WorldWideScience

Sample records for canonical transient receptor

  1. Integration of transient receptor potential canonical channels with lipids

    OpenAIRE

    Beech, D. J.

    2012-01-01

    Transient receptor potential canonical (TRPC) channels are the canonical (C) subset of the TRP proteins, which are widely expressed in mammalian cells. They are thought to be primarily involved in determining calcium and sodium entry and have wide-ranging functions that include regulation of cell proliferation, motility and contraction. The channels are modulated by a multiplicity of factors, putatively existing as integrators in the plasma membrane. This review considers the sensitivities of...

  2. Transient receptor potential canonical type 3 channels and blood pressure in humans

    DEFF Research Database (Denmark)

    Thilo, Florian; Baumunk, Daniel; Krause, Hans;

    2009-01-01

    There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blood...

  3. Do cysteine residues regulate transient receptor potential canonical type 6 (TRPC6) channel protein expression?

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Krueger, Katharina;

    2012-01-01

    The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed that patie......The regulation of calcium influx through transient receptor potential canonical type 6 channel is mandatory for the activity of human monocytes. We submit the first evidence that cysteine residues of homocysteine or acetylcysteine affect TRPC6 expression in human monocytes. We observed...... that patients with chronic renal failure had significantly elevated homocysteine levels and TRPC6 mRNA expression levels in monocytes compared to control subjects. We further observed that administration of homocysteine or acetylcysteine significantly increased TRPC6 channel protein expression compared...

  4. Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats

    DEFF Research Database (Denmark)

    Liu, Daoyan; Yang, Dachun; He, Hongbo; Chen, Xiaoping; Cao, Tingbing; Feng, Xiaoli; Ma, Liqun; Luo, Zhidan; Wang, Lijuan; Yan, Zhencheng; Zhu, Zhiming; Tepel, Martin

    2009-01-01

    We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by immunohistochem......We tested the hypothesis that transient receptor potential canonical type 3 (TRPC3) channels are increased in vascular smooth muscle cells and aortic tissue from spontaneously hypertensive rats (SHR) compared with normotensive Wistar Kyoto rats. Expression of TRPC3 was analyzed by...... immunohistochemistry and Western blotting. TRPC3 gene knockdown was performed by specific small interfering RNA and TRPC3 overexpression using the pAdEasy-1 system. Cytosolic calcium was measured using fluorescence spectrophotometry and vasoconstriction of aortic rings using a force transducer. In SHR, the expression...

  5. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels

    DEFF Research Database (Denmark)

    Chen, Xiaoping; Yang, Dachun; Ma, Shuangtao;

    2010-01-01

    Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor...... potential canonical (TRPC) channels, in the present study we tested the hypothesis that increased vasomotion in hypertension is directly linked to increased TRPC expression. Using a small vessel myograph we observed significantly increased norepinephrine-induced vasomotion in mesenteric arterioles from SHR...... vasomotion in hypertension....

  6. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Kiso, Hironori [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ohba, Takayoshi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Iino, Kenji; Sato, Kazuhiro; Terata, Yutaka [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Murakami, Manabu [Department of Pharmacology, Hirosaki University Graduate School of Medicine (Japan); Ono, Kyoichi [Department of Cell Physiology, Akita University Graduate School of Medicine (Japan); Watanabe, Hiroyuki, E-mail: hirow@doc.med.akita-u.ac.jp [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan); Ito, Hiroshi [Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine (Japan)

    2013-07-05

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.

  7. Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy

    International Nuclear Information System (INIS)

    Highlights: •Transient receptor potential canonical (TRPC1, 3 and 6) are up-regulated by ET-1. •Sildenafil inhibited hypertrophic responses (BNP, Ca entry, NFAT activation). •Sildenafil suppressed TRPC1, 3 and 6 expression. -- Abstract: Background: Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy. Methods and results: In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes. Conclusions: These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression

  8. High glucose enhances transient receptor potential channel canonical type 6-dependent calcium influx in human platelets via phosphatidylinositol 3-kinase-dependent pathway

    DEFF Research Database (Denmark)

    Liu, Daoyan; Maier, Alexandra; Scholze, Alexandra; Rauch, Ursula; Boltzen, Ulrike; Zhao, Zhigang; Zhu, Zhiming; Tepel, Martin

    2008-01-01

    Transient receptor potential canonical type 6 (TRPC6) channels mediating 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced calcium entry have been identified on human platelets. In the present study we tested the hypothesis that hyperglycemia increases the expression of TRPC6 channels....

  9. Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

    DEFF Research Database (Denmark)

    Johansson, S E; Andersen, X E D R; Hansen, R H;

    2015-01-01

    the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement......AIM: In this study, we aimed to investigate whether changes in cerebrovascular voltage-dependent calcium channels and non-selective cation channels contribute to the enhanced endothelin-1-mediated vasoconstriction in the delayed hypoperfusion phase after experimental transient forebrain ischaemia...... arteries from ischaemic or sham-operated rats to evaluate changes in vascular voltage-dependent calcium channels, transient receptor potential canonical channels as well as endothelin-1 receptor function and expression. RESULTS: The expression of transient receptor potential canonical channels 1 and 6 in...

  10. Mechanisms of activation of nucleus accumbens neurons by cocaine via sigma-1 receptor-inositol 1,4,5-trisphosphate-transient receptor potential canonical channel pathways.

    Science.gov (United States)

    Barr, Jeffrey L; Deliu, Elena; Brailoiu, G Cristina; Zhao, Pingwei; Yan, Guang; Abood, Mary E; Unterwald, Ellen M; Brailoiu, Eugen

    2015-08-01

    Cocaine promotes addictive behavior primarily by blocking the dopamine transporter, thus increasing dopamine transmission in the nucleus accumbens (nAcc); however, additional mechanisms are continually emerging. Sigma-1 receptors (σ1Rs) are known targets for cocaine, yet the mechanisms underlying σ1R-mediated effects of cocaine are incompletely understood. The present study examined direct effects of cocaine on dissociated nAcc neurons expressing phosphatidylinositol-linked D1 receptors. Endoplasmic reticulum-located σ1Rs and inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) were targeted using intracellular microinjection. IP3 microinjection robustly elevated intracellular Ca(2+) concentration, [Ca(2+)]i. While cocaine alone was devoid of an effect, the IP3-induced response was σ1R-dependently enhanced by cocaine co-injection. Likewise, cocaine augmented the [Ca(2+)]i increase elicited by extracellularly applying an IP3-generating molecule (ATP), via σ1Rs. The cocaine-induced enhancement of the IP3/ATP-mediated Ca(2+) elevation occurred at pharmacologically relevant concentrations and was mediated by transient receptor potential canonical channels (TRPC). IP3 microinjection elicited a slight, transient depolarization, further converted to a greatly enhanced, prolonged response, by cocaine co-injection. The cocaine-triggered augmentation was σ1R-dependent, TRPC-mediated and contingent on [Ca(2+)]i elevation. ATP-induced depolarization was similarly enhanced by cocaine. Thus, we identify a novel mechanism by which cocaine promotes activation of D1-expressing nAcc neurons: enhancement of IP3R-mediated responses via σ1R activation at the endoplasmic reticulum, resulting in augmented Ca(2+) release and amplified depolarization due to subsequent stimulation of TRPC. In vivo, intra-accumbal blockade of σ1R or TRPC significantly diminished cocaine-induced hyperlocomotion and locomotor sensitization, endorsing a physio-pathological significance of the pathway

  11. Decreased levels of canonical transient receptor potential channel 3 protein in the rat cerebral cortex after chronic treatment with lithium or valproate.

    Science.gov (United States)

    Zaeri, Sasan; Farjadian, Shirin; Emamghoreishi, Masoumeh

    2015-01-01

    Lithium and valproate modulate disturbances in intracellular calcium homeostasis implicated in the pathophysiology of bipolar disorder, but the molecular mechanisms are not fully understood. Two subtypes of transient receptor potential (TRP) channel family, i.e. TRPC3 and TRPM2, are potential candidates involved in calcium signaling and implicated in the pathophysiology of bipolar disorder. This study was designed to investigate whether mood stabilizers such as lithium and valproate affect the expression of TRPC3 and TRPM2. Rats were treated with intraperitoneal injections of lithium (2 mEq/kg b.i.d.) or valproate (300 mg/kg b.i.d.) acutely (for 24 h) or chronically (for 4 weeks). The changes in mRNA and protein levels of TRPC3 and TRPM2 were measured with real-time polymerase chain reaction and western blotting. The chronic administration of lithium and valproate significantly reduced levels of TRPC3 by 19.7% and 19.3%, respectively. No change was detected in the mRNA level of this channel. Neither acute nor chronic treatment with lithium or valproate had any effect on TRPM2 levels. The results suggest that downregulation of the TRPC3 channel is an important shared mechanism by which lithium and valproate can modulate calcium disturbances, whereas the TRPM2 channel does not appear to be affected by mood stabilizers, at least under non stressed conditions. PMID:26752988

  12. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

  13. Cellular Functions of Transient Receptor Potential channels

    OpenAIRE

    Dadon, Daniela; Minke, Baruch

    2010-01-01

    Transient Receptor Potential channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by increasing cellular Ca2+. In this review we focus on the roles of these channels in: i) cell death ii) proliferation and differentiation and iii) synaptic vesicle release.

  14. The role of transient receptor potential channels in metabolic syndrome

    DEFF Research Database (Denmark)

    Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2008-01-01

    Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP......) canonical (TRPC), vanilloid (TRPV), and melastatin (TRPM) channels, have been associated with the development of cardiovascular diseases. Thus, disruption of TRP channel expression or function may account for the observed increased cardiovascular risk in metabolic syndrome patients. TRPV1 regulates...... evidence that a single TRP channelopathy may be the cause of all metabolic syndrome characteristics, further studies will help to clarify the role of specific TRP channels involved in the metabolic syndrome. (Hypertens Res 2008; 31: 1989-1995)....

  15. Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor.

    Science.gov (United States)

    Landry, Mélissa; Pomerleau, Véronique; Saucier, Caroline

    2016-06-01

    Met receptor tyrosine kinase (RTK) is known to bind to the three distinct protein isoforms encoded by the ShcA (Shc) gene. Structure-function studies have unveiled critical roles for p52Shc-dependent signalling pathways in Met-regulated biological functions. The molecular basis of the interaction between the Met and p52Shc proteins is well-defined, but not for the longest protein isoform, p66Shc. In the present study, co-immunoprecipitation assays were performed in human embryonic kidney 293 (HEK293) cells, transiently co-transfected with Met and p66Shc mutants, in order to define the molecular determinants involved in mediating Met-p66Shc interaction. Our results show that p66Shc interacts constitutively with the receptor Met, and the Grb2 (growth factor receptor-bound protein-2) and Gab1 (Grb2-associated binder-1) adaptor proteins. Although its phosphotyrosine-binding domain (PTB) and Src homology 2 (SH2) domains co-ordinate p66Shc binding to non-activated Met receptor, these phosphotyrosine-binding modules, and its collagen homology domain 2 (CH2) region, exert negative constraints. In contrast, p66Shc interaction with the activated Met depends mainly on the integrity of its PTB domain, and to a lesser extent of its SH2 domain. Even though not required for the recruitment of p66Shc, tyrosine phosphorylation of p66Shc by activated Met enhances these interactions by mechanisms not reliant on the integrity of the Met multisubstrate-binding site. In turn, this increases phosphotyrosine-dependent p66Shc-Grb2-Gab1 complex formation away from the receptor, while blocking Grb2 and Gab1 recruitment to activated Met. In conclusion, we identify, for the first time, a novel non-canonical dynamic mode of interaction between Met and the p66 protein isoform of Shc and its effects on rewiring binding effector complexes according to the activation state of the receptor. PMID:27048591

  16. Transient Receptor Potential Channels and Corneal Stromal Inflammation.

    Science.gov (United States)

    Okada, Yuka; Reinach, Peter S; Shirai, Kumi; Kitano-Izutani, Ai; Miyajima, Masayasu; Yamanaka, Osamu; Sumioka, Takayoshi; Saika, Shizuya

    2015-11-01

    Corneal transparency is dependent on the maintenance of the structural integrity and functional activity of its epithelial and endothelial limiting layers and the stroma. Different transient receptor potential (TRP) channel subtypes are expressed in cells and on corneal sensory nerve endings. They serve as sensors and transducers of environmental stimuli that can reduce tissue transparency. These nonselective cation channels are members of a superfamily sharing TRP box protein sequence homology having 6 membrane spanning domains with a pore between the fifth and sixth segments. TRP channels are composed of 4 monomeric subunits that oligomerize in homomeric or heteromeric configurations derived from different TRP subtypes belonging to the same or any of 6 different subfamilies. TRP subfamily members identified in the cornea include those belonging to the canonical, vanilloid, ankyrin, or melastatin subfamilies. In this review, we specifically focus on the functional roles of TRPV1 and TRPA1 expression in the cornea as their activation provides adaptive nociceptive and immune responses to noxious environmental stresses such as irritating ligands, temperature fluctuations, rises in ambient osmolarity, mechanical stretch, decline in pH, and tissue injury. Our previous studies have indicated that TRPV1 and TRPA1 subtypes are potential drug targets for improving corneal wound healing after alkali burns, because injury-induced fibrosis, neovascularization, and inflammation in either TRPV1 or TRPA1 gene-silenced mice were all significantly reduced. PMID:26448171

  17. Exploring the Potential of Transient Receptor Potential: Troubleshooting Troublesome Calcium Thoroughfares in Biomedicine

    Directory of Open Access Journals (Sweden)

    Ammad Ahmad Farooqi

    2010-12-01

    Full Text Available Transient Receptor Potential-Canonical (TRPC channels are the border guards residing in the supra-molecular assembly of plasma membrane. TRPCs represent a family of channels that have dual functions of store-operated and second messenger-operated channels in a diversity of cell types. Any disruption in the spatio-temporal organization drastically influences the calcium homeostasis. This review summarizes current interpretations on the infrastructure and characteristic divalent ions regulation in molecular anomalies. A specific targeting of these channels will enable us to get a step closer to personalized medicines.

  18. Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling.

    Science.gov (United States)

    Gao, Hua; Chakraborty, Goutam; Zhang, Zhanguo; Akalay, Intissar; Gadiya, Mayur; Gao, Yaquan; Sinha, Surajit; Hu, Jian; Jiang, Cizhong; Akram, Muzaffar; Brogi, Edi; Leitinger, Birgit; Giancotti, Filippo G

    2016-06-30

    Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCα. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain. Bioinformatic analyses and pathological studies corroborate the clinical relevance of these findings. We conclude that non-canonical DDR1 signaling enables breast cancer cells to exploit the ubiquitous interstitial matrix component collagen I to undergo metastatic reactivation in multiple target organs. PMID:27368100

  19. Transient Receptor Potential (TRP) Channels and Taste Sensation

    OpenAIRE

    Ishimaru, Y.; Matsunami, H

    2009-01-01

    Humans have 5 basic taste sensations: sweet, bitter, sour, salty, and umami (taste of 1-amino acids). Among 33 genes related to transient receptor potential (TRP) channels, 3—including TRP-melastatin 5 (TRPM5), polycystic kidney disease-1-like 3 (PKD1L3), and polycystic kidney disease-2-like 1 (PKD2L1)—are specifically and abundantly expressed in taste receptor cells. TRP-melastatin 5 is co-expressed with taste receptors T1Rs and T2Rs, and functions as a common downstream component in sweet, ...

  20. Non-canonical kinase signaling by the death ligand TRAIL in cancer cells : discord in the death receptor family

    NARCIS (Netherlands)

    Azijli, K.; Weyhenmeyer, B.; Peters, G. J.; de Jong, S.; Kruyt, F. A. E.

    2013-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapy is currently evaluated in clinical studies as a tumor cell selective pro-apoptotic approach. However, besides activating canonical caspase-dependent apoptosis by binding to TRAIL-specific death receptors, the TRAIL ligand

  1. Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma.

    Science.gov (United States)

    Ilmer, Matthias; Garnier, Agnès; Vykoukal, Jody; Alt, Eckhard; von Schweinitz, Dietrich; Kappler, Roland; Berger, Michael

    2015-12-01

    The substance P (SP)/NK-1 receptor (NK1R) complex represents an intriguing anticancer target for a variety of tumors, including hepatoblastoma (HB). Therefore, NK1R antagonists, such as the clinical drug aprepitant, recently have been proposed as potent anticancer agents. However, very little is known regarding the molecular basis of NK1R inhibition in cancer. Using reverse phase protein array, Western blot, Super TOP/FOP, confocal microscopy, and sphere formation ability (SFA) assays, we identified the AKT and Wnt signaling pathways as the key targets of aprepitant in three human HB cell lines (HepT1, HepG2, and HuH6). Following NK1R blockage, we observed decreased phosphorylation of p70S6K and 4E-BP1/2 and inhibition of the canonical Wnt pathway with subsequent decrease of HB cell growth. This effect was dependent of high baseline Wnt activity either by mutational status of β-catenin or extrinsic Wnt activation. Wnt inhibition seemed to be strengthened by disruption of the FOXM1-β-catenin complex. Furthermore, treatment of HB cells with aprepitant led to reduced expression of (liver) stemness markers (AFP, CD13, SOX2, NANOG, and OCT4) and SFA when grown under cancer stem cell conditions. Taken together, we show for the first time that targeting the SP/NK1R signaling cascade inhibits canonical Wnt signaling in HB cells. These findings reveal important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. PMID:26516161

  2. Design of chimeric antigen receptors with integrated controllable transient functions

    OpenAIRE

    Alexandre Juillerat; Alan Marechal; Jean-Marie Filhol; Julien Valton; Aymeric Duclert; Laurent Poirot; Philippe Duchateau

    2016-01-01

    The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug.

  3. Design of chimeric antigen receptors with integrated controllable transient functions.

    Science.gov (United States)

    Juillerat, Alexandre; Marechal, Alan; Filhol, Jean-Marie; Valton, Julien; Duclert, Aymeric; Poirot, Laurent; Duchateau, Philippe

    2016-01-01

    The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug. PMID:26750734

  4. Cross-regulation of signaling pathways: An example of nuclear hormone receptors and the canonical Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Beildeck, Marcy E. [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States); Gelmann, Edward P. [Columbia University, Department of Medicine, New York, NY (United States); Byers, Stephen W., E-mail: byerss@georgetown.edu [Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057 (United States)

    2010-07-01

    Predicting the potential physiological outcome(s) of any given molecular pathway is complex because of cross-talk with other pathways. This is particularly evident in the case of the nuclear hormone receptor and canonical Wnt pathways, which regulate cell growth and proliferation, differentiation, apoptosis, and metastatic potential in numerous tissues. These pathways are known to intersect at many levels: in the intracellular space, at the membrane, in the cytoplasm, and within the nucleus. The outcomes of these interactions are important in the control of stem cell differentiation and maintenance, feedback loops, and regulating oncogenic potential. The aim of this review is to demonstrate the importance of considering pathway cross-talk when predicting functional outcomes of signaling, using nuclear hormone receptor/canonical Wnt pathway cross-talk as an example.

  5. Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway.

    Science.gov (United States)

    Dhopeshwarkar, Amey; Mackie, Ken

    2016-08-01

    The CB2 cannabinoid receptor (CB2) remains a tantalizing, but unrealized therapeutic target. CB2 receptor ligands belong to varied structural classes and display extreme functional selectivity. Here, we have screened diverse CB2 receptor ligands at canonical (inhibition of adenylyl cyclase) and noncanonical (arrestin recruitment) pathways. The nonclassic cannabinoid (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55940) was the most potent agonist for both pathways, while the classic cannabinoid ligand (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran JWH133) was the most efficacious agonist among all the ligands profiled in cyclase assays. In the cyclase assay, other classic cannabinoids showed little [(-)-trans-Δ(9)-tetrahydrocannabinol and (-)-(6aR,7,10,10aR)-tetrahydro-6,6,9-trimethyl-3-(1-methyl-1-phenylethyl)-6H-dibenzo[b,d]pyran-1-ol] (KM233) to no efficacy [(6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene(L759633) and (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,8,9,10,10a-hexahydro-1-methoxy-6,6-dimethyl-9-methylene-6H-dibenzo[b,d]pyran]L759656. Most aminoalkylindoles, including [(3R)-​2,​3-​dihydro-​5-​methyl-​3-​(4-​morpholinylmethyl)pyrrolo[1,​2,​3-​de]-​1,​4-​benzoxazin-​6-​yl]-​1-​naphthalenyl-​methanone,​ monomethanesulfonate (WIN55212-2), were moderate efficacy agonists. The cannabilactone 3-(1,1-dimethyl-heptyl)-1-hydroxy-9-methoxy-benzo(c)chromen-6-one (AM1710) was equiefficacious to CP55940 to inhibit adenylyl cyclase, albeit with lower potency. In the arrestin recruitment assays, all classic cannabinoid ligands failed to recruit arrestins, indicating a bias toward G-protein coupling for this class of compound. All aminoalkylindoles tested, except for WIN55212-2 and (1-​pentyl-​1H-​indol-​3-​yl)(2,​2,​3,​3-​tetramethylcyclopropyl)-​methanone (UR144), failed

  6. Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1-induced inflammatory responses to corneal injury

    OpenAIRE

    Yang, Y.; Yang, H.; Wang, Z; Varadaraj, K; Kumari, S.S.; Mergler, S; Okada, Y.; Saika, S.; Kingsley, P J; Marnett, L J; Reinach, P.S.

    2012-01-01

    Cannabinoid receptor type 1 (CB1)-induced suppression of transient receptor potential vanilloid type 1 (TRPV1) activation provides a therapeutic option to reduce inflammation and pain in different animal disease models through mechanisms involving dampening of TRPV1 activation and signaling events. As we found in both mouse corneal epithelium and human corneal epithelial cells (HCEC) that there is CB1 and TRPV1 expression colocalization based on overlap of coimmunostaining, we determined in m...

  7. Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.

    Science.gov (United States)

    Diaz-Franulic, Ignacio; Poblete, Horacio; Miño-Galaz, Germán; González, Carlos; Latorre, Ramón

    2016-07-01

    The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation. In this review we first discuss the allosteric coupling between the temperature and voltage sensor modules and the pore domain, and then discuss the thermodynamic foundations of thermo-TRP channel activation. We provide a structural overview of the molecular determinants of temperature sensing. We also posit an anisotropic thermal diffusion model that may explain the large temperature sensitivity of TRP channels. Additionally, we examine the effect of several ligands on TRP channel function and the evidence regarding their mechanisms of action. PMID:27297398

  8. Transient receptor potential (TRP gene superfamily encoding cation channels

    Directory of Open Access Journals (Sweden)

    Pan Zan

    2011-01-01

    Full Text Available Abstract Transient receptor potential (TRP non-selective cation channels constitute a superfamily, which contains 28 different genes. In mammals, this superfamily is divided into six subfamilies based on differences in amino acid sequence homology between the different gene products. Proteins within a subfamily aggregate to form heteromeric or homomeric tetrameric configurations. These different groupings have very variable permeability ratios for calcium versus sodium ions. TRP expression is widely distributed in neuronal tissues, as well as a host of other tissues, including epithelial and endothelial cells. They are activated by environmental stresses that include tissue injury, changes in temperature, pH and osmolarity, as well as volatile chemicals, cytokines and plant compounds. Their activation induces, via intracellular calcium signalling, a host of responses, including stimulation of cell proliferation, migration, regulatory volume behaviour and the release of a host of cytokines. Their activation is greatly potentiated by phospholipase C (PLC activation mediated by coupled GTP-binding proteins and tyrosine receptors. In addition to their importance in maintaining tissue homeostasis, some of these responses may involve various underlying diseases. Given the wealth of literature describing the multiple roles of TRP in physiology in a very wide range of different mammalian tissues, this review limits itself to the literature describing the multiple roles of TRP channels in different ocular tissues. Accordingly, their importance to the corneal, trabecular meshwork, lens, ciliary muscle, retinal, microglial and retinal pigment epithelial physiology and pathology is reviewed.

  9. Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature

    DEFF Research Database (Denmark)

    Chen, L; Kaßmann, M; Sendeski, M; Tsvetkov, D; Marko, L; Michalick, L; Riehle, M; Liedtke, W B; Kuebler, W M; Harteneck, C; Tepel, Martin; Patzak, A; Gollasch, M

    2015-01-01

    AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized...... that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse...... mesenteric arteries with an EC50 of 25 nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist...

  10. Association of transient receptor potential canonical type 3 (TRPC3) channel transcripts with proinflammatory cytokines

    DEFF Research Database (Denmark)

    Thilo, Florian; Scholze, Alexandra; Liu, Dao Yan;

    2008-01-01

    necrosis factor-alpha (TNF-alpha) in monocytes from 15 patients with essential hypertension and 16 age- and sex-matched normotensive control subjects. We observed an approximately 8-fold increase of TRPC3 transcripts in monocytes from patients with essential hypertension compared to normotensive control...

  11. Interaction with Dopamine D2 Receptor Enhances Expression of Transient Receptor Potential Channel 1 at the Cell Surface

    OpenAIRE

    Hannan, Meredith A.; Kabbani, Nadine; Paspalas, Constantinos D.; Levenson, Robert

    2008-01-01

    Receptor signaling is mediated by direct protein interaction with various types of cytoskeletal, adapter, effector, and additional receptor molecules. In brain tissue and in cultured neurons, activation of dopamine D2 receptors (D2Rs) has been found to impact cellular calcium signaling. Using a yeast two-hybrid approach, we have uncovered a direct physical interaction between the D2R and the transient receptor potential channel (TRPC) subtypes 1, 4 and 5. The TRPC/D2R interaction was further ...

  12. Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients.

    Directory of Open Access Journals (Sweden)

    Andreas Binder

    Full Text Available Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K was associated with the presence of paradoxical heat sensation (p = 0.03, and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V with cold hypoalgesia (p = 0.0035. Two main subgroups characterized by preserved (1 and impaired (2 sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and pG (rs222747, M315I to cold hypaesthesia (p = 0.002, but there was absence of associations in subgroup 2. In this study we found no evidence that genetic

  13. Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in severe asthma

    OpenAIRE

    McGarvey, Lorcan P.; Butler, Claire A; Stokesberry, Susan; Polley, Liam; McQuaid, Stephen; Abdullah, Hani'ah; Ashraf, Sadaf; McGahon, Mary K; Curtis, Tim M; Arron, Joe; Choy, David; Warke, Tim J.; Bradding, Peter; Ennis, Madeleine; Zholos, Alexander

    2014-01-01

    BACKGROUND: The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma. The functional expression of ...

  14. Transient Receptor Potential Vanilloid 4: The Sixth Sense of the Musculoskeletal System?

    OpenAIRE

    Guilak, Farshid; Leddy, Holly A; Liedtke, Wolfgang

    2010-01-01

    The critical discovery in the past two decades of the Transient Receptor Potential (TRP) superfamily of ion channels has revealed the potential mechanisms by which cells sense diverse stimuli beyond the prototypical “five senses”, identifying ion channels that are gated by heat, cold, mechanical loading, osmolarity, and other physical and chemical stimuli. Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that appears to play a mechano- or osmos...

  15. Bimodal action of menthol on the transient receptor potential channel TRPA1

    OpenAIRE

    Karashima, Yuji; Damann, Nils; Prenen, Jean; Talavera Pérez, Karel; Segal Stanciu, Andrei; Voets, Thomas; Nilius, Bernd

    2007-01-01

    TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In who...

  16. Serotonin Receptor 2B Mediates Mechanical Hyperalgesia by Regulating Transient Receptor Potential Vanilloid 1.

    Science.gov (United States)

    Su, Yeu-Shiuan; Chiu, Yuan-Yi; Lin, Shih-Yuan; Chen, Chih-Cheng; Sun, Wei-Hsin

    2016-05-01

    Serotonin [5-hydroxytryptamine (5-HT)], an inflammatory mediator, contributes to inflammatory pain. The presence of multiple 5-HT subtype receptors on peripheral and central nociceptors complicates the role of 5-HT in pain. Previously, we found that 5-HT2B/2C antagonist could block 5-HT-induced mechanical hyperalgesia. However, the types of neurons or circuits underlying this effect remained unsolved. Here, we demonstrate that the Gq/11-phospholipase Cβ-protein kinase Cε (PKCε) pathway mediated by 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia in mice. Administration of a transient receptor potential vanilloid 1 (TRPV1) antagonist inhibited the 5-HT-induced mechanical hyperalgesia. 5-HT injection enhanced 5-HT- and capsaicin-evoked calcium signals specifically in isolectin B4 (IB4)-negative neurons; signals were inhibited by a 5-HT2B/2C antagonist and PKCε blocker. Thus, 5-HT2B mediates 5-HT-induced mechanical hyperalgesia by regulating TRPV1 function. PMID:26635025

  17. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1)

    OpenAIRE

    Bhave, Gautam; HU, HUI-JUAN; Glauner, Kathi S.; Zhu, Weiguo; Wang, Haibin; Brasier, D. J.; Oxford, Gerry S; Gereau, Robert W.

    2003-01-01

    Protein kinase C (PKC) modulates the function of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). This modulation manifests as increased current when the channel is activated by capsaicin. In addition, studies have suggested that phosphorylation by PKC might directly gate the channel, because PKC-activating phorbol esters induce TRPV1 currents in the absence of applied ligands. To test whether PKC both modulates and gates the TRPV1 function by direct phosphorylation, w...

  18. Expressional changes in cerebrovascular receptors after experimental transient forebrain ischemia

    DEFF Research Database (Denmark)

    Johansson, Sara; Povlsen, Gro Klitgaard; Edvinsson, Lars

    2012-01-01

    insult, a phenomenon that leads to increased contraction of cerebral arteries, reduced perfusion of the affected area and worsened ischemic damage. Based on these findings, the aim of the present study was to investigate if transient global cerebral ischemia is associated with upregulation of...

  19. Pathogenic role of B-cell receptor signaling and canonical NF-κB activation in mantle cell lymphoma.

    Science.gov (United States)

    Saba, Nakhle S; Liu, Delong; Herman, Sarah E M; Underbayev, Chingiz; Tian, Xin; Behrend, David; Weniger, Marc A; Skarzynski, Martin; Gyamfi, Jennifer; Fontan, Lorena; Melnick, Ari; Grant, Cliona; Roschewski, Mark; Navarro, Alba; Beà, Sílvia; Pittaluga, Stefania; Dunleavy, Kieron; Wilson, Wyndham H; Wiestner, Adrian

    2016-07-01

    To interrogate signaling pathways activated in mantle cell lymphoma (MCL) in vivo, we contrasted gene expression profiles of 55 tumor samples isolated from blood and lymph nodes from 43 previously untreated patients with active disease. In addition to lymph nodes, MCL often involves blood, bone marrow, and spleen and is incurable for most patients. Recently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib demonstrated important clinical activity in MCL. However, the role of specific signaling pathways in the lymphomagenesis of MCL and the biologic basis for ibrutinib sensitivity of these tumors are unknown. Here, we demonstrate activation of B-cell receptor (BCR) and canonical NF-κB signaling specifically in MCL cells in the lymph node. Quantification of BCR signaling strength, reflected in the expression of BCR regulated genes, identified a subset of patients with inferior survival after cytotoxic therapy. Tumor proliferation was highest in the lymph node and correlated with the degree of BCR activation. A subset of leukemic tumors showed active BCR and NF-κB signaling apparently independent of microenvironmental support. In one of these samples, we identified a novel somatic mutation in RELA (E39Q). This sample was resistant to ibrutinib-mediated inhibition of NF-κB and apoptosis. In addition, we identified germ line variants in genes encoding regulators of the BCR and NF-κB pathway previously implicated in lymphomagenesis. In conclusion, BCR signaling, activated in the lymph node microenvironment in vivo, appears to promote tumor proliferation and survival and may explain the sensitivity of this lymphoma to BTK inhibitors. PMID:27127301

  20. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1) by Diacylglycerol (DAG)

    OpenAIRE

    Oh Seog; Kim Yong; Park Chul-Kyu; Zhu Mei; Jung Sung; Woo Dong; Lee C Justin

    2008-01-01

    Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1), is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC). However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG) directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root...

  1. MODULATION DES TRANSIENT RECEPTOR POTENTIAL VANILLOID 1 (TRPV1) IONENKANALS DURCH µ-REZEPTOR-AGONISTEN

    OpenAIRE

    Endres-Becker, Jeannette

    2010-01-01

    Opioids play an outstanding role in the treatment of acute, postoperative and tumor-caused pain frequently associated with tissue inflammation. The opioid mediated activation of peripheral μ-receptors modulates voltage-gated calcium channels and thus inhibits afferent neuron excitation. However, it is unclear if opioids affect the ligand-gated ion channel transient receptor potential vanilloid 1 (TRPV1). TRPV1 is crucially involved in the development of pain and thermal hypersensitivity ...

  2. Transient Receptor Potential Vanilloid Type 1 Channel May Modulate Opioid Reward

    OpenAIRE

    Nguyen, Thi-Lien; Kwon, Seung-Hwan; Hong, Sa-Ik; Ma, Shi-Xun; Jung, Yang-Hee; Hwang, Ji-Young; Kim, Hyoung-Chun; Lee, Seok-Yong; Jang, Choon-Gon

    2014-01-01

    Transient receptor potential vanilloid type 1 (TRPV1), a nonselective cation channel, is a well-known pain-related receptor. TRPV1 involvement in morphine-induced antinociception, tolerance, and withdrawal symptoms has been previously reported. Emerging evidence indicates that TRPV1 may be related to both the cellular and behavioral effects of addictive drugs. In the present study, we investigated the role of TRPV1 in morphine reward using the conditioned place preference (CPP) paradigm in mi...

  3. The low-density lipoprotein receptor-related protein 10 is a negative regulator of the canonical Wnt/β-catenin signaling pathway

    International Nuclear Information System (INIS)

    Wnt signaling pathways play fundamental roles in the differentiation, proliferation and functions of many cells as well as developmental, growth, and homeostatic processes in animals. Low-density lipoprotein receptor (LDLR)-related protein (LRP) 5 and LRP6 serve as coreceptors of Wnt proteins together with Frizzled receptors, triggering activation of canonical Wnt/β-catenin signaling. Here, we found that LRP10, a new member of the LDLR gene family, inhibits the canonical Wnt/β-catenin signaling pathway. The β-catenin/T cell factor (TCF) transcriptional activity in HEK293 cells was activated by transfection with Wnt3a or LRP6, which was then inhibited by co-transfection with LRP10. Deletion of the extracellular domain of LRP10 negated its inhibitory effect. The inhibitory effect of LRP10 was consistently conserved in HEK293 cells even when GSK3β phosphorylation was inhibited by incubation with lithium chloride and co-transfection with constitutively active S33Y-mutated β-catenin. Nuclear β-catenin accumulation was unaffected by LRP10. The present studies suggest that LRP10 may interfere with the formation of the β-catenin/TCF complex and/or its binding to target DNA in the nucleus, and that the extracellular domain of LRP10 is critical for inhibition of the canonical Wnt/β-catenin signaling pathway.

  4. High glucose-induced oxidative stress increases transient receptor potential channel expression in human monocytes

    DEFF Research Database (Denmark)

    Wuensch, Tilo; Thilo, Florian; Krueger, Katharina; Scholze, Alexandra; Ristow, Michael; Tepel, Martin

    2010-01-01

    Transient receptor potential (TRP) channel-induced cation influx activates human monocytes, which play an important role in the pathogenesis of atherosclerosis. In the present study, we investigated the effects of high glucose-induced oxidative stress on TRP channel expression in human monocytes....

  5. Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney

    DEFF Research Database (Denmark)

    Kassmann, M.; Harteneck, C.; Zhu, Z.;

    2013-01-01

    Recent preclinical data indicate that activators of transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) may improve the outcome of ischaemic acute kidney injury (AKI). The underlying mechanisms are unclear, but may involve TRPV1 channels in dorsal root ganglion...... channel agonists such as 20-HETE, phospholipase C and phosphatidylinositide 3-kinase (PI3 kinase). We review important roles of TRPV1 and TRPV4 in kidney physiology and renal ischaemia reperfusion injury; further studies are warranted to address renoprotective mechanism of vanilloid receptors in ischaemic...... pharmacological TRPV modulators may be a successful strategy for better treatment of acute or chronic kidney failure....

  6. Transients

    International Nuclear Information System (INIS)

    The lecture includes typical transients to be analyzed, the requirements put on computer codes and a description of the computer codes as well as results obtained with these codes. Transients analysis is necessary within the licensing of reactors, in risk evaluation and in other basic studies (e.g. on ATWS). The development of transient codes has been influenced by new requirements due to the extension in applications mentioned above. As examples the BWR model ALMOS and the PWR model ALMOD are described. These codes include a one-dimensional simulation of the neutron kinetics and the thermohydraulics in the coolant system. Also included in the simulation are all components of the control and safety systems, which are influencing the dynamic behaviour of the plant. Special emphasis is put on the problems of model verification (comparison with measurements). The transients behaviour of plants under extreme conditions, such as transients with a failure of the scram system, is described in detail. Examples are the loss of heat sink and the station black out for both a BWR and a PWR. (orig.)

  7. Signalling through the type 1 insulin-like growth factor receptor (IGF1R interacts with canonical Wnt signalling to promote neural proliferation in developing brain

    Directory of Open Access Journals (Sweden)

    Qichen Hu

    2012-07-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin−KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin−KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  8. The Transient Receptor Potential Vanilloid-1 Channel in Thermoregulation: A Thermosensor It Is Not

    OpenAIRE

    Romanovsky, Andrej A; Maria C. Almeida; Garami, Andras; Steiner, Alexandre A; Norman, Mark H.; Morrison, Shaun F.; Nakamura, Kazuhiro; Burmeister, Jeffrey J.; Nucci, Tatiane B.

    2009-01-01

    The development of antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel as pain therapeutics has revealed that these compounds cause hyperthermia in humans. This undesirable on-target side effect has triggered a surge of interest in the role of TRPV1 in thermoregulation and revived the hypothesis that TRPV1 channels serve as thermosensors. We review literature data on the distribution of TRPV1 channels in the body and on thermoregulatory responses to TRPV1 agonists and ...

  9. Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves via Transient Receptor Potential (TRP) Channels

    OpenAIRE

    Nesuashvili, Lika; Hadley, Stephen H; Parmvir K Bahia; Taylor-Clark, Thomas E.

    2013-01-01

    Mitochondrial dysfunction and subsequent oxidative stress has been reported for a variety of cell types in inflammatory diseases. Given the abundance of mitochondria at the peripheral terminals of sensory nerves and the sensitivity of transient receptor potential (TRP) ankyrin 1 (A1) and TRP vanilloid 1 (V1) to reactive oxygen species (ROS) and their downstream products of lipid peroxidation, we investigated the effect of nerve terminal mitochondrial dysfunction on airway sensory nerve excita...

  10. Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice

    OpenAIRE

    Wang, Jie; Guo, Tao; Peng, Qi-sheng; Yue, Shou-Wei; Wang, Shuang-Xi

    2015-01-01

    Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic ...

  11. Transient Receptor Potential A1 Channels: Insights Into Cough and Airway Inflammatory Disease

    OpenAIRE

    Belvisi, Maria G.; Dubuis, Eric; Birrell, Mark A

    2011-01-01

    Cough is a common symptom of diseases such as asthma and COPD and also presents as a disease in its own right. Treatment options are limited; a recent meta-analysis concluded that over-the-counter remedies are ineffective, and there is increasing concern about their use in children. Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) channels are nonselective cation channels that are activated by a range of natural products (eg, allyl isothiocyanate), a multitude of env...

  12. Adenosine transiently modulates stimulated dopamine release in the caudate putamen via A1 receptors

    OpenAIRE

    Ross, Ashley E.; Venton, B. Jill

    2014-01-01

    Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dop...

  13. Activation of the transient receptor potential vanilloid-1 (TRPV1) channel opens the gate for pain relief

    OpenAIRE

    Jancsó, G; Dux, M; Oszlács, O; Sántha, P

    2008-01-01

    Pharmacological modulation of the transient receptor potential vanilloid-1 (TRPV1) receptor function offers a promising means of producing pain relief at the level of the primary sensory neuron. In this issue of the BJP, the pharmacological approaches and the available experimental data that focus on the TRPV1 receptor to achieve therapeutically useful alleviation of pain and inflammation are reviewed. The potentials to inactivate TRPV1 receptor function by site- and modality-specific TRPV1 a...

  14. Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1 by Diacylglycerol (DAG

    Directory of Open Access Journals (Sweden)

    Oh Seog

    2008-10-01

    Full Text Available Abstract The capsaicin receptor, known as transient receptor potential channel vanilloid subtype 1 (TRPV1, is activated by a wide range of noxious stimulants and putative ligands such as capsaicin, heat, pH, anandamide, and phosphorylation by protein kinase C (PKC. However, the identity of endogenous activators for TRPV1 under physiological condition is still debated. Here, we report that diacylglycerol (DAG directly activates TRPV1 channel in a membrane-delimited manner in rat dorsal root ganglion (DRG neurons. 1-oleoyl-2-acetyl-sn-glycerol (OAG, a membrane-permeable DAG analog, elicited intracellular Ca2+ transients, cationic currents and cobalt uptake that were blocked by TRPV1-selective antagonists, but not by inhibitors of PKC and DAG lipase in rat DRG neurons or HEK 293 cells heterologously expressing TRPV1. OAG induced responses were about one fifth of capsaicin induced signals, suggesting that OAG displays partial agonism. We also found that endogenously produced DAG can activate rat TRPV1 channels. Mutagenesis of rat TRPV1 revealed that DAG-binding site is at Y511, the same site for capsaicin binding, and PtdIns(4,5P2binding site may not be critical for the activation of rat TRPV1 by DAG in heterologous system. We propose that DAG serves as an endogenous ligand for rat TRPV1, acting as an integrator of Gq/11-coupled receptors and receptor tyrosine kinases that are linked to phospholipase C.

  15. Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1.

    Science.gov (United States)

    Díaz-Franulic, Ignacio; Caceres-Molina, Javier; Sepulveda, Romina V; Gonzalez-Nilo, Fernando; Latorre, Ramon

    2016-09-01

    The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor that mediates the flux of cations across the membrane in response to several stimuli, including heat, voltage, and ligands. The best known agonist of TRPV1 channels is capsaicin, the pungent component of "hot" chili peppers. In addition, peptides found in the venom of poisonous animals, along with the lipids phosphatidylinositol 4,5-biphosphate, lysophosphatidic acid, and cholesterol, bind to TRPV1 with high affinity to modulate channel gating. Here, we discuss the functional evidence regarding ligand-dependent activation of TRPV1 channels in light of structural data recently obtained by cryoelectron microscopy. This review focuses on the mechanistic insights into ligand binding and allosteric gating of TRPV1 channels and the relevance of accurate polymodal receptor biophysical characterization for drug design in novel pain therapies. PMID:27335334

  16. Role of the Transient Receptor Potential Canonical 6 ion channel in genetic and acquired forms of proteinuric kidney disease

    OpenAIRE

    Möller, Clemens Claudius

    2007-01-01

    Podocyte foot processes and the interposed glomerular slit diaphragm are critical components of the permeability barrier in the kidney. Mutations in several podocyte genes have been identified as the cause for progressive kidney failure and focal segmental glomerulosclerosis (FSGS). Podocyte injury is a hallmark of glomerular disease and usually involves the rearrangement of the podocyte actin cytoskeleton. Cell-specific therapies targeting podocyte injury are currently not available. In 2004...

