetry of the universe

    Science.gov (United States)

    Senjanovic, G.; Stecker, F. W.

    1980-01-01

    Scenarios for baryon production are considered within the context of SU(5) and SO(10) grand unified theories where CP violation arises spontaneously. The spontaneous CP symmetry breaking then results in a matter-antimatter domain structure in the universe. Two possible, distinct types of theories of soft CP violation are defined. In the first type the CP nonconservation originates only from the breaking of SU(2) sub L X U(1) symmetry, and in the second type, even at the unification temperature scale, CP violation can emerge as a result of symmetry breaking by the vacuum expectation values of the superheavy Higgs sector scalars.

  4. Development of a Data Acquisition System for the BaBar CP Violation Experiment

    International Nuclear Information System (INIS)

    Claus, Richard

    1999-01-01

    Experiences developing data acquisition system for the BaBar CP violation experiment located at the Stanford Linear Accelerator Center are presented. The BaBar detector consists of multiple independent subdetectors joined with a data acquisition system consisting of a large number of embedded PowerPC single board computers residing in VME crates. The data acquisition software is layered on the VxWorks real-time operating system. It is partitionable to allow subsystems (as well as test stands) to operate independently. Data is assimilated into events through a combination of shared memory and a high performance network. This system presents data to a UNIX farm via a high speed non-blocking ethernet switch at a rate of 2 KHz. Topics such as bootstrapping and loading 200 processors, NFS file access for these processors and software development and deployment are discussed

  5. Development of a Data Acquisition System for the BaBar CP Violation Experiment

    CERN Document Server

    Scott, I; Grosso, P; Hamilton, R T; Huffer, M E; O'Grady, C P; Russell, J J

    1999-01-01

    Experiences developing data acquisition system for the BaBar CP violation experiment located at the Stanford Linear Accelerator Center are presented. The BaBar detector consists of multiple independent subdetectors joined with a data acquisition system consisting of a large number of embedded PowerPC single board computers residing in VME crates. The data acquisition software is layered on the VxWorks real-time operating system. It is partitionable to allow subsystems (as well as test stands) to operate independently. Data is assimilated into events through a combination of shared memory and a high performance network. This system presents data to a UNIX farm via a high speed non-blocking ethernet switch at a rate of 2 KHz. Topics such as bootstrapping and loading 200 processors, NFS file access for these processors and software development and deployment are discussed.

  6. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.

    Science.gov (United States)

    Hanagata, Nobutaka

    2017-01-01

    Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

  7. P2Y1 receptor antagonists mitigate oxygen and glucose deprivation‑induced astrocyte injury.

    Science.gov (United States)

    Guo, Hui; Liu, Zhong-Qiang; Zhou, Hui; Wang, Zhi-Ling; Tao, Yu-Hong; Tong, Yu

    2018-01-01

    The aim of the present study was to elucidate the effects of blocking the calcium signaling pathway of astrocytes (ASs) on oxygen and glucose deprivation (OGD)‑induced AS injury. The association between the changes in the concentrations of AS‑derived transmitter ATP and glutamic acid, and the changes in calcium signaling under the challenge of OGD were investigated. The cortical ASs of Sprague Dawley rats were cultured to establish the OGD models of ASs. The extracellular concentrations of ATP and glutamic acid in the normal group and the OGD group were detected, and the intracellular concentration of calcium ions (Ca2+) was detected. The effects of 2'‑deoxy‑N6‑methyl adenosine 3', 5'‑diphosphate diammonium salt (MRS2179), a P2Y1 receptor antagonist, on the release of calcium and glutamic acid of ASs under the condition of OGD were observed. The OGD challenge induced the release of glutamic acid and ATP by ASs in a time‑dependent manner, whereas elevation in the concentration of glutamic acid lagged behind that of the ATP and Ca2+. The concentration of Ca2+ inside ASs peaked 16 h after OGD, following which the concentration of Ca2+ was decreased. The effects of elevated release of glutamic acid by ASs when challenged by OGD may be blocked by MRS2179, a P2Y1 receptor antagonist. Furthermore, MRS2179 may significantly mitigate OGD‑induced AS injury and increase cell survival. The ASs of rats cultured in vitro expressed P2Y1 receptors, which may inhibit excessive elevation in the concentration of intracellular Ca2+. Avoidance of intracellular calcium overload and the excessive release of glutamic acid may be an important reason why MRS2179 mitigates OGD‑induced AS injury.

  8. Future prospects for studying CP violation in B-meson decays

    International Nuclear Information System (INIS)

    Nakada, T.

    1997-01-01

    Experimental prospects for observing CP violation in B-meson decays are reviewed. Comparisons are made for various options: experiments a e + e - B-Meson Factories, HERA and the TEVATRON will produce results n near future. They will have a good chance to discover CP violation in B-meson decays. On a longer time scale, experiments at the LHC will aim at accurate measurements to make a precision test of the standard model in CP violation. (author)

  9. CP Violation in Heavy MSSM Higgs Scenarios

    CERN Document Server

    Carena, M; Lee, J S; Pilaftsis, A; Wagner, C E M

    2016-01-01

    We introduce and explore new heavy Higgs scenarios in the Minimal Supersymmetric Standard Model (MSSM) with explicit CP violation, which have important phenomenological implications that may be testable at the LHC. For soft supersymmetry-breaking scales M_S above a few TeV and a charged Higgs boson mass M_H+ above a few hundred GeV, new physics effects including those from explicit CP violation decouple from the light Higgs boson sector. However, such effects can significantly alter the phenomenology of the heavy Higgs bosons while still being consistent with constraints from low-energy observables, for instance electric dipole moments. To consider scenarios with a charged Higgs boson much heavier than the Standard Model (SM) particles but much lighter than the supersymmetric particles, we revisit previous calculations of the MSSM Higgs sector. We compute the Higgs boson masses in the presence of CP violating phases, implementing improved matching and renormalization group (RG) effects, as well as two-loop RG...

  10. CP violation in rare K decays

    International Nuclear Information System (INIS)

    Ecker, G.

    1990-01-01

    The investigation of rare K decays calls for a unified treatment of short- and long-distance aspects as provided by chiral perturbation theory. For the standard model with three generations, the theoretical predictions for signals of CP violation in those decays are reviewed. With direct CP violation as the main target, special emphasis is given to the charge asymmetries in charged K decays and to the especially rare decays K L → π 0 ll-bar. Time dependent rate asymmetries in K 0 decays and the longitudinal muon polarization in K L → μ + μ - are also discussed. 50 refs., 3 figs., 1 tab. (Author)

  11. Physical properties of superbulky lanthanide metallocenes: synthesis and extraordinary luminescence of [Eu(II)(Cp(BIG))2] (Cp(BIG) = (4-nBu-C6H4)5-cyclopentadienyl).

    Science.gov (United States)

    Harder, Sjoerd; Naglav, Dominik; Ruspic, Christian; Wickleder, Claudia; Adlung, Matthias; Hermes, Wilfried; Eul, Matthias; Pöttgen, Rainer; Rego, Daniel B; Poineau, Frederic; Czerwinski, Kenneth R; Herber, Rolfe H; Nowik, Israel

    2013-09-09

    The superbulky deca-aryleuropocene [Eu(Cp(BIG))2], Cp(BIG) = (4-nBu-C6H4)5-cyclopentadienyl, was prepared by reaction of [Eu(dmat)2(thf)2], DMAT = 2-Me2N-α-Me3Si-benzyl, with two equivalents of Cp(BIG)H. Recrystallizyation from cold hexane gave the product with a surprisingly bright and efficient orange emission (45% quantum yield). The crystal structure is isomorphic to those of [M(Cp(BIG))2] (M = Sm, Yb, Ca, Ba) and shows the typical distortions that arise from Cp(BIG)⋅⋅⋅Cp(BIG) attraction as well as excessively large displacement parameter for the heavy Eu atom (U(eq) = 0.075). In order to gain information on the true oxidation state of the central metal in superbulky metallocenes [M(Cp(BIG))2] (M = Sm, Eu, Yb), several physical analyses have been applied. Temperature-dependent magnetic susceptibility data of [Yb(Cp(BIG))2] show diamagnetism, indicating stable divalent ytterbium. Temperature-dependent (151)Eu Mössbauer effect spectroscopic examination of [Eu(Cp(BIG))2] was examined over the temperature range 93-215 K and the hyperfine and dynamical properties of the Eu(II) species are discussed in detail. The mean square amplitude of vibration of the Eu atom as a function of temperature was determined and compared to the value extracted from the single-crystal X-ray data at 203 K. The large difference in these two values was ascribed to the presence of static disorder and/or the presence of low-frequency torsional and librational modes in [Eu(Cp(BIG))2]. X-ray absorbance near edge spectroscopy (XANES) showed that all three [Ln(Cp(BIG))2] (Ln = Sm, Eu, Yb) compounds are divalent. The XANES white-line spectra are at 8.3, 7.3, and 7.8 eV, for Sm, Eu, and Yb, respectively, lower than the Ln2O3 standards. No XANES temperature dependence was found from room temperature to 100 K. XANES also showed that the [Ln(Cp(BIG))2] complexes had less trivalent impurity than a [EuI2(thf)x] standard. The complex [Eu(Cp(BIG))2] shows already at room temperature

  12. Interference Cancellation Schemes for Single-Carrier Block Transmission with Insufficient Cyclic Prefix

    Directory of Open Access Journals (Sweden)

    Hayashi Kazunori

    2008-01-01

    Full Text Available Abstract This paper proposes intersymbol interference (ISI and interblock interference (IBI cancellation schemes at the transmitter and the receiver for the single-carrier block transmission with insufficient cyclic prefix (CP. The proposed scheme at the transmitter can exterminate the interferences by only setting some signals in the transmitted signal block to be the same as those of the previous transmitted signal block. On the other hand, the proposed schemes at the receiver can cancel the interferences without any change in the transmitted signals compared to the conventional method. The IBI components are reduced by using previously detected data signals, while for the ISI cancellation, we firstly change the defective channel matrix into a circulant matrix by using the tentative decisions, which are obtained by our newly derived frequency domain equalization (FDE, and then the conventional FDE is performed to compensate the ISI. Moreover, we propose a pilot signal configuration, which enables us to estimate a channel impulse response whose order is greater than the guard interval (GI. Computer simulations show that the proposed interference cancellation schemes can significantly improve bit error rate (BER performance, and the validity of the proposed channel estimation scheme is also demonstrated.

  13. CPLEAR and BaBar: CP violation in all its states

    CERN Document Server

    Yeche, Christophe

    2003-01-01

    This report of French 'Habilitation a diriger les recherches' summarizes my scientific activity from 1993 to 2003. During this decade, my research work was related to two particle physics experiments: CPLEAR and BABAR. The first one, CPLEAR, has recorded data from 1988 to 1995 on the low energy anti-proton ring (LEAR) at CERN. This experiment was devoted to the study of T, CPT et CP discrete symmetries. The second experiment, BABAR, has been running since 1999, on the PEP-II B factory at SLAC. This experiment searches for CP violation and tests the Standard Model through the measurements of the angles and the sides of the Unitarity Triangle. My research work is divided in five main topics: Study of CP and CPT violation in K0 → π+ π- decays; Performance optimization of the particle identification detector (DIRC) of the BABAR experiment; B meson tagging in BABAR experiment; Δmd measurement and Search for CP and T violation in mixing with dilepton events; Search for CP violation in B0 → ρ± π± and B0 �...

  14. Flavour physics and CP violation

    Indian Academy of Sciences (India)

    status and prospectives of the flavour physics associated with the strange, charm and .... might reveal something completely unexpected. Standard Model weak ..... Thus, in order to have an observable CP violation effect in the SM, the mixing.

  15. The effects of intraperitoneal and intracerebroventricular administration of the GABAB receptor antagonist CGP 35348 on food intake in rats.

    Science.gov (United States)

    Patel, Sunit M; Ebenezer, Ivor S

    2004-10-25

    In order to test the hypothesis that endogenous gamma-aminobutyric acid (GABA), acting at central GABAB receptors, plays a physiological role in the control of feeding behaviour, it was reasoned that blocking these receptors with a centrally active GABAB receptor antagonist should reduce food intake in hungry rats. In the present study, experiments were carried out to test this possibility using the GABAB receptor antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid (CGP 35348), which is water-soluble and can penetrate the blood-brain barrier from the systemic circulation. CGP 35348 (50 and 100 mg/kg, i.p.) had no effect on food intake in 22-h fasted rats, but a higher dose (i.e. 500 mg/kg., i.p.) significantly reduced cumulative food consumption. These findings are consistent with previous observations that high systemic doses of CGP 35348 are needed to block central GABAB receptors. However, to eliminate the possibility that the 500 mg/kg dose of CGP 35348 decreased food intake by a peripheral, rather than a central mode of action, further experiments were undertaken where the drug was given directly into the brain by the intracerebroventricular (i.c.v.) route. I.c.v. administration of CGP 35348 (5 and 10 microg) significantly decreased cumulative food intake food intake in rats that had been fasted for 22 h. By contrast, i.c.v. administration of CGP 35348 (10 microg) had no effect on water intake in 16-h water-deprived rats. The results indicate that CGP 35348 reduces food consumption in hungry rats by blocking central GABAB receptors in a behaviourally specific manner. These findings suggest that endogenous GABA acting at central GABAB receptors plays a physiological role in the regulation of feeding behaviour.