  17. Lack of Kinase Regulation of Canonical Transient Receptor Potential 3 (TRPC3) Channel-dependent Currents in Cerebellar Purkinje Cells

    OpenAIRE

    Nelson, Charmaine; Glitsch, Maike D.

    2011-01-01

    Background: TRPC3 channels are inhibited by PKC and PKG, which also induce cerebellar LTD. We investigate if PKC- and PKG-mediated modulation of cerebellar TRPC3 channels contributes to cerebellar LTD.

  18. Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Ni, Yinxing; Chen, Jing; Zhong, Jian; Yu, Hao; Xu, Xingsen; He, Hongbo; Yan, Zhencheng; Scholze, Alexandra; Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2012-01-01

    in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2-aminoethoxydiphenylborane (2-APB) and small...... interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246 ± 14% vs 151 ± 10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also...... significantly increased compared to normotensive control subjects (221 ± 20% vs 138 ± 18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from...

  19. Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor: Structure, Modulators, and Therapeutic Applications.

    Science.gov (United States)

    Cui, Minghua; Gosu, Vijayakumar; Basith, Shaherin; Hong, Sunhye; Choi, Sun

    2016-01-01

    Transient receptor potential (TRP) channels belong to a superfamily of sensory-related ion channels responding to a wide variety of thermal, mechanical, or chemical stimuli. In an attempt to comprehend the piquancy and pain mechanism of the archetypal vanilloids, transient receptor potential vanilloid (TRPV) 1 was discovered. TRPV1, a well-established member of the TRP family, is implicated in a range of functions including inflammation, painful stimuli sensation, and mechanotransduction. TRPV1 channels are nonselective cation receptors that are gated by a broad array of noxious ligands. Such polymodal-sensor aspect makes the TRPV1 channel extremely versatile and important for its role in sensing burning pain. Besides ligands, TRPV1 signaling can also be modulated by lipids, secondary messengers, protein kinases, cytoskeleton, and several other proteins. Due to its central role in hyperalgesia transduction and inflammatory processes, it is considered as the primary pharmacological pain target. Moreover, understanding the structural and functional intricacies of the channel is indispensable for the therapeutic intervention of TRPV1 in pain and other pathological disorders. In this chapter, we seek to give a mechanistic outlook on the TRPV1 channel. Specifically, we will explore the TRPV1 structure, activation, modulation, ligands, and its therapeutic targeting. However, the major objective of this review is to highlight the fact that TRPV1 channel can be treated as an effective therapeutic target for treating several pain- and nonpain-related physiological and pathological states. PMID:27038373

  20. Role of the transient receptor potential vanilloid 1 in inflammation and sepsis

    Directory of Open Access Journals (Sweden)

    Devesa I

    2011-05-01

    Full Text Available Isabel Devesa1, Rosa Planells-Cases2, Gregorio Fernández-Ballester1, José Manuel González-Ros1, Antonio Ferrer-Montiel1, Asia Fernández-Carvajal11Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Alicante; 2Centro de Investigación Príncipe Felipe, Valencia, SpainAbstract: The transient receptor potential vanilloid 1 (TRPV1 is a thermoreceptor that responds to noxious temperatures, as well as to chemical agonists, such as vanilloids and protons. In addition, its channel activity is notably potentiated by proinflammatory mediators released upon tissue damage. The TRPV1 contribution to sensory neuron sensitization by proalgesic agents has signaled this receptor as a prime target for analgesic and anti-inflammatory drug intervention. However, TRPV1 antagonists have notably failed in clinical and preclinical studies because of their unwanted side effects. Recent reports have unveiled previously unrecognized anti-inflammatory and protective functions of TRPV1 in several diseases. For instance, this channel has been suggested to play an anti-inflammatory role in sepsis. Therefore, the use of potent TRPV1 antagonists as a general strategy to treat inflammation must be cautiously considered, given the deleterious effects that may arise from inhibiting the population of channels that have a protective function. The use of TRPV1 antagonists may be limited to treating those pathologies where enhanced receptor activity contributes to the inflamed state. Alternatively, therapeutic paradigms, such as reduction of inflammatory-mediated increase of receptor expression in the cell surface, may be a better strategy to prevent abrogation of the TRPV1 subpopulation involved in anti-inflammatory and protective processes.Keywords: transient receptor potential, nociceptor, capsaicin, pain, ion channel, analgesia

  1. Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators.

    Science.gov (United States)

    LeGay, Christina M; Gorobets, Evgueni; Iftinca, Mircea; Ramachandran, Rithwik; Altier, Christophe; Derksen, Darren J

    2016-06-01

    A library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca(2+) assays and electrophysiology. PMID:27171974

  2. Charakterisierung der E179K-Variante des Transient Receptor Potential Ankyrin 1 Proteins in vitro

    OpenAIRE

    Baastrup, Jonas Marius

    2015-01-01

    Der TRPA1-Kanal gehört zur Familie der transient receptor potential-Kanäle (TRPs) und wird nach heutigem Wissensstand der Untergruppe der thermosensitiven TRP-Kanäle zugeordnet. Er wird bevorzugt im Nervensystem exprimiert, wo er hauptsächlich die Aufgabe eines Kälterezeptors, insbesondere für schmerzhafte Kälte erfüllt. Eine Transition von Guanin zu Adenin an Position 710 der TRPA1 DNA (710G>A) führt zu einer Aminosäuresubstitution von Glutamat (E) zu Lysin (K) an Position 179 (E179K) in der...

  3. Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Schulz, Nico; Gergs, Ulrich; Neumann, Joachim; Loddenkemper, Christoph; Gollasch, Maik; Tepel, Martin

    2010-01-01

    The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1......-/- mice. Transcripts of TRPV1, matrix metalloproteinase 9 (MMP9), discoidin domain receptor family, member 2 (DDR-2), atrial natriuretic peptide (ANP), GATA 4, and regulatory microRNA (miR-21) were analyzed using quantitative real-time PCR. Ventricle-to-body-weight-ratio was significantly higher in PP2Ac...... alpha transgenic mice compared to wild-type mice and TRPV1-/- mice (8.6±1.3mg/g; 5.4±0.3mg/g; and 5.4±0.4mg/g; respectively; p...

  4. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity

    DEFF Research Database (Denmark)

    Zhang, Li Li; Yan Liu, Dao; Ma, Li Qun;

    2007-01-01

    We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect...... of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator......-activated receptor-gamma, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced...

  5. Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia

    International Nuclear Information System (INIS)

    The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area

  6. Expression and function of transient receptor potential channels in the female bovine reproductive tract.

    Science.gov (United States)

    Ghavideldarestani, Maryam; Atkin, Stephen L; Leese, Henry J; Sturmey, Roger G

    2016-07-15

    The epithelium lining the oviduct is critical for early reproductive events, many of which are mediated via intracellular calcium ions. Despite this, little is known about the regulation of calcium homeostasis in the oviductal epithelium. Epithelial transient receptor potential channels (TRPCs) modulate calcium flux in other tissues, and their expression and functional regulation have therefore been examined using the bovine oviduct as a model for the human. The effects of FSH, LH, 17β-estradiol, and progesterone on TRPCs expression and intracellular calcium flux were determined. Transient receptor potential channels 1, 2, 3, 4, and 6 were expressed in the bovine reproductive tract, and their gene expression varied throughout the estrous cycle. In more detailed studies undertaken on TRPC1 and 6, we show that protein expression varied through the estrus cycle; specifically, 17β-estradiol, FSH, and LH individually and in combination upregulated TRPC1 and 6 expression in cultured bovine oviduct epithelial cells although progesterone antagonized these effects. Functional studies showed changes in calcium mobilization in bovine oviduct epithelial cells were dependent on TRPCs. In conclusion, TRPC1, 2, 3, 4, and 6 are present in the epithelium lining the bovine oviduct, and TRPC1 and 6 vary through the estrous cycle suggesting an important role in early reproductive function. PMID:27001231

  7. Propacetamol-Induced Injection Pain Is Associated with Activation of Transient Receptor Potential Vanilloid 1 Channels.

    Science.gov (United States)

    Schillers, Florian; Eberhardt, Esther; Leffler, Andreas; Eberhardt, Mirjam

    2016-10-01

    Propacetamol (PPCM) is a prodrug of paracetamol (PCM), which was generated to increase water solubility of PCM for intravenous delivery. PPCM is rapidly hydrolyzed by plasma esterases to PCM and diethylglycine and shares some structural and metabolic properties with lidocaine. Although PPCM is considered to be comparable to PCM regarding its analgesic properties, injection pain is a common side effect described for PPCM but not PCM. Injection pain is a frequent and unpleasant side effect of numerous drugs in clinical use, and previous reports have indicated that the ligand gated ion channels transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) can mediate this effect on sensory neurons. This study aimed to investigate molecular mechanisms by which PPCM, in contrast to PCM, causes injection pain. Therefore, human TRPV1 and TRPA1 receptors were expressed in human embryonic kidney 293 cells and investigated by means of whole-cell patch clamp and ratiometric calcium imaging. PPCM (but not PCM) activated TRPV1, sensitized heat-induced currents, and caused an increase in intracellular calcium. In TRPA1-expressing cells however, both PPCM and PCM evoked calcium responses but failed to induce inward currents. Intracutaneous injection of PPCM, but not of PCM, in human volunteers induced an intense and short-lasting pain and an increase in superficial blood flow, indicating activation of nociceptive C fibers and subsequent neuropeptide release. In conclusion, activation of human TRPV1 by PPCM seems to be a relevant mechanism for induction of pain upon intracutaneous injection and thus also for pain reported as an adverse side effect upon intravenous administration. PMID:27457427

  8. Suppression of sustained and transient ON signals of amacrine cells by GABA is mediated by different receptor subtypes

    Institute of Scientific and Technical Information of China (English)

    张道启; 杨如; 杨雄里

    1999-01-01

    Intracellular recordings were made from amacrine cells in the isolated, superfused carp retina, and the effects of γ-aminobutyric acid (GABA) on sustained and transient ON signals of these cells were studied. Exogenous GABA application partially suppressed the sustained response of ON amacrine cells, which could be completely reversed by picrotoxin (PTX), a chloride channel blocker, and by bicuculline (BCC), a specific GABA_A receptor antagonist. On the other hand, suppression by GABA of the ON response which was predominantly driven by rod signals in a certain portion of transient ON-OFF amacrine cells was completely blocked by PTX, but not by BCC, indicating that GABA_C receptors may be involved in the effect. These results suggest that GABA_A and GABA_C receptors may be respectively involved in mediating the transmission of sustained and transient signals in the carp inner retina.

  9. Radiosynthesis of [11C]SB-705498, a selective transient receptor potential Vanilloid 1 (TRPV1) receptor antagonist

    International Nuclear Information System (INIS)

    Complete text of publication follows: Objectives: The transient receptor potential vanilloid 1 (TRPV1) receptor, previously known as the vanilloid receptor 1 (VR1), is a non-selective cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptor is involved in pain and sensitisation associated with tissue injury and inflammation and therefore represents a pharmacological target of choice for the development of novel therapeutic agents for the treatment of chronic pain, migraine and gastrointestinal disorders. Among a novel series of pyrrolidinyl ureas recently discovered by GSK, SB-705498 (1, namely 1-(2-bromophenyl)-3-[(R)-1-(5- trifluoromethylpyridin-2-yl)pyrrolidin-3-yl]urea) has been identified as a potent, selective and orally bioavailable TRPV1 antagonist and considered for positron emission tomography studies. SB-705498 (1) has therefore been isotopically labelled with the short-lived positron-emitter carbon-11 (t1/2: 20.38 min) at its urea site using [11C]phosgene in a one-pot two-step process, via the intermediate preparation of 2-bromophenyl [11C]isocyanate. Methods: Carbon-11-labeling of SB-705498 comprises: (A) Trapping of [11C]phosgene (radio-synthesized from cyclotron-produced [11C]methane via [11C]carbon tetrachloride using minor modifications of published processes) at room temperature for 1 to 2 minutes in 250 μL of acetonitrile containing 0.6 μmole of 2-bromoaniline (2) giving 2-bromophenyl [11C]isocyanate ([11C]-3), followed by (B) addition of an excess of chiral (R)-1-(5- trifluoromethylpyridin-2-yl)pyrrolidin-3-ylamine (4, 40 μmoles in 500 μL of acetonitrile) as the second amine and reaction at room temperature for an additional one minute giving the desired urea derivative ([11C]SB-705498 ([11C]-1)), (C) dilution of the crude reaction mixture with water (500 μL) containing 4% (v:v) of DEA, injection and purification on a semi-preparative Waters SymmetryR C18 HPLC column (eluent: H2O / CH

  10. Gain-of-function mutations in the transient receptor potential channels TRPV1 and TRPA1: how painful?

    Czech Academy of Sciences Publication Activity Database

    Boukalová, Štěpána; Touška, Filip; Maršáková, Lenka; Hynková, Anna; Surá, Lucie; Chvojka, Štěpán; Dittert, Ivan; Vlachová, Viktorie

    2014-01-01

    Roč. 63, Suppl.1 (2014), S205-S213. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/0081; GA ČR(CZ) GBP304/12/G069 Grant ostatní: Univerzita Karlova(CZ) 500512; Univerzita Karlova(CZ) 888513 Institutional support: RVO:67985823 Keywords : transient receptor potential * ion channel * mutagenesis * vanilloid receptor * gating Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

  11. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells

    DEFF Research Database (Denmark)

    Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex; Krueger, Katharina; Liu, Ying; Baumunk, Daniel; Zakrzewicz, Andreas; Tepel, Martin

    2012-01-01

    The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined...... shear stress, producing a constant laminar flow (generating a shear stress of 6 dyne/cm(2)), laminar pulsatile atheroprotective flow (with a mean shear stress of 20 dyne/cm(2)), or laminar atheroprone bidirectional flow (with a mean shear stress of 0 dyne/cm(2)) differentially induced TRPC6 and TRPV1 m......RNA as measured by quantitative real-time RT-PCR and normalized to GAPDH expression. Thereby, TRPC6 and TRPV1 mRNA expressions were significantly increased after 24 hours of exposure to an atheroprone flow profile compared with an atheroprotective flow profile. Furthermore, the expression of...

  12. Activation of transient receptor potential ankyrin 1 by quercetin and its analogs.

    Science.gov (United States)

    Nakamura, Toshiyuki; Miyoshi, Noriyuki; Ishii, Takeshi; Nishikawa, Miyu; Ikushiro, Shinichi; Watanabe, Tatsuo

    2016-05-01

    The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1. PMID:26806540

  13. Transient Receptor Potential Melastatin-3 (TRPM3) Mediates Nociceptive-Like Responses in Hydra vulgaris.

    Science.gov (United States)

    Malafoglia, Valentina; Traversetti, Lorenzo; Del Grosso, Floriano; Scalici, Massimiliano; Lauro, Filomena; Russo, Valeria; Persichini, Tiziana; Salvemini, Daniela; Mollace, Vincenzo; Fini, Massimo; Raffaeli, William; Muscoli, Carolina; Colasanti, Marco

    2016-01-01

    The ability of mammals to feel noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors, which express specific membrane receptors, such as the Transient Receptor Potential (TRP) family. Here, we show that one of the most important nociceptive-like pathways is conserved in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system. In particular, we found that H. vulgaris expresses TRPM3, a nociceptor calcium channel involved in the detection of noxious heat in mammals. Furthermore, we detected that both heat shock and TRPM3 specific agonist (i.e., pregnenolone sulfate) induce the modulation of the heat shock protein 70 (HSP70) and the nitric oxide synthase (NOS), two genes activated by TRP-mediated heat painful stimuli in mammals. As expected, these effects are inhibited by a TRPM3 antagonist (i.e., mefenamic acid). Interestingly, the TRPM3 agonist and heat shock also induce the expression of nuclear transcription erythroid 2-related factor (Nrf2) and superoxide dismutase (SOD), known markers of oxidative stress; noteworthy gene expression was also inhibited by the TRPM3 antagonist. As a whole, our results demonstrate the presence of conserved molecular oxidative/nociceptive-like pathways at the primordial level of the animal kingdom. PMID:26974325

  14. Transient Receptor Potential Channel 1 (TRPC1) Reduces Calcium Permeability in Heteromeric Channel Complexes

    Science.gov (United States)

    Storch, Ursula; Forst, Anna-Lena; Philipp, Maximilian; Gudermann, Thomas; Mederos y Schnitzler, Michael

    2012-01-01

    Specific biological roles of the classical transient receptor potential channel 1 (TRPC1) are still largely elusive. To investigate the function of TRPC1 proteins in cell physiology, we studied heterologously expressed TRPC1 channels and found that recombinant TRPC1 subunits do not form functional homomeric channels. Instead, by electrophysiological analysis TRPC1 was shown to form functional heteromeric, receptor-operated channel complexes with TRPC3, -4, -5, -6, and -7 indicating that TRPC1 proteins can co-assemble with all members of the TRPC subfamily. In all TRPC1-containing heteromers, TRPC1 subunits significantly decreased calcium permeation. The exchange of select amino acids in the putative pore-forming region of TRPC1 further reduced calcium permeability, suggesting that TRPC1 subunits contribute to the channel pore. In immortalized immature gonadotropin-releasing hormone neurons endogenously expressing TRPC1, -2, -5, and -6, down-regulation of TRPC1 resulted in increased calcium permeability and elevated basal cytosolic calcium concentrations. We did not observe any involvement of TRPC1 in store-operated cation influx. Notably, TRPC1 suppressed the migration of gonadotropin-releasing hormone neurons without affecting cell proliferation. Conversely, in TRPC1 knockdown neurons, specific migratory properties like distance covered, locomotion speed, and directionality were increased. These findings suggest a novel regulatory mechanism relying on the expression of TRPC1 and the subsequent formation of heteromeric TRPC channel complexes with reduced calcium permeability, thereby fine-tuning neuronal migration. PMID:22157757

  15. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

  16. Cannabinoid 1 and transient receptor potential vanilloid 1 receptors discretely modulate evoked glutamate separately from spontaneous glutamate transmission.

    Science.gov (United States)

    Fawley, Jessica A; Hofmann, Mackenzie E; Andresen, Michael C

    2014-06-11

    Action potentials trigger synaptic terminals to synchronously release vesicles, but some vesicles release spontaneously. G-protein-coupled receptors (GPCRs) can modulate both of these processes. At cranial primary afferent terminals, the GPCR cannabinoid 1 (CB1) is often coexpressed with transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel present on most afferents. Here we tested whether CB1 activation modulates synchronous, action potential-evoked (eEPSCs) and/or spontaneous (sEPSCs) EPSCs at solitary tract nucleus neurons. In rat horizontal brainstem slices, activation of solitary tract (ST) primary afferents generated ST-eEPSCs that were rapidly and reversibly inhibited from most afferents by activation of CB1 with arachidonyl-2'-chloroethylamide (ACEA) or WIN 55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate]. The CB1 antagonist/inverse agonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] blocked these responses. Despite profound depression of ST-eEPSCs during CB1 activation, sEPSCs in these same neurons were unaltered. Changes in temperature changed sEPSC frequency only from TRPV1(+) afferents (i.e., thermal sEPSC responses only occurred in TRPV1(+) afferents). CB1 activation failed to alter these thermal sEPSC responses. However, the endogenous arachidonate metabolite N-arachidonyldopamine (NADA) promiscuously activated both CB1 and TRPV1 receptors. NADA inhibited ST-eEPSCs while simultaneously increasing sEPSC frequency, and thermally triggered sEPSC increases in neurons with TRPV1(+) afferents. We found no evidence for CB1/TRPV1 interactions suggesting independent regulation of two separate vesicle pools. Together, these data demonstrate that action potential-evoked synchronous glutamate release is modulated separately from TRPV1-mediated glutamate release despite coexistence

  17. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Stephanie C Stotz

    Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  18. Role of the transient receptor potential vanilloid type 1 channel in renal inflammation induced by lipopolysaccharide in mice

    OpenAIRE

    Wang, Youping; Wang, Donna H.

    2012-01-01

    To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS, 3 mg/kg) was intraperitoneally injected into wild-type (WT) and TRPV1-null mutant (TRPV1−/−) mice. The kidney and serum were collected 6 or 24 h after LPS injection for morphological analysis and proinflammatory cytokine assay. LPS injection led to a similar degree of transient hypotension and bradycardia in WT and TRPV1−/− mice determine...

  19. Canonical and non-canonical pathways of osteoclast formation

    OpenAIRE

    Knowles, H.J.; Athanasou, N A

    2009-01-01

    Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The canonical pathway of osteoclast formation requires the presence of the receptor activator for NFkB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Noncanonical pathways of osteoclast formation have been described in which cytokines / growth factors can substitute for RANKL or M-CSF to...

  20. Expression of Transient Receptor Potential Vanilloid (TRPV Channels in Different Passages of Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Richard Barrett-Jolley

    2012-04-01

    Full Text Available Ion channels play important roles in chondrocyte mechanotransduction. The transient receptor potential vanilloid (TRPV subfamily of ion channels consists of six members. TRPV1-4 are temperature sensitive calcium-permeable, relatively non-selective cation channels whereas TRPV5 and TRPV6 show high selectivity for calcium over other cations. In this study we investigated the effect of time in culture and passage number on the expression of TRPV4, TRPV5 and TRPV6 in articular chondrocytes isolated from equine metacarpophalangeal joints. Polyclonal antibodies raised against TRPV4, TRPV5 and TRPV6 were used to compare the expression of these channels in lysates from first expansion chondrocytes (P0 and cells from passages 1–3 (P1, P2 and P3 by western blotting. TRPV4, TRPV5 and TRPV6 were expressed in all passages examined. Immunohistochemistry and immunofluorescence confirmed the presence of these channels in sections of formalin fixed articular cartilage and monolayer cultures of methanol fixed P2 chondrocytes. TRPV5 and TRPV6 were upregulated with time and passage in culture suggesting that a shift in the phenotype of the cells in monolayer culture alters the expression of these channels. In conclusion, several TRPV channels are likely to be involved in calcium signaling and homeostasis in chondrocytes.

  1. Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice

    Directory of Open Access Journals (Sweden)

    Pinghui eJie

    2015-04-01

    Full Text Available Brain edema is an important pathological process during stroke. Activation of transient receptor potential vanilloid 4 (TRPV4 causes an up-regulation of matrix metalloproteinases (MMPs in lung tissue. MMP can digest the endothelial basal lamina to destroy blood brain barrier, leading to vasogenic brain edema. Herein, we tested whether TRPV4-blockage could inhibit brain edema through inhibiting MMPs in middle cerebral artery occlusion (MCAO mice. We found that the brain water content and Evans blue extravasation at 48 h post-MCAO were reduced by a TRPV4 antagonist HC-067047. The increased MMP-2/9 protein in hippocampus of MCAO mice was attenuated by HC-067046, but only the increased MMP-9 activity was blocked by HC-067047. The loss of zonula occluden-1 (ZO-1 and occludin protein in MCAO mice was also attenuated by HC-067047. Moreover, MMP-2/9 protein increased in mice treated with a TRPV4 agonist GSK1016790A, but only MMP-9 activity was increased by GSK1016790A. Finally, ZO-1 and occludin protein was decreased by GSK1016790A, which was reversed by an MMP-9 inhibitor. We conclude that blockage of TRPV4 may inhibit brain edema in cerebral ischemia through inhibiting MMP-9 activation and the loss of tight junction protein.

  2. Transient receptor potential A1 channels: insights into cough and airway inflammatory disease.

    Science.gov (United States)

    Belvisi, Maria G; Dubuis, Eric; Birrell, Mark A

    2011-10-01

    Cough is a common symptom of diseases such as asthma and COPD and also presents as a disease in its own right. Treatment options are limited; a recent meta-analysis concluded that over-the-counter remedies are ineffective, and there is increasing concern about their use in children. Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) channels are nonselective cation channels that are activated by a range of natural products (eg, allyl isothiocyanate), a multitude of environmental irritants (eg, acrolein, which is present in air pollution, vehicle exhaust, and cigarette smoke), and inflammatory mediators (eg, cyclopentenone prostaglandins). TRPA1 is primarily expressed in small-diameter, nociceptive neurons where its activation probably contributes to the perception of noxious stimuli. Inhalational exposure to irritating gases, fumes, dusts, vapors, chemicals, and endogenous mediators can lead to the development of cough. The respiratory tract is innervated by primary sensory afferent nerves, which are activated by mechanical and chemical stimuli. Recent data suggest that activation of TRPA1 on these vagal sensory afferents by these irritant substances could lead to central reflexes, including dyspnea, changes in breathing pattern, and cough, which contribute to the symptoms and pathophysiology of respiratory diseases. PMID:21972382

  3. Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7 channels.

    Science.gov (United States)

    Inoue, Koichi; Branigan, Deborah; Xiong, Zhi-Gang

    2010-03-01

    Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca(2+)-permeable non-selective cation channels ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in cellular Mg(2+) homeostasis, diseases caused by abnormal magnesium absorption, and in Ca(2+)-mediated neuronal injury under ischemic conditions. Here we show strong evidence suggesting that TRPM7 channels also play an important role in cellular Zn(2+) homeostasis and in Zn(2+)-mediated neuronal injury. Using a combination of fluorescent Zn(2+) imaging, small interfering RNA, pharmacological analysis, and cell injury assays, we show that activation of TRPM7 channels augmented Zn(2+)-induced injury of cultured mouse cortical neurons. The Zn(2+)-mediated neurotoxicity was inhibited by nonspecific TRPM7 blockers Gd(3+) or 2-aminoethoxydiphenyl borate, and by knockdown of TRPM7 channels with small interfering RNA. In addition, Zn(2+)-mediated neuronal injury under oxygen-glucose deprivation conditions was also diminished by silencing TRPM7. Furthermore, we show that overexpression of TRPM7 channels in HEK293 cells increased intracellular Zn(2+) accumulation and Zn(2+)-induced cell injury, while silencing TRPM7 by small interfering RNA attenuated the Zn(2+)-mediated cell toxicity. Thus, TRPM7 channels may represent a novel target for neurological disorders where Zn(2+) toxicity plays an important role. PMID:20048154

  4. Involvement of Transient Receptor Potential Cation Channel Vanilloid 1 (TRPV1) in Myoblast Fusion.

    Science.gov (United States)

    Kurosaka, Mitsutoshi; Ogura, Yuji; Funabashi, Toshiya; Akema, Tatsuo

    2016-10-01

    The mechanisms that underlie the complex process of muscle regeneration after injury remain unknown. Transient receptor potential cation channel vanilloid 1 (TRPV1) is expressed in several cell types, including skeletal muscle, and is activated by high temperature and by certain molecules secreted during tissue inflammation. Severe inflammation and local temperature perturbations are induced during muscle regeneration, which suggests that TRPV1 might be activated and involved in the process. The aim of this study, was to clarify the role of TRPV1 in the myogenic potential of satellite cells responsible for muscle regeneration. We found that mRNA and protein levels of TRPV1 increased during regeneration after cardiotoxin (CTX)-induced muscle injury in mice. Using isolated mouse satellite cells (i.e., myoblasts), we observed that activation of TRPV1 by its agonist capsaicin (CAP) augmented myogenin protein levels. Whereas CAP did not alter myoblast proliferation, it facilitated myoblast fusion (evaluated using myonucleii number per myotube and fusion index). In contrast, suppression of TRPV1 by siRNA impaired myoblast fusion. Using mice, we also demonstrated that intramuscular injection of CAP facilitated muscle repair after CTX-induced muscle injury. Moreover, we showed that these roles of TRPV1 might be mediated by interleukin-4 and calcium signaling during myoblast fusion. Collectively, these results suggest that TRPV1 underlies normal myogenesis through promotion of myoblast fusion. J. Cell. Physiol. 231: 2275-2285, 2016. © 2016 Wiley Periodicals, Inc. PMID:26892397

  5. Effects of Transient Receptor Potential Channel Blockers on Pacemaker Activity in Interstitial Cells of Cajal from Mouse Small Intestine

    OpenAIRE

    Kim, Byung Joo; Nam, Joo Hyun; Kim, Seon Jeong

    2011-01-01

    The interstitial cells of Cajal (ICCs) are pacemakers in the gastrointestinal tract and transient receptor potential melastatin type 7 (TRPM7) is a candidate for pacemaker channels. The effect of the 5-lipoxygenase (5-LOX) inhibitors NDGA, AA861, MK886 and zileuton on pacemaking activity of ICCs was examined using the whole cell patch clamp technique. NDGA and AA861 decreased the amplitude of pacemaker potentials in ICC clusters, but the resting membrane potentials displayed little change, re...

  6. Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

    OpenAIRE

    Fei Ren; Hong Zhang; Chao Qi; Mei-ling Gao; Hong Wang; Xia-qing Li

    2015-01-01

    The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes befo...

  7. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  8. Effect of lesogaberan, a novel GABAB-receptor agonist, on transient lower esophageal sphincter relaxations in male subjects

    OpenAIRE

    Guy E. Boeckxstaens; Rydholm, Hans; Lei, Aaltje; Adler, John; Ruth, Magnus

    2010-01-01

    Abstract Background: Transient lower esophageal sphincter relaxations (TLESRs) are a major mechanism behind gastroesophageal reflux disease (GERD). Aim: To assess the effect of lesogaberan (AZD3355) ? a novel peripherally active GABAB receptor agonist ? on TLESRs. Methods: Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of leso...

  9. Influence of dexamethasone on the expression and distribution of transient receptor potential cation channel 6 in glomerular podocytes

    Institute of Scientific and Technical Information of China (English)

    王辉阳

    2014-01-01

    Objective To observe the changes of foot processes,expression and distribution of transient receptor potential cation channel 6(TRPC6)in podocytes by puromycin aminonucleoside(PAN)and dexamethasone(DEX)intervention,then to investigate the function of TRPC6 in podocytes and its relation to proteinuria in kidney diseases.Methods Podocytes cultured in vitro were divided into three group:control group,PAN stimulation group and DEX intervention group.Mouse podocyte cell line

  10. Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors.

    Science.gov (United States)

    Almaghrabi, Safa; Geraghty, Dominic; Ahuja, Kiran; Adams, Murray

    2016-06-01

    Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors. PMID:26991025

  11. Constrained Canonical Correlation.

    Science.gov (United States)

    DeSarbo, Wayne S.; And Others

    1982-01-01

    A variety of problems associated with the interpretation of traditional canonical correlation are discussed. A response surface approach is developed which allows for investigation of changes in the coefficients while maintaining an optimum canonical correlation value. Also, a discrete or constrained canonical correlation method is presented. (JKS)

  12. Noninvasive diode laser activation of transient receptor potential proteins and nociceptors

    Science.gov (United States)

    Jiang, Nan; Cooper, Brian Y.; Nemenov, Michael I.

    2007-02-01

    We investigated diode laser (980 nm) evoked activation of transient receptor potential proteins (TRPV1 and TRPV2). C and A-delta (Aδ) nociceptor families are primarily responsible for pain mediation in the peripheral nervous system. TRPV1 proteins have been associated with heat evoked pain in C fibers while Aδ fibers have been associated with TRPV2. Diode laser stimulation allows a margin of safety between non-invasive activation and damage 19, 22, 34. Laser pulses (20-50 ms, 0.1-10 W, 980 nm) were used to stimulate: A) in vitro: excised patches from HEK293 cells expressing TRPV1; B) in vitro: rat DRG nociceptors expressing either TRPV1 or TRPV2; and C) in vivo: C-fibers of the rat saphenous nerve (SN) trunk. Cell currents were recorded using standard patch clamp methods. The SN was also stimulated electrically with bipolar electrodes. Stimulation (20-50 ms) of HEK and DRG cells expressing TRPV1 was highly reproducible. Activation and peak currents were achieved at estimated peak temperatures of 55°C and 70°C. Threshold activation was also observed in DRG neurons expressing TRPV2. The conduction velocity for laser-activated saphenous nerve afferents was in the C fiber range (0.5-1 m/s). Electrically stimulated nerve contained stimulation artifacts and complex neural components with conduction velocities ranging from 0.3-30 m/s. Diode laser activation of TRPV1 protein is a reproducible and effective means to probe TRP activity in both in vivo and in vitro preparations

  13. Transient receptor potential genes, smoking, occupational exposures and cough in adults

    Directory of Open Access Journals (Sweden)

    Smit Lidwien AM

    2012-03-01

    Full Text Available Abstract Background Transient receptor potential (TRP vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs in TRP genes and irritant exposures on cough. Methods Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA and the European Community Respiratory Health Survey (ECRHS. Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model. Results Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10-6 and usual cough (9-SNP haplotype: p-global = 4.5 × 10-6. Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p Conclusions TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.

  14. Transient Receptor Potential Ankyrin 1 Channel Involved in Atherosclerosis and Macrophage-Foam Cell Formation

    Science.gov (United States)

    Zhao, Jin-Feng; Shyue, Song-Kun; Kou, Yu Ru; Lu, Tse-Min; Lee, Tzong-Shyuan

    2016-01-01

    Transient receptor potential ankyrin 1 channel (TRPA1) plays an important role in the pathogenesis of inflammatory diseases, yet its role and the underlying mechanism in atherosclerosis remain unclear. We aimed to investigate the role of TRPA1 in atherosclerosis and foam-cell formation in vivo in mice and in vitro in mouse macrophages. Histopathology was examined by hematoxylin and eosin staining, levels of cytokines and lipid profile were evaluated by assay kits, and protein expression was determined by western blot analysis. TRPA1 expression was increased in macrophage foam cells in atherosclerotic aortas of apolipoprotein E-deficient (apoE-/-) mice. Atherosclerotic lesions, hyperlipidemia and systemic inflammation were worsened with chronic administration of the TRPA1 channel antagonist HC030031 or genetic ablation of TRPA1 (TRPA1-/-) in apoE-/- mice. Treatment with allyl isothiocyanate (AITC, a TRPA1 agonist) retarded the progression of atherosclerosis in apoE-/- mice but not apoE-/-TRPA1-/- mice. Mouse macrophages showed oxidized low-density lipoprotein (oxLDL) activated TRPA1 channels. OxLDL-induced lipid accumulation of macrophages was exacerbated by HC030031 or loss of function of TRPA1. Inhibition of TRPA1 activity did not alter oxLDL internalization but impaired cholesterol efflux by downregulating the ATP-binding cassette transporters. Furthermore, tumor necrosis factor-α-induced inflammatory response was attenuated in AITC-activated macrophages. TRPA1 may be a pivotal regulator in the pathogenesis of atherosclerosis and cholesterol metabolism of macrophage foam cells.

  15. The transient receptor potential vanilloid 4 channel modulates uterine tone during pregnancy.

    Science.gov (United States)

    Ying, Lihua; Becard, Margaux; Lyell, Deirdre; Han, Xiaoyuan; Shortliffe, Linda; Husted, Cristiana Iosef; Alvira, Cristina M; Cornfield, David N

    2015-12-23

    The importance of gaining insight into the mechanisms underlying uterine quiescence and contractility is highlighted by the absence of an effective strategy to prevent or treat preterm labor, the greatest cause of perinatal mortality and morbidity worldwide. Although current evidence suggests that in myometrial smooth muscle cells (mSMCs) calcium homeostasis is modulated near term to promote uterine contractility, the efficacy of blocking voltage-operated calcium channels is limited by dose-related cardiovascular side effects. Thus, we considered whether uterine contractility might be modulated by calcium entry via transient receptor potential vanilloid 4 (TRPV4) channels. In mSMC, TRPV4 gene and protein expression increased with gestation, and TRPV4-mediated Ca(2+) entry and contractility were increased in mSMC from pregnant compared to nonpregnant rats. Cell membrane TRPV4 expression was specifically increased, whereas the expression of β-arrestin-1 and β-arrestin-2, molecules that can sequester TRPV4 in the cytoplasm, decreased. Physical interaction of β-arrestin-2 and TRPV4 was apparent in nonpregnant, but absent in pregnant, mouse uterus. Moreover, direct pharmacologic activation of TRPV4 increased uterine contraction, but oxytocin-induced myometrial contraction was blocked by pharmacologic inhibition of TRPV4 and decreased in mice with global deletion of TRPV4. Finally, TRPV4 channel blockade prolonged pregnancy in two distinct in vivo murine models of preterm labor, whereas the absence of either β-arrestin-1 or β-arrestin-2 increased susceptibility to preterm labor. These data suggest that TRPV4 channel activity modulates uterine contractility and might represent a therapeutic target to address preterm labor. PMID:26702092

  16. Activation of mu opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1 via β-arrestin-2-mediated cross-talk.

    Directory of Open Access Journals (Sweden)

    Matthew P Rowan

    Full Text Available The transient receptor potential family V1 channel (TRPV1 is activated by multiple stimuli, including capsaicin, acid, endovanilloids, and heat (>42C. Post-translational modifications to TRPV1 result in dynamic changes to the sensitivity of receptor activation. We have previously demonstrated that β-arrestin2 actively participates in a scaffolding mechanism to inhibit TRPV1 phosphorylation, thereby reducing TRPV1 sensitivity. In this study, we evaluated the effect of β-arrestin2 sequestration by G-protein coupled receptors (GPCRs on thermal and chemical activation of TRPV1. Here we report that activation of mu opioid receptor by either morphine or DAMGO results in β-arrestin2 recruitment to mu opioid receptor in sensory neurons, while activation by herkinorin does not. Furthermore, treatment of sensory neurons with morphine or DAMGO stimulates β-arrestin2 dissociation from TRPV1 and increased sensitivity of the receptor. Conversely, herkinorin treatment has no effect on TRPV1 sensitivity. Additional behavioral studies indicate that GPCR-driven β-arrestin2 sequestration plays an important peripheral role in the development of thermal sensitivity. Taken together, the reported data identify a novel cross-talk mechanism between GPCRs and TRPV1 that may contribute to multiple clinical conditions.

  17. β-Catenin-dependent pathway activation by both promiscuous "canonical" WNT3a-, and specific "noncanonical" WNT4- and WNT5a-FZD receptor combinations with strong differences in LRP5 and LRP6 dependency.

    Science.gov (United States)

    Ring, Larisa; Neth, Peter; Weber, Christian; Steffens, Sabine; Faussner, Alexander

    2014-02-01

    The WNT/β-catenin signalling cascade is the best-investigated frizzled receptor (FZD) pathway, however, whether and how specific combinations of WNT/FZD and co-receptors LRP5 and LRP6 differentially affect this pathway are not well understood. This is mostly due to the fact that there are 19 WNTs, 10 FZDs and at least two co-receptors. In our attempt to identify the signalling capabilities of specific WNT/FZD/LRP combinations we made use of our previously reported TCF/LEF Gaussia luciferase reporter gene HEK293 cell line (Ring et al., 2011). Generation of WNT/FZD fusion constructs - but not their separate transfection - without or with additional isogenic overexpression of LRP5 and LRP6 in our reporter cells permitted the investigation of specific WNT/FZD/LRP combinations. The canonical WNT3a in fusion to almost all FZDs was able to induce β-catenin-dependent signalling with strong dependency on LRP6 but not LRP5. Interestingly, noncanonical WNT ligands, WNT4 and WNT5a, were also able to act "canonically" but only in fusion with specific FZDs and with selective dependence on LRP5 or LRP6. These data and extension of this experimental setup to the poorly characterized other WNTs should facilitate deeper insight into the complex WNT/FZD signalling system and its function. PMID:24269653

  18. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    Science.gov (United States)

    Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

    1999-10-01

    We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium. PMID:10490972

  19. Transient Receptor Potential Vanilloid 4 Inhibits γ-Aminobutyric Acid-Activated Current in Hippocampal Pyramidal Neurons

    Science.gov (United States)

    Hong, Zhiwen; Tian, Yujing; Qi, Mengwen; Li, Yingchun; Du, Yimei; Chen, Lei; Liu, Wentao; Chen, Ling

    2016-01-01

    The balance between excitatory and inhibitory neurotransmitter systems is crucial for the modulation of neuronal excitability in the central nervous system (CNS). The activation of transient receptor potential vanilloid 4 (TRPV4) is reported to enhance the response of hippocampal glutamate receptors, but whether the inhibitory neurotransmitter system can be regulated by TRPV4 remains unknown. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS. Here, we show that application of transient receptor potential vanilloid 4 (TRPV4) synthetic (GSK1016790A or 4α-PDD) or endogenous agonist (5,6-EET) inhibited GABA-activated current (IGABA) in hippocampal CA1 pyramidal neurons, which was blocked by specific antagonists of TRPV4 and of GABAA receptors. GSK1016790A increased the phosphorylated AMP-activated protein kinase (p-AMPK) and decreased the phosphorylated protein kinase B (p-Akt) protein levels, which was attenuated by removing extracellular calcium or by a calcium/calmodulin-dependent protein kinase kinase-β antagonist. GSK1016790A-induced decrease of p-Akt protein level was sensitive to an AMPK antagonist. GSK1016790A-inhibited IGABA was blocked by an AMPK antagonist or a phosphatidyl inositol 3 kinase (PI3K) agonist. GSK1016790A-induced inhibition of IGABA was also significantly attenuated by a protein kinase C (PKC) antagonist but was unaffected by protein kinase A or calcium/calmodulin-dependent protein kinase II antagonist. We conclude that activation of TRPV4 inhibits GABAA receptor, which may be mediated by activation of AMPK and subsequent down-regulation of PI3K/Akt signaling and activation of PKC signaling. Inhibition of GABAA receptors may account for the neuronal hyperexcitability caused by TRPV4 activation.

  20. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Ahern, Christopher A; Schwarz, Stephan K W

    2011-01-01

    BACKGROUND: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently...... has been shown to interact with and permeate these channels to produce nociceptive and sensory blockade in animals in vivo. However, little is known about the specific interactions between QX-314 and TRPV1 channels. Thus, the authors examined the mechanistic basis by which QX-314 acts on TRPV1...... channels. METHODS: The authors conducted an in vitro laboratory study in which they expressed TRPV1 and TRPV4 channels in Xenopus laevis oocytes and recorded cation currents with the two-electrode voltage clamp method. They used confocal microscopy for Ca²⁺ imaging in TRPV1 transient transfected tsA201...

  1. Canonical Correlation Forests

    OpenAIRE

    Rainforth, Tom; Wood, Frank

    2015-01-01

    We introduce canonical correlation forests (CCFs), a new decision tree ensemble method for classification. Individual canonical correlation trees are binary decision trees with hyperplane splits based on canonical correlation components. Unlike axis-aligned alternatives, the decision surfaces of CCFs are not restricted to the coordinate system of the input features and therefore more naturally represent data with correlation between the features. Additionally we introduce a novel alternative ...

  2. Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.

    Directory of Open Access Journals (Sweden)

    Alexander M Many

    Full Text Available The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.

  3. Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies

    OpenAIRE

    Lee, Jin Hee; Lee, Yoonji; Ryu, HyungChul; Kang, Dong Wook; Lee, Jeewoo; Lazar, Jozsef; Pearce, Larry V.; Pavlyukovets, Vladimir A.; Blumberg, Peter M.; Choi, Sun

    2011-01-01

    The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rTRPV1. We experimentally evaluated by mutational analysis the contribution of residues of rat TRPV1 (rTRPV1) contributing to ligand binding by th...

  4. 20-Hydroxyeicosatetraenoic Acid (20-HETE) Is a Novel Activator of Transient Receptor Potential Vanilloid 1 (TRPV1) Channel*

    OpenAIRE

    Wen, Hairuo; Östman, Johan; Bubb, Kristen J; Panayiotou, Catherine; Priestley, John V; Baker, Mark D.; Ahluwalia, Amrita

    2012-01-01

    TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid arachidonic acid. It is a powerful vasoconstrictor and has structural similarities with other TRPV1 agonists, e.g. the ...