  16. Physical Properties of Superbulky Lanthanide Metallocenes : Synthesis and Extraordinary Luminescence of [Eu-II(Cp-BIG)(2)] (Cp-BIG=(4-nBu-C6H4)(5)-Cyclopentadienyl)

    NARCIS (Netherlands)

    Harder, Sjoerd; Naglav, Dominik; Ruspic, Christian; Wickleder, Claudia; Adlung, Matthias; Hermes, Wilfried; Eul, Matthias; Poettgen, Rainer; Rego, Daniel B.; Poineau, Frederic; Czerwinski, Kenneth R.; Herber, Rolfe H.; Nowik, Israel

    2013-01-01

    The superbulky deca-aryleuropocene [Eu(Cp-BIG)(2)], Cp-BIG=(4-nBu-C6H4)(5)-cyclopentadienyl, was prepared by reaction of [Eu(dmat)(2)(thf)(2)], DMAT=2-Me2N--Me3Si-benzyl, with two equivalents of (CpH)-H-BIG. Recrystallizyation from cold hexane gave the product with a surprisingly bright and

  17. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  18. CpG islands undermethylation in human genomic regions under selective pressure.

    Directory of Open Access Journals (Sweden)

    Sergio Cocozza

    Full Text Available DNA methylation at CpG islands (CGIs is one of the most intensively studied epigenetic mechanisms. It is fundamental for cellular differentiation and control of transcriptional potential. DNA methylation is involved also in several processes that are central to evolutionary biology, including phenotypic plasticity and evolvability. In this study, we explored the relationship between CpG islands methylation and signatures of selective pressure in Homo Sapiens, using a computational biology approach. By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. To define genomic regions under selective pressure, we used three different methods, each oriented to provide distinct information about selective events. Independently of the method and of the cell type used, we found evidences of undermethylation of CGIs in human genomic regions under selective pressure. Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. Our findings suggest that the CpG islands in regions under selective pressure seem to be somehow more "protected" from methylation when compared with other regions of the genome.

  19. [Stress-corrosion test of TIG welded CP-Ti].

    Science.gov (United States)

    Li, H; Wang, Y; Zhou, Z; Meng, X; Liang, Q; Zhang, X; Zhao, Y

    2000-12-01

    In this study TIG (Tungsten Inert Gas) welded CP-Ti were subjected to stress-corrosion test under 261 MPa in artificial saliva of 37 degrees C for 3 months. No significant difference was noted on mechanical test (P > 0.05). No color-changed and no micro-crack on the sample's surface yet. These results indicate that TIG welded CP-Ti offers excellent resistance to stress corrosion.

  20. Quark flavor mixing, CP violation, and all that

    International Nuclear Information System (INIS)

    Gilman, F.J.

    1988-04-01

    We review the present state of knowledge of the mixing of quark flavors under weak interactions and the associated explanation of CP violation inherent in the single nontrivial phase present in the three-generation mixing matrix. In this context we present the phenomenological basis for the increasing possibility that large CP violation asymmetries can be experimentally observed in the B meson system. 39 refs., 11 figs.,

  1. Measurement of CP observables for the decays B±→DCP0K*±

    International Nuclear Information System (INIS)

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; Grauges, E.; Palano, A.; Pappagallo, M.; Pompili, A.; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; Eigen, G.; Ofte, I.

    2005-01-01

    Using a sample of 232x10 6 Υ(4S)→BB events collected with the BABAR detector at the PEP-II B Factory in 1999-2004, we study B - →D 0 K*(892) - decays where K* - →K S 0 π - and D 0 →K - π + , K - π + π 0 , K - π + π + π - (non-CP final states); K + K - , π + π - (CP+ eigenstates); K S 0 π 0 , K S 0 φ, and K S 0 ω (CP- eigenstates). We measure four observables that are sensitive to the angle γ of the CKM unitarity triangle; the partial-rate charge asymmetries A CP± and the ratios of the B-decay branching fraction in CP± and non-CP decays R CP± : A CP+ =-0.08±0.19(stat)±0.08(syst), A CP- =-0.26±0.40(stat)±0.12(syst), R CP+ =1.96±0.40(stat)±0.11(syst), and R CP- =0.65±0.26(stat)±0.08(syst)

  2. Selective Glucocorticoid Receptor (GR-II Antagonist Reduces Body Weight Gain in Mice

    Directory of Open Access Journals (Sweden)

    Tomoko Asagami

    2011-01-01

    Full Text Available Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (=8 received one of the following: CORT 108297 (80 mg/kg QD, CORT 108297 (40 mg/kg BID, mifepristone (30 mg/kg BID, rosiglitazone (10 mg/kg QD, or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain.

  3. Insertion Chemistry of Cp*2Y(2-pyridyl) and Molecular Structure of the Unexpected CO Insertion Product (Cp*2Y)2(μ-η2 : η2-OC(NC5H4)2)

    NARCIS (Netherlands)

    Deelman, Berth-Jan; Stevels, Willem M.; Teuben, Jan H.; Lakin, Miles T.; Spek, Anthony L.

    1994-01-01

    Pyridine is metalated selectively at the 2-position by (Cp*2YH)2 to yield Cp*2Y(2-pyridyl) (1). Compound 1 reacts with H2 to give the hydride addition product Cp*2Y(NC5H6) (2). With THF and pyridine the adducts Cp*2Y(η2-2-pyridyl)(THF) (3) and Cp*2Y(η1-2-pyridyl)(py) (4) are formed. The pyridine

  4. A possible explanation of the CP puzzle

    International Nuclear Information System (INIS)

    Takhtamyshev, Georgij

    1996-03-01

    The problem of mirror-reflection symmetry (MRS) and time-reversal symmetry (TRS) in our world is discussed. The opinion is expressed, that well-known experiments on parity violation and CP-violation can be treated as signals of some new, yet unknown, level of matter. An hypothesis, which can be used as a base for some future model or theory is formulated. In the framework of this hypothesis, experiments will demonstrate parity violation or CP-violation do not contradict MRS or TRS conservation. (author). 14 refs

  5. Maximal CP violation via Higgs-boson exchange

    International Nuclear Information System (INIS)

    Lavoura, L.

    1992-01-01

    The unitarity of the mixing matrix of the charged Higgs bosons, and the orthogonality of the mixing matrix of the neutral Higgs bosons, are used to derive upper bounds on the values of general CP-violating expressions. The bounds are independent of the total number of Higgs fields in any specific model. They allow is to relax the usual assumption of only one Higgs boson being light. It is natural that the CP violation in the exchange of neutral Higgs bosons between bottom quarks be particularly large

  6. The CP-odd nucleon interaction and the value of T-violation in nuclei

    International Nuclear Information System (INIS)

    Gudkov, V.P.

    1997-01-01

    The relations between the value of T- and P-violating correlations in neutron scattering and different models of CP violation are discussed. It is shown that a specific structure of CP-odd nucleon interactions gives the possibility to obtain the essential information about CP-odd interaction at the quark-gluon level from nuclear experimental data. The up-to-date estimations for CP-violating nucleon coupling constants show that each class of CP-violating models can give a measurable effect for the neutron scattering experiments. 57 refs

  7. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    2010-01-01

    Full Text Available In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear.In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents.We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  8. D-amino acid substitution enhances the stability of antimicrobial peptide polybia-CP.

    Science.gov (United States)

    Jia, Fengjing; Wang, Jiayi; Peng, Jinxiu; Zhao, Ping; Kong, Ziqing; Wang, Kairong; Yan, Wenjin; Wang, Rui

    2017-10-01

    With the increasing emergence of resistant microbes toward conventional antimicrobial agents, there is an urgent need for the development of antimicrobial agents with novel action mode. Antimicrobial peptides (AMPs) are believed to be one kind of ideal alternatives. However, AMPs can be easily degraded by protease, which limited their therapeutic use. In the present study, D-amino acid substitution strategy was employed to enhance the stability of polybia-CP. We investigated the stability of peptides against the degradation of trypsin and chymotrypsin by determining the antimicrobial activity or determining the HPLC profile of peptides after incubation with proteases. Our results showed that both the all D-amino acid derivative (D-CP) and partial D-lysine substitution derivative (D-lys-CP) have an improved stability against trypsin and chymotrypsin. Although D-CP takes left-hand α-helical conformation and D-lys-CP loses some α-helical content, both of the D-amino acid-substituted derivatives maintain their parental peptides' membrane active action mode. In addition, D-lys-CP showed a slight weaker antimicrobial activity than polybia-CP, but the hemolytic activity decreased greatly. These results suggest that D-CP and D-lys-CP can offer strategy to improve the property of AMPs and may be leading compounds for the development of novel antimicrobial agents. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-12-01

    Full Text Available Jing Wang,1,* Chunxia Qiao,1,* He Xiao,1 Zhou Lin,1 Yan Li,1 Jiyan Zhang,1 Beifen Shen,1 Tinghuan Fu,2 Jiannan Feng1 1Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, 2First Affiliated Hospital of PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: According to the three-dimensional (3D complex structure of (hIL-6·hIL-6R·gp 1302 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD and MDL Drug Data Report (MDDR, by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist. Keywords: virtual screening, structural optimization, human interlukin-6, small molecular antagonist, XG-7 cells, apoptosis

  10. High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists

    Science.gov (United States)

    Fung, Eileen; Sugianto, Priscilla; Hsu, Jason; Damoiseaux, Robert; Ganz, Tomas

    2013-01-01

    Anemia of inflammation (AI) is common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease. Unless the underlying condition can be reversed, treatment options are limited to erythropoiesis-stimulating agents with or without intravenous iron therapy, modalities that are not always effective and can cause serious adverse effects. Hepcidin, the iron regulatory hormone, has been identified as a pathogenic factor in the development of AI. To explore new therapeutic options for AI and other iron-related disorders caused by hepcidin excess, we developed a cell-based screen to identify hepcidin antagonists. Of the 70,000 small molecules in the library, we identified 14 compounds that antagonized the hepcidin effect on ferroportin. One of these was fursultiamine, a Food and Drug Administration (FDA)–approved thiamine derivative. Fursultiamine directly interfered with hepcidin binding to its receptor, ferroportin, by blocking ferroportin C326 thiol residue essential for hepcidin binding. Consequently, fursultiamine prevented hepcidin-induced ferroportin ubiquitination, endocytosis, and degradation in vitro and allowed continuous cellular iron export despite the presence of hepcidin, with IC50 in the submicromolar range. Thiamine, the fursultiamine metabolite, and benfotiamine, another thiamine derivative, did not interfere with the effect of hepcidin on ferroportin. Other FDA-approved thiol-reactive compounds were at least 1000-fold less potent than fursultiamine in antagonizing hepcidin. In vivo, fursultiamine did not reproducibly antagonize the effect of hepcidin on serum iron, likely because of its rapid conversion to inactive metabolites. Fursultiamine is a unique antagonist of hepcidin in vitro that could serve as a template for the development of drug candidates that inhibit the hepcidin-ferroportin interaction. PMID:23292796

  11. Accurate CpG and non-CpG cytosine methylation analysis by high-throughput locus-specific pyrosequencing in plants.

    Science.gov (United States)

    How-Kit, Alexandre; Daunay, Antoine; Mazaleyrat, Nicolas; Busato, Florence; Daviaud, Christian; Teyssier, Emeline; Deleuze, Jean-François; Gallusci, Philippe; Tost, Jörg

    2015-07-01

    Pyrosequencing permits accurate quantification of DNA methylation of specific regions where the proportions of the C/T polymorphism induced by sodium bisulfite treatment of DNA reflects the DNA methylation level. The commercially available high-throughput locus-specific pyrosequencing instruments allow for the simultaneous analysis of 96 samples, but restrict the DNA methylation analysis to CpG dinucleotide sites, which can be limiting in many biological systems. In contrast to mammals where DNA methylation occurs nearly exclusively on CpG dinucleotides, plants genomes harbor DNA methylation also in other sequence contexts including CHG and CHH motives, which cannot be evaluated by these pyrosequencing instruments due to software limitations. Here, we present a complete pipeline for accurate CpG and non-CpG cytosine methylation analysis at single base-resolution using high-throughput locus-specific pyrosequencing. The devised approach includes the design and validation of PCR amplification on bisulfite-treated DNA and pyrosequencing assays as well as the quantification of the methylation level at every cytosine from the raw peak intensities of the Pyrograms by two newly developed Visual Basic Applications. Our method presents accurate and reproducible results as exemplified by the cytosine methylation analysis of the promoter regions of two Tomato genes (NOR and CNR) encoding transcription regulators of fruit ripening during different stages of fruit development. Our results confirmed a significant and temporally coordinated loss of DNA methylation on specific cytosines during the early stages of fruit development in both promoters as previously shown by WGBS. The manuscript describes thus the first high-throughput locus-specific DNA methylation analysis in plants using pyrosequencing.

  12. Solution of the strong CP problem by color exchange

    International Nuclear Information System (INIS)

    Barr, S.M.; Zee, A.

    1985-08-01

    We present a new way to solve the strong CP problem in models with a spontaneously broken CP invariance. It is simpler than existing non-Peccei-Quinn approaches. It predicts the existence of light (i.e. weak scale) colored Higgs bosons which could be seen in colliders. 25 refs., 3 figs

  13. CP Methods for Scheduling and Routing with Time-Dependent Task Costs

    DEFF Research Database (Denmark)

    Tierney, Kevin; Kelareva, Elena; Kilby, Philip

    2013-01-01

    a cost function, and Mixed Integer Programming (MIP) are often used for solving such problems. However, Constraint Programming (CP), particularly with Lazy Clause Genera- tion (LCG), has been found to be faster than MIP for some scheduling problems with time-varying action costs. In this paper, we...... compare CP and LCG against a solve-and-improve approach for two recently introduced problems in maritime logistics with time-varying action costs: the Liner Shipping Fleet Repositioning Problem (LSFRP) and the Bulk Port Cargo Throughput Optimisation Problem (BPCTOP). We present a novel CP model...... for the LSFRP, which is faster than all previous methods and outperforms a simplified automated planning model without time-varying costs. We show that a LCG solver is faster for solving the BPCTOP than a standard finite domain CP solver with a simplified model. We find that CP and LCG are effective methods...

  14. Methylation-mediated deamination of 5-methylcytosine appears to give rise to mutations causing human inherited disease in CpNpG trinucleotides, as well as in CpG dinucleotides

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2010-08-01

    Full Text Available Abstract The cytosine-guanine (CpG dinucleotide has long been known to be a hotspot for pathological mutation in the human genome. This hypermutability is related to its role as the major site of cytosine methylation with the attendant risk of spontaneous deamination of 5-methylcytosine (5mC to yield thymine. Cytosine methylation, however, also occurs in the context of CpNpG sites in the human genome, an unsurprising finding since the intrinsic symmetry of CpNpG renders it capable of supporting a semi-conservative model of replication of the methylation pattern. Recently, it has become clear that significant DNA methylation occurs in a CpHpG context (where H = A, C or T in a variety of human somatic tissues. If we assume that CpHpG methylation also occurs in the germline, and that 5mC deamination can occur within a CpHpG context, then we might surmise that methylated CpHpG sites could also constitute mutation hotspots causing human genetic disease. To test this postulate, 54,625 missense and nonsense mutations from 2,113 genes causing inherited disease were retrieved from the Human Gene Mutation Database http://www.hgmd.org. Some 18.2 per cent of these pathological lesions were found to be C → T and G → A transitions located in CpG dinucleotides (compatible with a model of methylation-mediated deamination of 5mC, an approximately ten-fold higher proportion than would have been expected by chance alone. The corresponding proportion for the CpHpG trinucleotide was 9.9 per cent, an approximately two-fold higher proportion than would have been expected by chance. We therefore estimate that ~5 per cent of missense/nonsense mutations causing human inherited disease may be attributable to methylation-mediated deamination of 5mC within a CpHpG context.

  15. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  16. CP violating mixings of toponium states

    International Nuclear Information System (INIS)

    Loew, U.

    1988-01-01

    In the present thesis the possibility of an admixture χ of the 2 1 P 1 toponium state which has the CP quantum number -1 to the 2 3 S 1 toponium state with CP quantum number +1 is discussed. The value of χ was estimated in 3 different models of the electroweak interaction. In the standard model the lowest contribution to χ is of 6th order in the weak coupling g or of 4th order in g and of 2nd order in the strong coupling g S . The Feynman diagrams which contribute to χ contain 2 loops. According to a crude estimate of these diagrams it is expected that they yield a contribution smaller than 10 -10 . In the model with extended Higgs sector - for a top-quark mass of 45 GeV - a value of 7x10 -4 resulted for χ. For a top-quark mass of 100 GeV it is expected that χ is even of the order of magnitude of 10 -2 . The large contributions originate from CP violating coupling neutral Higgs particles. In the right-left symmetric model two contributions to χ were calculated. The first one results from the exchange of the right- and left-handed W bosons. For a mass m R =500 GeV this contribution lies at χ ≅ 10 -14 . The second contribution is again based on the exchange of two neutral CP violating coupling Higgs particles. It lies in the order of magnitude at 10 -8 . Possibilities were indicated to find the estimated admixture χ in an experiment. A correlation in the 3-gluon decay of toponium and the decay of toponium into exclusive decays was discussed. (orig./HSI) [de

  17. Conventional methods fail to measure cp(omega) of glass-forming liquids

    DEFF Research Database (Denmark)

    Christensen, Tage Emil; Olsen, Niels Boye; Dyre, Jeppe

    2007-01-01

    thermal-wave method does not measure the isobaric frequency-dependent specific heat cp(omega). This method rather measures a "longitudinal" frequency-dependent specific heat, a quantity defined and detailed here that is in between cp(omega) and cV(omega). This result means that no reliable wide......-frequency measurements of cp(omega) on liquids approaching the calorimetric glass transition exist. We briefly discuss consequences for experiment....

  18. Constraints on CP violating four-fermion interactions

    International Nuclear Information System (INIS)

    He, X.G.; McKellar, B.

    1996-04-01

    It has been shown that CP violating electron-nucleon and nucleon-nucleon interactions can induce atomic electric dipole moments and are therefore constrained from experimental data. We show that using the experimental upper bounds on neutron and electron electric dipole moments, one can also obtain constraints, in some cases better ones, on these interactions. In addition stringent constraints can also be obtained for muon-quark and tauon-quark four-fermion CP violating interactions, which cannot be constrained from atomic electric dipole moment experiments. 12 refs., 2 tabs., 1 fig

  19. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  20. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Chen, Man; Liu, Lian [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Cheng, Huaiyan [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Yan, You-E [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Feng, Ying-Hong, E-mail: yhfeng@usuhs.edu [Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2011-12-15

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination

  1. Two Discrete RuCp* (Cp*=Pentamethylcyclopentadienyl) Binding Modes of N-Confused Porphyrins: Peripheral π Complex and Sitting Atop Ruthenocenophane Complex by Skeletal Transformation.

    Science.gov (United States)

    Yamamoto, Takaaki; Mitsuno, Koki; Mori, Shigeki; Itoyama, Shuhei; Shiota, Yoshihito; Yoshizawa, Kazunari; Ishida, Masatoshi; Furuta, Hiroyuki

    2018-05-07

    Complexation of a RuCp* cation with N-confused tetraarylporphyrins (NCPs) forms directly bound ruthenium(II) pentamethylcyclopentadienyl (Cp*) π-complex on a specific meso-aryl group (e.g., phenyl) neighboring peripheral imino nitrogen of NCPs in high yields. In contrast, in the case of NCPs bearing bulky meso-substituents (e.g., 3,5-di-tert-butylphenyl), new ruthenocenophane-like complex embedded on an N-confused calix[4]phyrin was formed through multiple C-H bond activation of methyl groups of Cp* ligand. The mechanistic insight into the formation of the ruthenocenophane was derived from DFT calculations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. CP violation in a multi-Higgs-doublet model with flavor-changing neutral currents

    International Nuclear Information System (INIS)

    Deshpande, N.G.; He, X.

    1994-01-01

    We study CP violation in multi-Higgs-doublet model based on a S 3 xZ 3 horizontal symmetry where the CKM phase is not the principal source of CP violation. We consider two mechanisms for CP violation in this model: (a) CP violation due to complex Yukawa couplings, and (b) CP violation due to scalar-pseudoscalar Higgs boson mixings. Both mechanisms can explain the observed CP violation in the neutral kaon system. ε'/ε due to neutral Higgs boson exchange is small in both mechanisms, but charged Higgs boson contributions can be as large as 10 -4 for (a) and 10 -3 for (b). CP violation in the neutral B system is, however, quite different from the minimal standard model. The neutron electric dipole moment can be as large as the present experimental bound, and can be used to constrain charged Higgs boson masses. The electron EDM is one order of magnitude below the experimental bound in case (b) and smaller in case (a)

  3. A mini review on CP-violating minimal supersymmetric Standard

    Indian Academy of Sciences (India)

    We discuss the present status of the Higgs sector of the CP-violating minimal supersymmetric Standard Model (CPVMSSM). In the Standard Model (SM) of particle physics, the only source of CP violation is the complex phase in the Cabibbo–Kobayashi–Maskawa (CKM) matrix. By now we all know that this singlephase is ...

  4. The CP 1 type separators-superheaters

    International Nuclear Information System (INIS)

    Palacio, G.

    1984-01-01

    Analysis of the functionnement of the separators superheaters in the first French 900 MW PWR units (Fessenhein 1-2 and Bugey 2-3-4-5) and in the program CP 1 units: localization of the separators superheaters, design, tests and choice of the materials, description of the separators superheaters (shells, separators, superheater bundles, internal lagging, purging tank and condensate stank, steam line equipments); study of the various operation modes (nominals, transients, malfunctions, conservation during shutdowns) and the in service behaviour of the components; study of the modifications on the CP 1 equipments and their behaviour; description of the measures, tests and on site controls (controls during planned shutdowns and controls during service) [fr

  5. P stabilizes dark matter and with CP can predict leptonic phases

    Energy Technology Data Exchange (ETDEWEB)

    Kuchimanchi, Ravi

    2014-02-15

    We find that spontaneously broken parity (P) or left-right symmetry stabilizes darkmatter in a beautiful way. If dark matter has a non-real intrinsic parity ±i (e.g. if it entails Majorana fermions), parity can ensure that it cannot decay to all normal particles with real intrinsic parities. However, if Majorana couplings are absent either in the lepton or the dark sector, P symmetry can be redefined to remove relative non-real intrinsic phases. It is therefore predicted that neutrinos and dark matter fermions must have Majorana masses if dark matter is stable due to parity. The strong CP problem is solved by additionally imposing CP and including vectorlike fermions that help generate CP violation. If leptonlike heavy fermions are provided purely imaginary intrinsic parity phase, they do not couple to the usual leptons, and leptonic CP phases are not generated, which is a testable prediction. Experimentally if leptonic CP phases are not found (if they are consistent with 0 or π) it can be evidence for the type of models in this work where CP is spontaneously or softly broken and there is also a second hidden or softly broken symmetry such as P, Z{sub 2} or Z{sub 4}. However, leptonic CP violation can be present in closely related or some nonminimal versions of these models, such as by also including vectorlike leptons with real intrinsic parities. (orig.)

  6. Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda P; Werge, Thomas

    2011-01-01

    81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.......0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated...... for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A....

  7. Preparation and Anodizing of SiCp/Al Composites with Relatively High Fraction of SiCp

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2018-01-01

    Full Text Available By properly proportioned SiC particles with different sizes and using squeeze infiltration process, SiCp/Al composites with high volume fraction of SiC content (Vp = 60.0%, 61.2%, 63.5%, 67.4%, and 68.0% were achieved for optical application. The flexural strength of the prepared SiCp/Al composites was higher than 483 MPa and the elastic modulus was increased from 174.2 to 206.2 GPa. With an increase in SiC volume fraction, the flexural strength and Poisson’s ratio decreased with the increase in elastic modulus. After the anodic oxidation treatment, an oxidation film with porous structure was prepared on the surface of the composite and the oxidation film was uniformly distributed. The anodic oxide growth rate of composite decreased with SiC content increased and linearly increased with anodizing time.

  8. Preparation and Anodizing of SiCp/Al Composites with Relatively High Fraction of SiCp

    Science.gov (United States)

    2018-01-01

    By properly proportioned SiC particles with different sizes and using squeeze infiltration process, SiCp/Al composites with high volume fraction of SiC content (Vp = 60.0%, 61.2%, 63.5%, 67.4%, and 68.0%) were achieved for optical application. The flexural strength of the prepared SiCp/Al composites was higher than 483 MPa and the elastic modulus was increased from 174.2 to 206.2 GPa. With an increase in SiC volume fraction, the flexural strength and Poisson's ratio decreased with the increase in elastic modulus. After the anodic oxidation treatment, an oxidation film with porous structure was prepared on the surface of the composite and the oxidation film was uniformly distributed. The anodic oxide growth rate of composite decreased with SiC content increased and linearly increased with anodizing time. PMID:29682145

  9. Cohort profile: cerebral palsy in the Norwegian and Danish birth cohorts (MOBAND-CP)

    Science.gov (United States)

    Tollånes, Mette C; Strandberg-Larsen, Katrine; Forthun, Ingeborg; Petersen, Tanja Gram; Moster, Dag; Andersen, Anne-Marie Nybo; Stoltenberg, Camilla; Olsen, Jørn; Wilcox, Allen J

    2016-01-01

    Purpose The purpose of MOthers and BAbies in Norway and Denmark cerebral palsy (MOBAND-CP) was to study CP aetiology in a prospective design. Participants MOBAND-CP is a cohort of more than 210 000 children, created as a collaboration between the world's two largest pregnancy cohorts—the Norwegian Mother and Child Cohort study (MoBa) and the Danish National Birth Cohort. MOBAND-CP includes maternal interview/questionnaire data collected during pregnancy and follow-up, plus linked information from national health registries. Findings to date Initial harmonisation of data from the 2 cohorts has created 140 variables for children and their mothers. In the MOBAND-CP cohort, 438 children with CP have been identified through record linkage with validated national registries, providing by far the largest such sample with prospectively collected detailed pregnancy data. Several studies investigating various hypotheses regarding CP aetiology are currently on-going. Future plans Additional data can be harmonised as necessary to meet requirements of new projects. Biological specimens collected during pregnancy and at delivery are potentially available for assay, as are results from assays conducted on these specimens for other projects. The study size allows consideration of CP subtypes, which is rare in aetiological studies of CP. In addition, MOBAND-CP provides a platform within the context of a merged birth cohort of exceptional size that could, after appropriate permissions have been sought, be used for cohort and case-cohort studies of other relatively rare health conditions of infants and children. PMID:27591025

  10. CP Violation in b- and c-hadron decays at LHCb

    Science.gov (United States)

    Steinkamp, Olaf; LHCb Collaboration

    2017-07-01

    Testing the Standard Model of particle physics by precision measurements of CP violating observables in the decays of b and c hadrons has been one of the design goals of the LHCb experiment. World-leading measurements have been performed of the semileptonic asymmetry, {a}ssl, and of the mixing-induced CP-violating phase ϕs in the {B}s0{\\bar{B}}s0 system. The CKM angle γ is still the least known angle of the Unitarity Triangle, and the only one easily accessible using tree-level decays. A recent combination of LHCb measurements in various B → DK decay modes has yielded the most precise determination of γ from a single experiment to date. The LHCb experiment is collecting unprecedented samples of beauty baryons, allowing for the first time to study CP violating observables in their decays. A recent analysis provided the first evidence for CP violation in the beauty baryon sector. Finally, LHCb has the largest samples of charmed hadron decays collected by any experiment to date. These samples yield some of the world’s most sensitive searches for direct and indirect CP violation in the charm sector.