  5. Extracellular quaternary ammonium blockade of transient receptor potential vanilloid subtype 1 channels expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Schwarz, Stephan K W;

    2012-01-01

    expressed in Xenopus laevis oocytes, whereas the neutral local anesthetic, benzocaine, does not, suggesting that a titratable amine is required for high-affinity inhibition. Consistent with this possibility, extracellular tetraethylammonium (TEA) and tetramethylammonium application produces potent, voltage......-dependent pore block. Alanine substitutions at Phe649 and Glu648, residues in the putative TRPV1 pore region, significantly abrogated the concentration-dependent TEA inhibition. The results suggest that large cations, shown previously to enter cells through activated transient receptor potential channels, can...

  6. Cannabinoid Type 1 Receptors Transiently Silence Glutamatergic Nerve Terminals of Cultured Cerebellar Granule Cells

    OpenAIRE

    Ramírez-Franco, Jorge; Bartolomé-Martín, David; Alonso, Beatris; Torres, Magdalena; Sánchez-Prieto, José

    2014-01-01

    Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclea...

  7. Calcium currents and transients of native and heterologously expressed mutant skeletal muscle DHP receptor alpha1 subunits (R528H)

    Science.gov (United States)

    Jurkat-Rott, K; Uetz, U; Pika-Hartlaub, U; Powell, J; Fontaine, B; Melzer, W; Lehmann-Horn, F

    1998-02-20

    Rabbit cDNA of the alpha1 subunit of the skeletal muscle dihydropyridine (DHP) receptor was functionally expressed in a muscular dysgenesis mouse (mdg) cell line, GLT. L-type calcium currents and transients were recorded for the wild type and a mutant alpha1 subunit carrying an R528H substitution in the supposed voltage sensor of the second channel domain that is linked to a human disease, hypokalemic periodic paralysis. L-type channels expressed in GLT myotubes exhibited currents similar to those described for primary cultured mdg cells injected with rabbit wild type cDNA, indicating this system to be useful for functional studies of heterologous DHP receptors. Voltage dependence and kinetics of activation and inactivation of L-type calcium currents from mutant and wild type channels did not differ significantly. Intracellular calcium release activation measured by fura-2 microfluorimetry was not grossly altered by the mutation either. Analogous measurements on myotubes of three human R528H carriers revealed calcium transients comparable to controls while the voltage dependence of both activation and inactivation of the L-type current showed a shift to more negative potentials of approximately 6 mV. Similar effects on the voltage dependence of the fast T-type current and changes in the expression level of the third-type calcium current point to factors not primarily associated with the mutation perhaps participating in disease pathogenesis. PMID:9512357

  8. Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons.

    Science.gov (United States)

    Weber, Martin; Motin, Leonid; Gaul, Simon; Beker, Friederike; Fink, Rainer H A; Adams, David J

    2005-01-01

    The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca(2+) concentration ([Ca(2+)](i)) and membrane currents were investigated in neonatal rat intracardiac neurons. In fura-2-loaded neurons, nAChR activation evoked a transient increase in [Ca(2+)](I), which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half-maximal concentration for thiopental inhibition of nAChR-induced [Ca(2+)](i) transients was 28 microM, close to the estimated clinical EC(50) (clinically relevant (half-maximal) effective concentration) of thiopental. In fura-2-loaded neurons, voltage clamped at -60 mV to eliminate any contribution of voltage-gated Ca(2+) channels, thiopental (25 microM) simultaneously inhibited nAChR-induced increases in [Ca(2+)](i) and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by approximately 40% at -120, -80 and -40 mV holding potential, indicating that the inhibition is voltage independent. The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC(50) were also shown to inhibit nAChR-induced increases in [Ca(2+)](i) by approximately 40%. Thiopental (25 muM) did not inhibit caffeine-, muscarine- or ATP-evoked increases in [Ca(2+)](i), indicating that inhibition of Ca(2+) release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely. Depolarization-activated Ca(2+) channel currents were unaffected in the presence of thiopental (25 microM), pentobarbital (50 microM) and ketamine (10 microM). In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and [Ca(2+)](i) transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions. PMID:15644873

  9. El canon literario peruano

    Directory of Open Access Journals (Sweden)

    Carlos García-Bedoya Maguiña

    2011-05-01

    Full Text Available Canon es un concepto clave en la historia literaria. En el presente artículo,se revisa la evolución histórica del canon literario peruano. Es solo con la llamada República Aristocrática, en las primeras décadas del siglo XX, que cabe hablar en el caso peruano de la formación de un auténtico canon nacional. El autor denomina a esta primera versión del canon literario peruano como canon oligárquico y destaca la importancia de la obra de Riva Agüero y de Ventura García Calderón en su configuración. Es solo más tarde, desde los años 20 y de modo definitivo desde los años 50, que puede hablarse de la emergencia de un nuevo canon literarioal que el autor propone determinar canon posoligárquico.

  10. Potentiation of the Transient Receptor Potential Vanilloid 1 Channel Contributes to Pruritogenesis in a Rat Model of Liver Disease*

    Science.gov (United States)

    Belghiti, Majedeline; Estévez-Herrera, Judith; Giménez-Garzó, Carla; González-Usano, Alba; Montoliu, Carmina; Ferrer-Montiel, Antonio; Felipo, Vicente; Planells-Cases, Rosa

    2013-01-01

    Persistent pruritus is a common disabling dermatologic symptom associated with different etiologic factors. These include primary skin conditions, as well as neuropathic, psychogenic, or systemic disorders like chronic liver disease. Defective clearance of potential pruritogenic substances that activate itch-specific neurons innervating the skin is thought to contribute to cholestatic pruritus. However, because the underlying disease-specific pruritogens and itch-specific neuronal pathways and mechanism(s) are unknown, symptomatic therapeutic intervention often leads to no or only limited success. In the current study, we aimed to first validate rats with bile duct ligation (BDL) as a model for hepatic pruritus and then to evaluate the contribution of inflammation, peripheral neuronal sensitization, and specific signaling pathways and subpopulations of itch-responsive neurons to scratching behavior and thermal hypersensitivity. Chronic BDL rats displayed enhanced scratching behavior and thermal hyperalgesia indicative of peripheral neuroinflammation. BDL-induced itch and hypersensitivity involved a minor contribution of histaminergic/serotonergic receptors, but significant activation of protein-activated receptor 2 (PAR2) receptors, prostaglandin PGE2 formation, and potentiation of transient receptor potential vanilloid 1 (TRPV1) channel activity. The sensitization of dorsal root ganglion nociceptors in BDL rats was associated with increased surface expression of PAR2 and TRPV1 proteins and an increase in the number of PAR2- and TRPV1-expressing peptidergic neurons together with a shift of TRPV1 receptor expression to medium sized dorsal root ganglion neurons. These results suggest that pruritus and hyperalgesia in chronic cholestatic BDL rats are associated with neuroinflammation and involve PAR2-induced TRPV1 sensitization. Thus, pharmacological modulation of PAR2 and/or TRPV1 may be a valuable therapeutic approach for patients with chronic liver pruritus

  11. Potentiation of the transient receptor potential vanilloid 1 channel contributes to pruritogenesis in a rat model of liver disease.

    Science.gov (United States)

    Belghiti, Majedeline; Estévez-Herrera, Judith; Giménez-Garzó, Carla; González-Usano, Alba; Montoliu, Carmina; Ferrer-Montiel, Antonio; Felipo, Vicente; Planells-Cases, Rosa

    2013-04-01

    Persistent pruritus is a common disabling dermatologic symptom associated with different etiologic factors. These include primary skin conditions, as well as neuropathic, psychogenic, or systemic disorders like chronic liver disease. Defective clearance of potential pruritogenic substances that activate itch-specific neurons innervating the skin is thought to contribute to cholestatic pruritus. However, because the underlying disease-specific pruritogens and itch-specific neuronal pathways and mechanism(s) are unknown, symptomatic therapeutic intervention often leads to no or only limited success. In the current study, we aimed to first validate rats with bile duct ligation (BDL) as a model for hepatic pruritus and then to evaluate the contribution of inflammation, peripheral neuronal sensitization, and specific signaling pathways and subpopulations of itch-responsive neurons to scratching behavior and thermal hypersensitivity. Chronic BDL rats displayed enhanced scratching behavior and thermal hyperalgesia indicative of peripheral neuroinflammation. BDL-induced itch and hypersensitivity involved a minor contribution of histaminergic/serotonergic receptors, but significant activation of protein-activated receptor 2 (PAR2) receptors, prostaglandin PGE2 formation, and potentiation of transient receptor potential vanilloid 1 (TRPV1) channel activity. The sensitization of dorsal root ganglion nociceptors in BDL rats was associated with increased surface expression of PAR2 and TRPV1 proteins and an increase in the number of PAR2- and TRPV1-expressing peptidergic neurons together with a shift of TRPV1 receptor expression to medium sized dorsal root ganglion neurons. These results suggest that pruritus and hyperalgesia in chronic cholestatic BDL rats are associated with neuroinflammation and involve PAR2-induced TRPV1 sensitization. Thus, pharmacological modulation of PAR2 and/or TRPV1 may be a valuable therapeutic approach for patients with chronic liver pruritus

  12. The Pyrexia transient receptor potential channel mediates circadian clock synchronization to low temperature cycles in Drosophila melanogaster

    Science.gov (United States)

    Wolfgang, Werner; Simoni, Alekos; Gentile, Carla; Stanewsky, Ralf

    2013-01-01

    Circadian clocks are endogenous approximately 24 h oscillators that temporally regulate many physiological and behavioural processes. In order to be beneficial for the organism, these clocks must be synchronized with the environmental cycles on a daily basis. Both light : dark and the concomitant daily temperature cycles (TCs) function as Zeitgeber (‘time giver’) and efficiently entrain circadian clocks. The temperature receptors mediating this synchronization have not been identified. Transient receptor potential (TRP) channels function as thermo-receptors in animals, and here we show that the Pyrexia (Pyx) TRP channel mediates temperature synchronization in Drosophila melanogaster. Pyx is expressed in peripheral sensory organs (chordotonal organs), which previously have been implicated in temperature synchronization. Flies deficient for Pyx function fail to synchronize their behaviour to TCs in the lower range (16–20°C), and this deficit can be partially rescued by introducing a wild-type copy of the pyx gene. Synchronization to higher TCs is not affected, demonstrating a specific role for Pyx at lower temperatures. In addition, pyx mutants speed up their clock after being exposed to TCs. Our results identify the first TRP channel involved in temperature synchronization of circadian clocks. PMID:23926145

  13. Canonical Information Analysis

    DEFF Research Database (Denmark)

    Vestergaard, Jacob Schack; Nielsen, Allan Aasbjerg

    2015-01-01

    Canonical correlation analysis is an established multivariate statistical method in which correlation between linear combinations of multivariate sets of variables is maximized. In canonical information analysis introduced here, linear correlation as a measure of association between variables is...... replaced by the information theoretical, entropy based measure mutual information, which is a much more general measure of association. We make canonical information analysis feasible for large sample problems, including for example multispectral images, due to the use of a fast kernel density estimator...... for entropy estimation. Canonical information analysis is applied successfully to (1) simple simulated data to illustrate the basic idea and evaluate performance, (2) fusion of weather radar and optical geostationary satellite data in a situation with heavy precipitation, and (3) change detection in...

  14. Canonical Big Operators

    OpenAIRE

    Bertot, Yves; Gonthier, Georges; Ould Biha, Sidi; Pasca, Ioana

    2008-01-01

    In this paper, we present an approach to describe uniformly iterated “big” operations and to provide lemmas that encapsulate all the commonly used reasoning steps on these constructs. We show that these iterated operations can be handled generically using the syntactic notation and canonical structure facilities provided by the Coq system. We then show how these canonical big operations played a crucial enabling role in the study of various parts of linear algebra and multi-dimensional real a...

  15. Expression of store-operated Ca2+ entry and transient receptor potential canonical and vanilloid-related proteins in rat distal pulmonary venous smooth muscle

    OpenAIRE

    Peng, Gongyong; Lu, Wenju; LI, XIAOYAN; Chen, Yuqin; Zhong, Nanshan; Ran, Pixin; Wang, Jian

    2010-01-01

    Chronic hypoxia causes remodeling and alters contractile responses in both pulmonary arteries and pulmonary veins. Although pulmonary arteries have been studied extensively in these disorders, the mechanisms by which pulmonary veins respond to hypoxia and whether these responses contribute to chronic hypoxic pulmonary hypertension remain poorly understood. In pulmonary arterial smooth muscle, we have previously demonstrated that influx of Ca2+ through store-operated calcium channels (SOCC) th...

  16. Transient receptor potential vanilloid type 1 receptor regulates glutamatergic synaptic inputs to the spinothalamic tract neurons of the spinal cord deep dorsal horn.

    Science.gov (United States)

    Kim, H; Cui, L; Kim, J; Kim, S J

    2009-05-01

    The spinothalamic tract (STT) neurons in the spinal dorsal horn play an important role in transmission and processing of nociceptive sensory information. Although transient receptor potential vanilloid type 1 (TRPV1) receptors are present in the spinal cord dorsal horn, their physiological function is not fully elucidated. In this study, we examined the role of TRPV1 in modulating neuronal activity of the STT neurons through excitatory and inhibitory synaptic inputs. Whole-cell patch-clamp recordings were performed on STT neurons labeled by a retrograde fluorescent tracer injected into the ventral posterior lateral (VPL) nucleus of the thalamus. Capsaicin (1 microM) increased the frequency of miniature excitatory postsynaptic currents (mEPSC) without changing the amplitude or decay time constant of mEPSC. In contrast, capsaicin had no distinct effect on GABAergic miniature inhibitory postsynaptic currents (mIPSC). Capsazepine (10 microM), a TRPV1 receptor antagonist, abolished the effect of capsaicin on mEPSCs. Capsazepine itself did not affect the baseline amplitude and frequency of mEPSC. The effect of capsaicin on mEPSC was also abolished by removal of external Ca(2+), but not by treatment with Cd(2+). Furthermore, capsaicin increased the firing activity of the STT neurons and this increase in neuronal activity by capsaicin was abolished in the presence of non-N-methyl-d-aspartic acid (NMDA) and NMDA receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and (R)-amino-5-phosphonovaleric acid (APV). These data suggest that activation of TRPV1 potentiates the glutamate release from excitatory terminals of primary afferent fibers and subsequently increases the neural activity of STT neurons of the rat spinal cord deep dorsal horn. PMID:19236908

  17. Evolution of vertebrate transient receptor potential vanilloid 3 channels: opposite temperature sensitivity between mammals and western clawed frogs.

    Directory of Open Access Journals (Sweden)

    Shigeru Saito

    2011-04-01

    Full Text Available Transient Receptor Potential (TRP channels serve as temperature receptors in a wide variety of animals and must have played crucial roles in thermal adaptation. The TRP vanilloid (TRPV subfamily contains several temperature receptors with different temperature sensitivities. The TRPV3 channel is known to be highly expressed in skin, where it is activated by warm temperatures and serves as a sensor to detect ambient temperatures near the body temperature of homeothermic animals such as mammals. Here we performed comprehensive comparative analyses of the TRPV subfamily in order to understand the evolutionary process; we identified novel TRPV genes and also characterized the evolutionary flexibility of TRPV3 during vertebrate evolution. We cloned the TRPV3 channel from the western clawed frog Xenopus tropicalis to understand the functional evolution of the TRPV3 channel. The amino acid sequences of the N- and C-terminal regions of the TRPV3 channel were highly diversified from those of other terrestrial vertebrate TRPV3 channels, although central portions were well conserved. In a heterologous expression system, several mammalian TRPV3 agonists did not activate the TRPV3 channel of the western clawed frog. Moreover, the frog TRPV3 channel did not respond to heat stimuli, instead it was activated by cold temperatures. Temperature thresholds for activation were about 16 °C, slightly below the lower temperature limit for the western clawed frog. Given that the TRPV3 channel is expressed in skin, its likely role is to detect noxious cold temperatures. Thus, the western clawed frog and mammals acquired opposite temperature sensitivity of the TRPV3 channel in order to detect environmental temperatures suitable for their respective species, indicating that temperature receptors can dynamically change properties to adapt to different thermal environments during evolution.

  18. Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status

    OpenAIRE

    Nakahara, Thiago S.; Cardozo, Leonardo M.; Ibarra-Soria, Ximena; Bard, Andrew D.; Carvalho, Vinicius M. A.; Trintinalia, Guilherme Z.; Logan, Darren W.; Papes, Fabio

    2016-01-01

    Background Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of ...

  19. Relations between canonical and non-canonical inflation

    Energy Technology Data Exchange (ETDEWEB)

    Gwyn, Rhiannon [Max-Planck-Institut fuer Gravitationsphysik (Albert-Einstein-Institut), Potsdam (Germany); Rummel, Markus [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Westphal, Alexander [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group

    2012-12-15

    We look for potential observational degeneracies between canonical and non-canonical models of inflation of a single field {phi}. Non-canonical inflationary models are characterized by higher than linear powers of the standard kinetic term X in the effective Lagrangian p(X,{phi}) and arise for instance in the context of the Dirac-Born-Infeld (DBI) action in string theory. An on-shell transformation is introduced that transforms non-canonical inflationary theories to theories with a canonical kinetic term. The 2-point function observables of the original non-canonical theory and its canonical transform are found to match in the case of DBI inflation.

  20. Relations between canonical and non-canonical inflation

    International Nuclear Information System (INIS)

    We look for potential observational degeneracies between canonical and non-canonical models of inflation of a single field φ. Non-canonical inflationary models are characterized by higher than linear powers of the standard kinetic term X in the effective Lagrangian p(X,φ) and arise for instance in the context of the Dirac-Born-Infeld (DBI) action in string theory. An on-shell transformation is introduced that transforms non-canonical inflationary theories to theories with a canonical kinetic term. The 2-point function observables of the original non-canonical theory and its canonical transform are found to match in the case of DBI inflation.

  1. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a novel activator of transient receptor potential vanilloid 1 (TRPV1) channel.

    Science.gov (United States)

    Wen, Hairuo; Östman, Johan; Bubb, Kristen J; Panayiotou, Catherine; Priestley, John V; Baker, Mark D; Ahluwalia, Amrita

    2012-04-20

    TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid arachidonic acid. It is a powerful vasoconstrictor and has structural similarities with other TRPV1 agonists, e.g. the hydroperoxyeicosatetraenoic acid 12-HPETE, and we hypothesized that it may be an endogenous ligand for TRPV1 in sensory neurons innervating the vasculature. Here, we demonstrate that 20-HETE both activates and sensitizes mouse and human TRPV1, in a kinase-dependent manner, involving the residue Ser(502) in heterologously expressed hTRPV1, at physiologically relevant concentrations. PMID:22389490

  2. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    DEFF Research Database (Denmark)

    Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W;

    2010-01-01

    feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies......Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the...... was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and...

  3. Rapid, Opioid-sensitive Mechanisms Involved in Transient Receptor Potential Vanilloid 1 Sensitization*S⃞

    OpenAIRE

    Vetter, Irina; Cheng, Wei; Peiris, Madusha; Wyse, Bruce D; Sarah J. Roberts-Thomson; Zheng, Jie; Monteith, Gregory R.; Cabot, Peter J.

    2008-01-01

    TRPV1 is a nociceptive, Ca2+-selective ion channel involved in the development of several painful conditions. Sensitization of TRPV1 responses by cAMP-dependent PKA crucially contributes to the development of inflammatory hyperalgesia. However, the pathways involved in potentiation of TRPV1 responses by cAMP-dependent PKA remain largely unknown. Using HEK cells stably expressing TRPV1 and the μ opioid receptor, we demonstrated that treatment with the adenylate cyclase ...

  4. Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels

    OpenAIRE

    Yao, Jing; Liu, Beiying; Qin, Feng

    2011-01-01

    The molecular basis of the thermal sensitivity of temperature-sensitive channels appears to arise from a specific protein domain rather than integration of global thermal effects. Using systematic chimeric analysis, we show that the N-terminal region that connects ankyrin repeats to the first transmembrane segment is crucial for temperature sensing in heat-activated vanilloid receptor channels. Changing this region both transformed temperature-insensitive isoforms into temperature-sensitive c...

  5. Co-administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis

    NARCIS (Netherlands)

    Charrua, A.; Cruz, C.D.; Jansen, D.; Rozenberg, B.; Heesakkers, J.P.; Cruz, F.

    2015-01-01

    OBJECTIVE: To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis. MATERIAL AND METHODS: TRPV4 expression in bladder afferents

  6. Effect of delta(9)-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans

    NARCIS (Netherlands)

    H. Beaumont; J. Jensen; A. Carlsson; M. Ruth; A. Lehmann; G.E. Boeckxstaens

    2009-01-01

    Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB(1)/CB(2) receptor agonist Delta(9)-tetrahydrocannabinol (Delta(9)-THC

  7. Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

    DEFF Research Database (Denmark)

    Mitrovic, Martina; Shahbazian, Anaid; Bock, Elisabeth; Pabst, Maria A; Holzer, Peter

    2010-01-01

    Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified...

  8. Agonist-dependence of functional properties for common nonsynonymous variants of human transient receptor potential vanilloid 1.

    Science.gov (United States)

    Wang, Sen; Joseph, John; Diatchenko, Luda; Ro, Jin Y; Chung, Man-Kyo

    2016-07-01

    Transient receptor potential vanilloid 1 (TRPV1) is a polymodal receptor activated by capsaicin, heat, and acid, which plays critical roles in thermosensation and pain. In addition, TRPV1 also contributes to multiple pathophysiological states in respiratory, cardiovascular, metabolic, and renal systems. These contributions are further supported by evidence that variations in the human TRPV1 (hTRPV1) gene are associated with various physiological and pathological phenotypes. However, it is not well understood how the variations in hTRPV1 affect channel functions. In this study, we examined functional consequences of amino acid variations of hTRPV1 induced by 5 nonsynonymous single-nucleotide polymorphisms (SNPs) that most commonly exist in the human population. Using electrophysiological assays in HEK293 cells, we examined 9 parameters: activation, Ca permeation, and desensitization after activation by capsaicin, acid, and heat. Our results demonstrated that the 5 SNPs differentially affected functional properties of hTRPV1 in an agonist-dependent manner. Based upon the directionality of change of each phenotype and cumulative changes in each SNP, we classified the 5 SNPs into 3 presumptive functional categories: gain of function (hTRPV1 Q85R, P91S, and T469I), loss of function (I585V), and mixed (M315I). These results reveal a spectrum of functional variation among common hTRPV1 polymorphisms in humans and may aid mechanistic interpretation of phenotypes associated with nonsynonymous hTRPV1 SNPs under pathophysiological conditions. PMID:26967694

  9. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

    Science.gov (United States)

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

    2009-04-01

    The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals. PMID:19036859

  10. Canonical field theory

    Science.gov (United States)

    You, Setthivoine

    2015-11-01

    A new canonical field theory has been developed to help interpret the interaction between plasma flows and magnetic fields. The theory augments the Lagrangian of general dynamical systems to rigourously demonstrate that canonical helicity transport is valid across single particle, kinetic and fluid regimes, on scales ranging from classical to general relativistic. The Lagrangian is augmented with two extra terms that represent the interaction between the motion of matter and electromagnetic fields. The dynamical equations can then be re-formulated as a canonical form of Maxwell's equations or a canonical form of Ohm's law valid across all non-quantum regimes. The field theory rigourously shows that helicity can be preserved in kinetic regimes and not only fluid regimes, that helicity transfer between species governs the formation of flows or magnetic fields, and that helicity changes little compared to total energy only if density gradients are shallow. The theory suggests a possible interpretation of particle energization partitioning during magnetic reconnection as canonical wave interactions. This work is supported by US DOE Grant DE-SC0010340.

  11. Unique Responses are Observed in Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPA1 and TRPV1) Co-Expressing Cells

    OpenAIRE

    Sadofsky, Laura R; Sreekrishna, Koti T.; Yakang Lin; Renee Schinaman; Kate Gorka; Yogita Mantri; John Christian Haught; Thomas G. Huggins; Isfort, Robert J.; Charles C. Bascom; Morice, Alyn H

    2014-01-01

    Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are implicated in modulation of cough and nociception. In vivo, TRPA1 and TRPV1 are often co-expressed in neurons and TRPA1V1 hetero-tetramer formation is noted in cells co-transfected with the respective expression plasmids. In order to understand the impact of TRP receptor interaction on activity, we created stable cell lines expressing the TRPA1, TRPV1 and co-expressing the TRPA1 and TRPV1 (TRPA1V1) rece...

  12. Canonical affordances in context

    Directory of Open Access Journals (Sweden)

    Alan Costall

    2012-12-01

    Full Text Available James Gibson’s concept of affordances was an attempt to undermine the traditional dualism of the objective and subjective. Gibson himself insisted on the continuity of “affordances in general” and those attached to human artifacts. However, a crucial distinction needs to be drawn between “affordances in general” and the “canonical affordances” that are connected primarily to artifacts. Canonical affordances are conventional and normative. It is only in such cases that it makes sense to talk of the affordance of the object. Chairs, for example, are for sitting-on, even though we may also use them in many other ways. A good deal of confusion has arisen in the discussion of affordances from (1 the failure to recognize the normative status of canonical affordances and (2 then generalizing from this special case.

  13. Canonical variate regression.

    Science.gov (United States)

    Luo, Chongliang; Liu, Jin; Dey, Dipak K; Chen, Kun

    2016-07-01

    In many fields, multi-view datasets, measuring multiple distinct but interrelated sets of characteristics on the same set of subjects, together with data on certain outcomes or phenotypes, are routinely collected. The objective in such a problem is often two-fold: both to explore the association structures of multiple sets of measurements and to develop a parsimonious model for predicting the future outcomes. We study a unified canonical variate regression framework to tackle the two problems simultaneously. The proposed criterion integrates multiple canonical correlation analysis with predictive modeling, balancing between the association strength of the canonical variates and their joint predictive power on the outcomes. Moreover, the proposed criterion seeks multiple sets of canonical variates simultaneously to enable the examination of their joint effects on the outcomes, and is able to handle multivariate and non-Gaussian outcomes. An efficient algorithm based on variable splitting and Lagrangian multipliers is proposed. Simulation studies show the superior performance of the proposed approach. We demonstrate the effectiveness of the proposed approach in an [Formula: see text] intercross mice study and an alcohol dependence study. PMID:26861909

  14. The canonical and grand canonical models for nuclear multifragmentation

    Indian Academy of Sciences (India)

    G Chaudhuri; S Das Gupta

    2010-08-01

    Many observables seen in intermediate energy heavy-ion collisions can be explained on the basis of statistical equilibrium. Calculations based on statistical equilibrium can be implemented in microcanonical ensemble, canonical ensemble or grand canonical ensemble. This paper deals with calculations with canonical and grand canonical ensembles. A recursive relation developed recently allows calculations with arbitrary precision for many nuclear problems. Calculations are done to study the nature of phase transition in nuclear matter.

  15. CB1 cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substande P release in cultured rat dorsal root ganglion cells

    OpenAIRE

    Ohshita, Kyoko

    2005-01-01

    Cannabinoids have been reported to have analgesic properties in animals of acute nociception or of inflammatory and neuropathic pain models, but the mechanisms by which they exert such alleviative effects are not yet fully understood. We investigated whether the CB1- cannabinoid-receptor agonist HU210 modulates the capsaicin-induced 45Ca2+ influx and substance P like-immunoreactivity (SPLI) release in cultured rat dorsal root ganglion (DRG) cells. HU210 attenuated the capsaicin-induced 45Ca2+...

  16. Quaternion Linear Canonical Transform Application

    OpenAIRE

    Bahri, Mawardi

    2015-01-01

    Quaternion linear canonical transform (QLCT) is a generalization of the classical linear canonical transfom (LCT) using quaternion algebra. The focus of this paper is to introduce an application of the QLCT to study of generalized swept-frequency filter

  17. Realizations of the Canonical Representation

    Indian Academy of Sciences (India)

    M K Vemuri

    2008-02-01

    A characterisation of the maximal abelian subalgebras of the bounded operators on Hilbert space that are normalised by the canonical representation of the Heisenberg group is given. This is used to classify the perfect realizations of the canonical representation.

  18. The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity.

    Science.gov (United States)

    Iordanov, Iordan; Mihályi, Csaba; Tóth, Balázs; Csanády, László

    2016-01-01

    Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s(-1)), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 μM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies. PMID:27383051

  19. Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange

    Science.gov (United States)

    Weissmann, Norbert; Dietrich, Alexander; Fuchs, Beate; Kalwa, Hermann; Ay, Mahmut; Dumitrascu, Rio; Olschewski, Andrea; Storch, Ursula; Mederos y Schnitzler, Michael; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo; Pinkenburg, Olaf; Seeger, Werner; Grimminger, Friedrich; Gudermann, Thomas

    2006-01-01

    Regional alveolar hypoxia causes local vasoconstriction in the lung, shifting blood flow from hypoxic to normoxic areas, thereby maintaining gas exchange. This mechanism is known as hypoxic pulmonary vasoconstriction (HPV). Disturbances in HPV can cause life-threatening hypoxemia whereas chronic hypoxia triggers lung vascular remodeling and pulmonary hypertension. The signaling cascade of this vitally important mechanism is still unresolved. Using transient receptor potential channel 6 (TRPC6)-deficient mice, we show that this channel is a key regulator of acute HPV as this regulatory mechanism was absent in TRPC6−/− mice whereas the pulmonary vasoconstrictor response to the thromboxane mimetic U46619 was unchanged. Accordingly, induction of regional hypoventilation resulted in severe arterial hypoxemia in TRPC6−/− but not in WT mice. This effect was mirrored by a lack of hypoxia-induced cation influx and currents in smooth-muscle cells from precapillary pulmonary arteries (PASMC) of TRPC6−/− mice. In both WT and TRPC6−/− PASMC hypoxia caused diacylglycerol (DAG) accumulation. DAG seems to exert its action via TRPC6, as DAG kinase inhibition provoked a cation influx only in WT but not in TRPC6−/− PASMC. Notably, chronic hypoxia-induced pulmonary hypertension was independent of TRPC6 activity. We conclude that TRPC6 plays a unique and indispensable role in acute hypoxic pulmonary vasoconstriction. Manipulation of TRPC6 function may thus offer a therapeutic strategy for the control of pulmonary hemodynamics and gas exchange. PMID:17142322

  20. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling

    DEFF Research Database (Denmark)

    Adams, T E; Hansen, J A; Starr, R;

    1998-01-01

    Four members (SOCS-1, SOCS-2, SOCS-3, and CIS) of a family of cytokine-inducible, negative regulators of cytokine receptor signaling have recently been identified. To address whether any of these genes are induced in response to growth hormone (GH), serum-starved 3T3-F442A fibroblasts were...... incubated with GH for various time points, and the expression of the SOCS gene family was analyzed by Northern blotting. GH stimulated the rapid, transient induction of SOCS-3 mRNA, peaking 30 min after the initiation of GH exposure and declining to basal levels by 2 h. Expression of the other SOCS genes...... (SOCS-1, SOCS-2, CIS) was also up-regulated by GH, although to a lesser extent than SOCS-3 and with differing kinetics. SOCS-3 expression was also strongly induced in 3T3-F442A cells treated with leukemia-inhibitory factor (LIF), with weaker induction of SOCS-1 and CIS being observed. The preferential...

  1. Expression and cellular distribution of transient receptor potential vanilloid 4 in cortical tubers of the tuberous sclerosis complex.

    Science.gov (United States)

    Chen, Xin; Yang, Meihua; Sun, Feiji; Liang, Chao; Wei, Yujia; Wang, Lukang; Yue, Jiong; Chen, Bing; Li, Song; Liu, Shiyong; Yang, Hui

    2016-04-01

    Cortical tubers in patients with tuberous sclerosis complex (TSC) are highly associated with intractable epilepsy. Recent evidence has shown that transient receptor potential vanilloid 4 (TRPV4) has direct effects on both neurons and glial cells. To understand the role of TRPV4 in pathogenesis of cortical tubers, we investigated the expression patterns of TRPV4 in cortical tubers of TSC compared with normal control cortex (CTX). We found that TRPV4 was clearly up-regulated in cortical tubers at the protein levels. Immunostaining indicated that TRPV4 was specially distributed in abnormal cells, including dysplastic neurons (DNs) and giant cells (GCs). In addition, double immunofluorescent staining revealed that TRPV4 was localized on neurofilament proteins (NF200) positive neurons and glial fibrillary acidic portein (GFAP) positive reactive astrocytes. Moreover, TRPV4 co-localized with both glutamatergic and GABAergic neurons. Furthermore, protein levels of protein kinase C (PKC), but not protein kinase A (PKA), the important upstream factors of the TRPV4, were significantly increased in cortical tubers. Taken together, the overexpression and distribution patterns of TRPV4 may be linked with the intractable epilepsy caused by TSC. PMID:26874068

  2. Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

    Directory of Open Access Journals (Sweden)

    Chi-Ming Lee

    2013-01-01

    Full Text Available Rutaecarpine (RUT, the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT, which showed no cytotoxicity at 20 μM. Br-RUT suppressed nitric oxide (NO production and tumor necrosis factor-α release in concentration-dependent (0~20 μM manners in lipopolysaccharide (LPS-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.

  3. Rhythmic canons and modular tiling

    OpenAIRE

    Caure, Hélianthe

    2016-01-01

    This thesis is a contribution to the study of modulo p tiling. Many mathematical and computational tools were used for the study of rhythmic tiling canons. Recent research has mainly focused in finding tiling without inner periodicity, being called Vuza canons. Those canons are a constructive basis for all rhythmic tiling canons, however, they are really difficult to obtain. Best current method is a brut force exploration that, despite a few recent enhancements, is exponential. Many technics ...

  4. Canonical quantization of macroscopic electromagnetism

    OpenAIRE

    Philbin, Thomas Gerard

    2010-01-01

    Application of the standard canonical quantization rules of quantum field theory to macroscopic electromagnetism has encountered obstacles due to material dispersion and absorption. This has led to a phenomenological approach to macroscopic quantum electrodynamics where no canonical formulation is attempted. In this paper macroscopic electromagnetism is canonically quantized. The results apply to any linear, inhomogeneous, magnetodielectric medium with dielectric functions that obey the Krame...

  5. Revisiting Canonical Quantization

    OpenAIRE

    Klauder, John R.

    2012-01-01

    Conventional canonical quantization procedures directly link various c-number and q-number quantities. Here, we advocate a different association of classical and quantum quantities that renders classical theory a natural subset of quantum theory with \\hbar>0, in conformity with the real world wherein nature has chosen \\hbar>0 rather than \\hbar=0. While keeping the good results of conventional procedures, some examples are presented for which the new procedures offer better results than conven...

  6. Canonical Infinitesimal Deformations

    OpenAIRE

    Ran, Ziv

    1998-01-01

    This paper gives a canonical construction, in terms of additive cohomological functors, of the universal formal deformation of a compact complex manifold without vector fields (more generally of a faithful $g$-module, where $g$ is a sheaf of Lie algebras without sections). The construction is based on a certain (multivariate) Jacobi complex $J(g)$ associatd to $g$: indeed ${\\mathbb C}\\oplus {\\mathbb H}^0(J(g))^*$ is precisely the base ring of the universal deformation.

  7. Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory

    OpenAIRE

    Wanner, Samuel P.; Garami, Andras; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Coimbra, Cândido C.; Romanovsky, Andrej A

    2012-01-01

    Studies in young rodents have shown that the transient receptor potential vanilloid-1 (TRPV1) channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)α and possibly by other mechanisms. We asked whether the anti-inflammatory role of TRPV1 changes with age. First, we studied the effect of AMG517, a selective and potent TRPV1 antagonist, on aseptic, lipopolysaccharide (LPS)-induced SIRS in young (12 wk) mice. ...

  8. Transient receptor potential cation channel subfamily V member 1 expressing corneal sensory neurons can be subdivided into at least three subpopulations

    OpenAIRE

    Abdulhakeem eAlamri; Romke eBron; James Alexander Brock; Jason eIvanusic

    2015-01-01

    The cornea is innervated by three main functional classes of sensory neurons: polymodal nociceptors, pure mechano-nociceptors and cold-sensing neurons. Here we explored transient receptor potential cation channel subfamily V member 1 (TRPV1) expression in guinea pig corneal sensory neurons, a widely used molecular marker of polymodal nociceptors. We used retrograde tracing to identify corneal afferent neurons in the trigeminal ganglion (TG) and double label in situ hybridization and/or immuno...

  9. Osmosensitivity of transient receptor potential vanilloid 1 is synergistically enhanced by distinct activating stimuli such as temperature and protons.

    Directory of Open Access Journals (Sweden)

    Eri Nishihara

    Full Text Available In animals, body-fluid osmolality is continuously monitored to keep it within a narrow range around a set point (∼300 mOsm/kg. Transient receptor potential vanilloid 1 (TRPV1, a cation channel, has been implicated in body-fluid homeostasis in vivo based on studies with the TRPV1-knockout mouse. However, the response of TRPV1 to hypertonic stimuli has not been demonstrated with heterologous expression systems so far, despite intense efforts by several groups. Thus, the molecular entity of the hypertonic sensor in vivo still remains controversial. Here we found that the full-length form of TRPV1 is sensitive to an osmotic increase exclusively at around body temperature using HEK293 cells stably expressing rat TRPV1. At an ambient temperature of 24°C, a slight increase in the intracellular calcium concentration ([Ca(2+](i was rarely observed in response to hypertonic stimuli. However, the magnitude of the osmosensitive response markedly increased with temperature, peaking at around 36°C. Importantly, the response at 36°C showed a robust increase over a hypertonic range, but a small decrease over a hypotonic range. A TRPV1 antagonist, capsazepine, and a nonspecific TRP channel inhibitor, ruthenium red, completely blocked the increase in [Ca(2+](i. These results endorse the view that the full-length form of TRPV1 is able to function as a sensor of hypertonic stimuli in vivo. Furthermore, we found that protons and capsaicin likewise synergistically potentiated the response of TRPV1 to hypertonic stimuli. Of note, HgCl(2, which blocks aquaporins and inhibits cell-volume changes, significantly reduced the osmosensitive response. Our findings thus indicate that TRPV1 integrates multiple different types of activating stimuli, and that TRPV1 is sensitive to hypertonic stimuli under physiologically relevant conditions.

  10. Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells.

    Science.gov (United States)

    Ikari, Akira; Sanada, Ayumi; Sawada, Hayato; Okude, Chiaki; Tonegawa, Chie; Sugatani, Junko

    2011-06-01

    Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is used in treatments for transplantation and cancer. Rapamycin causes hypomagnesemia, although precisely how has not been examined. Here, we investigated the effect of rapamycin on the expression of transient receptor potential melastatin 6 (TRPM6), a Mg2+ channel. Rapamycin and LY-294002, an inhibitor of phosphatidilinositol-3 kinase (PI3K) located upstream of mTOR, inhibited epidermal growth factor (EGF)-induced expression of the TRPM6 protein without affecting TRPM7 expression in rat renal NRK-52E epithelial cells. Both rapamycin and LY-294002 decreased EGF-induced Mg2+ influx. U0126, a MEK inhibitor, inhibited EGF-induced increases in c-Fos, p-ERK, and TRPM6 levels. In contrast, neither rapamycin nor LY-294002 inhibited EGF-induced increases in p-ERK and c-Fos levels. EGF increased p-Akt level, an effect inhibited by LY-294002 and 1L-6-hydroxymethyl-chiro-inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate] (Akt inhibitor). Akt inhibitor decreased TRPM6 level similar to rapamycin and LY-294002. These results suggest that a PI3K/Akt/mTOR pathway is involved in the regulation of TRPM6 expression. Rapamycin inhibited the EGF-induced increase in TRPM6 mRNA but did not inhibit human TRPM6 promoter activity. In the presence of actinomycin D, a transcriptional inhibitor, rapamycin accelerated the decrease in TRPM6 mRNA. Rapamycin decreased the expression and activity of a luciferase linked with the 3'-untranslated region of human TRPM6 mRNA. These results suggest that TRPM6 expression is up-regulated by a PI3K/Akt/mTOR pathway and rapamycin reduces TRPM6 mRNA stability, resulting in a decrease in the reabsorption of Mg2+. PMID:21073857

  11. Endotoxin Induces Fibrosis in Vascular Endothelial Cells through a Mechanism Dependent on Transient Receptor Protein Melastatin 7 Activity

    Science.gov (United States)

    Echeverría, Cesar; Montorfano, Ignacio; Hermosilla, Tamara; Armisén, Ricardo; Velásquez, Luis A.; Cabello-Verrugio, Claudio; Varela, Diego; Simon, Felipe

    2014-01-01

    The pathogenesis of systemic inflammatory diseases, including endotoxemia-derived sepsis syndrome, is characterized by endothelial dysfunction. It has been demonstrated that the endotoxin lipopolysaccharide (LPS) induces the conversion of endothelial cells (ECs) into activated fibroblasts through endothelial­to­mesenchymal transition mechanism. Fibrogenesis is highly dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the specific molecular identity of the calcium channel that mediates the Ca2+ influx during endotoxin-induced endothelial fibrosis is still unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel that is expressed in many cell types, including ECs. TRPM7 is involved in a number of crucial processes such as the conversion of fibroblasts into activated fibroblasts, or myofibroblasts, being responsible for the development of several characteristics of them. However, the role of the TRPM7 ion channel in endotoxin-induced endothelial fibrosis is unknown. Thus, our aim was to study whether the TRPM7 calcium channel participates in endotoxin-induced endothelial fibrosis. Using primary cultures of ECs, we demonstrated that TRPM7 is a crucial protein involved in endotoxin-induced endothelial fibrosis. Suppression of TRPM7 expression protected ECs from the fibrogenic process stimulated by endotoxin. Downregulation of TRPM7 prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase in ECs. In addition, TRPM7 downregulation abolished the endotoxin-induced increase in ECM proteins in ECs. Furthermore, we showed that intracellular Ca2+ levels were greatly increased upon LPS challenge in a mechanism dependent on TRPM7 expression. These results demonstrate that TRPM7 is a key protein involved in the mechanism underlying endotoxin-induced endothelial fibrosis. PMID:24710004

  12. Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision.

    Science.gov (United States)

    Agosto, Melina A; Zhang, Zhixian; He, Feng; Anastassov, Ivan A; Wright, Sara J; McGehee, Jennifer; Wensel, Theodore G

    2014-09-26

    Transient receptor potential melastatin-1 (TRPM1) is essential for the light-induced depolarization of retinal ON bipolar cells. TRPM1 likely forms a multimeric channel complex, although almost nothing is known about the structure or subunit composition of channels formed by TRPM1 or any of its close relatives. Recombinant TRPM1 was robustly expressed in insect cells, but only a small fraction was localized to the plasma membrane. Similar intracellular localization was observed when TRPM1 was heterologously expressed in mammalian cells. TRPM1 was affinity-purified from Sf9 cells and complexed with amphipol, followed by detergent removal. In blue native gels and size exclusion chromatography, TRPM1 migrated with a mobility consistent with detergent- or amphipol-bound dimers. Cross-linking experiments were also consistent with a dimeric subunit stoichiometry, and cryoelectron microscopy and single particle analysis without symmetry imposition yielded a model with approximate 2-fold symmetrical features. Finally, electron microscopy of TRPM1-antibody complexes revealed a large particle that can accommodate TRPM1 and two antibody molecules. Taken together, these data indicate that purified TRPM1 is mostly dimeric. The three-dimensional structure of TRPM1 dimers is characterized by a small putative transmembrane domain and a larger domain with a hollow cavity. Blue native gels of solubilized mouse retina indicate that TRPM1 is present in two distinct complexes: one similar in size to the recombinant protein and one much larger. Because dimers are likely not functional ion channels, these results suggest that additional partner subunits participate in forming the transduction channel required for dim light vision and the ON pathway. PMID:25112866

  13. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    Directory of Open Access Journals (Sweden)

    Schneider Andreas

    2010-10-01

    Full Text Available Abstract Background The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1 agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human. The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results Screening: Dihydrocapsaicin (DHC, a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

  14. Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn.