  11. 50 years of CP violation — What have we learned?

    Energy Technology Data Exchange (ETDEWEB)

    McKellar, Bruce H. J. [Centre of Excellence for Particle Physics at the Terrascale School of Physics, University of Melbourne, Australia 3010 (Australia)

    2015-04-24

    Early after the discovery of CP violation, the explanation of how the Standard Model of particle physics could allow CP violation was quickly given, but it took many years for the original observation to be unequivocally explained on that basis. It was also proposed that this observation opened up the possibility that we could now explain the fact that the universe is made of matter. Remarkably, 50 years later we have no evidence in particle physics that there is any CP violation except that of the Kobayashi Maskawa mechanism of the standard model. Yet we fail completely to explain the baryon asymmetry of the Universe through that mechanism. After reviewing the main points in the history I describe the present experimental attempts to find CP violation beyond the standard model, and explain the theoretical attempts to explain the matter in the Universe.

  12. The Pattern of CP Asymmetries in $b\\to s$ Transitions

    CERN Document Server

    Buchalla, Gerhard; Nir, Y; Raz, G; Buchalla, Gerhard; Hiller, Gudrun; Nir, Yosef; Raz, Guy

    2005-01-01

    New CP violating physics in $b\\to s$ transitions will modify the CP asymmetries in B decays into final CP eigenstates ($\\phi K_S$, $\\eta^\\prime K_S$, $\\pi^0 K_S$, $\\omega K_S$, $\\rho^0 K_S$ and $\\eta K_S$) from their Standard Model values. In a model independent analysis, the pattern of deviations can be used to probe which Wilson coefficients get a significant contribution from the new physics. We demonstrate this idea using several well-motivated models of new physics, and apply it to current data.

  13. Formulating weak CP-violation in terms of quark mass hierarchies

    International Nuclear Information System (INIS)

    Davidson, A.

    1982-06-01

    That physics which explains Cabibbo mixing is shown to also put a lower bound on Kobayashi-Maskawa CP-violation. The observed amount epsilon = 0.002 of CP-violation in the Ksub(L) - Ksub(S) system in turn sharply requires 25 GeV <= msub(t) <= 59 GeV; msub(t) being the top-quark mass. Assuming a vanishing weak (ala strong) CP-violation amplitude for msub(u) → 0, as strongly indicated by the data, epsilon is formulated as a second order quantity in the fermionic mass hierarchy. (author)

  14. CP violation in top pair production at an e^+e^- collider

    CERN Document Server

    Chang, Darwin; Phillips, Ivan

    1992-01-01

    We investigate a possible CP violating effect in $e^+e^-$ annihilation into $t\\bar t$ top quark pairs. As an illustrative example, we assume the source of the CP nonconservation is in the Yukawa couplings of a neutral Higgs boson which contain both scalar and pseudoscalar pieces. One of the interesting observable effects is the difference in production rates between the two CP conjugate polarized $t\\bar t$ states.

  15. Is the Weinberg model of CP violation really excluded?

    International Nuclear Information System (INIS)

    Cheng, H.

    1990-01-01

    We give an updated analysis on various CP-violating effects in the Weinberg three-Higgs-doublet model of CP violation. Because of the improved estimate of the η-η' mixing and of the K-η 0 transition, the sign of ε'/ε is predicted to be the same as that of the chiral suppression of CP-odd K→2π amplitudes (owing to the presence of tadpole contributions) and is most likely to be positive, contrary to previous calculations. The neutron electric dipole moment d n due to neutral-Higgs-boson exchange at the one-loop level is reexamined and is found to be below the present experimental limit for reasonable Higgs-boson mass. However, the Weinberg's three-gluon operator arising from charged-Higgs-boson exchange will produce an excessive d n even if the charged Higgs bosons are uncomfortably light. We conclude that the Weinberg CP-violation model is not necessarily inconsistent with experiment of measuring ε'/ε, but it tends to give too large a value of d n

  16. Towards a dynamical solution of the strong CP problem

    International Nuclear Information System (INIS)

    Schierholz, G.

    1994-01-01

    One may argue that QCD solves the strong CP problem by itself. To test this idea, a lattice simulation suggests itself. In view of the difficulty of such a calculation we have, as a first step, investigated the problem in the CP 3 model. The CP 3 model is in many respects similar to QCD. In this talk I present some first results of our calculation. Among other things it is shown that the model has a first order deconfining phase transition in θ and that the critical value of θ decreases towards zero as β is taken to infinity. This suggests that θ is tuned to zero in the continuum limit. ((orig.))

  17. CP violation and B0-(B0)-bar mixing

    International Nuclear Information System (INIS)

    Aleksan, R.

    1996-01-01

    The status of CP violation and B 0 -(B 0 )-bar mixing is given and the subsequent constraints in the framework of the Standard Model are discussed. Recent result on CP violation in the kaon system and related topics are reviewed, including the status of T violation and the tests of the CPT symmetry. The results on B 0 -(B 0 )-bar mixing are presented followed by the studies on B d 0 -(B d 0 )-bar and B s 0 -(B s 0 )-bar oscillations. Finally, the prospects of progress on understanding CP violation are discussed in framework of the new projects expected to produce results at the turn of the century. (author)

  18. Techniques for studies of unbinned model independent CP violation

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, Nicholas; Weisser, Constantin; Parkes, Chris; Gersabeck, Marco; Brodzicka, Jolanta; Chen, Shanzhen [University of Manchester (United Kingdom)

    2016-07-01

    Charge-Parity (CP) violation is a known part of the Standard Model and has been observed and measured in both the B and K meson systems. The observed levels, however, are insufficient to explain the observed matter-antimatter asymmetry in the Universe, and so other sources need to be found. One area of current investigation is the D meson system, where predicted levels of CP violation are much lower than in the B and K meson systems. This means that more sensitive methods are required when searching for CP violation in this system. Several unbinned model independent methods have been proposed for this purpose, all of which need to be optimised and their sensitivities compared.

  19. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

    DEFF Research Database (Denmark)

    Tricoci, Pierluigi; Huang, Zhen; Held, Claes

    2012-01-01

    Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.......Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation....

  20. Leptonic CP violation induced by approximately μ-τ symmetric seesaw mechanism

    International Nuclear Information System (INIS)

    Baba, Teppei; Yasue, Masaki

    2008-01-01

    Assuming a minimal seesaw model with two heavy neutrinos (N), we examine effects of leptonic CP violation induced by approximate μ-τ symmetric interactions. As long as N is subject to the μ-τ symmetry, we can choose CP phases of Dirac mass terms without loss of generality in such a way that these phases arise from μ-τ symmetry breaking interactions. In the case that no phase is present in heavy neutrino mass terms, leptonic CP phases are controlled by two phases α and β. The similar consideration is extended to N blind to the μ-τ symmetry. It is argued that N subject (blind) to the μ-τ symmetry necessarily describes the normal (inverted) mass hierarchy. We restrict ourselves to μ-τ symmetric textures giving the tribimaximal mixing and calculate flavor neutrino masses to estimate CP-violating Dirac and Majorana phases as well as neutrino mixing angles as functions of α and β. Since α and β are generated by μ-τ symmetry breaking interactions, the CP-violating Majorana phase tends to be suppressed and is found to be at most O(0.1) radian. On the other hand, the CP-violating Dirac phase tends to show a proportionality to α or to β.

  1. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Science.gov (United States)

    Meuwese, Julia D I; van Loon, Anouk M; Scholte, H Steven; Lirk, Philipp B; Vulink, Nienke C C; Hollmann, Markus W; Lamme, Victor A F

    2013-01-01

    Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  2. NMDA receptor antagonist ketamine impairs feature integration in visual perception.

    Directory of Open Access Journals (Sweden)

    Julia D I Meuwese

    Full Text Available Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans.

  3. Changes in haematological indices following local application of interleukin-1 receptor antagonist protein after tenotomy in rabbits

    Directory of Open Access Journals (Sweden)

    Marko Pecin

    2017-01-01

    Full Text Available Interleukin-1 (IL-1 is the most important cytokine in the inflammation cascade activation in all tissues and is present in acute and chronic phases of inflammation. By blocking IL-1 binding to target cells, numerous inflammation processes are prevented. The use of autologous conditioned serum rich with IL-1 receptor antagonist protein (IL-1Ra is a novel treatment method of tendon inflammation in domestic animals and humans. Injections of autologous conditioned serum (ACS have demonstrated clinical efficacy and safety in animal models and humans in the treatment of osteoarthritis, disc prolapse and muscles and tendons injuries with low side effect. Neutropaenia, reduced white blood cell count, and infections or local irritations are described as side effects of IL-1 antagonist use in humans. Therefore, a study of blood changes in rabbits after local administration of IL-1Ra in the Achilles tendon tissue after iatrogenic inflammation was conducted. Interleukin-1 receptor antagonist protein was used to prevent and reduce tendon inflammation after longitudinal tenotomy. The study was done on 26 white Californian rabbits, divided into two equal groups consisting of 13 animals each; the experimental interleukin-1 receptor antagonist protein (irap group, and the control group. In the irap group, autologous serum rich with IL-1Ra was used (Orthokine®vet irap, Alfa-Arthro, Croatia. Differences between two groups were considered significant as changes in the blood for certain blood elements at P < 0.01. The P value was P = 0.0153 for the white blood cells, P = 0.00153 for neutrophils, P = 0.00017 and for platelets. In the control group, an increased platelet count was noticed in 70% of blood samples and a decreased neutrophil count was found in all of the irap group samples at the end of the study in comparison to the initial blood count prior to application.

  4. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells

    International Nuclear Information System (INIS)

    Feagins, Alicia R.; Basler, Christopher F.

    2015-01-01

    Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targeting phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.

  5. Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells

    Energy Technology Data Exchange (ETDEWEB)

    Feagins, Alicia R.; Basler, Christopher F., E-mail: chris.basler@mssm.edu

    2015-11-15

    Lloviu virus (LLOV) is a new member of the filovirus family that also includes Ebola virus (EBOV) and Marburg virus (MARV). LLOV has not been cultured; however, its genomic RNA sequence indicates the coding capacity to produce homologs of the EBOV and MARV VP24, VP35, and VP40 proteins. EBOV and MARV VP35 proteins inhibit interferon (IFN)-alpha/beta production and EBOV VP35 blocks activation of the antiviral kinase PKR. The EBOV VP24 and MARV VP40 proteins inhibit IFN signaling, albeit by different mechanisms. Here we demonstrate that LLOV VP35 suppresses Sendai virus induced IFN regulatory factor 3 (IRF3) phosphorylation, IFN-α/β production, and PKR phosphorylation. Additionally, LLOV VP24 blocks tyrosine phosphorylated STAT1 binding to karyopherin alpha 5 (KPNA5), STAT1 nuclear accumulation, and IFN-induced gene expression. LLOV VP40 lacks detectable IFN antagonist function. These activities parallel EBOV IFN inhibitory functions. EBOV and LLOV VP35 and VP24 proteins also inhibit IFN responses in bat cells. These data suggest that LLOV infection will block innate immune responses in a manner similar to EBOV. - Highlights: • Lloviu virus (LLOV) is a new member of the filovirus family. • LLOV VP35 blocks IRF3 phosphorylation, IFN-α/β production and PKR phosphorylation. • LLOV VP24 inhibits IFN responses by targeting phospho-STAT1 KPNA interaction. • Infection by LLOV may block innate immune responses in a manner similar to EBOV.

  6. Neutrino mass hierarchy and δCP investigation within the biprobability (P-PT) plane

    International Nuclear Information System (INIS)

    Singh, Mandip

    2016-01-01

    This article illustrates the possibility of investigating the mass hierarchy and CP-violating phase δ CP in the context of CP trajectory diagrams in the biprobability plane. The separation between the normal mass hierarchy (NH) and inverted mass hierarchy (IH) CP trajectory ellipses in the P-P T plane seems to be very promising as a means of investigating the mass hierarchy. An illustration of the separation between the two hierarchy ellipses in the E-L plane is very helpful to cover all the desired baselines and beam energies and also to analyze the benefits and drawbacks in one step. If we know the mass hierarchy, then, from the large sizes of CP trajectory ellipses that are possible at appropriately long baselines (L) and at specific values of beam energy (E), it becomes possible to investigate at least narrow ranges of the CP/T-violating phase δ CP . The possibility of more than one set of (θ 13 ,δ CP ) parameters corresponding to any chosen coordinate in the P-P T plane, known as parameter degeneracy, may hinder the exact determination of the mass hierarchy as well as the δ CP value. To circumvent this degeneracy in the (θ 13 ,δ CP ) parameter space, in the case of opposite-sign solutions corresponding to the NH and IH cases, sufficiently long baselines are needed, so as to separate the opposite hierarchy ellipses to create an observable separation; in the case of same-sign solutions corresponding to either NH or IH, we need to choose an experimental configuration with L≃2535 km, E≃5 GeV for the n=1 scenario

  7. Experimental searches for CP and CPT symmetries violation in the neutral kaons system

    International Nuclear Information System (INIS)

    Debu, P.