    Directory of Open Access Journals (Sweden)

    Yun Sook Kim

    Full Text Available Transient receptor potential melastatin 8 (TRPM8 ion channels mediate the detection of noxious and innocuous cold and are expressed by primary sensory neurons, but little is known about the processing of the TRPM8-mediated cold information within the trigeminal sensory nuclei (TSN and the spinal dorsal horn (DH. To address this issue, we characterized TRPM8-positive (+ neurons in the trigeminal ganglion and investigated the distribution of TRPM8+ axons and terminals, and their synaptic organization in the TSN and in the DH using light and electron microscopic immunohistochemistry in transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. TRPM8 was expressed in a fraction of small myelinated primary afferent fibers (23.7% and unmyelinated fibers (76.3%, suggesting that TRPM8-mediated cold is conveyed via C and Aδ afferents. TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, which dominantly receive sensory afferents from intra- and peri-oral structures and from the face, respectively. While synaptic boutons arising from Aδ and non-peptidergic C afferents usually receive many axoaxonic contacts and form complex synaptic arrangements, TRPM8+ boutons arising from afferents of the same classes of fibers showed a unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. These findings suggest that TRPM8-mediated cold is conveyed via a specific subset of C and Aδ afferent neurons and is processed in a unique manner and differently in the TSN and DH.

  15. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

    Science.gov (United States)

    Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

    2014-06-27

    Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. PMID:24811179

  16. Extracellular ATP-induced nuclear Ca{sup 2+} transient is mediated by inositol 1,4,5-trisphosphate receptors in mouse pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zheng; Li, Zhengzheng; Peng, Gong; Chen, Xiaoli; Yin, Wenxuan [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Kotlikoff, Michael I. [Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States); Yuan, Zeng-qiang, E-mail: zqyuan@sun5.ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China); Ji, Guangju, E-mail: gj28@ibp.ac.cn [National Laboratory of Biomacromolecules, Institute of Biophysics of Chinese Academy of Sciences, 15 Datun Rd., Beijing 100101 (China)

    2009-05-01

    Extracellular ATP (eATP) induces an intracellular Ca{sup 2+} transient by activating phospholipase C (PLC)-associated P2X4 purinergic receptors, leading to production of inositol 1,4,5-trisphosphate (IP3) and subsequent Ca{sup 2+} release from intracellular stores in mouse pancreatic {beta}-cells. Using laser scanning confocal microscopy, Ca{sup 2+} indicator fluo-4 AM, and the cell permeable nuclear indicator Hoechst 33342, we examined the properties of eATP-induced Ca{sup 2+} release in pancreatic {beta}-cell nuclei. eATP induced a higher nuclear Ca{sup 2+} transient in pancreatic {beta}-cell nuclei than in the cytosol. After pretreatment with thapsigargin (TG), an inhibitor of sarco-endoplasmic reticulum Ca{sup 2+}-ATPase (SERCA) pumps, the amplitude of eATP-induced Ca{sup 2+} transients in the nucleus was still much higher than those in the cytosol. This effect of eATP was not altered by inhibition of either the plasma membrane Ca{sup 2+}-ATPase (PMCA) or the plasma membrane Na{sup +}/Ca{sup 2+} exchanger (NCX) by LaCl{sub 3} or by replacement of Na{sup +} with N-Methyl-Glucosamine. eATP-induced nuclear Ca{sup 2+} transients were abolished by a cell-permeable IP3R inhibitor, 2-aminoethoxydiphenyl borate (2-APB), but were not blocked by the ryanodine receptor (RyR) antagonist ryanodine. Immunofluorescence studies showed that IP3Rs are expressed on the nuclear envelope of pancreatic {beta}-cells. These results indicate that eATP triggers nuclear Ca{sup 2+} transients by mobilizing a nuclear Ca{sup 2+} store via nuclear IP3Rs.

  17. [Epilepsy and Canon Law].

    Science.gov (United States)

    Bonduelle, M

    1987-01-01

    The Canon Law (Codex Iuris Canonici), promulgated in 1917, was a classification of laws and jurisprudence which ruled the early Church, governed the ecclesiastical condition of Roman Church until its reorganisation in 1983. It forbade to be ordained or to exercise orders already received to "those who are or were epileptics either not quite in their right mind or possessed by the Evil One". All the context and in particular the paragraph which treated of bodily lacks, indicated that between these three conditions, there was juxtaposition and no confusion. The texts specified the foundations of these dispositions, not in a malefic view of epilepsy inherited from Morbus Sacer of Antiquity, but in decency and on account of risk incured by Eucharist in case of fit. Some derogations could attenuate the severity of these dispositions--as jurisprudence had taken progresses of Epileptology and therapeutics into consideration. In the new Code of Canon Law (1983) physical disabilities were removed from the text and also possessed evil and epilepsy, the only impediment being "insanity or other psychic defect" appreciation of which is done by experts. Concerning poorly controlled epilepsies, we believe that experts will be allowed to express their opinion and a new jurisprudence will make up for the silence of the law. PMID:3310183

  18. NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.

    Science.gov (United States)

    Mukherjea, Debashree; Jajoo, Sarvesh; Sheehan, Kelly; Kaur, Tejbeer; Sheth, Sandeep; Bunch, Jennifer; Perro, Christopher; Rybak, Leonard P; Ramkumar, Vickram

    2011-03-15

    Transient receptor potential vanilloid 1 (TRPV1) is implicated in cisplatin ototoxicity. Activation of this channel by cisplatin increases reactive oxygen species generation, which contribute to loss of outer hair cells in the cochlea. Knockdown of TRPV1 by short interfering RNA protected against cisplatin ototoxicity. In this study, we examined the mechanism underlying TRPV1-mediated ototoxicity using cultured organ of Corti transformed cells (UB/OC-1) and rats. Trans-tympanic injections of capsaicin produced transient hearing loss within 24 h, which recovered by 72 h. In UB/OC-1 cells, capsaicin increased NOX3 NADPH oxidase activity and activation of signal transducer and activator of transcription 1 (STAT1). Intratympanic administration of capsaicin transiently increased STAT1 activity and expression of downstream proinflammatory molecules. Capsaicin produced a transient increase in CD14-positive inflammatory cells into the cochlea, which mimicked the temporal course of STAT1 activation but did not alter the expression of apoptotic genes or damage to outer hair cells. In addition, trans-tympanic administration of STAT1 short interfering RNA protected against capsaicin-induced hearing loss. These data suggest that activation of TRPV1 mediates temporary hearing loss by initiating an inflammatory process in the cochlea via activation of NOX3 and STAT1. Thus, these proteins represent reasonable targets for ameliorating hearing loss. PMID:20712533

  19. Regularized Generalized Canonical Correlation Analysis

    Science.gov (United States)

    Tenenhaus, Arthur; Tenenhaus, Michel

    2011-01-01

    Regularized generalized canonical correlation analysis (RGCCA) is a generalization of regularized canonical correlation analysis to three or more sets of variables. It constitutes a general framework for many multi-block data analysis methods. It combines the power of multi-block data analysis methods (maximization of well identified criteria) and…

  20. Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor β-subunit: an animal model of startle disease

    OpenAIRE

    Becker, Lore; Hartenstein, Bettina; Schenkel, Johannes; Kuhse, Jochen; Betz, Heinrich; Weiher, Hans

    2000-01-01

    Startle disease or hereditary hyperekplexia has been shown to result from mutations in the α1-subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss-of-function mutations of GlyR α or β-subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into th...

  1. Antipruritic effect of cold-induced and transient receptor potential-agonist-induced counter-irritation on histaminergic itch in humans

    DEFF Research Database (Denmark)

    Andersen, Hjalte H.; Melholt, Camilla; Hilborg, Sigurd D.; Jerwiarz, Anne; Randers, Amalie; Simoni, Amalie; Elberling, Jesper; Arendt-Nielsen, Lars

    2016-01-01

    A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists...... (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheal and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-testing lancets. Recorded outcome-parameters were itch intensity, wheal reactions and neurogenic......-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p < 0.05). Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value....

  2. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Chu Ketan

    2012-04-01

    Full Text Available Abstract Background Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R injury. The P2X7 receptor (P2X7R has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Methods Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG, adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL. In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. Results The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg and A-0438079 (3 μg, and a low dosage of OxATP (1 μg significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Conclusions Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of

  3. Transient expression of functional serotonin 5-HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum

    NARCIS (Netherlands)

    M. Oostland; J. Sellmeijer; J.A. van Hooft

    2011-01-01

    The serotonin 5-HT3 receptor is the only ligand-gated ion channel activated by serotonin and is expressed by GABAergic interneurons in many brain regions, including the cortex, amygdala and hippocampus. Furthermore, 5-HT3 receptors are expressed by glutamatergic Cajal-Retzius cells in the cerebral c

  4. Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.

    Science.gov (United States)

    Zhou, Hui-Ren; Pestka, James J

    2015-06-01

    Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models. PMID:25787141

  5. Canonical versus grand canonical treatment of the conservation laws

    International Nuclear Information System (INIS)

    The differences between the canonical and the grand canoncial treatment of the conservation laws in the relativistic statistical thermodynamics are discussed. The possible implications on the thermodynamics description of hadronic matter created in particle or ion collisions are considered

  6. Canonical phylogenetic ordination.

    Science.gov (United States)

    Giannini, Norberto P

    2003-10-01

    A phylogenetic comparative method is proposed for estimating historical effects on comparative data using the partitions that compose a cladogram, i.e., its monophyletic groups. Two basic matrices, Y and X, are defined in the context of an ordinary linear model. Y contains the comparative data measured over t taxa. X consists of an initial tree matrix that contains all the xj monophyletic groups (each coded separately as a binary indicator variable) of the phylogenetic tree available for those taxa. The method seeks to define the subset of groups, i.e., a reduced tree matrix, that best explains the patterns in Y. This definition is accomplished via regression or canonical ordination (depending on the dimensionality of Y) coupled with Monte Carlo permutations. It is argued here that unrestricted permutations (i.e., under an equiprobable model) are valid for testing this specific kind of groupwise hypothesis. Phylogeny is either partialled out or, more properly, incorporated into the analysis in the form of component variation. Direct extensions allow for testing ecomorphological data controlled by phylogeny in a variation partitioning approach. Currently available statistical techniques make this method applicable under most univariate/multivariate models and metrics; two-way phylogenetic effects can be estimated as well. The simplest case (univariate Y), tested with simulations, yielded acceptable type I error rates. Applications presented include examples from evolutionary ethology, ecology, and ecomorphology. Results showed that the new technique detected previously overlooked variation clearly associated with phylogeny and that many phylogenetic effects on comparative data may occur at particular groups rather than across the entire tree. PMID:14530135

  7. Transient receptor potential cation channel subfamily V member 1 expressing corneal sensory neurons can be subdivided into at least three subpopulations

    Directory of Open Access Journals (Sweden)

    Jason Ivanusic

    2015-06-01

    Full Text Available The cornea is innervated by 3 main functional classes of sensory neurons: polymodal nociceptors, pure mechano-nociceptors and cold-sensing neurons. Here we explored transient receptor potential cation channel subfamily V member 1 (TRPV1 expression in guinea pig corneal sensory neurons, a widely used molecular marker of polymodal nociceptors. We used retrograde tracing to identify corneal afferent neurons in the trigeminal ganglion and double label in situ hybridization and/or immunohistochemistry to determine their molecular profile. In addition, we used immunohistochemistry to reveal the neurochemistry and structure of TRPV1 expressing nerve endings in the corneal epithelium. Approximately 45% of corneal afferent neurons expressed TRPV1, 28% expressed Piezo2 (a marker of putative pure mechano-nociceptors and 8% expressed the transient receptor potential cation channel subfamily M member 8 (TRPM8; a marker of cold-sensing neurons. There was no co-expression of TRPV1 and Piezo2 in corneal afferent neurons, but 6% of TRPV1 neurons co-expressed TRPM8. The TRPV1 expressing corneal afferent neurons could be divided into 3 subpopulations on the basis of calcitonin gene-related peptide (CGRP and/or or glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3 co-expression. In the corneal epithelium, the TRPV1 axons that co-expressed CGRP and GFRα3 ended as simple unbranched endings in the wing cell layer. In contrast, those that only co-expressed GFRα3 had ramifying endings that branched and terminated in the squamous cell layer, whereas those that only co-expressed CGRP had simple endings in the basal epithelium. This study shows that the majority of TRPV1 expressing corneal afferent neurons (>90% are likely to be polymodal nociceptors. Furthermore, TRPV1 expressing corneal afferent neurons can be subdivided into specific subpopulations based on their molecular phenotype, nerve terminal morphology and distribution in the corneal

  8. Changes in synaptic plasticity and expression of glutamate receptor subunits in the CA1 and CA3 areas of the hippocampus after transient global ischemia.

    Science.gov (United States)

    Han, Xin-Jia; Shi, Zhong-Shan; Xia, Luo-Xing; Zhu, Li-Hui; Zeng, Ling; Nie, Jun-Hua; Xu, Zao-Cheng; Ruan, Yi-Wen

    2016-07-01

    Excess glutamate release from the presynaptic membrane has been thought to be the major cause of ischemic neuronal death. Although both CA1 and CA3 pyramidal neurons receive presynaptic glutamate input, transient cerebral ischemia induces CA1 neurons to die while CA3 neurons remain relatively intact. This suggests that changes in the properties of pyramidal cells may be the main cause related to ischemic neuronal death. Our previous studies have shown that the densities of dendritic spines and asymmetric synapses in the CA1 area are increased at 12h and 24h after ischemia. In the present study, we investigated changes in synaptic structures in the CA3 area and compared the expression of glutamate receptors in the CA1 and CA3 hippocampal regions of rats after ischemia. Our results demonstrated that the NR2B/NR2A ratio became larger after ischemia although the expression of both the NR2B subunit (activation of apoptotic pathway) and NR2A subunit (activation of survival pathway) decreased in the CA1 area from 6h to 48h after reperfusion. Furthermore, expression of the GluR2 subunit (calcium impermeable) of the AMPA receptor class significantly decreased while the GluR1 subunit (calcium permeable) remained unchanged at the same examined reperfusion times, which subsequently caused an increase in the GluR1/GluR2 ratio. Despite these notable differences in subunit expression, there were no obvious changes in the density of synapses or expression of NMDAR and AMPAR subunits in the CA3 area after ischemia. These results suggest that delayed CA1 neuronal death may be related to the dramatic fluctuation in the synaptic structure and relative upregulation of NR2B and GluR1 subunits induced by transient global ischemia. PMID:27090818

  9. Periodicity, the Canon and Sport

    Directory of Open Access Journals (Sweden)

    Thomas F. Scanlon

    2015-10-01

    Full Text Available The topic according to this title is admittedly a broad one, embracing two very general concepts of time and of the cultural valuation of artistic products. Both phenomena are, in the present view, largely constructed by their contemporary cultures, and given authority to a great extent from the prestige of the past. The antiquity of tradition brings with it a certain cachet. Even though there may be peripheral debates in any given society which question the specifics of periodization or canonicity, individuals generally accept the consensus designation of a sequence of historical periods and they accept a list of highly valued artistic works as canonical or authoritative. We will first examine some of the processes of periodization and of canon-formation, after which we will discuss some specific examples of how these processes have worked in the sport of two ancient cultures, namely Greece and Mesoamerica.

  10. Existence of log canonical closures

    CERN Document Server

    Hacon, Christopher D

    2011-01-01

    Let $f:X\\to U$ be a projective morphism of normal varieties and $(X,\\Delta)$ a dlt pair. We prove that if there is an open set $U^0\\subset U$, such that $(X,\\Delta)\\times_U U^0$ has a good minimal model over $U^0$ and the images of all the non-klt centers intersect $U^0$, then $(X,\\Delta)$ has a good minimal model over $U$. As consequences we show the existence of log canonical compactifications for open log canonical pairs, and the fact that the moduli functor of stable schemes satisfies the valuative criterion for properness.

  11. Gauge Theory by canonical Transformations

    CERN Document Server

    Koenigstein, Adrian; Stoecker, Horst; Struckmeier, Juergen; Vasak, David; Hanauske, Matthias

    2016-01-01

    Electromagnetism, the strong and the weak interaction are commonly formulated as gauge theories in a Lagrangian description. In this paper we present an alternative formal derivation of U(1)-gauge theory in a manifestly covariant Hamilton formalism. We make use of canonical transformations as our guiding tool to formalize the gauging procedure. The introduction of the gauge field, its transformation behaviour and a dynamical gauge field Lagrangian/Hamiltonian are unavoidable consequences of this formalism, whereas the form of the free gauge Lagrangian/Hamiltonian depends on the selection of the gauge dependence of the canonically conjugate gauge fields.

  12. Case studies in canonical stewardship.

    Science.gov (United States)

    Cafardi, N P; Hite, J

    1985-11-01

    In facing the challenges that confront Catholic health care today, it is important to know which civil law forms will assist in preserving the Church's ministry. The proper meshing of civil law and canon law thus provides a vehicle to strengthen the apostolate's work. The case studies presented here suggest several means of applying the principles in the new Code of Canon Law to three potentially problematic situations: the merger of a Catholic and non-Catholic hospital, the leasing of a Catholic hospital to an operating company, and the use of the multicorporate format. PMID:10274590

  13. Canonical density matrix perturbation theory.

    Science.gov (United States)

    Niklasson, Anders M N; Cawkwell, M J; Rubensson, Emanuel H; Rudberg, Elias

    2015-12-01

    Density matrix perturbation theory [Niklasson and Challacombe, Phys. Rev. Lett. 92, 193001 (2004)] is generalized to canonical (NVT) free-energy ensembles in tight-binding, Hartree-Fock, or Kohn-Sham density-functional theory. The canonical density matrix perturbation theory can be used to calculate temperature-dependent response properties from the coupled perturbed self-consistent field equations as in density-functional perturbation theory. The method is well suited to take advantage of sparse matrix algebra to achieve linear scaling complexity in the computational cost as a function of system size for sufficiently large nonmetallic materials and metals at high temperatures. PMID:26764847

  14. Canonical and grand canonical theory of spinodal instabilities

    International Nuclear Information System (INIS)

    In the context of the mean field approximation to the Landau-Ginzburg-Wilson functional integral, describing the equilibrium properties of a system with a conserved order parameter, the conditions for critical instabilities in the canonical ensemble are analysed. (A.C.A.S.)

  15. Streptococcus pneumoniae Infection of Host Epithelial Cells via Polymeric Immunoglobulin Receptor Transiently Induces Calcium Release from Intracellular Stores*

    OpenAIRE

    Asmat, T. M.; Agarwal, V; Rath, S.; Hildebrandt, J.-P.; Hammerschmidt, S.

    2011-01-01

    The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae (pneumococci) that interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. This interaction promotes bacterial colonization and bacterial internalization by initiating host signal transduction cascades. Here, we examined alterations of intracellular calcium ([Ca2+]i) levels in epithelial cells during host cell...

  16. TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells

    Directory of Open Access Journals (Sweden)

    Hofmann Thomas

    2007-07-01

    Full Text Available Abstract Background A growing number of TRP channels have been identified as key players in the sensation of smell, temperature, mechanical forces and taste. TRPM5 is known to be abundantly expressed in taste receptor cells where it participates in sweet, amino acid and bitter perception. A role of TRPM5 in other sensory systems, however, has not been studied so far. Results Here, we systematically investigated the expression of TRPM5 in rat and mouse tissues. Apart from taste buds, where we found TRPM5 to be predominantly localized on the basolateral surface of taste receptor cells, TRPM5 immunoreactivity was seen in other chemosensory organs – the main olfactory epithelium and the vomeronasal organ. Most strikingly, we found solitary TRPM5-enriched epithelial cells in all parts of the respiratory and gastrointestinal tract. Based on their tissue distribution, the low cell density, morphological features and co-immunostaining with different epithelial markers, we identified these cells as brush cells (also known as tuft, fibrillovesicular, multivesicular or caveolated cells. In terms of morphological characteristics, brush cells resemble taste receptor cells, while their origin and biological role are still under intensive debate. Conclusion We consider TRPM5 to be an intrinsic signaling component of mammalian chemosensory organs, and provide evidence for brush cells being an important cellular correlate in the periphery.

  17. Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Thebault, S.C.; Lemonnier, L.; Bidaux, G.; Flourakis, M.; Bavencoffe, A.; Gordienko, D.; Roudbaraki, M.; Delcourt, P.; Panchin, Y.; Shuba, Y.; Skryma, R.; Prevarskaya, N.

    2005-01-01

    Recent cloning of a cold/menthol-sensitive TRPM8 channel (transient receptor potential melastatine family member 8) from rodent sensory neurons has provided the molecular basis for the cold sensation. Surprisingly, the human orthologue of rodent TRPM8 also appears to be strongly expressed in the pro

  18. Application of the TRAC-PD2 code to the simulation of the CANON experiment

    International Nuclear Information System (INIS)

    A comparison between the TRAC -PD2 code calculations and results from the CANON experiment is presented. The CANON experiment simulates the loss of coolant accident through the depressurization of a horizontal tube containing water at different temperatures. The experiment consist of the instantaneous rupture at one end of the tubing and the corresponding pressure and void fraction measurements during the transient. The comparison shows that the TRAC-PD2 code predicts satisfactorily the pressure and void fraction evolution in the CANON experiment. (F.C.)

  19. Resistant multiple sparse canonical correlation.

    Science.gov (United States)

    Coleman, Jacob; Replogle, Joseph; Chandler, Gabriel; Hardin, Johanna

    2016-04-01

    Canonical correlation analysis (CCA) is a multivariate technique that takes two datasets and forms the most highly correlated possible pairs of linear combinations between them. Each subsequent pair of linear combinations is orthogonal to the preceding pair, meaning that new information is gleaned from each pair. By looking at the magnitude of coefficient values, we can find out which variables can be grouped together, thus better understanding multiple interactions that are otherwise difficult to compute or grasp intuitively. CCA appears to have quite powerful applications to high-throughput data, as we can use it to discover, for example, relationships between gene expression and gene copy number variation. One of the biggest problems of CCA is that the number of variables (often upwards of 10,000) makes biological interpretation of linear combinations nearly impossible. To limit variable output, we have employed a method known as sparse canonical correlation analysis (SCCA), while adding estimation which is resistant to extreme observations or other types of deviant data. In this paper, we have demonstrated the success of resistant estimation in variable selection using SCCA. Additionally, we have used SCCA to find multiple canonical pairs for extended knowledge about the datasets at hand. Again, using resistant estimators provided more accurate estimates than standard estimators in the multiple canonical correlation setting. R code is available and documented at https://github.com/hardin47/rmscca. PMID:26963062

  20. Romanticism, Sexuality, and the Canon.

    Science.gov (United States)

    Rowe, Kathleen K.

    1990-01-01

    Traces the Romanticism in the work and persona of film director Jean-Luc Godard. Examines the contradictions posed by Godard's politics and representations of sexuality. Asserts, that by bringing an ironic distance to the works of such canonized directors, viewers can take pleasure in those works despite their contradictions. (MM)

  1. Tetrahydroisoquinoline-Derived Urea and 2,5-Diketopiperazine Derivatives as Selective Antagonists of the Transient Receptor Potential Melastatin 8 (TRPM8) Channel Receptor and Antiprostate Cancer Agents.

    Science.gov (United States)

    De Petrocellis, Luciano; Arroyo, Francisco J; Orlando, Pierangelo; Schiano Moriello, Aniello; Vitale, Rosa Maria; Amodeo, Pietro; Sánchez, Aránzazu; Roncero, Cesáreo; Bianchini, Giulia; Martín, M Antonia; López-Alvarado, Pilar; Menéndez, J Carlos

    2016-06-23

    Tetrahydroisoquinoline derivatives containing embedded urea functions were identified as selective TRPM8 channel receptor antagonists. Structure-activity relationships were investigated, with the following conclusions: (a) The urea function and the tetrahydroisoquinoline system are necessary for activity. (b) Bis(1-aryl-6,7dimethoxy-1,2,3,4-tetrahydroisoquinolyl)ureas are more active than compounds containing one tetrahydroisoquinoline ring and than an open phenetylamine ureide. (c) Trans compounds are more active than their cis isomers. (d) Aryl substituents are better than alkyls at the isoquinoline C-1 position. (e) Electron-withdrawing substituents lead to higher activities. The most potent compound is the 4-F derivative, with IC50 in the 10(-8) M range and selectivities around 1000:1 for most other TRP receptors. Selected compounds were found to be active in reducing the growth of LNCaP prostate cancer cells. TRPM8 inhibition reduces proliferation in the tumor cells tested but not in nontumor prostate cells, suggesting that the activity against prostate cancer is linked to TRPM8 inhibition. PMID:27232526

  2. Basic Canonical Brackets Without Canonical Conjugate Momenta: Supersymmetric Harmonic Oscillator

    CERN Document Server

    Shukla, A; Malik, R P

    2014-01-01

    We exploit the ideas of spin-statistics theorem, normal-ordering and the key concepts behind the symmetry principles to derive the canonical (anti)commutators for the case of a one (0 + 1)-dimensional (1D) supersymmetric (SUSY) harmonic oscillator without taking the help of the mathematical definition of the canonical conjugate momenta with respect to the bosonic and fermionic variables of this toy model for the Hodge theory (where the continuous and discrete symmetries of the theory provide the physical realizations of the de Rham cohomological operators of differential geometry). In our present endeavor, it is the full set of continuous symmetries and their corresponding generators that lead to the derivation of basic (anti)commutators amongst the creation and annihilation operators that appear in the normal mode expansions of the dynamical variables of our theory.

  3. Statistical thermodynamics in relativistic particle and ion physics: Canonical or grand canonical

    International Nuclear Information System (INIS)

    We consider relativistic statistical thermodynamics of an ideal Boltzmann gas consisting of the particles K, Λ, A, Σ and their antiparticles. Baryon number (B) and strangeness (S) are conserved. While any relativistic gas is necessarily grand canonical with respect to particle numbers, conservation laws can be treated canonically or grand canonically. We construct the partition function for canonical BxS conservation and compare it with the grand canonical one. It is found that the grand canonical partition function is equivalent to a large B approximation of the canonical one. The relative difference between canonical and grand canonical quantities seems to decrease like const/B (two numerical examples) and from this a simple thumb rule for computing canonical quantities from grand canonical ones is guessed. For precise calculations, an integral representation is given. (orig.)

  4. In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain.

    Science.gov (United States)

    Kinnunen, A; Lintunen, M; Karlstedt, K; Fukui, H; Panula, P

    1998-04-27

    In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the

  5. Functional Multiple-Set Canonical Correlation Analysis

    Science.gov (United States)

    Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

    2012-01-01

    We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

  6. Canonical proper time quantum gravitation

    Science.gov (United States)

    Lindesay, James

    2015-05-01

    At the root of the tensions involved in modeling the quantum dynamics of gravitating systems are the subtleties of quantum locality. Quantum mechanics describes physical phenomena using a theory of non-local phase relationships (non-local in the sense that quantum states maintain a space-like coherence that is acausal). However, the principle of equivalence in general relativity asserts that freely falling frames are locally inertial frames of reference. Thus, gravitating systems are often described using constituents that are freely falling, undergoing geodesic motion defining well localized trajectories. The canonical proper time formulation of relativistic dynamics is particularly useful for describing such inertial constituents using the coordinates of non-inertial observers. The physics of the simplest of gravitating inertial quantum systems, consistent with presented experimental evidence, will be examined. Subsequently, descriptions of both weakly and strongly gravitating quantum systems will be developed using canonical proper gravitation.

  7. Canonical computations of cerebral cortex.

    Science.gov (United States)

    Miller, Kenneth D

    2016-04-01

    The idea that there is a fundamental cortical circuit that performs canonical computations remains compelling though far from proven. Here we review evidence for two canonical operations within sensory cortical areas: a feedforward computation of selectivity; and a recurrent computation of gain in which, given sufficiently strong external input, perhaps from multiple sources, intracortical input largely, but not completely, cancels this external input. This operation leads to many characteristic cortical nonlinearities in integrating multiple stimuli. The cortical computation must combine such local processing with hierarchical processing across areas. We point to important changes in moving from sensory cortex to motor and frontal cortex and the possibility of substantial differences between cortex in rodents vs. species with columnar organization of selectivity. PMID:26868041

  8. Three Dimensional Canonical Quantum Gravity

    OpenAIRE

    Matschull, Hans-Juergen

    1995-01-01

    General aspects of vielbein representation, ADM formulation and canonical quantization of gravity are reviewed using pure gravity in three dimensions as a toy model. The classical part focusses on the role of observers in general relativity, which will later be identified with quantum observers. A precise definition of gauge symmetries and a classification of inequivalent solutions of Einstein's equations in dreibein formalism is given as well. In the quantum part the construction of the phys...

  9. Resistant Multiple Sparse Canonical Correlation

    OpenAIRE

    Coleman, Jacob; Replogle, Joseph; Chandler, Gabriel; Hardin, Johanna

    2014-01-01

    Canonical Correlation Analysis (CCA) is a multivariate technique that takes two datasets and forms the most highly correlated possible pairs of linear combinations between them. Each subsequent pair of linear combinations is orthogonal to the preceding pair, meaning that new information is gleaned from each pair. By looking at the magnitude of coefficient values, we can find out which variables can be grouped together, thus better understanding multiple interactions that are otherwise difficu...

  10. A novel 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime compound is a potent Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPA1 and V1) receptor antagonist.

    Science.gov (United States)

    Payrits, M; Sághy, É; Mátyus, P; Czompa, A; Ludmerczki, R; Deme, R; Sándor, Z; Helyes, Zs; Szőke, É

    2016-06-01

    Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPA1, TRPV1) ion channels expressed on nociceptive primary sensory neurons are important regulators of pain and inflammation. TRPA1 is activated by several inflammatory mediators including formaldehyde and methylglyoxal that are products of the semicarbazide-sensitive amine-oxidase enzyme (SSAO). SZV-1287 is a new 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime SSAO inhibitor, its chemical structure is similar to other oxime derivatives described as TRPA1 antagonists. Therefore, we investigated its effects on TRPA1 and TRPV1 receptor activation on the cell bodies and peripheral terminals of primary sensory neurons and TRPA1 or TRPV1 receptor-expressing cell lines. Calcium influx in response to the TRPA1 agonist allyl-isothiocyanate (AITC) (200μM) and the TRPV1 stimulator capsaicin (330nM) in rat trigeminal neurons or TRPA1 and TRPV1 receptor-expressing cell lines was measured by microfluorimetry or radioactive (45)Ca(2+) uptake experiments. Calcitonin gene-related peptide (CGRP) release as the indicator of 100μM AITC - or 100nM capsaicin-induced peripheral sensory nerve terminal activation was measured by radioimmunoassay. SZV-1287 (100, 500 and 1000nM) exerted a concentration-dependent significant inhibition on both AITC- and capsaicin-evoked calcium influx in trigeminal neurons and TRPA1 or TRPV1 receptor-expressing cell lines. It also significantly inhibited the TRPA1, but not the TRPV1 activation-induced CGRP release from the peripheral sensory nerve endings in a concentration-dependent manner. In contrast, the reference SSAO inhibitor LJP 1207 with a different structure had no effect on TRPA1 or TRPV1 activation in either model system. This is the first evidence that our novel oxime compound SZV-1287 originally developed as a SSAO inhibitor has a potent dual antagonistic action on TRPA1 and TRPV1 ion channels on primary sensory neurons. PMID:26930003

  11. Derivation of Mayer Series from Canonical Ensemble

    Science.gov (United States)

    Xian-Zhi, Wang

    2016-02-01

    Mayer derived the Mayer series from both the canonical ensemble and the grand canonical ensemble by use of the cluster expansion method. In 2002, we conjectured a recursion formula of the canonical partition function of a fluid (X.Z. Wang, Phys. Rev. E 66 (2002) 056102). In this paper we give a proof for this formula by developing an appropriate expansion of the integrand of the canonical partition function. We further derive the Mayer series solely from the canonical ensemble by use of this recursion formula.

  12. Toll-like receptor agonist augments virus-like particle-mediated protection from Ebola virus with transient immune activation.

    Directory of Open Access Journals (Sweden)

    Karen A O Martins

    Full Text Available Identifying safe and effective adjuvants is critical for the advanced development of protein-based vaccines. Pattern recognition receptor (PRR agonists are increasingly being explored as potential adjuvants, but there is concern that the efficacy of these molecules may be dependent on potentially dangerous levels of non-specific immune activation. The filovirus virus-like particle (VLP vaccine protects mice, guinea pigs, and nonhuman primates from viral challenge. In this study, we explored the impact of a stabilized dsRNA mimic, polyICLC, on VLP vaccination of C57BL/6 mice and Hartley guinea pigs. We show that at dose levels as low as 100 ng, the adjuvant increased the efficacy of the vaccine in mice. Antigen-specific, polyfunctional CD4 and CD8 T cell responses and antibody responses increased significantly upon inclusion of adjuvant. To determine whether the efficacy of polyICLC correlated with systemic immune activation, we examined serum cytokine levels and cellular activation in the draining lymph node. PolyICLC administration was associated with increases in TNFα, IL6, MCP1, MIP1α, KC, and MIP1β levels in the periphery and with the activation of dendritic cells (DCs, NK cells, and B cells. However, this activation resolved within 24 to 72 hours at efficacious adjuvant dose levels. These studies are the first to examine the polyICLC-induced enhancement of antigen-specific immune responses in the context of non-specific immune activation, and they provide a framework from which to consider adjuvant dose levels.

  13. Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model.

    Science.gov (United States)

    Wang, Juyong; Zhang, Ruixin; Dong, Changsheng; Jiao, Lijing; Xu, Ling; Liu, Jiyong; Wang, Zhengtao; Lao, Lixing

    2015-07-01

    Cancer pain management is a challenge for which Chinese herbal medicine might be useful. To study the spinal mechanisms of the Chinese medicated gel Long-Teng-Tong-Luo (LTTL), a 7-herb compound, on bone cancer pain, a bone cancer pain model was made by inoculating the tibias of female rats with Walker 256 cells. LTTL gel or inert gel, 0.5 g/cm(2)/d, was applied to the skin of tumor-bearing tibias for 21 days beginning a day after the inoculation. Mechanical threshold and paw withdrawal latency to thermal stimulation was measured. Transient receptor potential (TRP) cation channels in lumbar dorsal root ganglia (DRG) were immunostained and counted, and lumbar spinal cord interleukin-17A (IL-17A) was measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TRP antagonists and interleukin (IL)-17A antibodies were intrathecally administered to determine their effects on bone cancer pain. The gel significantly (P cancer-induced mechanical allodynia and thermal hyperalgesia and inhibited cancer-enhanced expression of IL-17A in spinal astrocytes and the TRP subfamily members V1, A1, and V4 in lumbar DRG. Intrathecal TRP antagonists at 10 µg significantly (P cancer pain. IL-17A antibodies inhibited cancer pain, suggesting that IL-17A promotes such pain. The data show that LTTL gel inhibits cancer pain, and this might be accounted for by the decrease in expression of DRG TRP channels and spinal astrocyte IL-17A. PMID:26100378

  14. Mutation of light-dependent phosphorylation sites of the Drosophila transient receptor potential-like (TRPL) ion channel affects its subcellular localization and stability.

    Science.gov (United States)

    Cerny, Alexander C; Oberacker, Tina; Pfannstiel, Jens; Weigold, Sebastian; Will, Carina; Huber, Armin

    2013-05-31

    The Drosophila phototransduction cascade terminates in the opening of the ion channel transient receptor potential (TRP) and TRP-like (TRPL). Contrary to TRP, TRPL undergoes light-dependent subcellular trafficking between rhabdomeric photoreceptor membranes and an intracellular storage compartment, resulting in long term light adaptation. Here, we identified in vivo phosphorylation sites of TRPL that affect TRPL stability and localization. Quantitative mass spectrometry revealed a light-dependent change in the TRPL phosphorylation pattern. Mutation of eight C-terminal phosphorylation sites neither affected multimerization of the channels nor the electrophysiological response of flies expressing the mutated channels. However, these mutations resulted in mislocalization and enhanced degradation of TRPL after prolonged dark-adaptation. Mutation of subsets of the eight C-terminal phosphorylation sites also led to a reduction of TRPL content and partial mislocalization in the dark. This suggests that a light-dependent switch in the phosphorylation pattern of the TRPL channel mediates stable expression of TRPL in the rhabdomeres upon prolonged dark-adaptation. PMID:23592784

  15. Mutation of Light-dependent Phosphorylation Sites of the Drosophila Transient Receptor Potential-like (TRPL) Ion Channel Affects Its Subcellular Localization and Stability*

    Science.gov (United States)

    Cerny, Alexander C.; Oberacker, Tina; Pfannstiel, Jens; Weigold, Sebastian; Will, Carina; Huber, Armin

    2013-01-01

    The Drosophila phototransduction cascade terminates in the opening of the ion channel transient receptor potential (TRP) and TRP-like (TRPL). Contrary to TRP, TRPL undergoes light-dependent subcellular trafficking between rhabdomeric photoreceptor membranes and an intracellular storage compartment, resulting in long term light adaptation. Here, we identified in vivo phosphorylation sites of TRPL that affect TRPL stability and localization. Quantitative mass spectrometry revealed a light-dependent change in the TRPL phosphorylation pattern. Mutation of eight C-terminal phosphorylation sites neither affected multimerization of the channels nor the electrophysiological response of flies expressing the mutated channels. However, these mutations resulted in mislocalization and enhanced degradation of TRPL after prolonged dark-adaptation. Mutation of subsets of the eight C-terminal phosphorylation sites also led to a reduction of TRPL content and partial mislocalization in the dark. This suggests that a light-dependent switch in the phosphorylation pattern of the TRPL channel mediates stable expression of TRPL in the rhabdomeres upon prolonged dark-adaptation. PMID:23592784

  16. Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

    Directory of Open Access Journals (Sweden)

    Hans-Joachim Anders

    2013-06-01

    Full Text Available The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling.

  17. Carbonyl stress-induced 5-hydroxytriptamine secretion from RIN-14B, rat pancreatic islet tumor cells, via the activation of transient receptor potential ankyrin 1.

    Science.gov (United States)

    Suzawa, Sayaka; Takahashi, Kenji; Shimada, Takahisa; Ohta, Toshio

    2016-07-01

    Methylglyoxal (MG), a highly reactive dicarbonyl substance, is known as an endogenous carbonyl stress-inducing substance related to various disease states. Irritable bowel syndrome (IBS) is one of the most frequently encountered gastrointestinal disorders and MG is considered to be its causal substance. An increased serum 5-hydroxytryptamine (5-HT) level is related to IBS symptoms and the majority of 5-HT originates from enterochromaffin (EC) cells in the intestine. Here we examine the mechanisms of MG-induced 5-HT secretion using RIN-14B cells derived from a rat pancreatic islet tumor since these cells are used as a model for EC cells. MG increased the intracellular Ca(2+) concentration ([Ca(2+)]i) and 5-HT secretion, both of which were inhibited by the removal of extracellular Ca(2+) and specific transient receptor potential ankyrin 1 (TRPA1) antagonists. MG elicited an inward current under voltage-clamped conditions. Prior application of MG evoked reciprocal suppression of subsequent [Ca(2+)]i responses to allylisothiocyanate, a TRPA1 agonist, and vice versa. Glyoxal, an analog of MG, also evoked [Ca(2+)]i and secretory responses but its potency was much lower than that of MG. The present results suggest that MG promotes 5-HT secretion through the activation of TRPA1 in RIN-14B cells. These results may indicate that TRPA1 is a promising target for the treatment of IBS and that the RIN-14B cell line is a useful model for investigation of IBS. PMID:27423812

  18. Possible involvement of the transient receptor potential vanilloid type 1 channel in postoperative adhesive obstruction and its prevention by a kampo (traditional Japanese) medicine, daikenchuto.

    Science.gov (United States)

    Tokita, Yohei; Yamamoto, Masahiro; Satoh, Kazuko; Nishiyama, Mitsue; Iizuka, Seiichi; Imamura, Sachiko; Kase, Yoshio

    2011-01-01

    This study focused on the localization of transient receptor potential vanilloid type 1 (TRPV1) in the intestines in postoperative adhesion model rats and investigated the underlying mechanism for the anti-adhesion action of daikenchuto (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA was examined by in situ hybridization and real-time RT-PCR. The effects of DKT and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP-channel antagonist, on talc-induced intestinal adhesions were evaluated. The level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA expression was identified in the submucosal plexus of both sham-operated and talc-treated rats; and in talc-treated rats, it was observed also in the myenteric plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool significantly prevented formation of intestinal adhesions. The effects of DKT and hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These results suggest that pharmacological modulation of TRPV1 might be a possible therapeutic option in postoperative intestinal adhesion, which might be relevant to the prevention of postoperative adhesive obstruction by DKT. PMID:21186335

  19. Optimization on scoliosis examination on Canons DR system

    DEFF Research Database (Denmark)

    Precht, Helle

    2007-01-01

    recordings of scoliosis today are carried out on CR systems even though most radiological departments have DR systems available. Theoretically speaking the two modalities are similar regarding dose and image quality. In this project consequently, the focus will be to obtain images of equal dose and quality...... at a DR system when using different receptors during the exam. This is a completely new opportunity, as it has earlier been difficult to compare distinct scintilators connected to the receptors due to unlike processing of the image. Given that Canon have released a receptor with CsI scintilator we...... study in which theory is used as a background for the test setup and later audit appraisal. Two tests are carried out on two different hospitals with each their receptor, and afterwards the results are compared. To guarantee comparable tests the results are verified through status checks and statistical...