    1996-01-01

    The aim of this lecture is to give an overview of the experiments devoted to the study and research of CP, T and CPT symmetries invariance violations in the system of neutral K mesons. The discovery of K mesons has provided crucial informations for the elaboration of the standard model. However, the observation of CP violation has remained confined to the K system. The origin of the observed CP violation remains hypothetic. Its origin could be a complex phase in the mixing matrix of quarks. In the standard model of electroweak interactions, several evidences of the CP violation exist: the observed K neutral mesons (K L and K S ) are not proper states of CP and are due to CP violation in the K 0 - anti-K 0 mixture. On the other hand, the model predicts also a CP violation in decay amplitudes, named direct CP violation. Important experiments have been carried out for its demonstration. The K system is also the most precise test for CPT invariance. A description of the experiments in progress developed to improve the precision of these tests is given. The plan of the lecture is the following: after a recall of K 0 - anti-K 0 phenomenology, some important steps in the CP violation study are described. Then, the regeneration phenomenon is briefly described and two of the most recent measurements of the direct CP violation parameter are analysed. Finally, the CPT invariance tests are described with their parameters and the measurements in progress. A review of the principal results is given in conclusion with their improvements expected in a near future. (J.S.). 71 refs., 4 figs., 4 tabs

  8. Progress in the development of histamine H3 receptor antagonists/inverse agonists: a patent review (2013-2017).

    Science.gov (United States)

    Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2018-03-01

    Since years, ligands blocking histamine H 3 receptor (H 3 R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H 3 R antagonists/inverse agonists. Some of them have reached to clinical trials. Areas covered: Patent applications from January 2013 to September 2017 and the most important topics connected with H 3 R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials. Expert opinion: The research interest in histamine H 3 R field is still high although the number of patent applications has decreased during the past 4 years (around 20 publications). Complexity of histamine H 3 R biology e.g. many isoforms, constitutive activity, heteromerization with other receptors (dopamine D 2 , D 1 , adenosine A 2A ) and pharmacology make not easy realization and evaluation of therapeutic potential of anti-H 3 R ligands. First results from clinical trials have verified potential utility of histamine H 3 R antagonist/inverse agonists in some diseases. However, more studies are necessary for better understanding of an involvement of the histaminergic system in CNS-related disorders and helping more ligands approach to clinical trials and the market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor; hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase; MAO - monoamine oxidase.

  9. Para-psychobiotic Lactobacillus gasseri CP2305 ameliorates stress-related symptoms and sleep quality.

    Science.gov (United States)

    Nishida, K; Sawada, D; Kawai, T; Kuwano, Y; Fujiwara, S; Rokutan, K

    2017-12-01

    To confirm the stress-relieving effects of heat-inactivated, enteric-colonizing Lactobacillus gasseri CP2305 (paraprobiotic CP2305) in medical students taking a cadaver dissection course. Healthy students (21 males and 11 females) took paraprobiotic CP2305 daily for 5 weeks during a cadaver dissection course. The General Health Questionnaire and the Pittsburgh Sleep Quality Index were employed to assess stress-related somatic symptoms and sleep quality respectively. The aggravation of stress-associated somatic symptoms was observed in female students (P = 0·029). Sleep quality was improved in the paraprobiotic CP2305 group (P = 0·038), particularly in men (P = 0·004). Among men, paraprobiotic CP2305 shortened sleep latency (P = 0·035) and increased sleep duration (P = 0·048). Diarrhoea-like symptoms were also effectively controlled with CP2305 (P = 0·005) in men. Thus, we observed sex-related differences in the effects of paraprobiotic CP2305. In addition, CP2305 affected the growth of faecal Bacteroides vulgatus and Dorea longicatena, which are involved in intestinal inflammation. CP2305 is a potential paraprobiotic that regulates stress responses, and its beneficial effects may depend on specific cell component(s). This study characterizes the effects of a stress-relieving para-psychobiotic in humans. © 2017 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

  10. A novel prognostic six-CpG signature in glioblastomas.

    Science.gov (United States)

    Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

    2018-03-01

    We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

  11. Search for nonstandard model CP or T violation at the τ-charm factory

    International Nuclear Information System (INIS)

    Huang, T.; Lu, W.; Tao, Z.

    1997-01-01

    We systematically investigate the possibility of finding CP or T violation in the τ sector at the τ-charm factory. CP or T violation may occur in the τ pair production process, expressed as an electric dipole moment, and in τ decay processes. By assuming that an electric dipole moment as large as 10 -19 ecm and CP or T violation effects originating from τ decay as large as 10 -3 are observable at the τ-charm factory, we study all the possible extensions of the SM which are relevant for generating CP or T violation in the τ sector. And we point out, there are a few kinds of models which are hopeful candidates for generating such CP or T violation. For these models we consider all the theoretical and current experimental constraints and find that there exists some parameter space which will result in a measurable CP or T violation. Therefore we conclude that the τ-charm factory is a hopeful place to discover CP or T violation in the τ sector. copyright 1997 The American Physical Society

  12. The investigation of CP violation through the decay of polarized tau leptons II

    International Nuclear Information System (INIS)

    Tsai, Y.S.

    1996-05-01

    Under the assumption that CP violation is caused by exchange of anew boson, the authors propose to measure the magnitudes and CP-violating phases of the coupling constants of this boson to five different vertices in tau decay. This can be accomplished by studying the decay of polarized tau leptons produced at an e + e - collider whose beams are polarized. These five coupling constants could be used to construct a future theory of CP violation. If CP is violated in any channel of tau decay, it will imply that there exists a new charged boson other than the W boson responsible for CP violation. It will also imply that CP violation is much more prevalent than the standard theory predicts and this may enable one to understand the preponderance of matter over antimatter in the present universe

  13. Reactivity of the cyanometalate Na[Cp[prime]Mn(CO)[sub 2]CN] with titanium, zirconium, and hafnium halides. Crystal and molecular structure of the [mu]-cyano [mu]-oxo tetranuclear complex [Cp[sub 2]Zr([mu]-NC)MnCp[prime]-(CO)[sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Braunstein, P. (Universite Louis Pasteur, Cedex (France)); Cauzzi, D. (Universite Louis Pasteur, Cedex (France) Universita di Parma (Italy)); Kelly, D. (Universite Louis Pasteur, Cedex (France)); Lanfranchi, M.; Tiripicchio, A. (Universita di Parma (Italy))

    1993-07-21

    In contrast to most carbonylmetalates of the transition metals, cyanide-substituted anionic complexes such as Na[Cp[prime]Mn-(CO)[sub 2]CN] (Cp[prime] = [eta]-MeC[sub 5]H[sub 4]) do not exhibit a metal-centered HOMO. Instead, this orbitals is essentially nitrogen-based, which favors coordination to metal centers through the cyanide moiety, thus generating Mn-CN-M[prime] chain systems. The cyanometalate ligand [Cp[prime]Mn(CO)[sub 2]CN][sup [minus

  14. Assay method for organic calcium antagonist drugs and a kit for such an assay

    International Nuclear Information System (INIS)

    Snyder, S. H.; Gould, R. J.

    1985-01-01

    A method for measuring the level of organic calcium antagonist drug in a body fluid comprises preparing a mixture of a radioactive calcium antagonist drug, a body fluid containing a calcium antagonist drug and a calcium antagonist receptor material, measuring the radioactivity of the radioactive calcium antagonist drug bound to said calcium antagonist receptor material and deriving the concentration of the calcium antagonist drug in the body fluid from a standard curve indicating the concentration of calcium antagonist drug versus inhibition of binding of said radioactive calcium antagonist drug to said receptor sites caused by the calcium antagonist drug in said body fluid. A kit for measuring the level of an organic calcium drug comprises a receptacle containing a radioactive calcium antagonist drug, a calcium antagonist receptor material and a standard amount of a nonradioactive calcium antagonist drug

  15. Apparent Affinity Estimates and Reversal of the Effects of Synthetic Cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by Rimonabant in Rhesus Monkeys.

    Science.gov (United States)

    Hruba, Lenka; McMahon, Lance R

    2017-08-01

    Synthetic cannabinoids have been prohibited due to abuse liability and toxicity. Four such synthetic cannabinoids, AM-2201 ([1-(5-fluoropentyl)indol-3-yl]-naphthalen-1-ylmethanone), CP-47,497 (2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenol), JWH-122 [(4-methylnaphthalen-1-yl)-(1-pentylindol-3-yl)methanone], and JWH-250 [2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone], were tested for their capacity to produce CB 1 receptor-mediated discriminative stimulus effects in two groups of rhesus monkeys. One group ( n = 4) discriminated Δ 9 -tetrahydrocannabinol (∆ 9 -THC; 0.1 mg/kg i.v.), and a second group ( n = 4) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving 1 mg/kg/12 hours of ∆ 9 -THC. AM-2201, JWH-122, CP-47,497, JWH-250, and ∆ 9 -THC increased ∆ 9 -THC lever responding. Duration of action was 1-2 hours for AM-2201, JWH-122, and JWH-250 and 4-5 hours for CP-47,497 and ∆ 9 -THC. Rimonabant (1 mg/kg) surmountably antagonized the discriminative stimulus effects of all cannabinoid agonists; the magnitude of rightward shift was 10.6-fold for AM-2201, 10.7-fold for JWH-122, 11.0-fold for CP-47,497, and 15.7-fold for JWH-250. The respective pK B values were not significantly different: 6.61, 6.65, 6.66, and 6.83. In ∆ 9 -THC-treated monkeys discriminating rimonabant, AM-2201 (0.1 and 0.32 mg/kg), JWH-122 (0.32 and 1 mg/kg), JWH-250 (1 and 3.2 mg/kg), and CP-47,497 (0.32, 1, and 3.2 mg/kg) produced not only rate-decreasing effects that were reversed by rimonabant, but also dose-dependent, rightward shifts in the rimonabant discrimination dose-effect function. These results show striking similarity in the CB 1 receptor mechanism mediating the subjective effects of AM-2201, JWH-122, JWH-250, and CP-47,497. For products containing AM-2201 and JWH-122, a short duration of action could lead to more frequent use; moreover, inattention to differences in potency among synthetic cannabinoids could underlie unexpected

  16. INSERTION CHEMISTRY OF CP-ASTERISK(2)Y(2-PYRIDYL) AND MOLECULAR-STRUCTURE OF THE UNEXPECTED CO INSERTION PRODUCT (CP-ASTERISK(2)Y)2(MU-ETA-2-ETA-2-OC(NC5H4)2)

    NARCIS (Netherlands)

    DEELMAN, BJ; STEVELS, WM; TEUBEN, JH; LAKIN, MT; SPEK, AL

    1994-01-01

    Pyridine is metalated selectively at the 2-position by (Cp*2YH)2 to yield Cp*2Y(2-pyridyl) (1). Compound 1 reacts with H2 to give the hydride addition product Cp*2Y(NC5H6) (2). With THF and pyridine the adducts Cp*2Y(eta2-2-pyridyl)(THF) (3) and Cp*2Y(eta1-2-pyridyl)-(py) (4) are formed. The

  17. Difficulty for Weinberg model of CP nonconservation through Higgs exchange

    International Nuclear Information System (INIS)

    Deshpande, N.G.

    1981-01-01

    We evaluate the CP violation parameter element of'/element of in the Weinberg model of CP nonconservation. When gluon exchange effects are included, we find element of'/element of approx. -.045, which is in conflict with the experimental measurement element of'/element of = -.003 +- .015

  18. Dynamical relaxation of the CP phases in next-to-minimal supersymmetry

    International Nuclear Information System (INIS)

    Demir, D.A.

    1999-11-01

    After promoting the phases of the soft masses to dynamical fields corresponding to Goldstone bosons of spontaneously broken global symmetries in the supersymmetry breaking sector, the next-to-minimal supersymmetric model is found to solve the μ problem and the strong CP problem simultaneously with an invisible axion. The domain wall problem persists in the form of axionic domain formation. Relaxation dynamics of the physical CP-violating phases is determined only by the short-distance physics and their relaxation values are not necessarily close to the CP-conserving points. Consequently, the solution of tile supersymmetric CP problem may require heavy enough superpartners and nonminimal flavor structures, where the latter may be also relevant for avoiding the formation of axionic domain walls. (author)

  19. CP violation as a probe of flavor origin in supersymmetry

    International Nuclear Information System (INIS)

    Demir, D.A.; Masiero, A.; Vives, O.

    1999-11-01

    We address the question of the relation between supersymmetry breaking and the origin of flavor in the context of CP violating phenomena. We prove that, in the absence of the Cabibbo-Kobayashi-Maskawa phase, a general Minimal Supersymmetric Standard Model with all possible phases in the soft-breaking terms, but no new flavor structure beyond the usual Yukawa matrices, can never give a sizeable contribution to ε K , ε'/ε or hadronic B 0 CP asymmetries. Observation of supersymmetric contributions to CP asymmetries in B decays would hint at a non-flavor blind mechanism of supersymmetry breaking. (author)

  20. First Search for {ital CP} Violation in Tau Lepton Decay

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.; Kubota, Y.; Lee, S.J.; ONeill, J.J.; Poling, R.; Riehle, T.; Smith, A. [University of Minnesota, Minneapolis, Minnesota 55455 (United States); Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York 12222 (United States); Anastassov, A.; Duboscq, J.E.; Fujino, D.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Schwarthoff, H.; Spencer, M.B.; Sung, M.; Undrus, A.; Wolf, A.; Zoeller, M.M. [The Ohio State University, Columbus, Ohio 43210 (United States); Richichi, S.J.; Severini, H.; Skubic, P. [University of Oklahoma, Norman, Oklahoma 73019 (United States); Bishai, M.; Fast, J.; Hinson, J.W.; Menson, N.; Miller, D.H.; Shibata, E.I.; Shipsey, I.P.; Yurko, M. [Purdue University, West Lafayette, Indiana 47907 (United States); Glenn, S.; Kwon, Y.; Lyon, A.L.; Roberts, S.; Thorndike, E.H. [University of Rochester, Rochester, New York 14627 (United States); Jessop, C.P.; Lingel, K.; Marsiske, H.; Perl, M.L.; Savinov, V.; Ugolini, D.; Zhou, X. [Stanford Linear Accelerator Center, Stanford University, Stanford, California 94309 (United States); Coan, T.E.; Fadeyev, V.; Korolkov, I.; Maravin, Y.; Narsky, I.; Shelkov, V.; Staeck, J.; Stroynowski, R.; Volobouev, I.; Ye, J. [Southern Methodist University, Dallas, Texas 75275 (United States); Artuso, M.; Azfar, F.; Efimov, A.; Goldberg, M.; He, D.; Kopp, S.; Moneti, G.C.; Mountain, R.; Schuh, S.; Skwarnicki, T.; Stone, S.; Viehhauser, G.; Wang, J.C.; Xing, X. [Syracuse University, Syracuse, New York 13244 (United States); Bartelt, J.; Csorna, S.E.; Jain, V.; McLean, K.W.; Marka, S. [Vanderbilt University, Nashville, Tennessee 37235 (United States); Godang, R.; Kinoshita, K.; Lai, I.C.; Pomianowski, P.; Schrenk, S. [Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Bonvicini, G.; Cinabro, D.; Greene, R.; Perera, L.P.; Zhou, G.J. [Wayne State Univ., (United States)

    1998-11-01

    We have performed the first search for CP violation in tau lepton decay. CP violation in lepton decay does not occur in the minimal standard model but can occur in extensions such as the multi-Higgs doublet model. It appears as a characteristic difference between the {tau}{sup {minus}} and {tau}{sup +} decay angular distributions for the semileptonic decay modes such as {tau}{sup {minus}}{r_arrow}K{sup 0}{pi}{sup {minus}}{nu} . We define an observable asymmetry to exploit this and find no evidence for any CP violation. {copyright} {ital 1998} {ital The American Physical Society }

  1. Measurements of CP Asymmetries in the Decay B --> {phi}K

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B

    2004-08-16

    The authors present a preliminary measurement of the time-dependent CP asymmetry for the neutral B-meson decay B{sup 0} --> {phi}K{sup 0}. They use a sample of approximately 227 million B-meson pairs recorded at the {Upsilon}(4S) resonance with the BABAR detector at the PEP-II B-meson Factory at SLAC. They reconstruct the CP eigenstates {phi}K{sub s}{sup 0} and {phi}K{sub L}{sup 0} where {phi} --> K{sup +}K{sup -}, K{sub s}{sup 0} --> {pi}{sup +}{pi}{sup -}, and K{sub L}{sup 0} is observed via its hadronic interactions. The other B meson in the event is tagged as either a B{sup 0} or {bar B}{sup 0} from its decay products. The values of the CP-violation parameters deived from the combined {phi}K{sup 0} dataset are S{sub {phi}K} = +0.50 {+-} 0.25(stat.){sub -0.04}{sup +0.07}(syst.) and C{sub {phi}K} = 0.00 {+-} 0.23(stat.) {+-}0.05(syst.). In addition, the authors measure the CP-violating charge asymmetry A{sub CP}(B{sup +} --> {phi}K{sup +}) = 0.054 {+-} 0.056(stat.) {+-} 0.012(syst.). All results are preliminary.

  2. Are there CP-violating processes in the standard model without loop corrections

    International Nuclear Information System (INIS)

    Nowakowski, M.; Pilaftsis, A.

    1989-01-01

    In an effort to find new CP-violating phenomena in the Standard Model, the authors present a new type of CP asymmetries which have interesting theoretical features. They investigate the possibility of CP nonconservation manifesting itself at Born level. They find that such processes indeed exist provided the reaction under consideration includes two W's coupled to two different flavors and an additional boson (γ, g, Z O , H O ). A second interesting aspect of these phenomena is the property that the CP-violation appears in a scattering process as opposed to that in a decay of a particle. The authors estimate the values of these CP asymmetries within the Standard Model with three and four generations and show that the effect is, in principle, measurable if the masses of the quarks belonging to the fourth generation are large

  3. Analgesic Effects of Botulinum Toxin in Children with CP

    DEFF Research Database (Denmark)

    Sandahl Michelsen, Josephine; Normann, Gitte; Wong, Christian

    2018-01-01

    Experiencing pain is the greatest contributor to a reduced quality of life in children with cerebral palsy (CP). The presence of pain is quite common (~60%) and increases with age. This leads to missed school days, less participation, and reduced ambulation. Despite these alarming consequences...... of disorders and could potentially have an analgesic effect in children with CP as well. Even though most of the studies presented here show promising results, many also have limitations in their methodology as it is unlikely to capture all dimensions of pain in this heterogeneous group using only one...... assessment tool. In this review, we present a new way of examining the analgesic effect of botulinum toxin in children with CP using a variety of pain scores....

  4. Prospects of search for CP-nonconservation in beauty hadrons

    International Nuclear Information System (INIS)

    Blinov, A.E.; Ural'tsev, N.G.; Khoze, V.A.

    1990-01-01

    The prospects of observation of CP-nonconservation in B-particles in the standard model are studied. Special attention is paid to e + e - -annihilation. The statistics required is found to be virtually independent of the value of |V ub |/|V cb |. The KM-forbidden b → u decays, B d 0 → π + π - , π ± ρ -+ , π ± a 1 -+ seem to be the most prospective. At very moderate values of the hadronic parameters, 3x10 7 Υ(4S) resonances are required to observe CP-asymmetry at the 3σ level. Simple dependences of the asymmetries and statistics on concrete values of the hadron parameters (f B , B K , etc.) are presented. CP-odd asymmetry effects in B particles are analyzed critically

  5. Evidence for leptonic CP phase from NOνA, T2K and ICAL

    International Nuclear Information System (INIS)

    Ghosh, Monojit; Goswami, Srubabati; Ghoshal, Pomita; Raut, Sushant K.

    2016-01-01

    The phenomenon of neutrino oscillation is now well understood from the solar, atmospheric, reactor and accelerator neutrino experiments. This oscillation is characterized by a unitary PMNS matrix which is parametrized by three mixing angles (θ 12 , θ 23 and θ 13 ) and one phase (δ CP ) known as the leptonic CP phase. Neutrino oscillation also involves two mass squared differences: the solar mass square difference (Δ 21 = m 2 2 - m 2 1 ) and the atmospheric mass square difference (Δ 31 = m 2 3 - m 2 1 ). Though there is already significant amount of information about the three mixing angles, the CP phase is still unknown. Apart from the CP phase, one should also know what is the true nature of the neutrino mass hierarchy, i.e., normal (m 3 > m 1 : NH) or inverted (m 1 > m 3 : IH) and what is the true octant of (θ 23 , i.e., lower (θ 23 < 45°: LO) or higher (θ 23 > 45°: HO). The long-baseline experiments (LBL) have CP sensitivity coming from the appearance channel (ν μ →ν e ). On the other hand, atmospheric neutrinos are known to have negligible CP sensitivity. In this work, we study the synergy between the LBL experiment NOνA, T2K and the atmospheric neutrino experiment ICAL@INO for obtaining the first hint of CP violation in the lepton sector. We find that due to the lack of knowledge of hierarchy and octant, CP sensitivity of NOνA/T2K is poorer for some parameter ranges. Addition of ICAL data to T2K and NOνA can exclude these spurious wrong-hierarchy and/or wrong-octant solutions and cause a significant increase in the range of δCP values for which a hint of CP violation can be achieved. Similarly, the precision with which δCP can be measured also improves with the inclusion of ICAL data. (author)

  6. Scientific programming on massively parallel processor CP-PACS

    International Nuclear Information System (INIS)

    Boku, Taisuke

    1998-01-01

    The massively parallel processor CP-PACS takes various problems of calculation physics as the object, and it has been designed so that its architecture has been devised to do various numerical processings. In this report, the outline of the CP-PACS and the example of programming in the Kernel CG benchmark in NAS Parallel Benchmarks, version 1, are shown, and the pseudo vector processing mechanism and the parallel processing tuning of scientific and technical computation utilizing the three-dimensional hyper crossbar net, which are two great features of the architecture of the CP-PACS are described. As for the CP-PACS, the PUs based on RISC processor and added with pseudo vector processor are used. Pseudo vector processing is realized as the loop processing by scalar command. The features of the connection net of PUs are explained. The algorithm of the NPB version 1 Kernel CG is shown. The part that takes the time for processing most in the main loop is the product of matrix and vector (matvec), and the parallel processing of the matvec is explained. The time for the computation by the CPU is determined. As the evaluation of the performance, the evaluation of the time for execution, the short vector processing of pseudo vector processor based on slide window, and the comparison with other parallel computers are reported. (K.I.)

  7. Sum Rules of Charm CP Asymmetries beyond the SU(3)_{F} Limit.

    Science.gov (United States)

    Müller, Sarah; Nierste, Ulrich; Schacht, Stefan

    2015-12-18

    We find new sum rules between direct CP asymmetries in D meson decays with coefficients that can be determined from a global fit to branching ratio data. Our sum rules eliminate the penguin topologies P and PA, which cannot be determined from branching ratios. In this way, we can make predictions about direct CP asymmetries in the standard model without ad hoc assumptions on the sizes of penguin diagrams. We consistently include first-order SU(3)_{F} breaking in the topological amplitudes extracted from the branching ratios. By confronting our sum rules with future precise data from LHCb and Belle II, one will identify or constrain new-physics contributions to P or PA. The first sum rule correlates the CP asymmetries a_{CP}^{dir} in D^{0}→K^{+}K^{-}, D^{0}→π^{+}π^{-}, and D^{0}→π^{0}π^{0}. We study the region of the a_{CP}^{dir}(D^{0}→π^{+}π^{-})-a_{CP}^{dir}(D^{0}→π^{0}π^{0}) plane allowed by current data and find that our sum rule excludes more than half of the allowed region at 95% C.L. Our second sum rule correlates the direct CP asymmetries in D^{+}→K[over ¯]^{0}K^{+}, D_{s}^{+}→K^{0}π^{+}, and D_{s}^{+}→K^{+}π^{0}.

  8. The impact of sterile neutrinos on CP measurements at long baselines

    International Nuclear Information System (INIS)

    Gandhi, Raj; Kayser, Boris; Masud, Mehedi; Prakash, Suprabh

    2015-01-01

    With the Deep Underground Neutrino Experiment (DUNE) as an example, we show that the presence of even one sterile neutrino of mass ∼1 eV can significantly impact the measurements of CP violation in long baseline experiments. Using a probability level analysis and neutrino-antineutrino asymmetry calculations, we discuss the large magnitude of these effects, and show how they translate into significant event rate deviations at DUNE. Our results demonstrate that measurements which, when interpreted in the context of the standard three family paradigm, indicate CP conservation at long baselines, may, in fact hide large CP violation if there is a sterile state. Similarly, any data indicating the violation of CP cannot be properly interpreted within the standard paradigm unless the presence of sterile states of mass O(1 eV) can be conclusively ruled out. Our work underscores the need for a parallel and linked short baseline oscillation program and a highly capable near detector for DUNE, in order that its highly anticipated results on CP violation in the lepton sector may be correctly interpreted.

  9. 50 CFR 660.160 - Catcher/processor (C/P) Coop Program.

    Science.gov (United States)

    2010-10-01

    ... Pacific whiting, canary rockfish, darkblotched rockfish, Pacific Ocean perch, widow rockfish; (ii) Species... issuance for C/P endorsement—(i) Eligibility criteria for C/P endorsement. Only current owners of a current... with the current limited entry trawl permit accrues to the current permit owner. NMFS will not...