  20. Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sebastian Gehlert

    Full Text Available BACKGROUND: While ryanodine receptor 1 (RyR1 critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³ results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. PURPOSE: Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers. METHODS: 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques. RESULTS: While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01 post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05. pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01 in type I and II myofibers and in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and

  1. Stroke in Canon of Medicine

    Science.gov (United States)

    Alorizi, Seyed Morteza Emami; Nimruzi, Majid

    2016-01-01

    Background: Stroke has a huge negative impact on the society and more adversely affect women. There is scarce evidence about any neuroprotective effects of commonly used drug in acute stroke. Bushnell et al. provided a guideline focusing on the risk factors of stroke unique to women, including reproductive factors, metabolic syndrome, obesity, atrial fibrillation, and migraine with aura. The ten variables cited by Avicenna in Canon of Medicine would compensate for the gaps mentioned in this guideline. The prescribed drugs should be selected qualitatively opposite to Mizaj (warm-cold and wet-dry qualities induced by disease state) of the disease and according to ten variables, including the nature of the affected organ, intensity of disease, sex, age, habit, season, place of living, occupation, stamina and physical status. Methods: Information related to stroke was searched in Canon of Medicine, which is an outstanding book in traditional Persian medicine written by Avicenna. Results: A hemorrhagic stroke is the result of increasing sanguine humor in the body. Sanguine has warm-wet quality, and should be treated with food and drugs that quench the abundance of blood in the body. An acute episode of ischemic stroke is due to the abundance of phlegm that causes a blockage in the cerebral vessels. Phlegm has cold-wet quality and treatment should be started with compound medicines that either solve the phlegm or eject it from the body. Conclusion: Avicenna has cited in Canon of Medicine that women have cold and wet temperament compared to men. For this reason, they are more prone to accumulation of phlegm in their body organs including the liver, joints and vessels, and consequently in the risk of fatty liver, degenerative joint disease, atherosclerosis, and stroke especially the ischemic one. This is in accordance with epidemiological studies that showed higher rate of ischemic stroke in women rather than hemorrhagic one. PMID:26722147

  2. Dibaryons as canonically quantized biskyrmions

    CERN Document Server

    Krupovnickas, T; Riska, D O

    2000-01-01

    The characteristic feature of the ground state configuration of the Skyrme model description of nuclei is the absence of recognizable individual nucleons. The ground state of the skyrmion with baryon number 2 is axially symmetric, and is well approximated by a simple rational map, which represents a direct generalization of Skyrme's hedgehog ansatz for the nucleon. If the Lagrangian density is canonically quantized this configuration may support excitations that lie close and possible below the threshold for pion decay, and therefore describe dibaryons. The quantum corrections stabilize these solutions, the mass density of which have the correct exponential fall off at large distances.

  3. Canonical metrics on complex manifold

    Institute of Scientific and Technical Information of China (English)

    YAU Shing-Tung

    2008-01-01

    @@ Complex manifolds are topological spaces that are covered by coordinate charts where the Coordinate changes are given by holomorphic transformations. For example, Riemann surfaces are one dimensional complex manifolds. In order to understand complex manifolds, it is useful to introduce metrics that are compatible with the complex structure. In general, we should have a pair (M, ds2M) where ds2M is the metric. The metric is said to be canonical if any biholomorphisms of the complex manifolds are automatically isometries. Such metrics can naturally be used to describe invariants of the complex structures of the manifold.

  4. Canonical metrics on complex manifold

    Institute of Scientific and Technical Information of China (English)

    YAU; Shing-Tung(Yau; S.-T.)

    2008-01-01

    Complex manifolds are topological spaces that are covered by coordinate charts where the coordinate changes are given by holomorphic transformations.For example,Riemann surfaces are one dimensional complex manifolds.In order to understand complex manifolds,it is useful to introduce metrics that are compatible with the complex structure.In general,we should have a pair(M,ds~2_M)where ds~2_M is the metric.The metric is said to be canonical if any biholomorphisms of the complex manifolds are automatically isometries.Such metrics can naturally be used to describe invariants of the complex structures of the manifold.

  5. Gauge fixing and canonical quantization

    International Nuclear Information System (INIS)

    We study the canonical quantization of non-Abelian gauge fields in the temporal gauge A0 = 0. We impose the constraint condition of Gauss's law by performing a point transformation into any of a large class of noncovariant gauges. The Faddeev and Popov operator arises naturally in this procedure; indeed, we prove the equivalence of all gauges in this class. We discuss the nonexistence of some simple gauges and show how topological considerations reduce the theory to quantum mechanics on an infinite-dimensional periodic hypersurface

  6. Canonical transient receptor potential ion channel is involved in sodium nitroprnsside-induced apoptosis of cultured rat hippocampal neurons%TRPC离子通道参与硝普钠诱导海马神经元凋亡

    Institute of Scientific and Technical Information of China (English)

    张贺; 王斌; 李文军; 邹飞

    2008-01-01

    目的 探讨TRPC离子通道在一氧化氮供体硝普钠(SNP)诱导原代培养海马神经元凋亡中的作用.方法 原代培养的海马神经元作为空白对照组,实验组分为3组,分别为原代培养神经元中加入SNP;SNP+TRPC通道阻断剂组;SNP+TRPC通道激活剂组.细胞处理24 h后MTT比色法检测各组细胞存活率,Hoechest33342荧光染色观察细胞凋亡.结果 SNP处理24h,神经元存活率为67.4%;与空白对照组有显著差异(P<0.05),SNP+TRPC阻断剂组神经元存活率分别为102%、92.7%,与SNP组有显著差异(P<0.05);而SNP+TRPC激活剂组神经元存活率为56.9%.与SNP组有统计学差异(P<0.05);单纯给予TRPC阻断剂或激动剂对神经元存活率无明显影响.荧光显微镜下观察.空白对照组神经元胞核均匀蓝染;SNP处理组胞核明显固缩、凝聚,可见凋亡小体;SNP+TRPC激动剂组可见大量凋亡细胞;而SNP+TRPC阻断剂组胞核均匀蓝染.结论 TRPC离子通道参与SNP诱导海马神经元凋亡.

  7. Quantitative determination of capsaicin, a transient receptor potential channel vanilloid 1 agonist, by liquid chromatography quadrupole ion trap mass spectrometry: evaluation of in vitro metabolic stability.

    Science.gov (United States)

    Beaudry, Francis; Vachon, Pascal

    2009-02-01

    Capsaicin is the most abundant pungent molecule present in red peppers and it is widely used for food flavoring, in pepper spray in self-defense devices and more recently in ointments for the relief of neuropathic pain. Capsaicin is a selective agonist of transient receptor potential channel, vanilloid subfamily member 1. A selective and sensitive quantitative method for the determination of capsaicin by LC-ESI/MS/MS was developed. The method consisted of a protein precipitation extraction followed by analysis using liquid chromatography electrospray quadrupole ion trap mass spectrometry. The chromatographic separation was achieved using a 100 x 2 mm C(18) Waters Symmetry column combined with a gradient mobile phase composed of acetonitrile and 0.1% formic acid aqueous solution at a flow rate of 220 microL/min. The mass spectrometer was operating in full-scan MS/MS mode using two-segment analysis. An analytical range of 10-5000 ng/mL was used in the calibration curve constructed in rat plasma. The interbatch precision and accuracy observed were 6.5, 6.7, 5.3 and 101.2, 102.7, 103.5% at 50, 500 and 5000 ng/mL, respectively. An in vitro metabolic stability study was performed in rat, dog and mouse liver microsomes and the novel analytical method was adapted and used to determine intrinsic clearance of capsaicin. Results suggest very rapid degradation with T(1/2) ranging from 2.3 to 4.1 min and high clearance values suggesting that drug bioavailability will be considerably reduced, consequently affecting drug response and efficacy. PMID:18816461

  8. Pattern-Recognition Receptor Signaling Regulator mRNA Expression in Humans and Mice, and in Transient Inflammation or Progressive Fibrosis

    Directory of Open Access Journals (Sweden)

    Maciej Lech

    2013-09-01

    Full Text Available The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2, CD180, SIGIRR, TANK, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, SHP1, SHP2, TOLLIP, IRF4, SIKE, NLRX1, ERBIN, CENTB1, and Clec4a2 in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. Additionally, we characterized their expression profiles in mononuclear blood cells upon bacterial endotoxin, which showed a consistent induction of A20, SOCS3, IRAK-M, and Clec4a2 in human and murine cells. Furthermore, we studied the expression pattern in transient kidney ischemia-reperfusion injury versus post-ischemic atrophy and fibrosis in mice. A20, CD180, ST2, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, IRF4, CENTB1, and Clec4a2 were all induced, albeit at different times of injury and repair. Progressive fibrosis was associated with a persistent induction of these factors. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to PRR-mediated innate immunity, which seems to be involved in tissue injury, tissue regeneration and in progressive tissue scarring.

  9. Involvement of Transient Receptor Potential Melastatin 7 Channels in Sophorae Radix-induced Apoptosis in Cancer Cells - Sophorae Radix and TRPM7 -

    Directory of Open Access Journals (Sweden)

    Kim Byung Joo

    2012-09-01

    Full Text Available Objective:Sophorae Radix (SR plays a role in a number of physiologic and pharmacologic functions in many organs. Methods:The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7 channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Results:The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose polymerase (PARP cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers (Gd3+ or 2-APB and small interfering RNA (siRNA were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Conclusions:The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by Gd3+ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.

  10. Transient potential receptor melastatin-2 (Trpm2) does not influence murine MLL-AF9-driven AML leukemogenesis or in vitro response to chemotherapy.

    Science.gov (United States)

    Haladyna, Jessica N; Pastuer, Taylor; Riedel, Simone S; Perraud, Anne-Laure; Bernt, Kathrin M

    2016-07-01

    Transient potential receptor melastatin-2 (TRPM2) is a nonselective cationic, Ca(2+)-permeable transmembrane pore that is preferentially expressed in cells of the myeloid lineage and modulates signaling pathways converging into NF-kB. This is of potential interest for acute myeloid leukemia (AML) therapy, as NF-κB signaling is emerging as a key pathway, mediating drug resistance and leukemia-initiating cell survival in AML. Inhibition of NF-κB signaling has been found to be synergistic with chemotherapy. TRPM2 is overexpressed in AML compared with normal bone marrow, with the highest levels in the FAB M3-6 subtypes. To determine the effect of TRPM2 depletions in a defined genetic model, we established MLL-AF9-driven AML on a Trpm2(-/-) genetic background. Trpm2(-/-) MLL-AF9 leukemias displayed reduced NF-κB phosphorylation as well as nuclear translocation. In vivo, primary and secondary recipients of Trpm2(-/-) MLL-AF9 leukemias exhibit increased latency compared with recipients of wild-type leukemia cells. However, the difference in latency was small and was lost in tertiary transplants. The effect of loss of Trpm2 in a BCR-ABL/NUP98-HOXA9 fusion model was even smaller. Given reports that loss or inhibition of TRPM2 enhanced killing by DNA-damaging agents in neuroblastoma, breast cancer, and prostate cancer cell lines, we exposed Trpm2(-/-) and Trpm2(wt) primary MLL-AF9 leukemias to doxorubicin, cytarabine, and etoposide, but found no difference in IC50 values. The in vitro response to decitabine was also unaffected. In summary, Trpm2 does not seem to play a major role in myeloid leukemogenesis. Additionally, loss of Trpm2 does not augment the cytotoxicity of standard AML chemotherapeutic agents. PMID:27033163

  11. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    International Nuclear Information System (INIS)

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  12. Protective effect of transient receptor potential vanilloid subtype 1 (TRPV1) modulator, against behavioral, biochemical and structural damage in experimental models of Alzheimer's disease.

    Science.gov (United States)

    Jayant, Shalini; Sharma, B M; Sharma, Bhupesh

    2016-07-01

    Alzheime's disease (AD) is an overwhelming neurodegenerative disorder, characterized by synaptic dysfunction, memory loss, neuro-inflammation and neural cell death. Very few treatments are in hand for the management of AD and they are only concentrating on peculiar aspects. Hence, an immense thrust is required to find utmost therapeutic targets to conquer this condition. This study investigates a potential role of vanillin, a selective agonist of transient receptor potential vanilloid subtype 1 (TRPV1) in the experimental models of AD viz. intracerebroventricular (i.c.v.) streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose induced AD in mice. The i.c.v. administration of STZ and intraperitoneally administration of AlCl3+d-galactose have significantly impaired learning-memory (Morris water maze and attentional set-shifting test), brain structure (hematoxylin, eosin and Congo red staining), enhanced brain oxidative stress (thiobarbituric acid reactive substance - TBARS and glutathione - GSH), nitrosative stress (nitrite/nitrate), acetylcholinesterase activity (AChE), inflammation (MPO), and calcium levels (Ca(++)). Treatment with vanillin in different doses and donepezil have significantly ameliorated i.c.v. STZ and AlCl3+d-galactose induced reduction in executive function, impaired reversal learning, cognition, memory and brain damage. Treatment with these drugs has also reduced the brain oxidative stress (TBARS and GSH), nitrosative stress (nitrite/nitrate), and AChE, MPO, and Ca(++) levels. These results indicate that vanillin, a selective agonist of TRPV1 and donepezil, a potent acetylcholine esterase inhibitor have attenuated i.c.v. STZ and AlCl3+d-galactose induced experimental AD. Hence, pharmacological positive modulation of TRPV1 channels may be a potential research target for mitigation of AD. PMID:27084583

  13. Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

    2012-11-01

    Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

  14. Integral canonical models for Spin Shimura varieties

    OpenAIRE

    Pera, Keerthi Madapusi

    2012-01-01

    We construct regular integral canonical models for Shimura varieties attached to Spin groups at (possibly ramified) odd primes. We exhibit these models as schemes of 'relative PEL type' over integral canonical models of larger Spin Shimura varieties with good reduction. Work of Vasiu-Zink then shows that the classical Kuga-Satake construction extends over the integral model and that the integral models we construct are canonical in a very precise sense. We also construct good compactification...

  15. Canonical curves with low apolarity

    CERN Document Server

    Ballico, Edoardo; Notari, Roberto

    2010-01-01

    Let $k$ be an algebraically closed field and let $C$ be a non--hyperelliptic smooth projective curve of genus $g$ defined over $k$. Since the canonical model of $C$ is arithmetically Gorenstein, Macaulay's theory of inverse systems allows to associate to $C$ a cubic form $f$ in the divided power $k$--algebra $R$ in $g-2$ variables. The apolarity of $C$ is the minimal number $t$ of linear form in $R$ needed to write $f$ as sum of their divided power cubes. It is easy to see that the apolarity of $C$ is at least $g-2$ and P. De Poi and F. Zucconi classified curves with apolarity $g-2$ when $k$ is the complex field. In this paper, we give a complete, characteristic free, classification of curves $C$ with apolarity $g-1$ (and $g-2$).

  16. El canon de la periferia

    Directory of Open Access Journals (Sweden)

    Karina Beatriz Lemes

    2010-11-01

    Full Text Available Intentaremos mostrar cómo venimos trabajando con la reconstrucción de la memoria literaria de la provincia de Misiones a partir de la recopilación de los manuscritos de sus autores más representativos. Hemos utilizado para nuestra lectura, en cruce con la crítica genética, las relaciones que Fernando Ainsa establece entre canon y periferia,  espacios de la memoria y construcción de la utopía. Ainsa concibe la escritura como proceso genético que en su origen es personal, visceral y solitario, una búsqueda constante de identidad que se enriquece en contacto con el mundo, con la apertura de fronteras. Estas vinculaciones nos han permitido interpretar las prácticas sociales que fundaron actividades estéticas en la distancia de los centros de poder argentinos.This paper shows some findings of our ongoing research project dealing with the recuperation of literary memory in the province of Misiones by analysing a compilation of the literary manuscripts by the most representative authors of this northern region of Argentina. Here, we follow Fernado Ainsa’s notions of canon and periphery, of memory spaces and construction of utopias. Ainsa sees the act of writing as a genetic process for it originates within a personal, visceral, and solitary realm. For Ainsa, writing is also a permanent search for identity which becomes richer when in contact with the world, when frontiers open up. These concepts allow us to interpret the social practices that gave birth to these aesthetic projects far away from Argentina’s power centers.

  17. Revisiting Interpretation of Canonical Correlation Analysis: A Tutorial and Demonstration of Canonical Commonality Analysis

    Science.gov (United States)

    Nimon, Kim; Henson, Robin K.; Gates, Michael S.

    2010-01-01

    In the face of multicollinearity, researchers face challenges interpreting canonical correlation analysis (CCA) results. Although standardized function and structure coefficients provide insight into the canonical variates produced, they fall short when researchers want to fully report canonical effects. This article revisits the interpretation of…

  18. CANONICAL EXTENSIONS OF SYMMETRIC LINEAR RELATIONS

    NARCIS (Netherlands)

    Sandovici, Adrian; Davidson, KR; Gaspar, D; Stratila, S; Timotin, D; Vasilescu, FH

    2006-01-01

    The concept of canonical extension of Hermitian operators has been recently introduced by A. Kuzhel. This paper deals with a generalization of this notion to the case of symmetric linear relations. Namely, canonical regular extensions of symmetric linear relations in Hilbert spaces are studied. The

  19. Properties of the linear canonical integral transformation.

    Science.gov (United States)

    Alieva, Tatiana; Bastiaans, Martin J

    2007-11-01

    We provide a general expression and different classification schemes for the general two-dimensional canonical integral transformations that describe the propagation of coherent light through lossless first-order optical systems. Main theorems for these transformations, such as shift, scaling, derivation, etc., together with the canonical integral transforms of selected functions, are derived. PMID:17975592

  20. 37 CFR 10.46 - Canon 3.

    Science.gov (United States)

    2010-07-01

    ... Responsibility § 10.46 Canon 3. A practitioner should assist in preventing the unauthorized practice of law. ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 3. 10.46 Section 10.46 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF...

  1. 37 CFR 10.83 - Canon 7.

    Science.gov (United States)

    2010-07-01

    ... Responsibility § 10.83 Canon 7. A practitioner should represent a client zealously within the bounds of the law. ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Canon 7. 10.83 Section 10.83 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF...

  2. Extending canonical Monte Carlo methods: II

    International Nuclear Information System (INIS)

    We have previously presented a methodology for extending canonical Monte Carlo methods inspired by a suitable extension of the canonical fluctuation relation C = β2(δE2) compatible with negative heat capacities, C α, as is shown in the particular case of the 2D seven-state Potts model where the exponent α = 0.14–0.18

  3. The Current Canon in British Romantics Studies.

    Science.gov (United States)

    Linkin, Harriet Kramer

    1991-01-01

    Describes and reports on a survey of 164 U.S. universities to ascertain what is taught as the current canon of British Romantic literature. Asserts that the canon may now include Mary Shelley with the former standard six major male Romantic poets, indicating a significant emergence of a feminist perspective on British Romanticism in the classroom.…

  4. Multiplicity fluctuations in heavy-ion collisions using canonical and grand-canonical ensemble

    Energy Technology Data Exchange (ETDEWEB)

    Garg, P. [Indian Institute of Technology Indore, Discipline of Physics, School of Basic Science, Simrol (India); Mishra, D.K.; Netrakanti, P.K.; Mohanty, A.K. [Bhabha Atomic Research Center, Nuclear Physics Division, Mumbai (India)

    2016-02-15

    We report the higher-order cumulants and their ratios for baryon, charge and strangeness multiplicity in canonical and grand-canonical ensembles in ideal thermal model including all the resonances. When the number of conserved quanta is small, an explicit treatment of these conserved charges is required, which leads to a canonical description of the system and the fluctuations are significantly different from the grand-canonical ensemble. Cumulant ratios of total-charge and net-charge multiplicity as a function of collision energies are also compared in grand-canonical ensemble. (orig.)

  5. Multiplicity fluctuations in heavy ion collisions using canonical and grand canonical ensemble

    CERN Document Server

    Garg, P; Netrakanti, P K; Mohanty, A K

    2015-01-01

    We report the higher order cumulants and their ratios for baryon, charge and strangeness multiplicity in canonical and grand-canonical ensembles in ideal thermal model including all the resonances. When the number of conserved quanta is small, an explicit treatment of these conserved charges is required, which leads to a canonical description of the system and the fluctuations are significantly different from the grand canonical ensemble. Cumulant ratios of total charge and net-charge multiplicity as a function of collision energies are also compared in grand canonical ensemble.

  6. Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.

    Science.gov (United States)

    Panama, Brian K; Korogyi, Adam S; Aschar-Sobbi, Roozbeh; Oh, Yena; Gray, Charles B B; Gang, Hongying; Brown, Joan Heller; Kirshenbaum, Lorrie A; Backx, Peter H

    2016-02-19

    The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation. PMID:26742842

  7. Extending canonical Monte Carlo methods

    Science.gov (United States)

    Velazquez, L.; Curilef, S.

    2010-02-01

    In this paper, we discuss the implications of a recently obtained equilibrium fluctuation-dissipation relation for the extension of the available Monte Carlo methods on the basis of the consideration of the Gibbs canonical ensemble to account for the existence of an anomalous regime with negative heat capacities C < 0. The resulting framework appears to be a suitable generalization of the methodology associated with the so-called dynamical ensemble, which is applied to the extension of two well-known Monte Carlo methods: the Metropolis importance sampling and the Swendsen-Wang cluster algorithm. These Monte Carlo algorithms are employed to study the anomalous thermodynamic behavior of the Potts models with many spin states q defined on a d-dimensional hypercubic lattice with periodic boundary conditions, which successfully reduce the exponential divergence of the decorrelation time τ with increase of the system size N to a weak power-law divergence \\tau \\propto N^{\\alpha } with α≈0.2 for the particular case of the 2D ten-state Potts model.

  8. Downregulation of transient receptor potential cation channel, subfamily C, member 1 (TRPC1 is associated with drug resistance and high histologic grade in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Xia Liu

    2015-12-01

    Full Text Available Purpose: Ovarian cancer (OC drug resistance, believed to result in treatment failure and death in more than 90% of patients with metastatic OC, is due to a myriad of contributing factors. However, no matter what mechanisms, dysregulation of critical genes essentially play important roles. Transient receptor potential cation channel, subfamily C, member 1 (TRPC1 contributes to various physiological functions, and is involved in the regulation of cancer development. However, the overall studies of TRPC1 with cancer are limited, the study with drug resistance or OC is rare, and the research on TRPC1 with drug resistance in OC has never been reported. In this study, we aimed to explain the associations of TRPC1 with drug resistance in OC.Methods: The expression of TRPC1 was determined by the microarrays retrieved from Oncomine (https://www.oncomine.org/resource/login.html and GEO Profiles (http://www.ncbi.nlm.nih.gov/geoprofiles/, and further confirmed by RT-qPCR. The clinical data of 341 OC patients with TRPC1 mRNA expression data in TCGA cohort was retrieved from cBioPortal (http://cbioportal.org. Comprehensive bioinformatics analyses including protein/gene interaction, protein-small molecule/chemical interaction, biological process annotation, microRNA-mRNA interaction and pathway enrichment analysis of microRNAs were performed to clarify the drug resistant-related functions of TRPC1. The data was analyzed by SPSS 20.0 software. P-values of <0.05 were considered to indicate statistically significant differences.Results: The mRNA expressions of TRPC1 were downregulated by 3.955-fold, 3.681-fold and 3.260-fold in ovarian cancers according to the Welsh Ovarian covering 28 cases of ovarian serous surface papillary carcinoma and 4 cases of ovaries, the Bonome Ovarian covering 185 cases of ovarian carcinomas and 10 cases of ovarian surface epitheliums, and the Yoshihara Ovarian covering 38 cases of ovarian serous adenocarcinomas and 10 cases of

  9. Canonical pseudotensors, Sparling's form and Noether currents

    International Nuclear Information System (INIS)

    The canonical energy - momentum and spin pseudotensors of the Einstein theory are studied in two ways. First they are studied in the framework of Lagrangian formalism. It is shown, that for first order Lagrangian and rigid basis description the canonical energy - momentum, the canonical spin, and the Noether current are tensorial quantities, and the canonial energy - momentum and spin tensors satisfy the tensorial Belinfante-Rosenfeld equations. Then the differential geometric unification and reformulation of the previous different pseudotensorial approaches is given. Finally, for any vector field on the spacetime an (m-1) form, called the Noether form is defined. (K.A.) 34 refs

  10. Differential Forms on Log Canonical Spaces

    CERN Document Server

    Greb, Daniel; Kovacs, Sandor J; Peternell, Thomas

    2010-01-01

    The present paper is concerned with differential forms on log canonical varieties. It is shown that any p-form defined on the smooth locus of a variety with canonical or klt singularities extends regularly to any resolution of singularities. In fact, a much more general theorem for log canonical pairs is established. The proof relies on vanishing theorems for log canonical varieties and on methods of the minimal model program. In addition, a theory of differential forms on dlt pairs is developed. It is shown that many of the fundamental theorems and techniques known for sheaves of logarithmic differentials on smooth varieties also hold in the dlt setting. Immediate applications include the existence of a pull-back map for reflexive differentials, generalisations of Bogomolov-Sommese type vanishing results, and a positive answer to the Lipman-Zariski conjecture for klt spaces.

  11. Regularized canonical correlation analysis with unlabeled data

    Institute of Scientific and Technical Information of China (English)

    Xi-chuan ZHOU; Hai-bin SHEN

    2009-01-01

    In standard canonical correlation analysis (CCA), the data from definite datasets are used to estimate their canonical correlation. In real applications, for example in bilingual text retrieval, it may have a great portion of data that we do not know which set it belongs to. This part of data is called unlabeled data, while the rest from definite datasets is called labeled data. We propose a novel method called regularized canonical correlation analysis (RCCA), which makes use of both labeled and unlabeled samples. Specifically, we learn to approximate canonical correlation as if all data were labeled. Then. we describe a generalization of RCCA for the multi-set situation. Experiments on four real world datasets, Yeast, Cloud, Iris, and Haberman, demonstrate that,by incorporating the unlabeled data points, the accuracy of correlation coefficients can be improved by over 30%.

  12. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  13. Subsets of configurations and canonical partition functions

    DEFF Research Database (Denmark)

    Bloch, J.; Bruckmann, F.; Kieburg, M.;

    2013-01-01

    We explain the physical nature of the subset solution to the sign problem in chiral random matrix theory: the subset sum over configurations is shown to project out the canonical determinant with zero quark charge from a given configuration. As the grand canonical chiral random matrix partition f...... function is independent of the chemical potential, the zero-quark-charge sector provides the full result. © 2013 American Physical Society....

  14. Canonical equations of Hamilton with beautiful symmetry

    OpenAIRE

    Liang, Guo; Guo, Qi

    2012-01-01

    The Hamiltonian formulation plays the essential role in constructing the framework of modern physics. In this paper, a new form of canonical equations of Hamilton with the complete symmetry is obtained, which are valid not only for the first-order differential system, but also for the second-order differential system. The conventional form of the canonical equations without the symmetry [Goldstein et al., Classical Mechanics, 3rd ed, Addison-Wesley, 2001] are only for the second-order differe...

  15. Heisenberg Uncertainty Relation for Three Canonical Observables

    OpenAIRE

    Kechrimparis, Spiros; Weigert, Stefan

    2014-01-01

    Uncertainty relations provide fundamental limits on what can be said about the properties of quantum systems. For a quantum particle, the commutation relation of position and momentum observables entails Heisenberg's uncertainty relation. A third observable is presented which satisfies canonical commutation relations with both position and momentum. The resulting triple of pairwise canonical observables gives rise to a Heisenberg-type uncertainty relation for the product of three standard dev...

  16. Refining inflation using non-canonical scalars

    Energy Technology Data Exchange (ETDEWEB)

    Unnikrishnan, Sanil; Sahni, Varun [Inter-University Centre for Astronomy and Astrophysics, Post Bag 4, Ganeshkhind, Pune 411 007 (India); Toporensky, Aleksey, E-mail: sanil@iucaa.ernet.in, E-mail: varun@iucaa.ernet.in, E-mail: atopor@rambler.ru [Sternberg Astronomical Institute, Moscow State University, Universitetsky Prospekt, 13, Moscow 119992 (Russian Federation)

    2012-08-01

    This paper revisits the Inflationary scenario within the framework of scalar field models possessing a non-canonical kinetic term. We obtain closed form solutions for all essential quantities associated with chaotic inflation including slow roll parameters, scalar and tensor power spectra, spectral indices, the tensor-to-scalar ratio, etc. We also examine the Hamilton-Jacobi equation and demonstrate the existence of an inflationary attractor. Our results highlight the fact that non-canonical scalars can significantly improve the viability of inflationary models. They accomplish this by decreasing the tensor-to-scalar ratio while simultaneously increasing the value of the scalar spectral index, thereby redeeming models which are incompatible with the cosmic microwave background (CMB) in their canonical version. For instance, the non-canonical version of the chaotic inflationary potential, V(φ) ∼ λφ{sup 4}, is found to agree with observations for values of λ as large as unity! The exponential potential can also provide a reasonable fit to CMB observations. A central result of this paper is that steep potentials (such as V∝φ{sup −n}) usually associated with dark energy, can drive inflation in the non-canonical setting. Interestingly, non-canonical scalars violate the consistency relation r = −8n{sub T}, which emerges as a smoking gun test for this class of models.

  17. Hori method for generalized canonical systems

    Science.gov (United States)

    da Silva Fernandes, Sandro

    2009-01-01

    In this paper, some special features on the canonical version of Hori method, when it is applied to generalized canonical systems (systems of differential equations described by a Hamiltonian function linear in the momenta), are presented. Two different procedures, based on a new approach for the integration theory recently presented for the canonical version, are proposed for determining the new Hamiltonian and the generating function for systems whose differential equations for the coordinates describe a periodic system with one fast phase. These procedures are equivalent and they are directly related to the canonical transformations defined by the general solution of the integrable kernel of the Hamiltonian. They provide the same near-identity transformation for the coordinates obtained through the non-canonical version of Hori method. It is also shown that these procedures are connected to the classic averaging principle through a canonical transformation. As examples, asymptotic solutions of a non-linear oscillations problem and of the elliptic perturbed problem are discussed.

  18. The application of the TRAC-PD2 code in the CANON experiment

    International Nuclear Information System (INIS)

    The TRAC code (Transient Reactor Analysis Code), developed in the Los Alamos National Laboratory, is used to accident analysis in light water reactor. The TRAC-PD2 version, used in this paper, has a refined dynamic flow model for two fluids, which is based on the conservation equations of mass, momentum and energy for liquid and vapor, allowing then a mechanical and thermal unbalance between phases. This paper presents a comparison of the TRAC-PD2 code with the CANON experiment, which simulates a Loss of Coolant Accident (LOCA) by depressurizing a horizontal tube filled with water at different temperatures. The experiment consists in a instantaneous rupture in one of the tube's edge, taking measures of pressure and void fraction during the transient. The TRAC-PD2 code results are in a good agreement with the pressure and void fraction evolution obtained in the CANON experiment. (author)

  19. Histamine H1-receptor-mediated increase in the Ca2+ transient without a change in the Ca2+ current in electrically stimulated guinea-pig atrial myocytes

    OpenAIRE

    Yoshimoto, Kimihiro; Hattori, Yuichi; Houzen, Hideki; Kanno, Morio; Yasuda, Keishu

    1998-01-01

    The effects of histamine on the intracellular Ca2+ concentration ([Ca2+]i), action potential and membrane currents were assessed in single atrial myocytes prepared from guinea-pigs.Histamine caused a concentration-dependent increase in the [Ca2+]i transient in indo1/AM loaded myocytes when stimulated electrically at 0.5 Hz. However, the maximum increase in [Ca2+]i transient produced by histamine was less than 50% of that elicited by isoprenaline. The histamine-induced increase in [Ca2+]i tran...

  20. The relevance of the non-canonical PTS1 of peroxisomal catalase

    OpenAIRE

    Williams, Chris; Aksam, Eda Bener; Gunkel, Katja; Veenhuis, Marten; van der Klei, Ida J.

    2012-01-01

    Catalase is sorted to peroxisomes via a C-terminal peroxisomal targeting signal 1 (PTS1), which binds to the receptor protein Pex5. Analysis of the C-terminal sequences of peroxisomal catalases from various species indicated that catalase never contains the typical C-terminal PTS1 tripeptide-SKL, but invariably is sorted to peroxisomes via a non-canonical sorting sequence. We analyzed the relevance of the non-canonical PTS1 of catalase of the yeast Hansenula polymorpha (-SKI). Using isotherma...

  1. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, RR; Nasser, A; Falk, S;

    2012-01-01

    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ......X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1...

  2. Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

    Science.gov (United States)

    Annas, Anita; Berg, Anna-Lena; Nyman, Eva; Meijer, Thomas; Lundgren, Viveka; Franzén, Bo; Ståhle, Lars

    2015-12-01

    During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 μM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model. PMID:26046936

  3. IFN signaling: how a non-canonical model led to the development of IFN mimetics

    Directory of Open Access Journals (Sweden)

    Howard M Johnson

    2013-07-01

    Full Text Available The classical model of cytokine signaling dominates our view of specific gene activation by cytokines such as the interferons (IFNs. The importance of the model extends beyond cytokines and applies to hormones such as growth hormone (GH and insulin, and growth factors such as epidermal growth factor (EGF and fibroblast growth factor (FGF. According to this model, ligand activates the cell via interaction with the extracellular domain of the receptor. This results in activation of receptor or receptor-associated tyrosine kinases, primarily of the Janus kinase (JAK family, phosphorylation and dimerization of the STAT transcription factors, which dissociate from the receptor cytoplasmic domain and translocate to the nucleus. This view ascribes no further role to the ligand, JAK kinase, or receptor in either specific gene activation or the associated epigenetic events. The presence of dimeric STATs in the nucleus essentially explains it all. Our studies have resulted in the development of a non-canonical, more complex model of IFNγ signaling that is akin to that of steroid hormone/steroid receptor signaling. We have shown that ligand, receptor, activated JAKs and STATs are associated with specific gene activation, where the receptor subunit IFNGR1 functions as a co-transcription factor and the JAKs are involved in associated epigenetic events. We found that the type I IFN system functions similarly. The fact that GH receptor, insulin receptor, EGF receptor, and FGF receptor undergo nuclear translocation upon ligand binding suggests that they may also function similarly. The steroid hormone/steroid receptor nature of type I and II IFN signaling provides insight into the specificity of signaling by members of cytokine families. The non-canonical model could also provide better understanding to more complex cytokine families such as those of IL-2 and IL-12, whose members often use the same JAKs and STATs, but also have different functions and

  4. Universal canonical entropy for gravitating systems

    Indian Academy of Sciences (India)

    Ashok Chatterjee; Parthasarathi Majumdar

    2004-10-01

    The thermodynamics of general relativistic systems with boundary, obeying a Hamiltonian constraint in the bulk, is determined solely by the boundary quantum dynamics, and hence by the area spectrum. Assuming, for large area of the boundary, (a) an area spectrum as determined by non-perturbative canonical quantum general relativity (NCQGR), (b) an energy spectrum that bears a power law relation to the area spectrum, (c) an area law for the leading order microcanonical entropy, leading thermal fluctuation corrections to the canonical entropy are shown to be logarithmic in area with a universal coefficient. Since the microcanonical entropy also has universal logarithmic corrections to the area law (from quantum space-time fluctuations, as found earlier) the canonical entropy then has a universal form including logarithmic corrections to the area law. This form is shown to be independent of the index appearing in assumption (b). The index, however, is crucial in ascertaining the domain of validity of our approach based on thermal equilibrium.

  5. Covariant Gauge Fixing and Canonical Quantization

    CERN Document Server

    McKeon, D G C

    2011-01-01

    Theories that contain first class constraints possess gauge invariance which results in the necessity of altering the measure in the associated quantum mechanical path integral. If the path integral is derived from the canonical structure of the theory, then the choice of gauge conditions used in constructing Faddeev's measure cannot be covariant. This shortcoming is normally overcome either by using the "Faddeev-Popov" quantization procedure, or by the approach of Batalin-Fradkin-Fradkina-Vilkovisky, and then demonstrating that these approaches are equivalent to the path integral constructed from the canonical approach with Faddeev's measure. We propose in this paper an alternate way of defining the measure for the path integral when it is constructed using the canonical procedure for theories containing first class constraints and that this new approach can be used in conjunction with covariant gauges. This procedure follows the Faddeev-Popov approach, but rather than working with the form of the gauge tran...

  6. The random-variable canonical distribution

    International Nuclear Information System (INIS)

    An alternative interpretation to Gibbs' concept of the canonical distribution for an ensemble of systems in statistical equilibrium is proposed. Whereas Gibbs' theory is based upon a consideration of systems subject to dynamical law, the present analysis relies neither on the classical equations of motion nor makes use of any a priori probability of a complexion; rather, it makes avail of the basic algebra of random variables and, specifically, invokes the law of large numbers. Thereby, a canonical distribution is derived which describes a macrosystem in probabilistic, rather than deterministic, terms, and facilitates the understanding of energy fluctuations which occur in macrosystems at an overall constant ensemble temperature. A discussion is given of a modified form of the Gibbs canonical distribution which takes full account of the effects of random energy fluctuations. It is demonstrated that the results from this modified analysis are entirely consonant with those derived from the random-variable approach. (author)

  7. A Canonical Analysis of the Massless Superparticle

    CERN Document Server

    McKeon, D G C

    2012-01-01

    The canonical structure of the action for a massless superparticle is considered in d = 2 + 1 and d = 3 + 1 dimensions. This is done by examining the contribution to the action of each of the components of the spinor {\\theta} present; no attempt is made to maintain manifest covariance. Upon using the Dirac Bracket to eliminate the second class constraints arising from the canonical momenta associated with half of these components, we find that the remaining components have canonical momenta that are all first class constraints. From these first class constraints, it is possible to derive the generator of half of the local Fermionic {\\kappa}-symmetry of Siegel; which half is contingent upon the choice of which half of the momenta associated with the components of {\\theta} are taken to be second class constraints. The algebra of the generator of this Fermionic symmetry transformation is examined.

  8. Functional linear regression via canonical analysis

    CERN Document Server

    He, Guozhong; Wang, Jane-Ling; Yang, Wenjing; 10.3150/09-BEJ228

    2011-01-01

    We study regression models for the situation where both dependent and independent variables are square-integrable stochastic processes. Questions concerning the definition and existence of the corresponding functional linear regression models and some basic properties are explored for this situation. We derive a representation of the regression parameter function in terms of the canonical components of the processes involved. This representation establishes a connection between functional regression and functional canonical analysis and suggests alternative approaches for the implementation of functional linear regression analysis. A specific procedure for the estimation of the regression parameter function using canonical expansions is proposed and compared with an established functional principal component regression approach. As an example of an application, we present an analysis of mortality data for cohorts of medflies, obtained in experimental studies of aging and longevity.

  9. Non-canonical NFκB activation promotes chemokine expression in podocytes

    Science.gov (United States)

    Valiño-Rivas, Lara; Gonzalez-Lafuente, Laura; Sanz, Ana B.; Ruiz-Ortega, Marta; Ortiz, Alberto; Sanchez-Niño, Maria D.

    2016-01-01

    TNF-like weak inducer of apoptosis (TWEAK) receptor Fn14 is expressed by podocytes and Fn14 deficiency protects from experimental proteinuric kidney disease. However, the downstream effectors of TWEAK/Fn14 in podocytes are poorly characterized. We have explored TWEAK activation of non-canonical NFκB signaling in cultured podocytes. In cultured podocytes, TWEAK increased the expression of the chemokines CCL21, CCL19 and RANTES in a time-dependent manner. The inhibitor of canonical NFκB activation parthenolide inhibited the CCL19 and the early RANTES responses, but not the CCL21 or late RANTES responses. In this regard, TWEAK induced non-canonical NFκB activation in podocytes, characterized by NFκB2/p100 processing to NFκB2/p52 and nuclear migration of RelB/p52. Silencing by a specific siRNA of NIK, the upstream kinase of the non-canonical NFκB pathway, prevented CCL21 upregulation but did not modulate CCL19 or RANTES expression in response to TWEAK, thus establishing CCL21 as a non-canonical NFκB target in podocytes. Increased kidney Fn14 and CCL21 expression was also observed in rat proteinuric kidney disease induced by puromycin, and was localized to podocytes. In conclusion, TWEAK activates the non-canonical NFκB pathway in podocytes, leading to upregulation of CCL21 expression. The non-canonical NFκB pathway should be explored as a potential therapeutic target in proteinuric kidney disease. PMID:27353019

  10. Canonical quantization of generally covariant systems

    International Nuclear Information System (INIS)

    Kretschmann (1917) argued that general relativity does not satisfy any relativity principle and that it is actually a theory of absolute space-time. The issues raised by Kretschmann, that of Hamiltonian dynamics and of canonical quantization of generally covariant systems, are discussed. The questions raised are: what is the role of space-time diffeomorphisms in Hamiltonian dynamics of generally covariant systems, what is the role of isometries in Hamiltonian dynamics of such systems and what happens to both problems in canonical quantization. (author)

  11. Canonic form of linear quaternion functions

    OpenAIRE

    Sangwine, Stephen J.

    2008-01-01

    The general linear quaternion function of degree one is a sum of terms with quaternion coefficients on the left and right. The paper considers the canonic form of such a function, and builds on the recent work of Todd Ell, who has shown that any such function may be represented using at most four quaternion coefficients. In this paper, a new and simple method is presented for obtaining these coefficients numerically using a matrix approach which also gives an alternative proof of the canonic ...

  12. Canonical transformations and Hamiltonian evolutionary systems

    International Nuclear Information System (INIS)

    In many Lagrangian field theories, one has a Poisson bracket defined on the space of local functionals. We find necessary and sufficient conditions for a transformation on the space of local functionals to be canonical in three different cases. These three cases depend on the specific dimensions of the vector bundle of the theory and the associated Hamiltonian differential operator. We also show how a canonical transformation transforms a Hamiltonian evolutionary system and its conservation laws. Finally, we illustrate these ideas with three examples.

  13. Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

    DEFF Research Database (Denmark)

    Bortz, D M; Mikkelsen, J D; Bruno, J P

    2013-01-01

    The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate level...

  14. Transients recorder

    International Nuclear Information System (INIS)

    KWU keeps a file on transients for the PWR plants. This file stores test data and significant graphs and curves of readings which are sent to the manufacturer for analysis. The data are used to produce analyses of the dynamics and incidents/deviations in operation. In addition, comprehensive simulation models are fed with readings from practical operation. The paper outlines the development aims, the historical evolution, the hardware and software concepts, the acquisition/detection method, applications and examples. (DG)

  15. Canonical vs. micro-canonical sampling methods in a 2D Ising model

    International Nuclear Information System (INIS)

    Canonical and micro-canonical Monte Carlo algorithms were implemented on a 2D Ising model. Expressions for the internal energy, U, inverse temperature, Z, and specific heat, C, are given. These quantities were calculated over a range of temperature, lattice sizes, and time steps. Both algorithms accurately simulate the Ising model. To obtain greater than three decimal accuracy from the micro-canonical method requires that the more complicated expression for Z be used. The overall difference between the algorithms is small. The physics of the problem under study should be the deciding factor in determining which algorithm to use. 13 refs., 6 figs., 2 tabs

  16. Kuidas Canon suureks kasvas / Andres Eilart

    Index Scriptorium Estoniae

    Eilart, Andres

    2004-01-01

    Jaapani kaamerate ja büroomasinate tootja Canon Groupi arengust, tegevusest kolmes regioonis - USA-s, Euroopas ja Aasias ning ettevõtte pikaajalise edu põhjustest - ärifilosoofiast ning ajastatud tootearendusest. Vt. samas: Firma esialgne nimi oli Kwanon; Konkurendid koonduvad

  17. On the canonical treatment of Lagrangian constraints

    International Nuclear Information System (INIS)

    The canonical treatment of dynamic systems with manifest Lagrangian constraints proposed by Berezin is applied to concrete examples: a special Lagrangian linear in velocities, relativistic particles in proper time gauge, a relativistic string in orthonormal gauge, and the Maxwell field in the Lorentz gauge

  18. Canonical Quantization of Higher-Order Lagrangians

    Directory of Open Access Journals (Sweden)

    Khaled I. Nawafleh

    2011-01-01

    Full Text Available After reducing a system of higher-order regular Lagrangian into first-order singular Lagrangian using constrained auxiliary description, the Hamilton-Jacobi function is constructed. Besides, the quantization of the system is investigated using the canonical path integral approximation.

  19. On the generalized Lorenz canonical form

    Czech Academy of Sciences Publication Activity Database

    Čelikovský, Sergej; Guanrong, Ch.

    2005-01-01

    Roč. 26, č. 5 (2005), s. 1271-1276. ISSN 0960-0779 R&D Projects: GA ČR GA102/05/0011; GA MŠk 1P05LA262 Institutional research plan: CEZ:AV0Z10750506 Keywords : chaos * synchronization * canonical form Subject RIV: BC - Control Systems Theory Impact factor: 1.938, year: 2005

  20. Infants' Recognition of Objects Using Canonical Color

    Science.gov (United States)

    Kimura, Atsushi; Wada, Yuji; Yang, Jiale; Otsuka, Yumiko; Dan, Ippeita; Masuda, Tomohiro; Kanazawa, So; Yamaguchi, Masami K.

    2010-01-01

    We explored infants' ability to recognize the canonical colors of daily objects, including two color-specific objects (human face and fruit) and a non-color-specific object (flower), by using a preferential looking technique. A total of 58 infants between 5 and 8 months of age were tested with a stimulus composed of two color pictures of an object…

  1. Canonical duties, liabilities of trustees and administrators.

    Science.gov (United States)

    Morrisey, F G

    1985-06-01

    The new Code of Canon Law outlines a number of duties of those who have responsibility for administering the Church's temporal goods. Before assuming office, administrators must pledge to be efficient and faithful, and they must prepare an inventory of goods belonging to the juridic person they serve. Among their duties, administrators must: Ensure that adequate insurance is provided; Use civilly valid methods to protect canonical ownership of the goods; Observe civil and canon law prescriptions as well as donors' intentions; Collect and safeguard revenues, repay debts, and invest funds securely; Maintain accurate records, keep documents secure, and prepare an annual budget; Prepare an annual report and present it to the Ordinary where prescribed; Observe civil law concerning labor and social policy, and pay employees a just and decent wage. Administrators who carry out acts that are invalid canonically are liable for such acts. The juridic person is not liable, unless it derived benefit from the transaction. Liability is especially high when the sale of property is involved or when a contract is entered into without proper cannonical consent. Although Church law is relatively powerless to punish those who have been negligent, stewards, administrators, and trustees must do all they can to be truthful to the responsibility with which they have been entrusted. PMID:10271510

  2. Conservation laws of semidiscrete canonical Hamiltonian equations

    International Nuclear Information System (INIS)

    There are many evolution partial differential equations which can be cast into Hamiltonian form. Conservation laws of these equations are related to one-parameter Hamiltonian symmetries admitted by the PDEs. The same result holds for semidiscrete Hamiltonian equations. In this paper we consider semidiscrete canonical Hamiltonian equations. Using symmetries, we find conservation laws for the semidiscretized nonlinear wave equation and Schroedinger equation. (author)

  3. Kelvin's Canonical Circulation Theorem in Hall Magnetohydrodynamics

    CERN Document Server

    Shivamoggi, B K

    2016-01-01

    The purpose of this paper is to show that, thanks to the restoration of the legitimate connection between the current density and the plasma flow velocity in Hall magnetohydrodynamics (MHD), Kelvin's Circulation Theorem becomes valid in Hall MHD. The ion-flow velocity in the usual circulation integral is now replaced by the canonical ion-flow velocity.

  4. Canonical Ensemble Model for Black Hole Radiation

    Indian Academy of Sciences (India)

    Jingyi Zhang

    2014-09-01

    In this paper, a canonical ensemble model for the black hole quantum tunnelling radiation is introduced. In this model the probability distribution function corresponding to the emission shell is calculated to second order. The formula of pressure and internal energy of the thermal system is modified, and the fundamental equation of thermodynamics is also discussed.

  5. Canonical brackets of a toy model for the Hodge theory without its canonical conjugate momenta

    CERN Document Server

    Shukla, D; Malik, R P

    2014-01-01

    We consider the toy model of a rigid rotor as an example of the Hodge theory within the framework of the Becchi-Rouet-Stora-Tyutin (BRST) formalism and show that the internal symmetries of this theory lead to the derivation of canonical brackets amongst the creation and annihilation operators of the dynamical variables where the definition of the canonical conjugate momenta is not required. We invoke only the spin-statistics theorem, normal ordering and basic concepts of continuous symmetries (and their generators) to derive the canonical brackets for the model of a one (0 + 1)-dimensional (1D) rigid rotor without using the definition of the canonical conjugate momenta anywhere. Our present method of derivation of the basic brackets is conjectured to be true for a class of theories that provide a set of tractable physical examples for the Hodge theory.

  6. Canonical brackets of a toy model for the Hodge theory without its canonical conjugate momenta

    Science.gov (United States)

    Shukla, D.; Bhanja, T.; Malik, R. P.

    2015-07-01

    We consider the toy model of a rigid rotor as an example of the Hodge theory within the framework of Becchi-Rouet-Stora-Tyutin (BRST) formalism and show that the internal symmetries of this theory lead to the derivation of canonical brackets amongst the creation and annihilation operators of the dynamical variables where the definition of the canonical conjugate momenta is not required. We invoke only the spin-statistics theorem, normal ordering and basic concepts of continuous symmetries (and their generators) to derive the canonical brackets for the model of a one (0 + 1)-dimensional (1D) rigid rotor without using the definition of the canonical conjugate momenta anywhere. Our present method of derivation of the basic brackets is conjectured to be true for a class of theories that provide a set of tractable physical examples for the Hodge theory.

  7. Canon musical y canon musicológico desde una perspectiva de la música chilena

    Directory of Open Access Journals (Sweden)

    Luis Merino Montero

    2006-06-01

    Full Text Available El canon y el acto de canonizar forman parte de un juicio de valor aplicable a la música de arte europea, en una tripartición que involucra al creador, su obra y el impacto de la música en un receptor o público como resultado del proceso social de comunicación. Durante muchos años la música centroeuropea y su canon representó en Latinoamérica el lenguaje musical por excelencia, al cual se subordinaban todos los otros lenguajes musicales cultivados en el continente. El proceso de canonizar lo realizaba el musicólogo, el compositor o, más raramente, los intérpretes, de manera generalmente disociada. Con la conformación de una cultura de masas de base industrial en la década de los 50, característica de la así llamada modernidad latinoamericana, y el desarrollo masivo de la creatividad en la pluralidad de tradiciones musicales cultivadas en el continente, la música de arte no constituye hoy día el único posible referente canónico. Por el contrario, los referentes canónicos en Chile y Latinoamérica están, en muchos casos, fuera de la música de arte. Esto plantea un desafío formidable a la musicología, el cual debe ser abordado mediante la convergencia disciplinaria intra y extra musicológica, además de la generación de una crítica musicológica, que sirva de base para la formulación del juicio de valor, en que se interactúen el musicólogo, el compositor y el intérpretemusic, within a tripartition involving the composer, his work and the impact of music upon an audience as a result of the social process of music comunication. For many years the music from Central Europe and its canon was considered in Latin America as the musical language par excellence. All other musics were valued by the yardstick of European art music. The canonizing was carried out by musicologists, composers or less frequently by performers, usually in a totally unrelated manner. With the establishment of a mass culture in the fifties, typical

  8. Canonical brackets of a toy model for the Hodge theory without its canonical conjugate momenta

    OpenAIRE

    D Shukla; Bhanja, T.; Malik, R. P.

    2014-01-01

    We consider the toy model of a rigid rotor as an example of the Hodge theory within the framework of the Becchi-Rouet-Stora-Tyutin (BRST) formalism and show that the internal symmetries of this theory lead to the derivation of canonical brackets amongst the creation and annihilation operators of the dynamical variables where the definition of the canonical conjugate momenta is not required. We invoke only the spin-statistics theorem, normal ordering and basic concepts of continuous symmetries...

  9. Triality and the grand canonical ensemble in QCD

    International Nuclear Information System (INIS)

    QCD in the usual finite temperature formulation is using the grand canonical ensemble with chemical potential zero. We demonstrate that this description may give wrong predictions. QCD in the canonical formulation does not explicitly break Z(3) symmetry. It behaves in this sense like pure gluonic QCD. There are no metastable states in the canonical ensemble description as predicted in the grand canonical ensemble formalism. ((orig.))

  10. An introduction to the theory of canonical matrices

    CERN Document Server

    Turnbull, H W

    2004-01-01

    Thorough and self-contained, this penetrating study of the theory of canonical matrices presents a detailed consideration of all the theory's principal features. Topics include elementary transformations and bilinear and quadratic forms; canonical reduction of equivalent matrices; subgroups of the group of equivalent transformations; and rational and classical canonical forms. The final chapters explore several methods of canonical reduction, including those of unitary and orthogonal transformations. 1952 edition. Index. Appendix. Historical notes. Bibliographies. 275 problems.

  11. Contribution of the putative inner-pore region to the gating of the Transient Receptor Potential Vanilloid Subtype 1 Channel (TRPV1)

    Czech Academy of Sciences Publication Activity Database

    Sušánková, Klára; Ettrich, Rüdiger; Vyklický st., Ladislav; Teisinger, Jan; Vlachová, Viktorie

    2007-01-01

    Roč. 27, č. 28 (2007), s. 7578-7585. ISSN 0270-6474 R&D Projects: GA ČR(CZ) GA305/06/0319; GA ČR(CZ) GA303/07/0915; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA MŠk LC06010 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z60870520 Keywords : capsaicin * vanilloid receptor * TRP channels Subject RIV: ED - Physiology Impact factor: 7.490, year: 2007

  12. Dunkl Operators and Canonical Invariants of Reflection Groups

    OpenAIRE

    Arkady Berenstein; Yurii Burman

    2008-01-01

    Using Dunkl operators, we introduce a continuous family of canonical invariants of finite reflection groups. We verify that the elementary canonical invariants of the symmetric group are deformations of the elementary symmetric polynomials. We also compute the canonical invariants for all dihedral groups as certain hypergeometric functions.

  13. Comparison between RELAP5/MOD1 and TRAC-PD2 codes in the CANON experience

    International Nuclear Information System (INIS)

    The present work reports comparisons between experimental and theoretical data done with the RELAP5/MOD1 and TRAC-PD2 codes, with particular emphasis on RELAP5/MOD1 code run with basic experimental data from the CANON depressurization simulation. This experiment simulates a Loss of Primary Coolant Accident due to a Large Rupture - LOCA, through the depressurization of a horizontal tube containing water with the instantaneous break of one side of the tube where measurements of pressure, temperature and void fraction are taken during the transient. The results of this comparison show that RELAP5/MOD1 code predict more satisfactorily the time dependent behavior of the pressure and void fraction than TRAC-PD2 code for several initial condition considered in the CANON experiment. (author)

  14. Canonical analysis based on mutual information

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2015-01-01

    Canonical correlation analysis (CCA) is an established multi-variate statistical method for finding similarities between linear combinations of (normally two) sets of multivariate observations. In this contribution we replace (linear) correlation as the measure of association between the linear...... combinations with the information theoretical measure mutual information (MI). We term this type of analysis canonical information analysis (CIA). MI allows for the actual joint distribution of the variables involved and not just second order statistics. While CCA is ideal for Gaussian data, CIA facilitates...... analysis of variables with different genesis and therefore different statistical distributions and different modalities. As a proof of concept we give a toy example. We also give an example with one (weather radar based) variable in the one set and eight spectral bands of optical satellite data in the...

  15. DNA pattern recognition using canonical correlation algorithm

    Indian Academy of Sciences (India)

    B K Sarkar; Chiranjib Chakraborty

    2015-10-01

    We performed canonical correlation analysis as an unsupervised statistical tool to describe related views of the same semantic object for identifying patterns. A pattern recognition technique based on canonical correlation analysis (CCA) was proposed for finding required genetic code in the DNA sequence. Two related but different objects were considered: one was a particular pattern, and other was test DNA sequence. CCA found correlations between two observations of the same semantic pattern and test sequence. It is concluded that the relationship possesses maximum value in the position where the pattern exists. As a case study, the potential of CCA was demonstrated on the sequence found from HIV-1 preferred integration sites. The subsequences on the left and right flanking from the integration site were considered as the two views, and statistically significant relationships were established between these two views to elucidate the viral preference as an important factor for the correlation.

  16. Genre, canon et monstruosités

    OpenAIRE

    2010-01-01

    Le numéro sept de notre revue réunit les collaborations d’Isabelle López García (posthume), transition intéressante entre canon littéraire, canon social et figuration des corps rendus monstrueux par le fléau du sida ; de Richard Cleminson, spécialiste de l’histoire de la sexualité (en annexe), ainsi que celles de plusieurs chercheures et chercheurs présent.e.s aux journées d’étude entre Toulouse et Tours : Cecilia González analyse le dialogue entre les “anciens et les modernes” à trav...

  17. Rewriting Canonical Love Stories from the Peripheries

    OpenAIRE

    Yang, Karen Ya-Chu

    2013-01-01

    In her article "Rewriting Canonical Love Stories from the Peripheries" Karen Ya-Chu Yang compares postcolonial and postmodern intertextuality in Taiwanese and the Caribbean texts. Hsien-Yung Pai's "Wandering in the Garden, Waking from a Dream" (1966) and Tien-Hsin Chu's "Breakfast at Tiffany's" (1997) are two short stories which depict identity crises of first generation and second generation 外省人 (waishen gren, mainland immigrants). In these two texts disillusionment towards the center's roma...

  18. On Complex Supermanifolds with Trivial Canonical Bundle

    CERN Document Server

    Groeger, Josua

    2016-01-01

    We give an algebraic characterisation for the triviality of the canonical bundle of a complex supermanifold in terms of a certain Batalin-Vilkovisky superalgebra structure. As an application, we study the Calabi-Yau case, in which an explicit formula in terms of the Levi-Civita connection is achieved. Our methods include the use of complex integral forms and the recently developed theory of superholonomy.

  19. Canonical quantization of substrate-less fields

    CERN Document Server

    Gründler, Gerold

    2015-01-01

    An improved law for the canonical quantization of fields is presented, which is based on the distinction between fields which have a material substrate, and substrate-less fields. It is shown that the improved quantization method solves the (old) cosmological constant problem for all fields of the standard model of elementary particles and for the metric field, but not for the hypothetical inflaton fields, without compromising any of the achievements of the established quantum field theories.

  20. THEOLOGY OF CANONS IN CATHOLIC UNIVERSITIES?

    OpenAIRE

    IVÁN FEDERICO MEJÍA A

    2010-01-01

    Is it useful today, or necessary, an interpretation of the Code of Canon Law from Christology? The article examines some opposition which consider as inappropriate to search for foundations or links from "outside" the Code itself and the normal legislative living tradition of the Catholic Church. The Second Vatican Council and Pope John Paul II sponsored a theological interpretation of the Code, and this article summarizes some features of the validation, method, and the successful applicatio...

  1. A canonical representation for aggregated Markov processes

    OpenAIRE

    Larget, Bret

    1998-01-01

    A deterministic function of a Markov process is called an aggregated Markov process. We give necessary and sufficient conditions for the equivalence of continuous-time aggregated Markov processes. For both discrete- and continuous-time, we show that any aggregated Markov process which satisfies mild regularity conditions can be directly converted to a canonical representation which is unique for each class of equivalent models, and furthermore, is a minimal parameterization ...

  2. Canonical Energy is Quantum Fisher Information

    CERN Document Server

    Lashkari, Nima

    2015-01-01

    In quantum information theory, Fisher Information is a natural metric on the space of perturbations to a density matrix, defined by calculating the relative entropy with the unperturbed state at quadratic order in perturbations. In gravitational physics, Canonical Energy defines a natural metric on the space of perturbations to spacetimes with a Killing horizon. In this paper, we show that the Fisher information metric for perturbations to the vacuum density matrix of a ball-shaped region B in a holographic CFT is dual to the canonical energy metric for perturbations to a corresponding Rindler wedge R_B of Anti-de-Sitter space. Positivity of relative entropy at second order implies that the Fisher information metric is positive definite. Thus, for physical perturbations to anti-de-Sitter spacetime, the canonical energy associated to any Rindler wedge must be positive. This second-order constraint on the metric extends the first order result from relative entropy positivity that physical perturbations must sat...

  3. Extending canonical Monte Carlo methods: II

    Science.gov (United States)

    Velazquez, L.; Curilef, S.

    2010-04-01

    We have previously presented a methodology for extending canonical Monte Carlo methods inspired by a suitable extension of the canonical fluctuation relation C = β2langδE2rang compatible with negative heat capacities, C < 0. Now, we improve this methodology by including the finite size effects that reduce the precision of a direct determination of the microcanonical caloric curve β(E) = ∂S(E)/∂E, as well as by carrying out a better implementation of the MC schemes. We show that, despite the modifications considered, the extended canonical MC methods lead to an impressive overcoming of the so-called supercritical slowing down observed close to the region of the temperature driven first-order phase transition. In this case, the size dependence of the decorrelation time τ is reduced from an exponential growth to a weak power-law behavior, \\tau (N)\\propto N^{\\alpha } , as is shown in the particular case of the 2D seven-state Potts model where the exponent α = 0.14-0.18.

  4. Juridic status: canonical provisions, possible applications.

    Science.gov (United States)

    Morrisey, F G

    1986-09-01

    The 1983 Code of Canon Law presents the basic legislation regarding juridic persons, which are entities brought into existence to assist in carrying out the Church's mission. Juridic persons by nature are perpetual and are not directly identified with their members. The private juridic person, a concept introduced in the 1983 code, operates collegially on behalf of its members or noncollegially on behalf of the things that constitute it. A ministry that receives private juridic status does not share as integrally in the Church's name. The latter therefore has more duties to fulfill in regard to observance of Church law, particularly that concerning the administration of temporal goods. The goods of a private juridic person, in contrast, are not ecclesiastical and thus are not subject to canon law. Instead, the private juridic persons' statutes provide norms for their administration. Canon law in establishing juridic persons enables the ministries they represent to last beyond the lives of those who initiated the ministries. Juridic persons offer both security and possibilities for concerted apostolic activity in the Church. PMID:10277620

  5. Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats.

    Science.gov (United States)

    Saad, M A; Abdelsalam, R M; Kenawy, S A; Attia, A S

    2015-01-01

    Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to study the possible neuroprotective effect of Montelukast, a CysLTR1 antagonist in global cerebral ischemia/reperfusion (IR) injury in rats. Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into three groups (n = 30 per group): Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid), Cys-LTs contents and CysLT1 receptor expression; as well as total brain infarct size and histopathological examination of the hippocampus were assessed. Montelukast protected hippocampal tissue by reducing oxidative stress, inflammatory and apoptotic markers. Furthermore, it reduced glutamate and lactate dehydrogenase activity as well as infarct size elevated by I/R. These results were consistent with the histopathological findings. Montelukast showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms. PMID:25403620

  6. The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Michal Entin-Meer

    Full Text Available PURPOSE: A novel family of transient receptor potential (TRP channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2 mRNA in the left ventricles (LV 3-5 days post-acute myocardial infarction (MI compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI. METHODS: Lewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham. The animals were terminated at various time points and an immunohistochemical (IHC and immunofluorescent (IFC staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted. RESULTS: The IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced. CONCLUSIONS: TRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions.

  7. Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation

    Science.gov (United States)

    Yuan, Xue; Cao, Jay; He, Xiaoning; Serra, Rosa; Qu, Jun; Cao, Xu; Yang, Shuying

    2016-01-01

    Intraflagellar transport proteins (IFT) are required for hedgehog (Hh) signalling transduction that is essential for bone development, however, how IFT proteins regulate Hh signalling in osteoblasts (OBs) remains unclear. Here we show that deletion of ciliary IFT80 in OB precursor cells (OPC) in mice results in growth retardation and markedly decreased bone mass with impaired OB differentiation. Loss of IFT80 blocks canonical Hh–Gli signalling via disrupting Smo ciliary localization, but elevates non-canonical Hh–Gαi–RhoA–stress fibre signalling by increasing Smo and Gαi binding. Inhibition of RhoA and ROCK activity partially restores osteogenic differentiation of IFT80-deficient OPCs by inhibiting non-canonical Hh–RhoA–Cofilin/MLC2 signalling. Cytochalasin D, an actin destabilizer, dramatically restores OB differentiation of IFT80-deficient OPCs by disrupting actin stress fibres and promoting cilia formation and Hh–Gli signalling. These findings reveal that IFT80 is required for OB differentiation by balancing between canonical Hh–Gli and non-canonical Hh–Gαi–RhoA pathways and highlight IFT80 as a therapeutic target for craniofacial and skeletal abnormalities. PMID:26996322

  8. Transient congenital hypothyroidism

    Directory of Open Access Journals (Sweden)

    Nisha Bhavani

    2011-01-01

    Full Text Available Transient thyroid function abnormalities in the new born which revert back to normal after varying periods of time are mostly identified in the neonatal screening tests for thyroid and are becoming more common because of the survival of many more premature infants. It can be due to factors primarily affecting the thyroid-like iodine deficiency or excess, maternal thyroid-stimulating hormone receptor (TSHR antibodies, maternal use of antithyroid drugs, DUOX 2 (dual oxidase 2 mutations, and prematurity or those that affect the pituitary-like untreated maternal hyperthyroidism, prematurity, and drugs. Most of these require only observation, whereas some, such as those due to maternal TSHR antibodies may last for upto three-to-six months and may necessitate treatment. Isolated hyperthyrotropinemia (normal Tetraiodothyronine (T4 and high Thyroid Stimulating hormone (TSH may persist as subclinical hypothyroidism in childhood. Transient hypothyroxinemia (low T4 and normal TSH is very common in premature babies. The recognition of these conditions will obviate the risks associated with unnecessary thyroxine supplementation in childhood and parental concerns of a life long illness in their offspring.

  9. Canonical Notch activation in osteocytes causes osteopetrosis.

    Science.gov (United States)

    Canalis, Ernesto; Bridgewater, David; Schilling, Lauren; Zanotti, Stefano

    2016-01-15

    Activation of Notch1 in cells of the osteoblastic lineage inhibits osteoblast differentiation/function and causes osteopenia, whereas its activation in osteocytes causes a distinct osteopetrotic phenotype. To explore mechanisms responsible, we established the contributions of canonical Notch signaling (Rbpjκ dependent) to osteocyte function. Transgenics expressing Cre recombinase under the control of the dentin matrix protein-1 (Dmp1) promoter were crossed with Rbpjκ conditional mice to generate Dmp1-Cre(+/-);Rbpjκ(Δ/Δ) mice. These mice did not have a skeletal phenotype, indicating that Rbpjκ is dispensable for osteocyte function. To study the Rbpjκ contribution to Notch activation, Rosa(Notch) mice, where a loxP-flanked STOP cassette is placed between the Rosa26 promoter and the NICD coding sequence, were crossed with Dmp1-Cre transgenic mice and studied in the context (Dmp1-Cre(+/-);Rosa(Notch);Rbpjκ(Δ/Δ)) or not (Dmp1-Cre(+/-);Rosa(Notch)) of Rbpjκ inactivation. Dmp1-Cre(+/-);Rosa(Notch) mice exhibited increased femoral trabecular bone volume and decreased osteoclasts and bone resorption. The phenotype was reversed in the context of the Rbpjκ inactivation, demonstrating that Notch canonical signaling was accountable for the phenotype. Notch activation downregulated Sost and Dkk1 and upregulated Axin2, Tnfrsf11b, and Tnfsf11 mRNA expression, and these effects were not observed in the context of the Rbpjκ inactivation. In conclusion, Notch activation in osteocytes suppresses bone resorption and increases bone volume by utilization of canonical signals that also result in the inhibition of Sost and Dkk1 and upregulation of Wnt signaling. PMID:26578715

  10. Canonical group quantization and boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Florian

    2012-07-16

    In the present thesis, we study quantization of classical systems with non-trivial phase spaces using the group-theoretical quantization technique proposed by Isham. Our main goal is a better understanding of global and topological aspects of quantum theory. In practice, the group-theoretical approach enables direct quantization of systems subject to constraints and boundary conditions in a natural and physically transparent manner -- cases for which the canonical quantization method of Dirac fails. First, we provide a clarification of the quantization formalism. In contrast to prior treatments, we introduce a sharp distinction between the two group structures that are involved and explain their physical meaning. The benefit is a consistent and conceptually much clearer construction of the Canonical Group. In particular, we shed light upon the 'pathological' case for which the Canonical Group must be defined via a central Lie algebra extension and emphasise the role of the central extension in general. In addition, we study direct quantization of a particle restricted to a half-line with 'hard wall' boundary condition. Despite the apparent simplicity of this example, we show that a naive quantization attempt based on the cotangent bundle over the half-line as classical phase space leads to an incomplete quantum theory; the reflection which is a characteristic aspect of the 'hard wall' is not reproduced. Instead, we propose a different phase space that realises the necessary boundary condition as a topological feature and demonstrate that quantization yields a suitable quantum theory for the half-line model. The insights gained in the present special case improve our understanding of the relation between classical and quantum theory and illustrate how contact interactions may be incorporated.

  11. Canonical group quantization and boundary conditions

    International Nuclear Information System (INIS)

    In the present thesis, we study quantization of classical systems with non-trivial phase spaces using the group-theoretical quantization technique proposed by Isham. Our main goal is a better understanding of global and topological aspects of quantum theory. In practice, the group-theoretical approach enables direct quantization of systems subject to constraints and boundary conditions in a natural and physically transparent manner -- cases for which the canonical quantization method of Dirac fails. First, we provide a clarification of the quantization formalism. In contrast to prior treatments, we introduce a sharp distinction between the two group structures that are involved and explain their physical meaning. The benefit is a consistent and conceptually much clearer construction of the Canonical Group. In particular, we shed light upon the 'pathological' case for which the Canonical Group must be defined via a central Lie algebra extension and emphasise the role of the central extension in general. In addition, we study direct quantization of a particle restricted to a half-line with 'hard wall' boundary condition. Despite the apparent simplicity of this example, we show that a naive quantization attempt based on the cotangent bundle over the half-line as classical phase space leads to an incomplete quantum theory; the reflection which is a characteristic aspect of the 'hard wall' is not reproduced. Instead, we propose a different phase space that realises the necessary boundary condition as a topological feature and demonstrate that quantization yields a suitable quantum theory for the half-line model. The insights gained in the present special case improve our understanding of the relation between classical and quantum theory and illustrate how contact interactions may be incorporated.

  12. Evidence of non-canonical NOTCH signaling

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads;

    2016-01-01

    Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si......Canonical NOTCH signaling, known to be essential for tissue development, requires the Delta-Serrate-LAG2 (DSL) domain for NOTCH to interact with its ligand. However, despite lacking DSL, Delta-like 1 homolog (DLK1), a protein that plays a significant role in mammalian development, has been...

  13. Canonical particle tracking in undulator fields

    International Nuclear Information System (INIS)

    A new algebraic mapping routine for particle tracking across wiggler and undulator fields in presented. It is based on a power series expansion of the generating function to guarantee fully canonical transformations. This method is 10 to 100 times faster than integration routines, applied in tracking codes like BETA or RACETRACK. The tracking method presented is not restricted to wigglers and undulators, it can be applied to other magnetic fields as well such as fringing fields of quadrupoles or dipoles if the suggested expansion converges

  14. Kato expansion in quantum canonical perturbation theory

    Science.gov (United States)

    Nikolaev, Andrey

    2016-06-01

    This work establishes a connection between canonical perturbation series in quantum mechanics and a Kato expansion for the resolvent of the Liouville superoperator. Our approach leads to an explicit expression for a generator of a block-diagonalizing Dyson's ordered exponential in arbitrary perturbation order. Unitary intertwining of perturbed and unperturbed averaging superprojectors allows for a description of ambiguities in the generator and block-diagonalized Hamiltonian. We compare the efficiency of the corresponding computational algorithm with the efficiencies of the Van Vleck and Magnus methods for high perturbative orders.

  15. Path integrals for arbitrary canonical transformations

    International Nuclear Information System (INIS)

    Some aspects of the path integral formulation of quantum mechanics are studied. This formalism is generalized to arbitrary canonical transformations, by means of an association between path integral probalility amplitudes and classical generators of transformations, analogous to the usual Hamiltonian time development phase space expression. Such association turns out to be equivalent to the Weyl quantization rule, and it is also shown that this formalism furnishes a path integral representation for a Lie algebra of a given set of classical generators. Some physical considerations about the path integral quantization procedure and about the relationship between classical and quantum dynamical structures are also discussed. (Author)

  16. Transient pseudohypoaldosteronism

    Directory of Open Access Journals (Sweden)

    Stajić Nataša

    2011-01-01

    Full Text Available Introduction. Infants with urinary tract malformations (UTM presenting with urinary tract infection (UTI are prone to develop transient type 1 pseudohypoaldosteronism (THPA1. Objective. Report on patient series with characteristics of THPA1, UTM and/or UTI and suggestions for the diagnosis and therapy. Methods. Patients underwent blood and urine electrolyte and acid-base analysis, serum aldosterosterone levels and plasma rennin activity measuring; urinalysis, urinoculture and renal ultrasound were done and medical and/or surgical therapy was instituted. Results. Hyponatraemia (120.9±5.8 mmol/L, hyperkalaemia (6.9±0.9 mmol/L, metabolic acidosis (plasma bicarbonate, 11±1.4 mmol/L, and a rise in serum creatinine levels (145±101 μmol/L were associated with inappropriately high urinary sodium (51.3±17.5 mmol/L and low potassium (14.1±5.9 mmol/L excretion. Elevated plasma aldosterone concentrations (170.4±100.5 ng/dL and the very high levels of the plasma aldosterone to potassium ratio (25.2±15.6 together with diminished urinary K/Na values (0.31±0.19 indicated tubular resistance to aldosterone. After institution of appropriate medical and/or surgical therapy, serum electrolytes, creatinine, and acid-base balance were normalized. Imaging studies showed ureteropyelic or ureterovesical junction obstruction in 3 and 2 patients, respectively, posterior urethral valves in 3, and normal UT in 1 patient. According to our knowledge, this is the first report on THPA1 in the Serbian literature. Conclusion. Male infants with hyponatraemia, hyperkalaemia and metabolic acidosis have to have their urine examined and the renal ultrasound has to be done in order to avoid both, the underdiagnosis of THPA1 and the inappropriate medication.

  17. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    Science.gov (United States)

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

  18. Face hallucination using orthogonal canonical correlation analysis

    Science.gov (United States)

    Zhou, Huiling; Lam, Kin-Man

    2016-05-01

    A two-step face-hallucination framework is proposed to reconstruct a high-resolution (HR) version of a face from an input low-resolution (LR) face, based on learning from LR-HR example face pairs using orthogonal canonical correlation analysis (orthogonal CCA) and linear mapping. In the proposed algorithm, face images are first represented using principal component analysis (PCA). Canonical correlation analysis (CCA) with the orthogonality property is then employed, to maximize the correlation between the PCA coefficients of the LR and the HR face pairs to improve the hallucination performance. The original CCA does not own the orthogonality property, which is crucial for information reconstruction. We propose using orthogonal CCA, which is proven by experiments to achieve a better performance in terms of global face reconstruction. In addition, in the residual-compensation process, a linear-mapping method is proposed to include both the inter- and intrainformation about manifolds of different resolutions. Compared with other state-of-the-art approaches, the proposed framework can achieve a comparable, or even better, performance in terms of global face reconstruction and the visual quality of face hallucination. Experiments on images with various parameter settings and blurring distortions show that the proposed approach is robust and has great potential for real-world applications.

  19. New constraints for canonical general relativity

    CERN Document Server

    Reisenberger, M

    1995-01-01

    Ashtekar's canonical theory of classical complex Euclidean GR (no Lorentzian reality conditions) is found to be invariant under the full algebra of infinitesimal 4-diffeomorphisms, but non-invariant under some finite proper 4-diffeos when the densitized dreibein, \\tilE^a_i, is degenerate. The breakdown of 4-diffeo invariance appears to be due to the inability of the Ashtekar Hamiltonian to generate births and deaths of \\tilE flux loops (leaving open the possibility that a new `causality condition' forbidding the birth of flux loops might justify the non-invariance of the theory). A fully 4-diffeo invariant canonical theory in Ashtekar's variables, derived from Plebanski's action, is found to have constraints that are stronger than Ashtekar's for rank\\tilE < 2. The corresponding Hamiltonian generates births and deaths of \\tilE flux loops. It is argued that this implies a finite amplitude for births and deaths of loops in the physical states of quantum GR in the loop representation, thus modifying this (part...

  20. Canonical Transformations can Dramatically Simplify Supersymmetry

    CERN Document Server

    Dixon, John

    2016-01-01

    A useful way to keep track of the SUSY invariance of a theory is by formulating it with a BRST Poisson Bracket. It turns out that there is a crucial subtlety that is hidden in this formulation. When the theory contains a Chiral Multiplet, the relevant BRST Poisson Bracket has a very important Canonical Transformation that leaves it invariant. This Canonical Transformation takes all or part of the Scalar Field $A$ and replaces it with a Zinn Source $J_A$, and also takes the related Zinn Source $\\Gamma_A$ and replaces it with an `Antighost' Field $\\eta_A$. Naively, this looks like it is just a change of notation. But in fact the interpretation means that one has moved some of the conserved Noether SUSY current from the Field Action, and placed it partly in the Zinn Sources Action, and so the SUSY current in the Field part of the Action is no longer conserved, because the Zinn Sources do not satisfy any equations of motion. They are not quantized, because they are Sources. So it needs to be recognized that SUSY ...

  1. Extension of warm inflation to non-canonical scalar fields

    CERN Document Server

    Zhang, Xiao-Min

    2014-01-01

    We extend the warm inflationary scenario to the case of the non-canonical scalar fields. The equation of motion and the other basic equations of this new scenario are obtained. The Hubble damped term is enhanced in non-canonical inflation. A linear stability analysis is performed to give the proper slow roll conditions in warm non-canonical inflation. We study the density fluctuations in the new picture and obtain an approximate analytic expression of the power spectrum. The energy scale at the horizon crossing is depressed by both non-canonical effect and thermal effect, so does the tensor-to-scalar ratio. Besides the synergy, the non-canonical effect and the thermal effect are competing in the case of the warm non-canonical inflation.

  2. [Huang Yizhou's study on Nei jing (Inner Canon)].

    Science.gov (United States)

    Hu, Benxiang; Huang, Youmei; Yu, Chengfen

    2002-01-01

    Being a great classical scholar of the late Qing dynasty, Huang Yizhou collated Nei jing (Inner Canon) by textual criticism. But most of his works were missing. By reviewing historical documents and literature, it has been found that his collated books include Huang di nei jing su wen jiao ben (Collated Edition of Huangdi's Inner Canon Plain Questions), Huang di nei jing su wen chong jiao zheng (Recollated Huangdi's Inner Canon Plain Questions), Nei jing zhen ci (Acupuncture in Inner Canon), Huang di nei jing jiu juan ji zhu (Variorum of Nine Volumes of Huangdi's Inner Canon), Huang di nei jing ming tang (Acupuncture Chart of Huangdi's Inner Canon), and Jiu chao tai su jiao ben (Old Extremely Plain Question Recension). Many of his disciples became famous scholars in the Republican period. PMID:12015056

  3. Expression of canonical WNT/β-CATENIN signaling components in the developing human lung

    Directory of Open Access Journals (Sweden)

    Zhang Mingfeng

    2012-07-01

    Full Text Available Abstract Background The WNT/β-CATENIN signaling cascade is crucial for the patterning of the early lung morphogenesis in mice, but its role in the developing human lung remains to be determined. In this study, expression patterns of canonical WNT/β-CATENIN signaling components, including WNT ligands (WNT2, WNT7B, receptors ( FZD4, FZD7, LRP5, LRP6, transducers ( DVL2, DVL3, GSK-3β, β-CATENIN, APC, AXIN2, transcription factors ( TCF4, LEF1 and antagonists ( SOSTDC1 were examined in human embryonic lung at 7, 12, 17 and 21 weeks of gestation (W by real-time qRT-PCR and in situ hybridization. Results qRT-PCR analysis showed that some of these components were gradually upregulated, while some were significantly downregulated from the 7 W to the 12 W. However, most components reached a high level at 17 W, with a subsequent decrease at 21 W. In situ hybridization showed that the canonical WNT ligands and receptors were predominantly located in the peripheral epithelium, whereas the canonical WNT signal transducers and transcription factors were not only detected in the respiratory epithelium, but some were also scattered at low levels in the surrounding mesenchyme in the developing human lung. Furthermore, Western blot, qRT-PCR and histological analysis demonstrated that the β-CATENIN-dependent WNT signaling in embryonic human lung was activated in vitro by CHIR 99021 stimulation. Conclusions This study of the expression patterns and in vitro activity of the canonical WNT/β-CATENIN pathways suggests that these components play an essential role in regulation of human lung development.

  4. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Mullasseril, Praseeda; Dawit, Sara; Kurtkaya, Natalie L; Yuan, Hongjie; Vance, Katie M; Orr, Anna G; Kvist, Trine; Ogden, Kevin K; Le, Phuong; Vellano, Kimberly M; Lewis, Iestyn; Kurtkaya, Serdar; Du, Yuhong; Qui, Min; Murphy, T J; Snyder, James P; Bräuner-Osborne, Hans; Traynelis, Stephen F

    2010-01-01

    NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine...

  5. Integral Canonical Models for Automorphic Vector Bundles of Abelian Type

    OpenAIRE

    Lovering, Tom

    2016-01-01

    We define and construct integral canonical models for automorphic vector bundles over Shimura varieties of abelian type. More precisely, we first build on Kisin's work to construct integral canonical models over rings of integers of number fields with finitely many primes inverted for Shimura varieties of abelian type with hyperspecial level at all primes we do not invert, compatible with Kisin's construction. We then define a notion of an integral canonical model for the standard principal b...

  6. The Geometry of Tangent Bundles: Canonical Vector Fields

    Directory of Open Access Journals (Sweden)

    Tongzhu Li

    2013-01-01

    Full Text Available A canonical vector field on the tangent bundle is a vector field defined by an invariant coordinate construction. In this paper, a complete classification of canonical vector fields on tangent bundles, depending on vector fields defined on their bases, is obtained. It is shown that every canonical vector field is a linear combination with constant coefficients of three vector fields: the variational vector field (canonical lift, the Liouville vector field, and the vertical lift of a vector field on the base of the tangent bundle.

  7. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies.

    Science.gov (United States)

    Yang, Ke; Wang, Xin; Zhang, Hongmei; Wang, Zhongliang; Nan, Guoxin; Li, Yasha; Zhang, Fugui; Mohammed, Maryam K; Haydon, Rex C; Luu, Hue H; Bi, Yang; He, Tong-Chuan

    2016-02-01

    The canonical WNT/β-catenin signaling pathway governs a myriad of biological processes underlying the development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the canonical pathway is the activation of β-catenin-mediated transcriptional activity. Canonical WNTs control the β-catenin dynamics as the cytoplasmic level of β-catenin is tightly regulated via phosphorylation by the 'destruction complex', consisting of glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), the scaffold protein AXIN, and the tumor suppressor adenomatous polyposis coli (APC). Aberrant regulation of this signaling cascade is associated with varieties of human diseases, especially cancers. Over the past decade, significant progress has been made in understanding the mechanisms of canonical WNT signaling. In this review, we focus on the current understanding of WNT signaling at the extracellular, cytoplasmic membrane, and intracellular/nuclear levels, including the emerging knowledge of cross-talk with other pathways. Recent progresses in developing novel WNT pathway-targeted therapies will also be reviewed. Thus, this review is intended to serve as a refresher of the current understanding about the physiologic and pathogenic roles of WNT/β-catenin signaling pathway, and to outline potential therapeutic opportunities by targeting the canonical WNT pathway. PMID:26618721

  8. The Deuteron as a Canonically Quantized Biskyrmion

    CERN Document Server

    Acus, A; Norvaisas, E; Riska, D O

    2003-01-01

    The ground state configurations of the solution to Skyrme's topological soliton model for systems with baryon number larger than 1 are well approximated with rational map ans"atze, without individual baryon coordinates. Here canonical quantization of the baryon number 2 system, which represents the deuteron, is carried out in the rational map approximation. The solution, which is described by the 6 parameters of the chiral group SU(2)$times$SU(2), is stabilized by the quantum corrections. The matter density of the variational quantized solution has the required exponential large distance falloff and the quantum numbers of the deuteron. Similarly to the axially symmetric semiclassical solution, the radius and the quadrupole moment are, however, only about half as large as the corresponding empirical values. The quantized deuteron solution is constructed for representations of arbitrary dimension of the chiral group.

  9. Linear canonical transforms theory and applications

    CERN Document Server

    Kutay, M; Ozaktas, Haldun; Sheridan, John

    2016-01-01

    This book provides a clear and accessible introduction to the essential mathematical foundations of linear canonical transforms from a signals and systems perspective. Substantial attention is devoted to how these transforms relate to optical systems and wave propagation. There is extensive coverage of sampling theory and fast algorithms for numerically approximating the family of transforms. Chapters on topics ranging from digital holography to speckle metrology provide a window on the wide range of applications. This volume will serve as a reference for researchers in the fields of image and signal processing, wave propagation, optical information processing and holography, optical system design and modeling, and quantum optics. It will be of use to graduate students in physics and engineering, as well as for scientists in other areas seeking to learn more about this important yet relatively unfamiliar class of integral transformations.

  10. Towards a 'canonical' agranular cortical microcircuit

    Directory of Open Access Journals (Sweden)

    Sarah F. Beul

    2015-01-01

    Full Text Available Based on regularities in the intrinsic microcircuitry of cortical areas, variants of a 'canonical' cortical microcircuit have been proposed and widely adopted, particularly in computational neuroscience and neuroinformatics. However, this circuit is founded on striate cortex, which manifests perhaps the most extreme instance of cortical organization, in terms of a very high density of cells in highly differentiated cortical layers. Most other cortical regions have a less well differentiated architecture, stretching in gradients from the very dense eulaminate primary cortical areas to the other extreme of dysgranular and agranular areas of low density and poor laminar differentiation. It is unlikely for the patterns of inter- and intra-laminar connections to be uniform in spite of strong variations of their structural substrate. This assumption is corroborated by reports of divergence in intrinsic circuitry across the cortex. Consequently, it remains an important goal to define local microcircuits for a variety of cortical types, in particular, agranular cortical regions. As a counterpoint to the striate microcircuit, which may be anchored in an exceptional cytoarchitecture, we here outline a tentative microcircuit for agranular cortex. The circuit is based on a synthesis of the available literature on the local microcircuitry in agranular cortical areas of the rodent brain, investigated by anatomical and electrophysiological approaches. A central observation of these investigations is a weakening of interlaminar inhibition as cortical cytoarchitecture becomes less distinctive. Thus, our study of agranular microcircuitry revealed deviations from the well-known 'canonical' microcircuit established for striate cortex, suggesting variations in the intrinsic circuitry across the cortex that may be functionally relevant.