  10. The CpG island methylator phenotype: What's in a name?

    NARCIS (Netherlands)

    L.A.E. Hughes (Laura A.); V. Melotte (Veerle); J.D. Schrijver (Joachim De); M.P.M. de Maat (Moniek); V.T.H.B.M. Smit (Vincent); J.V.M.G. Bovée (Judith); P.J. French (Pim); P.A. van den Brandt (Piet); L. Schouten (Leo); T. Meyer (Thorsten); W. van Criekinge (Wim); N. Ahuja (Nita); J.G. Herman (James); M.P. Weijenberg (Matty); M. van Engeland (Manon)

    2013-01-01

    textabstractAlthough the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast,

  11. Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

    NARCIS (Netherlands)

    R. de Wit (Ronald)

    2003-01-01

    textabstractThe advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients

  12. Opioid antagonists with minimal sedation for opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M

    2017-05-29

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies. We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants. We used standard methodological procedures expected by Cochrane. Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha 2 -adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient

  13. Observation of CP violation in the B(0) meson system.

    Science.gov (United States)

    Aubert, B; Boutigny, D; Gaillard, J M; Hicheur, A; Karyotakis, Y; Lees, J P; Robbe, P; Tisserand, V; Palano, A; Chen, G P; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Reinertsen, P L; Stugu, B; Abbott, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Clark, A R; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kluth, S; Kolomensky, Y G; Kral, J F; LeClerc, C; Levi, M E; Liu, T; Lynch, G; Meyer, A B; Momayezi, M; Oddone, P J; Perazzo, A; Pripstein, M; Roe, N A; Romosan, A; Ronan, M T; Shelkov, V G; Telnov, A V; Wenzel, W A; Zisman, M S; Bright-Thomas, P G; Harrison, T J; Hawkes, C M; Knowles, D J; O'Neale, S W; Penny, R C; Watson, A T; Watson, N K; Deppermann, T; Goetzen, K; Koch, H; Krug, J; Kunze, M; Lewandowski, B; Peters, K; Schmuecker, H; Steinke, M; Andress, J C; Barlow, N R; Bhimji, W; Chevalier, N; Clark, P J; Cottingham, W N; De Groot, N; Dyce, N; Foster, B; McFall, J D; Wallom, D; Wilson, F F; Abe, K; Hearty, C; Mattison, T S; McKenna, J A; Thiessen, D; Jolly, S; McKemey, A K; Tinslay, J; Blinov, V E; Bukin, A D; Bukin, D A; Buzykaev, A R; Golubev, V B; Ivanchenko, V N; Korol, A A; Kravchenko, E A; Onuchin, A P; Salnikov, A A; Serednyakov, S I; Skovpen, Y I; Telnov, V I; Yushkov, A N; Best, D; Lankford, A J; Mandelkern, M; McMahon, S; Stoker, D P; Ahsan, A; Arisaka, K; Buchanan, C; Chun, S; Branson, J G; MacFarlane, D B; Prell, S; Rahatlou, S; Raven, G; Sharma, V; Campagnari, C; Dahmes, B; Hart, P A; Kuznetsova, N; Levy, S L; Long, O; Lu, A; Richman, J D; Verkerke, W; Witherell, M; Yellin, S; Beringer, J; Dorfan, D E; Eisner, A M; Frey, A; Grillo, A A; Grothe, M; Heusch, C A; Johnson, R P; Kroeger, W; Lockman, W S; Pulliam, T; Sadrozinski, H; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Turri, M; Walkowiak, W; Williams, D C; Wilson, M G; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Metzler, S; Oyang, J; Porter, F C; Ryd, A; Samuel, A; Weaver, M; Yang, S; Zhu, R Y; Devmal, S; Geld, T L; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Barillari, T; Bloom, P; Dima, M O; Fahey, S; Ford, W T; Johnson, D R; Nauenberg, U; Olivas, A; Park, H; Rankin, P; Roy, J; Sen, S; Smith, J G; van Hoek, W C; Wagner, D L; Blouw, J; Harton, J L; Krishnamurthy, M; Soffer, A; Toki, W H; Wilson, R J; Zhang, J; Brandt, T; Brose, J; Colberg, T; Dahlinger, G; Dickopp, M; Dubitzky, R S; Hauke, A; Maly, E; Müller-Pfefferkorn, R; Otto, S; Schubert, K R; Schwierz, R; Spaan, B; Wilden, L; Behr, L; Bernard, D; Bonneaud, G R; Brochard, F; Cohen-Tanugi, J; Ferrag, S; Roussot, E; T'Jampens, S; Thiebaux, C; Vasileiadis, G; Verderi, M; Anjomshoaa, A; Bernet, R; Khan, A; Lavin, D; Muheim, F; Playfer, S; Swain, J E; Falbo, M; Borean, C; Bozzi, C; Dittongo, S; Folegani, M; Piemontese, L; Treadwell, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Falciai, D; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Xie, Y; Zallo, A; Bagnasco, S; Buzzo, A; Contri, R; Crosetti, G; Fabbricatore, P; Farinon, S; Lo Vetere, M; Macri, M; Monge, M R; Musenich, R; Pallavicini, M; Parodi, R; Passaggio, S; Pastore, F C; Patrignani, C; Pia, M G; Priano, C; Robutti, E; Santroni, A; Morii, M; Bartoldus, R; Dignan, T; Hamilton, R; Mallik, U; Cochran, J; Crawley, H B; Fischer, P A; Lamsa, J; Meyer, W T; Rosenberg, E I; Benkebil, M; Grosdidier, G; Hast, C; Höcker, A; Lacker, H M; Laplace, S; Lepeltier, V; Lutz, A M; Plaszczynski, S; Schune, M H; Trincaz-Duvoid, S; Valassi, A; Wormser, G; Bionta, R M; Brigljević, V; Lange, D J; Mugge, M; Shi, X; van Bibber, K; Wenaus, T J; Wright, D M; Wuest, C R; Carroll, M; Fry, J R; Gabathuler, E; Gamet, R; George, M; Kay, M; Payne, D J; Sloane, R J; Touramanis, C; Aspinwall, M L; Bowerman, D A; Dauncey, P D; Egede, U; Eschrich, I; Gunawardane, N J; Nash, J A; Sanders, P; Smith, D; Azzopardi, D E; Back, J J; Dixon, P; Harrison, P F; Potter, R J; Shorthouse, H W; Strother, P; Vidal, P B; Williams, M I; Cowan, G; George, S; Green, M G; Kurup, A; Marker, C E; McGrath, P; McMahon, T R; Ricciardi, S; Salvatore, F; Scott, I; Vaitsas, G; Brown, D; Davis, C L; Allison, J; Barlow, R J; Boyd, J T; Forti, A C; Fullwood, J; Jackson, F; Lafferty, G D; Savvas, N; Simopoulos, E T; Weatherall, J H; Farbin, A; Jawahery, A; Lillard, V; Olsen, J; Roberts, D A; Schieck, J R; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Moore, T B; Staengle, H; Willocq, S; Brau, B; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Milek, M; Patel, P M; Trischuk, J; Lanni, F; Palombo, F; Bauer, J M; Booke, M; Cremaldi, L; Eschenburg, V; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Martin, J P; Nief, J Y; Seitz, R; Taras, P; Zacek, V; Nicholson, H; Sutton, C S; Cartaro, C; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Paolucci, P; Piccolo, D; Sciacca, C; LoSecco, J M; Alsmiller, J R; Gabriel, T A; Handler, T; Brau, J; Frey, R; Iwasaki, M; Sinev, N B; Strom, D; Colecchia, F; Dal Corso, F; Dorigo, A; Galeazzi, F; Margoni, M; Michelon, G; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Torassa, E; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; de La Vaissière, C; Del Buono, L; Hamon, O; Le Diberder, F; Leruste, P; Lory, J; Roos, L; Stark, J; Versillé, S; Manfredi, P F; Re, V; Speziali, V; Frank, E D; Gladney, L; Guo, Q H; Panetta, J H; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Martinez-Vidal, F; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Sandrelli, F; Simi, G; Triggiani, G; Walsh, J; Haire, M; Judd, D; Paick, K; Turnbull, L; Wagoner, D E; Albert, J; Bula, C; Elmer, P; Lu, C; McDonald, K T; Miftakov, V; Schaffner, S F; Smith, A J; Tumanov, A; Varnes, E W; Cavoto, G; del Re, D; Faccini, R; Ferrarotto, F; Ferroni, F; Fratini, K; Lamanna, E; Leonardi, E; Mazzoni, M A; Morganti, S; Piredda, G; Safai Tehrani, F; Serra, M; Voena, C; Christ, S; Waldi, R; Adye, T; Franek, B; Geddes, N I; Gopal, G P; Xella, S M; Aleksan, R; De Domenico, G; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P F; Hamel De Monchenault, G; Kozanecki, W; Langer, M; London, G W; Mayer, B; Serfass, B; Vasseur, G; Yèche, C; Zito, M; Copty, N; Purohit, M V; Singh, H; Yumiceva, F X; Adam, I; Anthony, P L; Aston, D; Baird, K; Berger, J P; Bloom, E; Boyarski, A M; Bulos, F; Calderini, G; Claus, R; Convery, M R; Coupal, D P; Coward, D H; Dorfan, J; Dorser, M; Dunwoodie, W; Field, R C; Glanzman, T; Godfrey, G L; Gowdy, S J; Grosso, P; Himel, T; Hryn'ova, T; Huffer, M E; Innes, W R; Jessop, C P; Kelsey, M H; Kim, P; Kocian, M L; Langennegger, U; Leith, D W; Luitz, S; Luth, V; Lynch, H L; Marsiske, H; Menke, S; Messner, R; Moffeit, K C; Mount, R; Muller, D R; O'Grady, C P; Perl, M; Petrak, S; Quinn, H; Ratcliff, B N; Robertson, S H; Rochester, L S; Roodman, A; Schietinger, T; Schindler, R H; Schwiening, J; Seeman, J T; Serbo, V V; Snyder, S R; Soha, A; Spanier, S M; Stelzer, J; Su, D; Sullivan, M K; Tanaka, H A; Va'vra, J; Wagner, S R; Weinstein, A J; Wienands, U; Wisniewski, W J; Wright, D H; Young, C C; Burchat, P R; Cheng, C H; Kirkby, D; Meyer, T I; Roat, C; Henderson, R; Bugg, W; Cohn, H; Weidemann, A W; Izen, J M; Kitayama, I; Lou, X C; Turcotte, M; Bianchi, F; Bona, M; DiGirolamo, B; Gamba, D; Smol, A; Zanin, D; Bosisio, L; Della Ricci, G; Lanceri, L; Pompili, A; Poropat, P; Vuagnin, G; Panvini, R S; Brown, C M; De Silva, A; Kowalewski, R; Roney, J M; Band, H R; Charles, E; Dasu, S; Di Lodovico, F; Eichenbaum, A M; Hu, H; Johnson, J R; Liu, R; Nielsen, J; Pan, Y; Prepost, R; Scott, I J; Sekula, S J; von Wimmersperg-Toeller, J H; Wu, S L; Zobernig, H; Kordich, T M; Neal, H

    2001-08-27

    We present an updated measurement of time-dependent CP-violating asymmetries in neutral B decays with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. This result uses an additional sample of Upsilon(4S) decays collected in 2001, bringing the data available to 32 x 10(6) BB macro pairs. We select events in which one neutral B meson is fully reconstructed in a final state containing charmonium and the flavor of the other neutral B meson is determined from its decay products. The amplitude of the CP-violating asymmetry, which in the standard model is proportional to sin2 beta, is derived from the decay time distributions in such events. The result sin2 beta = 0.59+/-0.14(stat)+/-0.05(syst) establishes CP violation in the B(0) meson system. We also determine absolute value of lambda = 0.93+/-0.09(stat)+/-0.03(syst), consistent with no direct CP violation.

  14. Postural Dysfunction During Standing and Walking in Children With Cerebral Palsy: What are the Underlying Problems and What New Therapies Might Improve Balance?

    Directory of Open Access Journals (Sweden)

    Marjorie Hines Woollacott

    2005-01-01

    Full Text Available In this review we explore studies related to constraints on balance and walking in children with cerebral palsy (CP and the efficacy of training reactive balance (recovering from a slip induced by a platform displacement in children with both spastic hemiplegic and diplegic CP. Children with CP show (a crouched posture, contributing to decreased ability to recover balance (longer time/increased sway; (b delayed responses in ankle muscles; (c inappropriate muscle response sequencing; (d increased coactivation of agonists/antagonists. Constraints on gait include (a crouched gait; (b increased co-activation of agonists/antagonists; (c decreased muscle activation; (d spasticity. The efficiency of balance recovery can be improved in children with CP, indicated by both a reduction in the total center of pressure path used during balance recovery and in the time to restabilize balance after training. Changes in muscle response characteristics contributing to improved recovery include reductions in time of contraction onset, improved muscle response organization, and reduced co-contraction of agonists/antagonists. Clinical implications include the suggestion that improvement in the ability to recover balance is possible in school age children with CP.

  15. CP asymmetries in Strange Baryon Decays

    Science.gov (United States)

    Bigi, I. I.; Kang, Xian-Wei; Li, Hai-Bo

    2018-01-01

    While indirect and direct CP violation (CPV) has been established in the decays of strange and beauty mesons, no CPV has yet been found for baryons. There are different paths to finding CP asymmetry in the decays of strange baryons; they are all highly non-trivial. The HyperCP Collaboration has probed CPV in the decays of single Ξ and Λ [1]. We discuss future lessons from {{{e}}}+{{{e}}}- collisions at BESIII/BEPCII: probing decays of pairs of strange baryons, namely Λ, Σ and Ξ. Realistic goals are to learn about non-perturbative QCD. One can hope to find CPV in the decays of strange baryons; one can also dream of finding the impact of New Dynamics. We point out that an important new era will start with the BESIII/BEPCII data accumulated by the end of 2018. This also supports new ideas to trigger {{J}}/{{\\psi }}\\to \\bar{{{Λ }}}{{Λ }} at the LHCb collaboration. Supported by National Science Foundation (PHY-1520966), National Natural Science Foundation of China (11335009, 11125525), Joint Large-Scale Scientific Facility Funds of the NSFC and CAS (U1532257), the National Key Basic Research Program of China (2015CB856700), Key Research Program of Frontier Sciences, CAS, (QYZDJ-SSW-SLH003), XWK’s work is also supported by MOST (Taiwan) (104-2112-M-001-022)

  16. Search for CP violation in D0 decay

    International Nuclear Information System (INIS)

    Bartelt, J.; Csorna, S.E.; Egyed, Z.; Jain, V.; Gibaut, D.; Kinoshita, K.; Pomianowski, P.; Barish, B.; Chadha, M.; Chan, S.; Cowen, D.F.; Eigen, G.; Miller, J.S.; O'Grady, C.; Urheim, J.; Weinstein, A.J.; Wuerthwein, F.; Asner, D.M.; Athanas, M.; Bliss, D.W.; Brower, W.S.; Masek, G.; Paar, H.P.; Gronberg, J.; Korte, C.M.; Kutschke, R.; Menary, S.; Morrison, R.J.; Nakanishi, S.; Nelson, H.N.; Nelson, T.K.; Qiao, C.; Richman, J.D.; Roberts, D.; Ryd, A.; Tajima, H.; Witherell, M.S.; Balest, R.; Cho, K.; Ford, W.T.; Lohner, M.; Park, H.; Rankin, P.; Smith, J.G.; Alexander, J.P.; Bebek, C.; Berger, B.E.; Berkelman, K.; Bloom, K.; Browder, T.E.; Cassel, D.G.; Cho, H.A.; Coffman, D.M.; Crowcroft, D.S.; Dickson, M.; Drell, P.S.; Dumas, D.J.; Ehrlich, R.; Elia, R.; Gaidarev, P.; Garcia-Sciveres, M.; Gittelman, B.; Gray, S.W.; Hartill, D.L.; Heltsley, B.K.; Henderson, S.; Jones, C.D.; Jones, S.L.; Kandaswamy, J.; Katayama, N.; Kim, P.C.; Kreinick, D.L.; Lee, T.; Liu, Y.; Ludwig, G.S.; Masui, J.; Mevissen, J.; Mistry, N.B.; Ng, C.R.; Nordberg, E.; Patterson, J.R.; Peterson, D.; Riley, D.; Soffer, A.; Avery, P.; Freyberger, A.; Lingel, K.; Rodriguez, J.; Yang, S.; Yelton, J.; Brandenburg, G.; Cinabro, D.; Liu, T.; Saulnier, M.; Wilson, R.; Yamamoto, H.; Bergfeld, T.; Eisenstein, B.I.; Ernst, J.