  11. The canonical formalism in covariant theories

    International Nuclear Information System (INIS)

    The problem of quantizing General Relativity (GR) is a formidable one and may require for its solution a complete understanding of string theory and its relationship with the gravitational field. Here the author discusses a more conservative and localized approach based on a covariant canonical formalism developed in a number of papers in the last few years. The idea is to consider theories which can be expressed entirely in terms of differential forms and then to exploit the analogy between time derivative and exterior derivative of forms. In the case of supergravity the field variables have then a double grading, the conventional form grading and the Fermi grading. There is no preferred time direction and, in space-time dimension D + 1, the conjugate momenta of a field form of degree rho is a form of degree D - rho. This form contains the usual components of the momentum besides other components needed in order to preserve covariance. The theory leads naturally to a hamiltonian form H of degree D + 1 which can be used within formalism in order to compute canonically the exterior derivative of a field-form. Its role is therefore quite different to that of the ordinary Hamiltonian which leads instead to Lie derivatives of a field. It is however possible to relate these quantities, and it turns out that the conventional Hamiltonian is the time component of a Poincare multiplet of 3-forms which can be used in order to compute Lie derivatives in any direction. Also the authors approach is well suit for applications within the group manifold approach

  12. Current interruption transients calculation

    CERN Document Server

    Peelo, David F

    2014-01-01

    Provides an original, detailed and practical description of current interruption transients, origins, and the circuits involved, and how they can be calculated Current Interruption Transients Calculationis a comprehensive resource for the understanding, calculation and analysis of the transient recovery voltages (TRVs) and related re-ignition or re-striking transients associated with fault current interruption and the switching of inductive and capacitive load currents in circuits. This book provides an original, detailed and practical description of current interruption transients, origins,

  13. The "cause of Jesus" (Sache Jesu as the Canon behind the Canon

    Directory of Open Access Journals (Sweden)

    Andries G. van Aarde

    2001-01-01

    Full Text Available God, and not the Bible as such, is the church's primary authority. Jesus of Nazareth is the manifestation of God in history. In a post-Aufkllirung environment one cannot escape the demand to think historically. To discern what could be seen as the "ground" offaith, one needs to distinguish the "proclaiming Jesus" from the "proclaimed Jesus", though these two aspects are dialectically intertwined. This dialeclic can be described as the "Jesus kerygma" or the "cause of Jesus". The aim of this article is to argue that if Christians focus only on the church's kerygma they base their ultimate trust upon assertions of faith, rather than upon the cause of faith. The dictum that the cause of Jesus is the canon behind the canon is explained in terms of the distinction between ''fides qua creditur" and "fides quae creditur", and postmodern historical Jesus research.

  14. 经典瞬时受体电位通道蛋白1在致石豚鼠胆囊平滑肌中的表达%The expression of ransient receptor potential canonical 1 in the smooth muscle of guinea pig gallbladder and its role in stone formation

    Institute of Scientific and Technical Information of China (English)

    丁佑铭; 李红波; 汪斌; 聂云贵; 周明全

    2013-01-01

    目的 观察豚鼠胆囊结石形成过程中胆囊平滑肌经典瞬时受体电位通道蛋白1(TRPC1)的表达变化及其对胆囊平滑肌收缩功能的影响.方法 20只雄性豚鼠随机均分为对照组和实验组,对照组给予普通饲料喂养,实验组给予致石饲料喂养.喂养60d后剖杀,观察豚鼠胆囊结石形成,检测胆囊体积(FV)、空腹胆囊胆汁量(FB)和胆汁胆固醇含量(TC),并用实时定量聚合酶链反应(Real-time PCR)检测胆囊平滑肌组织TRPC1 mRNA的表达量.结果 实验组有7只豚鼠观察到有胆泥或胆囊结石形成,对照组胆囊未见胆泥或结石形成;实验组FV[(1.78 ±0.22) cm3]、FB[(1.39±0.16) ml]、TC[(0.05±0.01) mmol/L]水平均高于对照组(P<0.05);实验组TRPC1mRNA(0.7057 0.0627)在胆囊平滑肌的表达量较对照组显著下降(P<0.05).结论 高胆固醇饮食致石过程中胆囊平滑肌中TRPC1的表达降低,从而可能导致胆囊平滑肌收缩功能减弱,胆囊排空能力下降,使胆囊结石易于形成.%Objective To assess the expression of ransient receptor potential canonical 1(TRPC1) in gallbladder smooth muscle during the process of stone formation and its effects on contractile function of gallbladder smooth muscle.Methods:20 male guinea pigs were randomly divided into normal diet group(control group),high-cholesterol diet group(experiment group),each group has 10 guinea pigs.Both groups were fed for 60 days.Killing them and get the gallbladder to calculate the fasting gallbladder volume (FV),and measure the fasting gallbladder bile (FB),and collect some bile to test the content of cholesterol (TC).The biliary sludge or gallstone formation was observed.Real-time quantitative polymerase chain reaction (Real-time PCR) was adopted to detect TRPC1 mRNA in gallbladder smooth muscle.Results 7 guinea pigs in experiment group have formed biliary sludge or gallstone,no sludge or gallstone was formed in controle group.The FV [(1.78 ±0.22) cm3],FB [(1

  15. Canonical correlation analysis of course and teacher evaluation

    DEFF Research Database (Denmark)

    Sliusarenko, Tamara; Ersbøll, Bjarne Kjær

    2010-01-01

    information obtained from the course evaluation form overlaps with information obtained from the teacher evaluation form. Employing canonical correlation analysis it was found that course and teacher evaluations are correlated. However, the structure of the canonical correlation is subject to change with...... changes in teaching methods from one year to another....

  16. The Literary Canon in the Age of New Media

    DEFF Research Database (Denmark)

    Backe, Hans-Joachim

    mediality of the canon. In a development that has largely gone unnoticed outside German speaking countries, new approaches for discussing current and future processes of canonization have been developed in recent years. One pivotal element of this process has been a thorough re-evaluation new media as a...

  17. Canonical Quantum Teleportation of Two-Particle Arbitrary State

    Institute of Scientific and Technical Information of China (English)

    HAO Xiang; ZHU Shi-Qun

    2005-01-01

    The canonical quantum teleportation of two-particle arbitrary state is realized by means of phase operator and number operator. The maximally entangled eigenstates between the difference of phase operators and the sum of number operators are considered as the quantum channels. In contrast to the standard quantum teleportation, the different unitary local operation of canonical teleportation can be simplified by a general expression.

  18. Structuring Catholic Schools: Creative Imagination Meets Canon Law

    Science.gov (United States)

    Brown, Phillip J.

    2010-01-01

    This paper will explore the underlying requirements of canon law for establishing and administering Catholic schools, with a view toward helping to arrive at creative solutions to the question of how best to structure these schools civilly and canonically in order to ensure their temporal, spiritual, and religious well-being, and to assure that…

  19. Grand canonical potential of a magnetized neutron gas

    CERN Document Server

    Diener, Jacobus P W

    2015-01-01

    We compute the effective action for stationary and spatially constant magnetic fields, when coupled anomalously to charge neutral fermions, by integrating out the fermions. From this the grand canonical partition function and potential of the fermions and fields are computed. This also takes care of magnetic field dependent vacuum corrections to the grand canonical potential. Possible applications to neutron stars are indicated.

  20. LCPT: a program for finding linear canonical transformations

    International Nuclear Information System (INIS)

    This article describes a MACSYMA program to compute symbolically a canonical linear transformation between coordinate systems. The difficulties in implementation of this canonical small physics problem are also discussed, along with the implications that may be drawn from such difficulties about widespread MACSYMA usage by the community of computational/theoretical physicists

  1. Critical Literature Pedagogy: Teaching Canonical Literature for Critical Literacy

    Science.gov (United States)

    Borsheim-Black, Carlin; Macaluso, Michael; Petrone, Robert

    2014-01-01

    This article introduces Critical Literature Pedagogy (CLP), a pedagogical framework for applying goals of critical literacy within the context of teaching canonical literature. Critical literacies encompass skills and dispositions to understand, question, and critique ideological messages of texts; because canonical literature is often…

  2. The Asian American Fakeness Canon, 1972-2002

    Science.gov (United States)

    Oishi, Eve

    2007-01-01

    The year 1972 can be seen to inaugurate not a tradition of Asian American New York theater, but the rich and multigenre collection of writing that the author has called "the Asian American fakeness canon." The fakeness canon refers to a collection of writings that take as one of their central points of reference the question of cultural and ethnic…

  3. Structural Features for Functional Selectivity at Serotonin Receptors

    OpenAIRE

    Wacker, Daniel; Wang, Chong; Katritch, Vsevolod; Han, Gye Won; Huang, Xi-Ping; Vardy, Eyal; McCorvy, John D.; Jiang, Yi; Chu, Meihua; Siu, Fai Yiu; Liu, Wei; Xu, H Eric; Cherezov, Vadim; Roth, Bryan L.; Stevens, Raymond C.

    2013-01-01

    Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or non-canonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies that show that the hallucinogen lysergic acid diethylamide (LSD), its precursor ergotamine (ERG) and related ergolines display strong functional selectivity for β-arrestin signaling at the 5-hydroxytryptamine (5-HT) receptor 5-HT2B, while being relatively unbiased...

  4. A Canonical Approach to the Argument/Adjunct Distinction

    Directory of Open Access Journals (Sweden)

    Diana Forker

    2014-01-01

    Full Text Available This paper provides an account of the argument/adjunct distinction implementing the 'canonical approach'. I identify five criteria (obligatoriness, latency, co-occurrence restrictions, grammatical relations, and iterability and seven diagnostic tendencies that can be used to distinguish canonical arguments from canonical adjuncts. I then apply the criteria and tendencies to data from the Nakh-Daghestanian language Hinuq. Hinuq makes extensive use of spatial cases for marking adjunct-like and argument-like NPs. By means of the criteria and tendencies it is possible to distinguish spatial NPs that come close to canonical arguments from those that are canonical adjuncts, and to place the remaining NPs bearing spatial cases within the argument-adjunct continuum.

  5. Canonical correlations between chemical and energetic characteristics of lignocellulosic wastes

    Directory of Open Access Journals (Sweden)

    Thiago de Paula Protásio

    2012-09-01

    Full Text Available Canonical correlation analysis is a statistical multivariate procedure that allows analyzing linear correlation that may exist between two groups or sets of variables (X and Y. This paper aimed to provide canonical correlation analysis between a group comprised of lignin and total extractives contents and higher heating value (HHV with a group of elemental components (carbon, hydrogen, nitrogen and sulfur for lignocellulosic wastes. The following wastes were used: eucalyptus shavings; pine shavings; red cedar shavings; sugar cane bagasse; residual bamboo cellulose pulp; coffee husk and parchment; maize harvesting wastes; and rice husk. Only the first canonical function was significant, but it presented a low canonical R². High carbon, hydrogen and sulfur contents and low nitrogen contents seem to be related to high total extractives contents of the lignocellulosic wastes. The preliminary results found in this paper indicate that the canonical correlations were not efficient to explain the correlations between the chemical elemental components and lignin contents and higher heating values.

  6. The canon as text for a biblical theology

    Directory of Open Access Journals (Sweden)

    James A. Loader

    2005-10-01

    Full Text Available The novelty of the canonical approach is questioned and its fascination at least partly traced to the Reformation, as well as to the post-Reformation’s need for a clear and authoritative canon to perform the function previously performed by the church. This does not minimise the elusiveness and deeply contradictory positions both within the canon and triggered by it. On the one hand, the canon itself is a centripetal phenomenon and does play an important role in exegesis and theology. Even so, on the other hand, it not only contains many difficulties, but also causes various additional problems of a formal as well as a theological nature. The question is mooted whether the canonical approach alleviates or aggravates the dilemma. Since this approach has become a major factor in Christian theology, aspects of the Christian canon are used to gauge whether “canon” is an appropriate category for eliminating difficulties that arise by virtue of its own existence. Problematic uses and appropriations of several Old Testament canons are advanced, as well as evidence in the New Testament of a consciousness that the “old” has been surpassed(“Überbietungsbewußtsein”. It is maintained that at least the Childs version of the canonical approach fails to smooth out these and similar difficulties. As a method it can cater for the New Testament’s (superior role as the hermeneutical standard for evaluating the Old, but flounders on its inability to create the theological unity it claims can solve religious problems exposed by Old Testament historical criticism. It is concluded that canon as a category cannot be dispensed with, but is useful for the opposite of the purpose to which it is conventionally put: far from bringing about theological “unity” or producing a standard for “correct” exegesis, it requires different readings of different canons.

  7. Canonical (anti-)commutation rules in QCD abd unbroken gauge invariance, QCD - the two central anomalies and canonical structure

    CERN Document Server

    Minkowski, Peter

    2012-01-01

    The regularities at large distances of complete gauge invariance in QCD are shown to bear nontrivial consequences for the selection among inequivalent representations of canonical commutation (anticommutation) rules for gauge boson (quark) fields. The trace anomaly forces a modification of the gauge boson Lagrangean and by this of the entire associated canonical structure.

  8. El Escritor y las Normas del Canon Literario (The Writer and the Norms of the Literary Canon).

    Science.gov (United States)

    Policarpo, Alcibiades

    This paper speculates about whether a literary canon exists in contemporary Latin American literature, particularly in the prose genre. The paper points to Carlos Fuentes, Gabriel Garcia Marquez, and Mario Vargas Llosa as the three authors who might form this traditional and liberal canon with their works "La Muerte de Artemio Cruz" (Fuentes),…

  9. Canonical and Noncanonical G-Protein Signaling Helps Coordinate Actin Dynamics To Promote Macrophage Phagocytosis of Zymosan

    OpenAIRE

    Huang, Ning-Na; Becker, Steven; Boularan, Cedric; Kamenyeva, Olena; Vural, Ali; Hwang, Il-Young; Shi, Chong-Shan; Kehrl, John H

    2014-01-01

    Both chemotaxis and phagocytosis depend upon actin-driven cell protrusions and cell membrane remodeling. While chemoattractant receptors rely upon canonical G-protein signaling to activate downstream effectors, whether such signaling pathways affect phagocytosis is contentious. Here, we report that Gαi nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, Gαi proteins, an...

  10. Canonical cortical circuits: current evidence and theoretical implications

    Directory of Open Access Journals (Sweden)

    Capone F

    2016-04-01

    Full Text Available Fioravante Capone,1,2 Matteo Paolucci,1,2 Federica Assenza,1,2 Nicoletta Brunelli,1,2 Lorenzo Ricci,1,2 Lucia Florio,1,2 Vincenzo Di Lazzaro1,2 1Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy; 2Fondazione Alberto Sordi – Research Institute for Aging, Rome, ItalyAbstract: Neurophysiological and neuroanatomical studies have found that the same basic structural and functional organization of neuronal circuits exists throughout the cortex. This kind of cortical organization, termed canonical circuit, has been functionally demonstrated primarily by studies involving visual striate cortex, and then, the concept has been extended to different cortical areas. In brief, the canonical circuit is composed of superficial pyramidal neurons of layers II/III receiving different inputs and deep pyramidal neurons of layer V that are responsible for cortex output. Superficial and deep pyramidal neurons are reciprocally connected, and inhibitory interneurons participate in modulating the activity of the circuit. The main intuition of this model is that the entire cortical network could be modeled as the repetition of relatively simple modules composed of relatively few types of excitatory and inhibitory, highly interconnected neurons. We will review the origin and the application of the canonical cortical circuit model in the six sections of this paper. The first section (The origins of the concept of canonical circuit: the cat visual cortex reviews the experiments performed in the cat visual cortex, from the origin of the concept of canonical circuit to the most recent developments in the modelization of cortex. The second (The canonical circuit in neocortex and third (Toward a canonical circuit in agranular cortex sections try to extend the concept of canonical circuit to other cortical areas, providing some significant examples of circuit functioning in different cytoarchitectonic

  11. An $OSp$ extension of Canonical Tensor Model

    CERN Document Server

    Narain, Gaurav

    2015-01-01

    Tensor models are generalizations of matrix models, and are studied as discrete models of quantum gravity for arbitrary dimensions. Among them, the canonical tensor model (CTM for short) is a rank-three tensor model formulated as a totally constrained system with a number of first-class constraints, which have a similar algebraic structure as the constraints of the ADM formalism of general relativity. In this paper, we formulate a super-extension of CTM as an attempt to incorporate fermionic degrees of freedom. The kinematical symmetry group is extended from $O(N)$ to $OSp(N,\\tilde N)$, and the constraints are constructed so that they form a first-class constraint super-Poisson algebra. This is a straightforward super-extension, and the constraints and their algebraic structure are formally unchanged from the purely bosonic case, except for the additional signs associated to the order of the fermionic indices and dynamical variables. However, this extension of CTM leads to the existence of negative norm state...

  12. Transient drainage summary report

    International Nuclear Information System (INIS)

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage

  13. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  14. AN APOLOGY OF THE LITERARY CANON IN A LINGUISTIC STUDY

    Directory of Open Access Journals (Sweden)

    Alexey Vladimirovich Sosnin

    2015-10-01

    Full Text Available The article highlights the principles of selecting practical material for a linguistic study aspiring to objectivity and states that in such a study orientation to the literary text is absolutely essential, as a solid corpus of literary texts is indispensable for describing complicated linguistic phenomena and mental structures standing behind them. The article puts forward the postulate that any serious study into the English language should be constructed on the English literary canon – a global textual corpus on the basis of which the greatest part of the educated speakers’ conceptual sphere is formed. At the same time, the article considers certain problems related to the Anglicist’s orientation towards the canon – its definition, limits, central and peripheral authors, the criteria of a literary work canonic status, arguments of those opposing any canonicity in literature, reconstruction of the canon in other cultures. The article also analyzes the cognitive aspect and tells about the key transformation of the English mentality, which gave rise to thinking in the terms of the time, cause-and-effect, and probability in canonic literature. The author of the article comes up with a principal conclusion: orientation to the literary canon in a linguistic study allows reconciling of linguistics and literature studies and including into the analysis nonlinguistic semiotic systems as well as idiolectal systems of conceptualizing the world in literary works.

  15. Critical adsorption and critical Casimir forces in the canonical ensemble

    Science.gov (United States)

    Gross, Markus; Vasilyev, Oleg; Gambassi, Andrea; Dietrich, S.

    2016-08-01

    Critical properties of a liquid film between two planar walls are investigated in the canonical ensemble, within which the total number of fluid particles, rather than their chemical potential, is kept constant. The effect of this constraint is analyzed within mean-field theory (MFT) based on a Ginzburg-Landau free-energy functional as well as via Monte Carlo simulations of the three-dimensional Ising model with fixed total magnetization. Within MFT and for finite adsorption strengths at the walls, the thermodynamic properties of the film in the canonical ensemble can be mapped exactly onto a grand canonical ensemble in which the corresponding chemical potential plays the role of the Lagrange multiplier associated with the constraint. However, due to a nonintegrable divergence of the mean-field order parameter profile near a wall, the limit of infinitely strong adsorption turns out to be not well-defined within MFT, because it would necessarily violate the constraint. The critical Casimir force (CCF) acting on the two planar walls of the film is generally found to behave differently in the canonical and grand canonical ensembles. For instance, the canonical CCF in the presence of equal preferential adsorption at the two walls is found to have the opposite sign and a slower decay behavior as a function of the film thickness compared to its grand canonical counterpart. We derive the stress tensor in the canonical ensemble and find that it has the same expression as in the grand canonical case, but with the chemical potential playing the role of the Lagrange multiplier associated with the constraint. The different behavior of the CCF in the two ensembles is rationalized within MFT by showing that, for a prescribed value of the thermodynamic control parameter of the film, i.e., density or chemical potential, the film pressures are identical in the two ensembles, while the corresponding bulk pressures are not.

  16. Comparison between RELAP5/MOD1 and TRAC-PD2 computer codes in simulation of canon experience

    International Nuclear Information System (INIS)

    The present work reports comparisons between experimental and theoretical data done with the RELAP5/MOD1 and TRAC-FD2 codes, with particular emphasis on RELAP5/MOD1 code run with basic experimental data from the CANON depressurization simulation. This experiment simulates a Loss of Primary Coolant Accident due to a Large Rupture - LOCA, through the depressurization of a horizontal tube containing water with the instantaneous break of one side of the tube where measurements of pressure, temperature and void fraction are taken during the transient. The results of this comparison show that RELAP5/MOD1 code predict more satisfactorily the time dependent behavior of the pressure and void fraction than TRAC-PD2 code for several initial conditions considered in the CANON experiment. (Author)

  17. XEDAR activates the non-canonical NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Gardam, Sandra, E-mail: s.gardam@garvan.org.au [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Borghi, Alice, E-mail: Alice.Borghi@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Kreike, Marja, E-mail: Marja.Kreike@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Carpentier, Isabelle, E-mail: Isabelle.Carpentier@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Beyaert, Rudi, E-mail: Rudi.Beyaert@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium)

    2015-09-18

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.

  18. XEDAR activates the non-canonical NF-κB pathway

    International Nuclear Information System (INIS)

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20

  19. Canonical quantization of gravity without 'frozen formalism'

    International Nuclear Information System (INIS)

    We write down a quantum gravity equation which generalizes the Wheeler-DeWitt one in view of including a time dependence in the wave functional. The obtained equation provides a consistent canonical quantization of the 3-geometries resulting from a 'gauge-fixing' (3+1)-slicing of the space-time. Our leading idea relies on a criticism to the possibility that, in a quantum space-time, the notion of a (3+1)-slicing formalism (underlying the Wheeler-DeWitt approach) has yet a precise physical meaning. As solution to this problem we propose of adding to the gravity-matter action the so-called kinematical action (indeed in its reduced form, as implemented in the quantum regime), and then we impose the new quantum constraints. As consequence of this revised approach, the quantization procedure of the 3-geometries takes place in a fixed reference frame and the wave functional acquires a time evolution along a one-parameter family of spatial hypersurfaces filling the space-time. We show how the states of the new quantum dynamics can be arranged into an Hilbert space, whose associated inner product induces a conserved probability notion for the 3-geometries. Finally, since the constraints we quantize violate the classical symmetries (i.e., the vanishing nature of the super-Hamiltonian), then a key result is to find a (non-physical) restriction on the initial wave functional phase, ensuring that general relativity outcomes when taking the appropriate classical limit. However, we propose a physical interpretation of the kinematical variables which, based on the analogy with the so-called Gaussian reference fluid, makes allowance even for such classical symmetry violation

  20. A single NFκB system for both canonical and non-canonical signaling

    Institute of Scientific and Technical Information of China (English)

    Vincent Feng-Sheng Shih; Rachel Tsui; Andrew Caldwell; Alexander Hoffmann

    2011-01-01

    Two distinct nuclear factor κB(NFκB)signaling pathways have been described; the canonical pathway that mediates inflammatory responses,and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis.The former is dependent on the IκB kinase adaptor molecule NEMO,the latter is independent of it.Here,we review the molecular mechanisms of regulation in each signaling axis and attempt to relate the apparent regulatory logic to the physiological function.Further,we review the recent evidence for extensive cross-regulation between these two signaling axes and summarize them in a wiring diagram.These observations suggest that NEMO-dependent and-independent signaling should be viewed within the context of a single NFκB signaling system,which mediates signaling from both inflammatory and organogenic stimuli in an integrated manner.As in other regulatory biological systems,a systems approach including mathematical models that include quantitative and kinetic information will be necessary to characterize the network properties that mediate physiological function,and that may break down to cause or contribute to pathology.

  1. On the canonical quantization of local field theories

    International Nuclear Information System (INIS)

    A nonconventional extension of the canonical quantization method for local field theories is presented. Some difficulties of the conventional approach are avoided, e.g. there are no divergencies in the corresponding S-matrices. (author)

  2. Kerr black hole in canonically deformed space-time

    CERN Document Server

    Daszkiewicz, Marcin

    2014-01-01

    We investigate the Kerr black hole defined on canonically deformed space-time. Particulary, we find the corresponding event horizon, the ergosphere, the temperature and the entropy of such deformed object.

  3. Canonical singular hermitian metrics on relative logcanonical bundles

    OpenAIRE

    Tsuji, Hajime

    2010-01-01

    This supersedes 0704.0566. We prove the invariance of logarithmic plurigenera for a projective family of KLT pairs and the adjoint line bundle of KLT line bundles. The proof uses the canonical singular hermitian metrics on relative logcanonical bundles.

  4. Role of Wnt canonical pathway in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Wang Xin

    2010-09-01

    Full Text Available Abstract Wnt canonical signaling pathway plays a diverse role in embryonic development and maintenance of organs and tissues in adults. It has been observed that Wnt/β-catenin signaling pathway is involved in the pathogenesis of many carcinomas. Moreover, Wnt/β-catenin pathway has been revealed to be associated with angiogenesis. Wnt canonical pathway signaling has great potential as a therapeutic target. It has been disclosed that some hematological malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, may occur partly due to the constitutive activation of Wnt canonical signaling pathway. This review will summarize the latest development in Wnt canonical signaling pathway and its roles in tumorigenesis and angiogenesis.

  5. Canonical Duality Theory for Solving Minimization Problem of Rosenbrock Function

    OpenAIRE

    Gao, David Y.; Zhang, Jiapu

    2011-01-01

    This paper presents a canonical duality theory for solving nonconvex minimization problem of Rosenbrock function. Extensive numerical results show that this benchmark test problem can be solved precisely and efficiently to obtain global optimal solutions.

  6. Asymptotic distributions in the projection pursuit based canonical correlation analysis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this paper, associations between two sets of random variables based on the projection pursuit (PP) method are studied. The asymptotic normal distributions of estimators of the PP based canonical correlations and weighting vectors are derived.

  7. Canonical Approaches to Applications of the Virial Theorem.

    Science.gov (United States)

    Walton, Jay R; Rivera-Rivera, Luis A; Lucchese, Robert R; Bevan, John W

    2016-02-11

    Canonical approaches are applied for investigation of the extraordinarily accurate electronic ground state potentials of H2(+), H2, HeH(+), and LiH using the virial theorem. These approaches will be dependent on previous investigations involving the canonical nature of E(R), the Born-Oppenheimer potential, and F(R), the associated force of E(R), that have been demonstrated to be individually canonical to high accuracy in the case of the systems investigated. Now, the canonical nature of the remaining functions in the virial theorem [the electronic kinetic energy T(R), the electrostatic potential energy V(R), and the function W(R) = RF(R)] are investigated and applied to H2, HeH(+), and LiH with H2(+) chosen as reference. The results will be discussed in the context of a different perspective of molecular bonding that goes beyond previous direct applications of the virial theorem. PMID:26788937

  8. Ising model on random networks and the canonical tensor model

    International Nuclear Information System (INIS)

    We introduce a statistical system on random networks of trivalent vertices for the purpose of studying the canonical tensor model, which is a rank-three tensor model in the canonical formalism. The partition function of the statistical system has a concise expression in terms of integrals, and has the same symmetries as the kinematical ones of the canonical tensor model. We consider the simplest non-trivial case of the statistical system corresponding to the Ising model on random networks, and find that its phase diagram agrees with what is implied by regrading the Hamiltonian vector field of the canonical tensor model with N=2 as a renormalization group flow. Along the way, we obtain an explicit exact expression of the free energy of the Ising model on random networks in the thermodynamic limit by the Laplace method. This paper provides a new example connecting a model of quantum gravity and a random statistical system

  9. Unravelling the molecular mechanisms of the canonical Wnt signalling pathway

    OpenAIRE

    Ng, S. S.

    2010-01-01

    The Canonical Wnt signaling pathway (Wnt/beta-catenin pathway) is required during embryonic development and maintenance of adult-renewing tissue homeostasis. Deregulation of this pathway is found associated with cancer and other diseases. The main goal of this thesis is to discern the regulation mechanisms of canonical Wnt signaling and thereby identify potential drug targets. We found that, neither the dissembled of Axin1, APC or GSK3 from the destruction complex nor inactivation of GSK3 and...

  10. Canonical correlations between chemical and energetic characteristics of lignocellulosic wastes

    OpenAIRE

    Thiago de Paula Protásio; Gustavo Henrique Denzin Tonoli; Mário Guimarães Júnior; Lina Bufalino; Allan Motta Couto; Paulo Fernando Trugilho

    2012-01-01

    Canonical correlation analysis is a statistical multivariate procedure that allows analyzing linear correlation that may exist between two groups or sets of variables (X and Y). This paper aimed to provide canonical correlation analysis between a group comprised of lignin and total extractives contents and higher heating value (HHV) with a group of elemental components (carbon, hydrogen, nitrogen and sulfur) for lignocellulosic wastes. The following wastes were used: eucalyptus shavings; pine...

  11. Using lattice methods in non-canonical quantum statistics

    International Nuclear Information System (INIS)

    We define a natural coarse-graining procedure which can be applied to any closed equilibrium quantum system described by a density matrix ensemble and we show how the coarse-graining leads to the Gaussian and canonical ensembles. After this motivation, we present two ways of evaluating the Gaussian expectation values with lattice simulations. The first one is computationally demanding but general, whereas the second employs only canonical expectation values but it is applicable only for systems which are almost thermodynamical

  12. On Uncertainty Principle for Quaternionic Linear Canonical Transform

    Directory of Open Access Journals (Sweden)

    Kit Ian Kou

    2013-01-01

    Full Text Available We generalize the linear canonical transform (LCT to quaternion-valued signals, known as the quaternionic linear canonical transform (QLCT. Using the properties of the LCT we establish an uncertainty principle for the QLCT. This uncertainty principle prescribes a lower bound on the product of the effective widths of quaternion-valued signals in the spatial and frequency domains. It is shown that only a 2D Gaussian signal minimizes the uncertainty.

  13. Regression, Discriminant Analysis, and Canonical Correlation Analysis with Homals

    OpenAIRE

    Jan de Leeuw

    2009-01-01

    It is shown that the homals package in R can be used for multiple regression, multi-group discriminant analysis, and canonical correlation analysis. The homals solutions are only different from the more conventional ones in the way the dimensions are scaled by the eigenvalues.It is shown that the homals package in R can be used for multiple regression, multi-group discriminant analysis, and canonical correlation analysis. The homals solutions are only different from the more conventional ones...

  14. Accretion of the Moon from non-canonical disks

    CERN Document Server

    Salmon, Julien

    2014-01-01

    Impacts that leave the Earth-Moon system with a large excess in angular momentum have recently been advocated as a means of generating a protolunar disc with a composition that is nearly identical to that of the Earth's mantle. We here investigate the accretion of the Moon from discs generated by such "non-canonical" impacts, which are typically more compact than discs produced by canonical impacts and have a higher fraction of their mass initially located inside the Roche limit. Our model predicts a similar overall accretional history for both canonical and non-canonical discs, with the Moon forming in three consecutive steps over hundreds of years. However, we find that, to yield a lunar-mass Moon, the more compact non-canonical discs must initially be more massive than implied by prior estimates, and only a few of the discs produced by impact simulations to date appear to meet this condition. Non-canonical impacts require that capture of the Moon into the evection resonance with the Sun reduced the Earth-M...

  15. Congenital myasthenic syndromes and transient myasthenia gravis.

    Science.gov (United States)

    Gajda, Anna; Szabó, Hajnalka; Gergev, Gyurgyinka; Karcagi, Veronika; Szabó, Nóra; Endreffy, Emoke; Túri, Sándor; Sztriha, László

    2013-05-30

    Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis. PMID:23909021

  16. Process modelling on a canonical basis[Process modelling; Canonical modelling

    Energy Technology Data Exchange (ETDEWEB)

    Siepmann, Volker

    2006-12-20

    Based on an equation oriented solving strategy, this thesis investigates a new approach to process modelling. Homogeneous thermodynamic state functions represent consistent mathematical models of thermodynamic properties. Such state functions of solely extensive canonical state variables are the basis of this work, as they are natural objective functions in optimisation nodes to calculate thermodynamic equilibrium regarding phase-interaction and chemical reactions. Analytical state function derivatives are utilised within the solution process as well as interpreted as physical properties. By this approach, only a limited range of imaginable process constraints are considered, namely linear balance equations of state variables. A second-order update of source contributions to these balance equations is obtained by an additional constitutive equation system. These equations are general dependent on state variables and first-order sensitivities, and cover therefore practically all potential process constraints. Symbolic computation technology efficiently provides sparsity and derivative information of active equations to avoid performance problems regarding robustness and computational effort. A benefit of detaching the constitutive equation system is that the structure of the main equation system remains unaffected by these constraints, and a priori information allows to implement an efficient solving strategy and a concise error diagnosis. A tailor-made linear algebra library handles the sparse recursive block structures efficiently. The optimisation principle for single modules of thermodynamic equilibrium is extended to host entire process models. State variables of different modules interact through balance equations, representing material flows from one module to the other. To account for reusability and encapsulation of process module details, modular process modelling is supported by a recursive module structure. The second-order solving algorithm makes it

  17. High Energy Transients

    CERN Document Server

    Gehrels, Neil

    2012-01-01

    We present an overview of high energy transients in astrophysics, highlighting important advances over the past 50 years. We begin with early discoveries of gamma-ray transients, and then delve into physical details associated with a variety of phenomena. We discuss some of the unexpected transients found by Fermi and Swift, many of which are not easily classifiable or in some way challenge conventional wisdom. These objects are important insofar as they underscore the necessity of future, more detailed studies.

  18. MR of transient osteoporosis

    International Nuclear Information System (INIS)

    Transient osteoporosis or transient bone marrow oedema is a rare cause of acute hip pain that predominantly affects adults of middle and younger age. We report on the MR image in 8 patients with transient bone marrow oedema of the hip and in one patient with affection of the knee joint. In three of these, sympathetic nerve blockade has been performed. The MR image after sympathicolysis is discussed. (orig.)

  19. Receiving the non-Orthodox: A historical study of Greek Orthodox canon law

    OpenAIRE

    Heith-Stade, David

    2010-01-01

    This article analyzes the development of the practice for receiving non-Orthodox in Greek Orthodox canon law. The main argument is that the development of this canonical institution was influenced by a pneumatological realist ecclesiology. This historical study of the development of a canonical institution will shed light on how Greek Orthodox canon law has functioned in practice.

  20. Canonical WNT signaling pathway and human AREG.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2006-06-01

    AREG (Amphiregulin), BTC (beta-cellulin), EGF, EPGN (Epigen), EREG (Epiregulin), HBEGF, NRG1, NRG2, NRG3, NRG4 and TGFA (TGFalpha) constitute EGF family ligands for ERBB family receptors. Cetuximab (Erbitux), Pertuzumab (Omnitarg) and Trastuzumab (Herceptin) are anti-cancer drugs targeted to EGF family ligands, while Gefitinib (Iressa), Erlotinib (Tarceva) and Lapatinib (GW572016) are anti-cancer drugs targeted to ERBB family receptors. AREG and TGFA are biomarkers for Gefitinib non-responders. The TCF/LEF binding sites within the promoter region of human EGF family members were searched for by using bioinformatics and human intelligence (Humint). Because three TCF/LEF-binding sites were identified within the 5'-promoter region of human AREG gene, comparative genomics analyses on AREG orthologs were further performed. The EPGN-EREG-AREG-BTC cluster at human chromosome 4q13.3 was linked to the PPBP-CXCL segmental duplicons. AREG was the paralog of HBEGF at human chromosome 5q31.2. Chimpanzee AREG gene, consisting of six exons, was located within NW_105918.1 genome sequence. Chimpanzee AREG was a type I transmembrane protein showing 98.0% and 71.4% total amino-acid identity with human AREG and mouse Areg, respectively. Three TCF/LEF-binding sites within human AREG promoter were conserved in chimpanzee AREG promoter, but not in rodent Areg promoters. Primate AREG promoters were significantly divergent from rodent Areg promoters. AREG mRNA was expressed in a variety of human tumors, such as colorectal cancer, liver cancer, gastric cancer, breast cancer, prostate cancer, esophageal cancer and myeloma. Because human AREG was characterized as potent target gene of WNT/beta-catenin signaling pathway, WNT signaling activation could lead to Gefitinib resistance through AREG upregulation. AREG is a target of systems medicine in the field of oncology. PMID:16685431

  1. Activation of the Canonical Wnt Signaling Pathway Induces Cementum Regeneration.

    Science.gov (United States)

    Han, Pingping; Ivanovski, Saso; Crawford, Ross; Xiao, Yin

    2015-07-01

    Canonical Wnt signaling is important in tooth development but it is unclear whether it can induce cementogenesis and promote the regeneration of periodontal tissues lost because of disease. Therefore, the aim of this study is to investigate the influence of canonical Wnt signaling enhancers on human periodontal ligament cell (hPDLCs) cementogenic differentiation in vitro and cementum repair in a rat periodontal defect model. Canonical Wnt signaling was induced by (1) local injection of lithium chloride; (2) local injection of sclerostin antibody; and (3) local injection of a lentiviral construct overexpressing β-catenin. The results showed that the local activation of canonical Wnt signaling resulted in significant new cellular cementum deposition and the formation of well-organized periodontal ligament fibers, which was absent in the control group. In vitro experiments using hPDLCs showed that the Wnt signaling pathway activators significantly increased mineralization, alkaline phosphatase (ALP) activity, and gene and protein expression of the bone and cementum markers osteocalcin (OCN), osteopontin (OPN), cementum protein 1 (CEMP1), and cementum attachment protein (CAP). Our results show that the activation of the canonical Wnt signaling pathway can induce in vivo cementum regeneration and in vitro cementogenic differentiation of hPDLCs. PMID:25556853

  2. General relativity as an extended canonical gauge theory

    Science.gov (United States)

    Struckmeier, J.

    2015-04-01

    It is widely accepted that the fundamental geometrical law of nature should follow from an action principle. The particular subset of transformations of a system's dynamical variables that maintain the form of the action principle comprises the group of canonical transformations. In the context of canonical field theory, the adjective "extended" signifies that not only the fields but also the space-time geometry is subject to transformation. Thus, in order to be physical, the transition to another, possibly noninertial frame of reference must necessarily constitute an extended canonical transformation that defines the general mapping of the connection coefficients, hence the quantities that determine the space-time curvature and torsion of the respective reference frame. The canonical transformation formalism defines simultaneously the transformation rules for the conjugates of the connection coefficients and for the Hamiltonian. As will be shown, this yields unambiguously a particular Hamiltonian that is form-invariant under the canonical transformation of the connection coefficients and thus satisfies the general principle of relativity. This Hamiltonian turns out to be a quadratic function of the curvature tensor. Its Legendre-transformed counterpart then establishes a unique Lagrangian description of the dynamics of space-time that is not postulated but derived from basic principles, namely the action principle and the general principle of relativity. Moreover, the resulting theory satisfies the principle of scale invariance and is renormalizable.

  3. Canonical Entropy and Phase Transition of Rotating Black Hole

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ren; WU Yue-Qin; ZHANG Li-Chun

    2008-01-01

    Recently, the Hawking radiation of a black hole has been studied using the tunnel effect method. The radiation spectrum of a black hole is derived. By discussing the correction to spectrum of the rotating black hole, we obtain the canonical entropy. The derived canonical entropy is equal to the sum of Bekenstein-Hawking entropy and correction term. The correction term near the critical point is different from the one near others. This difference plays an important role in studying the phase transition of the black hole. The black hole thermal capacity diverges at the critical point. However, the canonical entropy is not a complex number at this point. Thus we think that the phase transition created by this critical point is the second order phase transition. The discussed black hole is a five-dimensional Kerr-AdS black hole. We provide a basis for discussing thermodynamic properties of a higher-dimensional rotating black hole.

  4. Non-Linear Canonical Transformations in Classical and Quantum Mechanics

    CERN Document Server

    Brodlie, A

    2004-01-01

    $p$-Mechanics is a consistent physical theory which describes both classical and quantum mechanics simultaneously through the representation theory of the Heisenberg group. In this paper we describe how non-linear canonical transformations affect $p$-mechanical observables and states. Using this we show how canonical transformations change a quantum mechanical system. We seek an operator on the set of $p$-mechanical observables which corresponds to the classical canonical transformation. In order to do this we derive a set of integral equations which when solved will give us the coherent state expansion of this operator. The motivation for these integral equations comes from the work of Moshinsky and a variety of collaborators. We consider a number of examples and discuss the use of these equations for non-bijective transformations.

  5. Canonical extensions of N\\'eron models of Jacobians

    CERN Document Server

    Cais, Bryden

    2009-01-01

    Let A be the N\\'eron model of an abelian variety A_K over the fraction field K of a discrete valuation ring R. Due to work of Mazur-Messing, there is a functorial way to prolong the universal extension of A_K by a vector group to a smooth and separated group scheme over R, called the canonical extension of A. In this paper, we study the canonical extension when A_K=J_K is the Jacobian of a smooth proper and geometrically connected curve X_K over K. Assuming that X_K admits a proper flat regular model X over R that has generically smooth closed fiber, our main result identifies the identity component of the canonical extension with a certain functor Pic^{\

  6. Canonical invariance of spatially covariant scalar-tensor theory

    CERN Document Server

    Saitou, Rio

    2016-01-01

    We investigate invariant canonical transformations of a spatially covariant scalar-tensor theory of gravity, called the XG theory, by which the action or the Hamiltonian and the primary constraints keep their forms invariant. We derive the Hamiltonian in a non perturbative manner and complete the Hamiltonian analysis for all regions of the theory. We confirm that the theory has at most 3 degrees of freedom in all regions of the theory as long as the theory has the symmetry under the spatial diffeormorphism. Then, we derive the invariant canonical transformation by using the infinitesimal transformation. The invariant metric transformation of the XG theory contains a vector product as well as the disformal transformation. The vector product and the disformal factor can depend on the higher order derivative terms of the scalar field and the metric. In addition, we discover the invariant canonical transformation which transforms the momentum of the metric. Using the invariant transformation, we study the relatio...

  7. Variation principle of piezothermoelastic bodies, canonical equation and homogeneous equation

    Institute of Scientific and Technical Information of China (English)

    LIU Yan-hong; ZHANG Hui-ming

    2007-01-01

    Combining the symplectic variations theory, the homogeneous control equation and isoparametric element homogeneous formulations for piezothermoelastic hybrid laminates problems were deduced. Firstly, based on the generalized Hamilton variation principle, the non-homogeneous Hamilton canonical equation for piezothermoelastic bodies was derived. Then the symplectic relationship of variations in the thermal equilibrium formulations and gradient equations was considered, and the non-homogeneous canonical equation was transformed to homogeneous control equation for solving independently the coupling problem of piezothermoelastic bodies by the incensement of dimensions of the canonical equation. For the convenience of deriving Hamilton isoparametric element formulations with four nodes, one can consider the temperature gradient equation as constitutive relation and reconstruct new variation principle. The homogeneous equation simplifies greatly the solution programs which are often performed to solve nonhomogeneous equation and second order differential equation on the thermal equilibrium and gradient relationship.

  8. On the relation between canonical and covariant loop quantum gravity

    International Nuclear Information System (INIS)

    Loop quantum gravity is a background independent and non-perturbative approach towards a quantum theory of gravity that divides into a canonical and covariant (or spin foam) model. Heuristically, spin foams can be understood as the Feynman graphs of Quantum Gravity. Yet, summing over all 'histories' would lead to a projector on the physical Hilbert space of the canonical theory rather than to a true propagator due to the constraint nature of GR. Following this idea we construct a spin-foam operator acting on the kinematic Hilbert space and analyze its properties.

  9. Magnetic phase diagrams from non-collinear canonical band theory

    DEFF Research Database (Denmark)

    Shallcross, Sam; Nordstrom, L.; Sharma, S.

    2007-01-01

    A canonical band theory of non-collinear magnetism is developed and applied to the close packed fcc and bcc crystal structures. This is a parameter-free theory where the crystal and magnetic symmetry and exchange splitting uniquely determine the electronic bands. In this way, we are able to...... construct phase diagrams of magnetic order for the fcc and bcc lattices. Several examples of non-collinear magnetism are seen to be canonical in origin, in particular, that of gamma-Fe. In this approach, the determination of magnetic stability results solely from changes in kinetic energy due to spin...