    1995-01-01

    Using 2.7 fb -1 of data taken with the CLEO II detector, we have searched for CP violation in the charm system. We looked for asymmetries in the number of decays of D 0 's and bar D 0 's to the CP eigenstates K + K - , K S 0 φ, and K S 0 π 0 . Confidence intervals (90%) on these asymmetries were found to be -0.020 KK KS 0 φ KS 0 π 0 <0.031, respectively

  17. A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Wenbo Yao

    2017-08-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

  18. Search for CP violation in $D^{+} \\to K^{-}K^{+}\\pi^{+}$ decays

    CERN Document Server

    Aaij, R.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A.A.; Amato, S.; Amhis, Y.; Anderson, J.; Appleby, R.B.; Aquines Gutierrez, O.; Archilli, F.; Arrabito, L.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Bachmann, S.; Back, J.J.; Bailey, D.S.; Balagura, V.; Baldini, W.; Barlow, R.J.; Barschel, C.; Barsuk, S.; Barter, W.; Bates, A.; Bauer, C.; Bauer, Th.; Bay, A.; Bediaga, I.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Benayoun, M.; Bencivenni, G.; Benson, S.; Benton, J.; Bernet, R.; Bettler, M.O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bizzeti, A.; Bjornstad, P.M.; Blake, T.; Blanc, F.; Blanks, C.; Blouw, J.; Blusk, S.; Bobrov, A.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T.J.V.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Brisbane, S.; Britsch, M.; Britton, T.; Brook, N.H.; Brown, H.; Buchler-Germann, A.; Burducea, I.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Caicedo Carvajal, J.M.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cattaneo, M.; Charles, M.; Charpentier, Ph.; Chiapolini, N.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P.E.L.; Clemencic, M.; Cliff, H.V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Collins, P.; Constantin, F.; Conti, G.; Contu, A.; Cook, A.; Coombes, M.; Corti, G.; Cowan, G.A.; Currie, R.; D'Almagne, B.; D'Ambrosio, C.; David, P.; De Bonis, I.; De Capua, S.; De Cian, M.; De Lorenzi, F.; De Miranda, J.M.; De Paula, L.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Degaudenzi, H.; Deissenroth, M.; Del Buono, L.; Deplano, C.; Deschamps, O.; Dettori, F.; Dickens, J.; Dijkstra, H.; Diniz Batista, P.; Donleavy, S.; Dordei, F.; Dosil Suarez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Dzhelyadin, R.; Eames, C.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisele, F.; Eisenhardt, S.; Ekelhof, R.; Eklund, L.; Elsasser, Ch.; d'Enterria, D.G.; Esperante Pereira, D.; Esteve, L.; Falabella, A.; Fanchini, E.; Farber, C.; Fardell, G.; Farinelli, C.; Farry, S.; Fave, V.; Fernandez Albor, V.; Ferro-Luzzi, M.; Filippov, S.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Frank, M.; Frei, C.; Frosini, M.; Furcas, S.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garnier, J-C.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauvin, N.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Gligorov, V.V.; Gobel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Grabalosa Gandara, M.; Graciani Diaz, R.; Granado Cardoso, L.A.; Grauges, E.; Graziani, G.; Grecu, A.; Gregson, S.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Haefeli, G.; Haen, C.; Haines, S.C.; Hampson, T.; Hansmann-Menzemer, S.; Harji, R.; Harnew, N.; Harrison, J.; Harrison, P.F.; He, J.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J.A.; van Herwijnen, E.; Hicks, E.; Hofmann, W.; Holubyev, K.; Hopchev, P.; Hulsbergen, W.; Hunt, P.; Huse, T.; Huston, R.S.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Ilten, P.; Imong, J.; Jacobsson, R.; Jaeger, A.; Jahjah Hussein, M.; Jans, E.; Jansen, F.; Jaton, P.; Jean-Marie, B.; Jing, F.; John, M.; Johnson, D.; Jones, C.R.; Jost, B.; Kandybei, S.; Karacson, M.; Karbach, T.M.; Keaveney, J.; Kerzel, U.; Ketel, T.; Keune, A.; Khanji, B.; Kim, Y.M.; Knecht, M.; Koblitz, S.; Koppenburg, P.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kruzelecki, K.; Kucharczyk, M.; Kukulak, S.; Kumar, R.; Kvaratskheliya, T.; La Thi, V.N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R.W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Le Gac, R.; van Leerdam, J.; Lees, J.P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Leroy, O.; Lesiak, T.; Li, L.; Li Gioi, L.; Lieng, M.; Liles, M.; Lindner, R.; Linn, C.; Liu, B.; Liu, G.; Lopes, J.H.; Lopez Asamar, E.; Lopez-March, N.; Luisier, J.; Machefert, F.; Machikhiliyan, I.V.; Maciuc, F.; Maev, O.; Magnin, J.; Malde, S.; Mamunur, R.M.D.; Manca, G.; Mancinelli, G.; Mangiafave, N.; Marconi, U.; Marki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martin, L.; Martin Sanchez, A.; Martinez Santos, D.; Martins Tostes, D.; Massafferri, A.; Mathe, Z.; Matteuzzi, C.; Matveev, M.; Maurice, E.; Maynard, B.; Mazurov, A.; McGregor, G.; McNulty, R.; Mclean, C.; Meissner, M.; Merk, M.; Merkel, J.; Messi, R.; Miglioranzi, S.; Milanes, D.A.; Minard, M.N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morawski, P.; Mountain, R.; Mous, I.; Muheim, F.; Muller, K.; Muresan, R.; Muryn, B.; Musy, M.; Mylroie-Smith, J.; Naik, P.; Nakada, T.; Nandakumar, R.; Nardulli, J.; Nasteva, I.; Nedos, M.; Needham, M.; Neufeld, N.; Nguyen-Mau, C.; Nicol, M.; Nies, S.; Niess, V.; Nikitin, N.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Otalora Goicochea, J.M.; Owen, P.; Pal, B.; Palacios, J.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C.J.; Passaleva, G.; Patel, G.D.; Patel, M.; Paterson, S.K.; Patrick, G.N.; Patrignani, C.; Pavel-Nicorescu, C.; Pazos Alvarez, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perego, D.L.; Perez Trigo, E.; Perez-Calero Yzquierdo, A.; Perret, P.; Perrin-Terrin, M.; Pessina, G.; Petrella, A.; Petrolini, A.; Pie Valls, B.; Pietrzyk, B.; Pilar, T.; Pinci, D.; Plackett, R.; Playfer, S.; Plo Casasus, M.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; du Pree, T.; Prisciandaro, J.; Pugatch, V.; Puig Navarro, A.; Qian, W.; Rademacker, J.H.; Rakotomiaramanana, B.; Rangel, M.S.; Raniuk, I.; Raven, G.; Redford, S.; Reid, M.M.; dos Reis, A.C.; Ricciardi, S.; Rinnert, K.; Roa Romero, D.A.; Robbe, P.; Rodrigues, E.; Rodrigues, F.; Rodriguez Perez, P.; Rogers, G.J.; Roiser, S.; Romanovsky, V.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Sabatino, G.; Saborido Silva, J.J.; Sagidova, N.; Sail, P.; Saitta, B.; Salzmann, C.; Sannino, M.; Santacesaria, R.; Santamarina Rios, C.; Santinelli, R.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schaack, P.; Schiller, M.; Schleich, S.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.H.; Schwemmer, R.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shao, B.; Shapkin, M.; Shapoval, I.; Shatalov, P.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Skottowe, H.P.; Skwarnicki, T.; Smith, A.C.; Smith, N.A.; Sobczak, K.; Soler, F.J.P.; Solomin, A.; Soomro, F.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Styles, N.; Subbiah, V.K.; Swientek, S.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teodorescu, E.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Topp-Joergensen, S.; Tran, M.T.; Tsaregorodtsev, A.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Urquijo, P.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; Velthuis, J.J.; Veltri, M.; Vervink, K.; Viaud, B.; Videau, I.; Vieira, D.; Vilasis-Cardona, X.; Visniakov, J.; Vollhardt, A.; Voong, D.; Vorobyev, A.; Voss, H.; Wacker, K.; Wandernoth, S.; Wang, J.; Ward, D.R.; Webber, A.D.; Websdale, D.; Whitehead, M.; Wiedner, D.; Wiggers, L.; Wilkinson, G.; Williams, M.P.; Williams, M.; Wilson, F.F.; Wishahi, J.; Witek, M.; Witzeling, W.; Wotton, S.A.; Wyllie, K.; Xie, Y.; Xing, F.; Yang, Z.; Young, R.; Yushchenko, O.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W.C.; Zhang, Y.; Zhelezov, A.; Zhong, L.; Zverev, E.; Zvyagin, A.

    2011-01-01

    A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \\to K^- K^+\\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.

  19. Evidence for CP violation in time-integrated $D^0 \\rightarrow h^-h^+$ decay rates

    CERN Document Server

    Aaij, R; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amhis, Y; Anderson, J; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Arrabito, L; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Bailey, D S; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bates, A; Bauer, C; Bauer, Th; Bay, A; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blanks, C; Blouw, J; Blusk, S; Bobrov, A; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Büchler-Germann, A; Burducea, I; Bursche, A; Buytaert, J; Cadeddu, S; Callot, O; 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Visniakov, J; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Voss, H; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Witzeling, W; Wotton, S A; Wyllie, K; Xie, Y; Xing, F; Xing, Z; Yang, Z; Young, R; Yushchenko, O; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhong, L; Zverev, E; Zvyagin, A

    2012-01-01

    A search for time-integrated $CP$ violation in $D^0 \\rightarrow h^-h^+$ ($h=K$, $\\pi$) decays is presented using 0.62~fb$^{-1}$ of data collected by LHCb in 2011. The flavor of the charm meson is determined by the charge of the slow pion in the $D^{*+} \\rightarrow D^0 \\pi^+$ and $D^{*-} \\rightarrow \\overline{D}^0 \\pi^-$ decay chains. The difference in $CP$ asymmetry between $D^0 \\rightarrow K^- K^+$ and $D^0 \\rightarrow \\pi^- \\pi^+$, $\\Delta A_{CP} \\equiv A_{CP}(K^-K^+) \\, - \\, A_{CP}(\\pi^-\\pi^+)$, is measured to be $\\left[ -0.82 \\pm 0.21 (\\mathrm{stat.}) \\pm 0.11 (\\mathrm{syst.}) \\right]\\%$. This differs from the hypothesis of $CP$ conservation by $3.5$ standard deviations.

  20. CP violation in inclusive and exclusive charmless B decays

    International Nuclear Information System (INIS)

    Gerard, J.; Hou, W.

    1991-01-01

    Absorptive parts in penguin amplitudes lead to CP-violating partial rate asymmetries in B-meson decays. A careful study of the inclusive process reveals a subtlety in the implementation of this mechanism. Because of (1) the smallness of V ub /V cb , (2) the fact that α s (m b ) is not too small, and (3) the kinematic suppression of c bar c absorptive contribution, O(α s 2 ) effects have to be kept consistently. We find a strong correlation between the CP rate asymmetries of the b→su bar u mode and the purely loop-induced b→sd bar d and ss bar s modes, which is a consequence of the constraints of CPT invariance. The semi-inclusive charmless b→su bar u decay rate asymmetry is therefore negligibly small. With the (semi-)inclusive result as a guide, we estimate the rates and CP asymmetries for several exclusive several exclusive modes. Keeping only the perturbative, penguin-induced absorptive part, one finds that the modes due to b→su bar u (e.g., B - →K - π 0 ) could have CP rate asymmetries opposite in sign with respect to pure penguin modes (such as B - →K - φ), contrary to naive expectations. Charmless b→d transitions are also discussed. We emphasize that exclusive b→d modes (such as B - →K - K S ) may be more promising for CP studies within the standard model. Many uncertainties and problems related to penguin processes are discussed and assessed in detail