  10. Twist-4 effects in electroproduction: Canonical operators and coefficient functions

    International Nuclear Information System (INIS)

    The interpretation of observed scaling violations in leptoproduction is complicated by the possible presence of significant higher-twist effects. We refine the machinery of the operator-product expansion sufficiently for a study of twist-4 effects. In particular, we introduce and review the advantages of a special, ''canonical'' basis. We demonstrate that the canonical basis is adequate for the necessary twist-4 perturbative calculations, and calculate the operator's tree-level coefficient functions in electroproduction. Our results establish a framework within which careful analysis of more accurate data can provide information regarding correlations among the constituents of the proton

  11. Canon Trouble: Intertextuality and Subversion in Queer as Folk

    OpenAIRE

    Ludot-Vlasak, Ronan

    2016-01-01

    Drawing on gender and queer theory, but also on cultural materialism, this article explores some intertextual references – mainly to Shakespeare and John Keats – at work in the American TV series Queer as Folk. The show recycles canonical works or figures, but considerably reconfigures them. Not only are these references pervaded with overt sexual innuendoes, but they also challenge the literary canon “from within,” regenerate it and invite us to revisit these works – to re-read them against ...

  12. Canonical extensions of the Johnson homomorphisms to the Torelli groupoid

    DEFF Research Database (Denmark)

    Bene, Alex; Kawazumi, Nariya; Penner, Robert

    2009-01-01

    We prove that every trivalent marked bordered fatgraph comes equipped with a canonical generalized Magnus expansion in the sense of Kawazumi. This Magnus expansion is used to give canonical extensions of the higher Johnson homomorphisms τm , for m 1 , to the Torelli groupoid, and we provide...... a recursive combinatorial formula for tensor representatives of these extensions. In particular, we give an explicit 1-cocycle in the dual fatgraph complex which extends τ2 and thus answer affirmatively a question of Morita and Penner. To illustrate our techniques for calculating higher Johnson homomorphisms...

  13. Common structural basis for constitutive activity of the ghrelin receptor family

    DEFF Research Database (Denmark)

    Holst, Birgitte; Holliday, Nicholas D; Bach, Anders;

    2004-01-01

    Three members of the ghrelin receptor family were characterized in parallel: the ghrelin receptor, the neurotensin receptor 2 and the orphan receptor GPR39. In transiently transfected COS-7 and human embryonic kidney 293 cells, all three receptors displayed a high degree of ligand-independent sig......Three members of the ghrelin receptor family were characterized in parallel: the ghrelin receptor, the neurotensin receptor 2 and the orphan receptor GPR39. In transiently transfected COS-7 and human embryonic kidney 293 cells, all three receptors displayed a high degree of ligand...

  14. [Transient epileptic amnesia].

    Science.gov (United States)

    Muramatsu, Kazuhiro; Yoshizaki, Takahito

    2016-03-01

    Transient amnesia is one of common clinical phenomenon of epilepsy that are encountered by physicians. The amnestic attacks are often associated with persistent memory disturbances. Epilepsy is common among the elderly, with amnesia as a common symptom and convulsions relatively uncommon. Therefore, amnesia due to epilepsy can easily be misdiagnosed as dementia. The term 'transient epileptic amnesia (TEA)' was introduced in the early 1990s by Kapur, who highlighted that amnestic attacks caused by epilepsy can be similar to those occurring in 'transient global amnesia', but are distinguished by features brevity and recurrence. In 1998, Zeman et al. proposed diagnostic criteria for TEA. PMID:27025088

  15. Linkage-specific conformational ensembles of non-canonical polyubiquitin chains.

    Science.gov (United States)

    Castañeda, Carlos A; Chaturvedi, Apurva; Camara, Christina M; Curtis, Joseph E; Krueger, Susan; Fushman, David

    2016-02-17

    Polyubiquitination is a critical protein post-translational modification involved in a variety of processes in eukaryotic cells. The molecular basis for selective recognition of the polyubiquitin signals by cellular receptors is determined by the conformations polyubiquitin chains adopt; this has been demonstrated for K48- and K63-linked chains. Recent studies of the so-called non-canonical chains (linked via K6, K11, K27, K29, or K33) suggest they play important regulatory roles in growth, development, and immune system pathways, but biophysical studies are needed to elucidate the physical/structural basis of their interactions with receptors. A first step towards this goal is characterization of the conformations these chains adopt in solution. We assembled diubiquitins (Ub2) comprised of every lysine linkage. Using solution NMR measurements, small-angle neutron scattering (SANS), and in silico ensemble generation, we determined population-weighted conformational ensembles that shed light on the structure and dynamics of the non-canonical polyubiquitin chains. We found that polyubiquitin is conformationally heterogeneous, and each chain type exhibits unique conformational ensembles. For example, K6-Ub2 and K11-Ub2 (at physiological salt concentration) are in dynamic equilibrium between at least two conformers, where one exhibits a unique Ub/Ub interface, distinct from that observed in K48-Ub2 but similar to crystal structures of these chains. Conformers for K29-Ub2 and K33-Ub2 resemble recent crystal structures in the ligand-bound state. Remarkably, a number of diubiquitins adopt conformers similar to K48-Ub2 or K63-Ub2, suggesting potential overlap of biological function among different lysine linkages. These studies highlight the potential power of determining function from elucidation of conformational states. PMID:26422168

  16. Transient Ischemic Attack

    Medline Plus

    Full Text Available ... TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an ... a short time. The only difference between a stroke and TIA is that with TIA the blockage ...

  17. Transient Microcavity Sensor

    CERN Document Server

    Shu, Fang-Jie; Özdemir, Şahin Kaya; Yang, Lan; Guo, Guang-Can

    2015-01-01

    A transient and high sensitivity sensor based on high-Q microcavity is proposed and studied theoretically. There are two ways to realize the transient sensor: monitor the spectrum by fast scanning of probe laser frequency or monitor the transmitted light with fixed laser frequency. For both methods, the non-equilibrium response not only tells the ultrafast environment variance, but also enable higher sensitivity. As examples of application, the transient sensor for nanoparticles adhering and passing by the microcavity is studied. It's demonstrated that the transient sensor can sense coupling region, external linear variation together with the speed and the size of a nanoparticle. We believe that our researches will open a door to the fast dynamic sensing by microcavity.

  18. Searches for radio transients

    CERN Document Server

    Bhat, N D R

    2011-01-01

    Exploration of the transient Universe is an exciting and fast-emerging area within radio astronomy. Known transient phenomena range in time scales from sub-nanoseconds to years or longer, thus spanning a huge range in time domain and hinting a rich diversity in their underlying physical processes. Transient phenomena are likely locations of explosive or dynamic events and they offer tremendous potential to uncover new physics and astrophysics. A number of upcoming next-generation radio facilities and recent advances in computing and instrumentation have provided a much needed impetus for this field which has remained a relatively uncharted territory for the past several decades. In this paper we focus mainly on the class of phenomena that occur on very short time scales (i.e. from $\\sim$ milliseconds to $\\sim$ nanoseconds), known as {\\it fast transients}, the detections of which involve considerable signal processing and data management challenges, given the high time and frequency resolutions required in the...

  19. The canonical and alternate duals of a wavelet frame

    DEFF Research Database (Denmark)

    Lemvig, Jakob; Bownik, Marcin

    2007-01-01

    We show that there exists a frame wavelet ψ with fast decay in the time domain and compact support in the frequency domain generating a wavelet system whose canonical dual frame cannot be generated by an arbitrary number of generators. On the other hand, there exists infinitely many alternate duals...

  20. The canonical and alternate duals of a wavelet frame

    DEFF Research Database (Denmark)

    Bownik, Marcin; Lemvig, Jakob

    We show that there exists a frame wavelet $\\psi$ with fast decay in the time domain and compact support in the frequency domain generating a wavelet system whose canonical dual frame cannot be generated by an arbitrary number of generators. On the other hand, there exists infinitely many alternate...

  1. The Hamiltonian Canonical Form for Euler-Lagrange Equations

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yu

    2002-01-01

    Based on the theory of calculus of variation, some suffcient conditions are given for some Euler-Lagrangcequations to be equivalently represented by finite or even infinite many Hamiltonian canonical equations. Meanwhile,some further applications for equations such as the KdV equation, MKdV equation, the general linear Euler Lagrangeequation and the cylindric shell equations are given.

  2. IDENTIFICATION OF IDEOTYPES BY CANONICAL ANALYSIS IN Panicum maximum

    Directory of Open Access Journals (Sweden)

    Janaina Azevedo Martuscello

    2015-04-01

    Full Text Available Grouping of genotypes by canonical variable analysis is an important tool in breeding. It allows the grouping of individuals with similar characteristics that are associated with superior agronomic performance and may indicate the ideal profile of a plant for the region. The objective of the present study was to define, by canonical analysis, the agronomic profile of Panicum maximum plants adapted to the Agreste region. The experiment was conducted in a completely randomized design with 28 treatments, 22 genotypes of Panicum maximum, and cultivars Mombasa, Tanzania, Massai, Milenio, BRS Zuri, and BRS Tamani in triplicate in 4-m² plots. Plots were harvested five times and the following traits were evaluated: plant height; total, leaf, and stem; dead dry matter yields; leaf:stem ratio; leaf percentage; and volumetric density of forage. The analysis of canonical variables was performed based on the phenotypic means of the evaluated traits and on the residual variance and covariance matrix. Genotype PM34 showed higher mean leaf dry matter yield under the conditions of the Agreste of Alagoas (on average 53% higher than cultivars Mombasa, Tanzania, Milenio and Massai. It was possible to summarize the variation observed in eight agronomic characteristics in only two canonical variables accounting for 81.44 % of the data variation. The ideotype plant adapted to the conditions of the Agreste should be tall and present high leaf yield, leaf percentage, and leaf:stem ratio, and intermediate values ​​of volumetric density of forage.

  3. An Alternative Method to Predict Performance: Canonical Redundancy Analysis.

    Science.gov (United States)

    Dawson-Saunders, Beth; Doolen, Deane R.

    1981-01-01

    The relationships between predictors of performance and subsequent measures of clinical performance in medical school were examined for two classes at Southern Illinois University of Medicine. Canonical redundancy analysis was used to evaluate the association between six academic and three biographical preselection characteristics and four…

  4. Canonical path integral quantization of Einstein's gravitational field

    OpenAIRE

    Muslih, Sami I.

    2000-01-01

    The connection between the canonical and the path integral formulations of Einstein's gravitational field is discussed using the Hamilton - Jacobi method. Unlike conventional methods, it is shown that our path integral method leads to obtain the measure of integration with no $\\delta$- functions, no need to fix any gauge and so no ambiguous deteminants will appear.

  5. Canonical bases and affine Hecke algebras of type B

    CERN Document Server

    Varagnolo, Michela

    2009-01-01

    We prove a series of conjectures of Enomoto and Kashiwara on canonical bases and branching rules of affine Hecke algebras of type B. The main ingredient of the proof is a new graded Ext-algebra associated with quiver with involutions that we compute explicitly.

  6. Uncertainty relations, zero point energy and the linear canonical group

    Science.gov (United States)

    Sudarshan, E. C. G.

    1993-01-01

    The close relationship between the zero point energy, the uncertainty relations, coherent states, squeezed states, and correlated states for one mode is investigated. This group-theoretic perspective enables the parametrization and identification of their multimode generalization. In particular the generalized Schroedinger-Robertson uncertainty relations are analyzed. An elementary method of determining the canonical structure of the generalized correlated states is presented.

  7. Testing the significance of canonical axes in redundancy analysis

    NARCIS (Netherlands)

    Legendre, P.; Oksanen, J.; Braak, ter C.J.F.

    2011-01-01

    1. Tests of significance of the individual canonical axes in redundancy analysis allow researchers to determine which of the axes represent variation that can be distinguished from random. Variation along the significant axes can be mapped, used to draw biplots or interpreted through subsequent anal

  8. Canonical orbital elements in terms of an arbitrary independent variable

    Science.gov (United States)

    Bond, V. R.; Janin, G.

    1981-01-01

    Within the framework of the Hamiltonian mechanics in the extended phase space, a set of canonical elements of the Delaunay type is developed in terms of an arbitary independent angular variable. Application to the four classical anomalies - eccentric, true, elliptic, and mean - is presented. Particular attention is given to the generalized time equation and its conjugate energy equation.

  9. Canonical transformations in quantum field theory and solitons

    International Nuclear Information System (INIS)

    In s sine-Gordon model we discuss a transformation which can be viewed as a quantum image of the Baecklund transformation. The soliton is described in terms of condensation of quanta; their confinement is ascribed to the non-implementability of unitary transformations among unitarily inequivalent representations of canonical commutators and to the related topological conservation law. (orig.)

  10. The Catholic School According to the Code of Canon Law

    Science.gov (United States)

    Grocholewski, Zenon Cardinal

    2008-01-01

    For close to three decades, his Eminence Zenon Cardinal Grocholeski, worked at the Supreme Tribunal of the Apostolic Signatura as notary, chancellor, secretary and prefect. A professor, scholar, and canonist of exceptional ability, he is considered one of the world's most prominent experts on the Code of Canon Law. In light of his competence and…

  11. The Canon Law revisions: a reflection of the postconciliar Church?

    Science.gov (United States)

    O'Connor, D F

    1979-11-01

    The postconciliar Church has approved many changes in Church life. Reactions to the proposed draft of the new canon law codes have ranged from favorable to strongly critical. The mature Catholic looks beyond the letter of the law to its spirit and purpose. PMID:488987

  12. Groups of automorphisms of the canonical commutation and anticommutation relations

    International Nuclear Information System (INIS)

    Observables of supersymmetric quantum mechanics are coded by taking the antisymmetric tensor product with anticommuting parameters. Next we define superunitary transformations, which mix bosonic and fermionic degrees of freedom, in order to construct automorphisms of the canonical (anti-) commutation relations. Conversely, every automorphism of the C(A)CR is implemented by an essentially unique superunitary transformation. 12 refs. (Author)

  13. AN ALGORITHM FOR JORDAN CANONICAL FORM OF A QUATERNION MATRIX

    Institute of Scientific and Technical Information of China (English)

    姜同松; 魏木生

    2003-01-01

    In this paper, we first introduce a concept of companion vector, and studythe Jordan canonical forms of quaternion matrices by using the methods of complex representation and companion vector, not only give out a practical algorithm for Jordancanonical form J of a quaternion matrix A, but also provide a practical algorithm forcorresponding nonsingular matrix P with P- 1 AP = J.

  14. Transient Radio Neutron Stars

    OpenAIRE

    Keane, E. F.

    2010-01-01

    Here I will review the high time resolution radio sky, focusing on millisecond scales. This is primarily occupied by neutron stars, the well-known radio pulsars and the recently identified group of transient sources known as Rotating RAdio Transients (RRATs). The RRATs appear to be abundant in the Galaxy, which at first glance may be difficult to reconcile with the observed supernova rate. However, as I will discuss, it seems that the RRATs can be explained as pulsars which are either extreme...

  15. Management of pediatric radiation dose using Canon digital radiography

    International Nuclear Information System (INIS)

    A Canon CXDI-11 digital radiography (DR) system has been in use at Shands Hospital at the University of Florida for the past 2 1/2 years. A first clinical implementation phase was utilized to develop imaging protocols for adult patients, with a second phase incorporating pediatric chest and abdominal studies a few months later. This paper describes some of the steps taken during the modality implementation stages, as well as the methodologies and procedures utilized to monitor compliance by the technologists. The Canon DR system provides the technologist with an indication of the radiation exposure received by the detector (and thus of the patient dose) by means of an indirect exposure level number called the reached exposure (REX) value. The REX value is calculated by the system based on the default grayscale curve preselected for a given anatomical view and used by the system to optimize the appearance of the image. The brightness and contrast of the image can be modified by the user at the QC/control screen for the purpose of improving the appearance of the image. Such changes modify the actual grayscale curve (position and slope, respectively) and thus the calculated REX value. Thus, undisciplined use of the brightness and contrast functions by the technologist can render the REX value meaningless as an exposure indicator. The paper also shows how it is possible to calibrate AEC (phototimer) systems for use with the Canon DR system, and utilize the REX value as a valuable dose indicator through proper training of technologists and strict, disciplined QC of studies. A team consisting of the site's medical physicist, radiologists, and technologists, as well as Canon engineers, can work together in properly calibrating and setting up the system for the purposes of monitoring patient doses (especially pediatric) in DR studies performed in a Canon DR system. (orig.)

  16. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action

    DEFF Research Database (Denmark)

    Lehmann, Anders; Antonsson, Madeleine; Holmberg, Ann Aurell;

    2009-01-01

    mice, AZD3355 produced considerably less central side effects than the prototypical GABA(B) receptor agonist baclofen but evoked hypothermia at very high doses (blocked by a GABA(B) receptor antagonist and absent in GABA(B)-/- mice). AZD3355 and baclofen differed markedly in their distribution in rat...... brain; AZD3355, but not baclofen, was concentrated in circumventricular organs as a result of active uptake (shown by avid intracellular sequestration) and related to binding of AZD3355 to native GABA transporters in rat cerebrocortical membranes. AZD3355 was also shown to be transported by all four...

  17. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    International Nuclear Information System (INIS)

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  18. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    Science.gov (United States)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

    2010-10-01

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  19. Climate Prediction Center(CPC)Ensemble Canonical Correlation Analysis Forecast of Temperature

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Ensemble Canonical Correlation Analysis (ECCA) temperature forecast is a 90-day (seasonal) outlook of US surface temperature anomalies. The ECCA uses Canonical...

  20. Canonical sound speed profile and related ray acoustic parameters in the Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Murty, T.V.R.; Sadhuram, Y.; Rao, M.M.M.; Rao, B.P.; SuryaPrakash, S.; Chandramouli, P.; Murthy, K.S.R.; Prasad, K.V.S.R.

    Following Munk's canonical theory, canonical parameters (i.e., B the stratification scale and epsilon the perturbation coefficient) in adiabatic ocean are obtained using SOFAR channel parameters (i.e., C sound velocity at the channel axis, Z sub(1...

  1. The LOFAR Transients Pipeline

    Science.gov (United States)

    Swinbank, John D.; Staley, Tim D.; Molenaar, Gijs J.; Rol, Evert; Rowlinson, Antonia; Scheers, Bart; Spreeuw, Hanno; Bell, Martin E.; Broderick, Jess W.; Carbone, Dario; Garsden, Hugh; van der Horst, Alexander J.; Law, Casey J.; Wise, Michael; Breton, Rene P.; Cendes, Yvette; Corbel, Stéphane; Eislöffel, Jochen; Falcke, Heino; Fender, Rob; Grießmeier, Jean-Mathias; Hessels, Jason W. T.; Stappers, Benjamin W.; Stewart, Adam J.; Wijers, Ralph A. M. J.; Wijnands, Rudy; Zarka, Philippe

    2015-06-01

    Current and future astronomical survey facilities provide a remarkably rich opportunity for transient astronomy, combining unprecedented fields of view with high sensitivity and the ability to access previously unexplored wavelength regimes. This is particularly true of LOFAR, a recently-commissioned, low-frequency radio interferometer, based in the Netherlands and with stations across Europe. The identification of and response to transients is one of LOFAR's key science goals. However, the large data volumes which LOFAR produces, combined with the scientific requirement for rapid response, make automation essential. To support this, we have developed the LOFAR Transients Pipeline, or TraP. The TraP ingests multi-frequency image data from LOFAR or other instruments and searches it for transients and variables, providing automatic alerts of significant detections and populating a lightcurve database for further analysis by astronomers. Here, we discuss the scientific goals of the TraP and how it has been designed to meet them. We describe its implementation, including both the algorithms adopted to maximize performance as well as the development methodology used to ensure it is robust and reliable, particularly in the presence of artefacts typical of radio astronomy imaging. Finally, we report on a series of tests of the pipeline carried out using simulated LOFAR observations with a known population of transients.

  2. Deprivation of ecclesiastical funeral in the Code of Canon Law of 1983

    OpenAIRE

    Kryspin Dubiel

    2015-01-01

    The article presents the canonical legislation about ecclesiastical burial. It exposes the canonical provisions concerning the fact of a christian death, referring also to the liturgical ones. The thesis was aimed at comparing the rules contained in the two codes of canon law. This document refers particularly to cases in which the church grants or denies the ecclesiastical burial with special reference to 1983 Code of Canon Law. It was taken into account the legislation issued after the code...

  3. Place Of Canon Law Of The Russian Empire In The System Io Humanitarian

    OpenAIRE

    Alexandra A. Dorskaya

    2014-01-01

    In the present article author examines place of canon law in the system of humanitarian sciences in the Russian Empire at the end of XVIII - early XX centuries. Author reveals interaction of canon law with philosophy, philology, jurisprudence. In particular, author shows influence of various philosophical schools on the development of the canon law science, value of foreign researches translation for the development of national science of canon law starting from the end of the XVIII century. ...

  4. Publication bias and the canonization of false facts

    CERN Document Server

    Nissen, Silas B; Gross, Kevin; Bergstrom, Carl T

    2016-01-01

    In the process of scientific inquiry, certain claims accumulate enough support to be established as facts. Unfortunately, not every claim accorded the status of fact turns out to be true. In this paper, we model the dynamic process by which claims are canonized as fact through repeated experimental confirmation. The community's confidence in a claim constitutes a Markov process: each successive published result shifts the degree of belief, until sufficient evidence accumulates to accept the claim as fact or to reject it as false. In our model, publication bias --- in which positive results are published preferentially over negative ones --- influences the distribution of published results. We find that when readers do not know the degree of publication bias and thus cannot condition on it, false claims often can be canonized as facts. Unless a sufficient fraction of negative results are published, the scientific process will do a poor job at discriminating false from true claims. This problem is exacerbated w...

  5. Canonical reduction for dilatonic gravity in 3+1 dimensions

    CERN Document Server

    Scott, T C; Mann, R B; Fee, G J

    2016-01-01

    We generalize the 1+1-dimensional gravity formalism of Ohta and Mann to 3+1 dimensions by developing the canonical reduction of a proposed formalism applied to a system coupled with a set of point particles. This is done via the Arnowitt-Deser-Misner method and by eliminating the resulting constraints and imposing coordinate conditions. The reduced Hamiltonian is completely determined in terms of the particles' canonical variables (coordinates, dilaton field and momenta). It is found that the equation governing the dilaton field under suitable gauge and coordinate conditions, including the absence of transverse-traceless metric components, is a logarithmic Schroedinger equation. Thus, although different, the 3+1 formalism retains some essential features of the earlier 1+1 formalism, in particular the means of obtaining a quantum theory for dilatonic gravity.

  6. Some reference formulas for the generating functions of canonical transformations

    Science.gov (United States)

    Anselmi, Damiano

    2016-02-01

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then we propose a standard way to express the generating function of a canonical transformation by means of a certain "componential" map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory.

  7. Some reference formulas for the generating functions of canonical transformations

    CERN Document Server

    Anselmi, Damiano

    2015-01-01

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then, we propose a standard way to express the generating function of a canonical transformation by means of a certain "componential" map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory.

  8. Some reference formulas for the generating functions of canonical transformations

    Energy Technology Data Exchange (ETDEWEB)

    Anselmi, Damiano [Universita di Pisa, Dipartimento di Fisica ' ' Enrico Fermi' ' , Pisa (Italy); INFN, Sezione di Pisa, Pisa (Italy)

    2016-02-15

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then we propose a standard way to express the generating function of a canonical transformation by means of a certain ''componential'' map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory. (orig.)

  9. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Marina Pasca di Magliano

    Full Text Available Pancreatic ductal adenocarcinoma (PDA is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease. The role of another embryonic signaling pathway, namely the canonical Wnt cascade, is still controversial. Here, we use gene array analysis as a platform to demonstrate general activation of the canonical arm of the Wnt pathway in human PDA. Furthermore, we provide evidence for Wnt activation in mouse models of pancreatic cancer. Our results also indicate that Wnt signaling might be activated downstream of Hedgehog signaling, which is an early event in PDA evolution. Wnt inhibition blocked proliferation and induced apoptosis of cultured adenocarcinoma cells, thereby providing evidence to support the development of novel therapeutical strategies for Wnt inhibition in pancreatic adenocarcinoma.

  10. Quantum canonical transformations in star-product formalism

    International Nuclear Information System (INIS)

    We study construction of the star-product version of three basic quantum canonical transformations which are known as the generators of the full canonical algebra. By considering the fact that star-product of c-number phase-space functions is in complete isomorphism to Hilbert-space operator algebra, it is shown that while the constructions of gauge and point transformations are immediate, generator of the interchanging transformation deforms this isomorphism. As an alternative approach, we study all of them within the deformed form. How to transform any c-number function under linear-nonlinear transformations and the intertwining method are shown within this argument as the complementary subjects of the text

  11. Canonical form of Euler-Lagrange equations and gauge symmetries

    International Nuclear Information System (INIS)

    The structure of the Euler-Lagrange equations for a general Lagrangian theory (e.g. singular, with higher derivatives) is studied. For these equations we present a reduction procedure to the so-called canonical form. In the canonical form the equations are solved with respect to highest-order derivatives of nongauge coordinates, whereas gauge coordinates and their derivatives enter the right-hand sides of the equations as arbitrary functions of time. The reduction procedure reveals constraints in the Lagrangian formulation of singular systems and, in that respect, is similar to the Dirac procedure in the Hamiltonian formulation. Moreover, the reduction procedure allows one to reveal the gauge identities between the Euler-Lagrange equations. Thus, a constructive way of finding all the gauge generators within the Lagrangian formulation is presented. At the same time, it is proved that for local theories all the gauge generators are local in time operators

  12. General quantization of canonical maps on a two-torus

    International Nuclear Information System (INIS)

    Canonical maps on a two-torus in phase space are quantized under most general conditions. Recent results by Keating et al (1999 Nonlinearity 12 579) are thus fully extended in two directions: (a) The translational component of a general canonical map is included in the quantization. (b) All values of Planck's constant, consistent with the toral boundary conditions (BCs), are considered; generically, these values are rational numbers whose numerator must satisfy a number-theoretical condition. Besides the condition on Planck's constant, the quantization is possible only for particular, 'allowed' BCs on the torus. The general equation determining these BCs is derived. Allowed BCs may not exist in some cases; representative examples are the irrational skew translations and Kronecker maps. Exact versions of Egorov's theorem are shown to hold under some conditions. Composition and representation properties of the quantization scheme are studied. (author)

  13. Some reference formulas for the generating functions of canonical transformations

    International Nuclear Information System (INIS)

    We study some properties of the canonical transformations in classical mechanics and quantum field theory and give a number of practical formulas concerning their generating functions. First, we give a diagrammatic formula for the perturbative expansion of the composition law around the identity map. Then we propose a standard way to express the generating function of a canonical transformation by means of a certain ''componential'' map, which obeys the Baker-Campbell-Hausdorff formula. We derive the diagrammatic interpretation of the componential map, work out its relation with the solution of the Hamilton-Jacobi equation and derive its time-ordered version. Finally, we generalize the results to the Batalin-Vilkovisky formalism, where the conjugate variables may have both bosonic and fermionic statistics, and describe applications to quantum field theory. (orig.)

  14. EL USO DEL CANON INTERNACIONAL DE LOS DERECHOS HUMANOS.

    Directory of Open Access Journals (Sweden)

    José de Jesús Becerra Ramírez

    2013-11-01

    Full Text Available El presente documento pretende hacer una aproximación a las nuevas construcciones jurídicas en la que el uso del canon internacional de los derechos humanos tiene una presencia e influencia innegable en los ordenamientos jurídicos nacionales. Esto, derivado de la coyuntura presente en la que las fuentes normativas, plasmadas en tratados, convenciones, protocolos e incluso declaraciones internacionales de derechos humanos, aunados a la jurisprudencia emanada de organismos supranacionales, se han convertido en referencia casi obligada de los operadores jurídicos de los Estados nacionales. Así, ante dicha premisa nos ocuparemos en el presente documento de analizar cómo se ha dado este proceso de articulación del ordenamiento internacional de los derechos humanos con el nacional, que ha llevado al uso del citado canon internacional para legitimar y motivar las resoluciones de parte de la jurisdicción nacional.

  15. Wet Gas Compressor Transients

    OpenAIRE

    Owren, Bjørn Berge

    2014-01-01

    This master thesis considers three subtasks related to transient operation of wet gas compressors.HYSYS Dynamics is used to establish a dynamic simulation model in the first subtask. The model is designed to predict transient behavior of the compressor test facility at NTNU during dry and wet gas trip scenarios. Its steady state performance has been validated against test data. The deviation of polytropic head and suction volume flow is less than 1% for all test points but one.Dry and wet gas...

  16. The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Bernd Willems

    Full Text Available During vertebrate neurulation, cranial neural crest cells (CNCCs undergo epithelial to mesenchymal transition (EMT, delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL receptor-related protein 5 (Lrp5 plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.

  17. Three-qubit pure-state canonical forms

    International Nuclear Information System (INIS)

    In this paper we analyse the canonical forms into which any pure three-qubit state can be cast. The minimal forms, i.e. the ones with the minimal number of product states built from local bases, are also presented and lead to a complete classification of pure three-qubit states. This classification is related to the values of the polynomial invariants under local unitary transformations by a one-to-one correspondence. (author)

  18. Fusing Face and Periocular biometrics using Canonical correlation analysis

    OpenAIRE

    Lakshmiprabha, N. S.

    2016-01-01

    This paper presents a novel face and periocular biometric fusion at feature level using canonical correlation analysis. Face recognition itself has limitations such as illumination, pose, expression, occlusion etc. Also, periocular biometrics has spectacles, head angle, hair and expression as its limitations. Unimodal biometrics cannot surmount all these limitations. The recognition accuracy can be increased by fusing dual information (face and periocular) from a single source (face image) us...

  19. Hierarchical computation in the canonical auditory cortical circuit

    OpenAIRE

    Atencio, Craig A.; Sharpee, Tatyana O.; Schreiner, Christoph E.

    2009-01-01

    Sensory cortical anatomy has identified a canonical microcircuit underlying computations between and within layers. This feed-forward circuit processes information serially from granular to supragranular and to infragranular layers. How this substrate correlates with an auditory cortical processing hierarchy is unclear. We recorded simultaneously from all layers in cat primary auditory cortex (AI) and estimated spectrotemporal receptive fields (STRFs) and associated nonlinearities. Spike-trig...

  20. Alphabet Sizes of Auxiliary Variables in Canonical Inner Bounds

    OpenAIRE

    Jana, Soumya

    2008-01-01

    Alphabet size of auxiliary random variables in our canonical description is derived. Our analysis improves upon estimates known in special cases, and generalizes to an arbitrary multiterminal setup. The salient steps include decomposition of constituent rate polytopes into orthants, translation of a hyperplane till it becomes tangent to the achievable region at an extreme point, and derivation of minimum auxiliary alphabet sizes based on Caratheodory's theorem.

  1. Nuclear Multifragmentation in the Non-extensive Statistics - Canonical Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Gudima, K.K. [Grand Accelerateur National d' Ions Lourds - GANIL, CEA/DSM - CNRS/IN2P3, BP 5027, F-14021 Caen Cedex (France); Institute of Applied Physics, Moldova Academy of Sciences, MD-2028 Kishineu (Moldova, Republic of); Parvan, A.S.; Toneev, V.D. [Institute of Applied Physics, Moldova Academy of Sciences, MD-2028 Kishineu (Moldova, Republic of); Bogolyubov Laboratory of Theoretical Physics, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Ploszajczak, M. [Grand Accelerateur National d' Ions Lourds - GANIL, CEA/DSM - CNRS/IN2P3, BP 5027, F-14076 Caen Cedex (France)

    2000-04-21

    We apply the canonical quantum statistical model of nuclear multifragmentation generalized in the framework of recently proposed Tsallis non-extensive thermo-statistics for the description of nuclear multifragmentation process. The test calculation in the system with A = 197 nucleons shows strong modification of the 'critical' behaviour associated with the nuclear liquid-gas phase transition for small deviations from the conventional Boltzmann-Gibbs statistical mechanics. (authors)

  2. Canonical Relativity and the Dimensionality of the World

    OpenAIRE

    Bojowald, Martin

    2008-01-01

    Different aspects of relativity, mainly in a canonical formulation, relevant for the question "Is spacetime nothing more than a mathematical space (which describes the evolution in time of the ordinary three-dimensional world) or is it a mathematical model of a real four-dimensional world with time entirely given as the fourth dimension?" are presented. The availability as well as clarity of the arguments depend on which framework is being used, for which currently special relativity, general...

  3. Canonical variables and quasilocal energy in general relativity

    OpenAIRE

    Lau, Stephen

    1993-01-01

    Recently Brown and York have devised a new method for defining quasilocal energy in general relativity. Their method yields expressions for the quasilocal energy and momentum surface densities associated with the two-boundary of a spacelike slice of a spatially bounded spacetime. These expressions are essentially Arnowitt-Deser-Misner variables, but with canonical conjugacy defined with respect to the time history of the two-boundary. This paper introduces Ashtekar-type variables on the time ...

  4. Generalized Gibbs canonical ensemble: A possible physical scenario

    OpenAIRE

    Velazquez, L.

    2007-01-01

    After reviewing some fundamental results derived from the introduction of the generalized Gibbs canonical ensemble, such as the called thermodynamic uncertainty relation, it is described a physical scenario where such a generalized ensemble naturally appears as a consequence of a modification of the energetic interchange mechanism between the interest system and its surrounding, which could be relevant within the framework of long-range interacting systems.

  5. Canonical formulation and path integral for local vacuum energy sequestering

    OpenAIRE

    Bufalo, R.; Klusoň, J.; Oksanen, M.

    2016-01-01

    We establish the Hamiltonian analysis and the canonical path integral for a local formulation of vacuum energy sequestering. In particular, by considering the state of the universe as a superposition of vacuum states corresponding to different values of the cosmological and gravitational constants, the path integral is extended to include integrations over the cosmological and gravitational constants. The result is an extension of the Ng-van Dam form of the path integral of unimodular gravity...

  6. The Canonization of German-language Digital Literature

    OpenAIRE

    Hartling, Florian

    2005-01-01

    In his paper, "The Canonization of German-language Digital Literature," Florian Hartling discusses "Net Literature," a relatively young phenomenon, that has its roots in experimental visual and concrete poetry and hypertext. With the use of new media technology, this new genre of literature has acquired much interest and is now considered to be one of the most important influences in contemporary art. Not only does Net Literature connect sound, video, and animation with interactivity and allo...

  7. A canonical theory of dynamic decision-making

    Directory of Open Access Journals (Sweden)

    John eFox

    2013-04-01

    Full Text Available Decision-making behaviour is studied in many very different fields, from medicine and economics to psychology and neuroscience, with major contributions from mathematics and statistics, computer science, AI and other technical disciplines. However the conceptualisation of what decision-making is and methods for studying it vary greatly and this has resulted in fragmentation of the field. A theory that can accommodate various perspectives may facilitate interdisciplinary working. We present such a theory in which decision-making is articulated as a set of canonical functions that are sufficiently general to accommodate diverse viewpoints, yet sufficiently precise that they can be instantiated in different ways for specific theoretical or practical purposes. The canons cover the whole decision cycle, from the framing of a decision based on the goals, beliefs, and background knowledge of the decision maker to the formulation of decision options, establishing preferences over them, and making commitments. Commitments can lead to the initiation of new decisions and any step in the cycle can incorporate reasoning about previous decisions and the rationales for them, and lead to revising or abandoning existing commitments. The theory situates decision making with respect to other high-level cognitive capabilities like problem-solving, planning and collaborative decision-making. The canonical approach is assessed in three domains: cognitive and neuro-psychology, artificial intelligence, and decision engineering.

  8. Transient Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten

    1998-01-01

    Analytical theory of transient heat conduction.Fourier's law. General heat conducation equation. Thermal diffusivity. Biot and Fourier numbers. Lumped analysis and time constant. Semi-infinite body: fixed surface temperature, convective heat transfer at the surface, or constant surface heat flux...

  9. On Detecting Transients

    CERN Document Server

    Belanger, G

    2013-01-01

    Transient phenomena are interesting and potentially highly revealing of details about the processes under observation and study that could otherwise go unnoticed. It is therefore important to maximise the sensitivity of the method used to identify such events. In this article we present a general procedure based on the use of the likelihood function for identifying transients that is particularly suited for real-time applications because it requires no grouping or pre-processing of the data. The method is optimal in the sense that all the information that is available in the data is used in the statistical decision making process, and is suitable for a wide range of applications. We here consider those most common in astrophysics which involve searching for transient sources, events or features in images, time series, energy spectra and power spectra, and demonstrate the use of the method in the cases of a transient in a time series or in a power spectrum. We derive a fit statistic that is ideal for fitting a...

  10. The Resurrection of Jesus: do extra-canonical sources change the landscape?

    Directory of Open Access Journals (Sweden)

    F P Viljoen

    2005-10-01

    Full Text Available The resurrection of Jesus is assumed by the New Testament to be a historical event. Some scholars argue, however, that there was no empty tomb, but that the New Testament accounts are midrashic or mythological stories about Jesus.� In this article extra-canonical writings are investigated to find out what light it may throw on intra-canonical tradition. Many extra-canonical texts seemingly have no knowledge of the passion and resurrection, and such traditions may be earlier than the intra-canonical traditions. Was the resurrection a later invention?� Are intra-canonical texts developments of extra-canonical tradition, or vice versa?� This article demonstrates that extra-canonical texts do not materially alter the landscape of enquiry.

  11. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Shan-Li [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Sun, Ming-Rui [Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China); Li, Ting-Ting; Yin, Xin [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China); Xu, Chang-Qing [Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China); Sun, Yi-Hua, E-mail: syh200415@126.com [Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)

    2011-03-11

    Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3

  12. Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

    International Nuclear Information System (INIS)

    Research highlights: → Calcium-sensing receptor (CaR) activation stimulates TRP channels. → CaR promoted transient receptor potential C3 (TRPC3) expression. → Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. → TRPC channels activation induced by CaR activator sustained the increased [Ca2+]i to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca2+ overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca2+ overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca2+]i levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca2+ stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca2+]i in the absence of [Ca2+]o and the subsequent restoration of [Ca2+]o sustained the increased [Ca2+]i for a few minutes, whereas, the persisting elevation of [Ca2+]i was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl3) or spermine also resulted in the same effect and the duration of [Ca2+]i increase was also shortened in the absence of [Ca2+]o. In adult and neonatal rat cardiomyocytes, GdCl3 increased the expression of TRPC3 mRNA and protein, which were reversed by SKF96365 but not by inhibitors of the L-type channels and the Na+/Ca2+ exchangers

  13. "Canonical and non-canonical actions of GRK5 in the heart".

    Science.gov (United States)

    Traynham, Christopher J; Hullmann, Jonathan; Koch, Walter J

    2016-03-01

    As the average world-wide lifespan continues to increase, heart failure (HF) has dramatically increased in incidence leading to the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) play a prominent role in regulation of cardiovascular function. GPCRs are effectively "turned off" by GPCR kinases (GRKs) in a process known as "desensitization". GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20years, the role of GRK2 in HF has been widely studied. However, until recently, the role of GRK5 in cardiac pathophysiology had yet to be elucidated. In the present review, we will focus on GRK5's role in the myocardium in normal physiology, and its apparent critical role in the progression of HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, gene therapy) that may have potential in combating the deleterious effects of GRK5 in HF. PMID:26829117

  14. Temporal changes in glial fibrillary acidic protein messenger RNA and [{sup 3}H]PK11195 binding in relation to imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Craven, J.A.; Gundlach, A.L.; Conway, E.L. [The University of Melbourne, Clinical Pharmacology and Therapeutics Unit (Australia); Department of Medicine, Austin and Repatriation Medical Centre (Australia)

    1997-10-24

    Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [{sup 3}H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I{sub 2}-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from {alpha}{sub 2}-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [{sup 3}H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [{sup 3}H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I{sub 2}-receptor binding sites detected using the specific radioligand, [{sup 3}H]2

  15. The VAO Transient Facility

    CERN Document Server

    Graham, Matthew J; Drake, Andrew; Mahabal, Ashish; Williams, Roy; Seaman, Rob

    2011-01-01

    The time domain community wants robust and reliable tools to enable production of and subscription to community-endorsed event notification packets (VOEvent). The VAO Transient Facility (VTF) is being designed to be the premier brokering service for the community, both collecting and disseminating observations about time-critical astronomical transients but also supporting annotations and the application of intelligent machine-learning to those observations. This distinguishes two types of activity associated with the facility: core infrastructure and user services. In this paper, we will review the prior art in both areas and describe the planned capabilities of the VTF. In particular, we will focus on scalability and quality-of-service issues required by the next generation of sky surveys, such as LSST and SKA.

  16. Familial Transient Global Amnesia

    OpenAIRE

    Davies, R Rhys; Larner, A J

    2012-01-01

    Following an episode of typical transient global amnesia (TGA), a female patient reported similar clinical attacks in 2 maternal aunts. Prior reports of familial TGA are few, and no previous account of affected relatives more distant than siblings or parents was discovered in a literature survey. The aetiology of familial TGA is unknown. A pathophysiological mechanism akin to that in migraine attacks, comorbidity reported in a number of the examples of familial TGA, is one possibility. The st...

  17. Multimoment Radio Transient Detection

    OpenAIRE

    Spitler, Laura; Cordes, Jim; Chatterjee, Shami; Stone, Julia

    2011-01-01

    We present a multimoment technique for signal classification and apply it to the detection of fast radio transients in incoherently dedispersed data. Specifically, we define a spectral modulation index in terms of the fractional variation in intensity across a spectrum. A signal whose intensity is distributed evenly across the entire band has a much lower modulation index than a spectrum with the same intensity localized in a single channel. We are interested in broadband pulses and use the m...

  18. Transient or Permanent Fisheye Views

    DEFF Research Database (Denmark)

    Jakobsen, Mikkel Rønne; Hornbæk, Kasper Anders Søren

    2012-01-01

    Transient use of information visualization may support specific tasks without permanently changing the user interface. Transient visualizations provide immediate and transient use of information visualization close to and in the context of the user’s focus of attention. Little is known, however, ...

  19. Bright Transients discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Denneau, L.; Stalder, B.; Heinze, A.; Sherstyuk, A.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-04-01

    Seven bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  20. Two Transients discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Two transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  1. Bright Transients discovered by PSST

    Science.gov (United States)

    Smith, K. W.; Wright, D.; Smartt, S. J.; Young, D. R.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Primak, N.; Schultz, A.; Gibson, B.; Magnier, E.; Waters, C.; Tonry, J.; Wainscoat, R. J.; Foley, R. J.; Jha, S. W.; Rest, A.; Scolnic, D.

    2016-08-01

    Six bright transients have been discovered as part of the Pan-STARRS Survey for Transients (PSST). Information on all objects discovered by the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  2. Does Canon Law speak of sponsorship of Catholic works?

    Science.gov (United States)

    Fr Francis G Morrisey

    2007-01-01

    Though the term "sponsorship" is not used in the Code of Canon Law, it is generally accepted today that "sponsorship" entails the use of a particular name and the exercise of certain responsibilities that arise from this use. A person's good name--whether the "person" is an individual or a group--is of primary importance today; and sponsorship responsibilities are exercised in relation to what the name stands for. In the case of church ministries such as the Catholic health ministry, the term refers to works undertaken in the name of Christ, on behalf of the Catholic Church. Traditionally, sponsorship had emphasized a position of corporate strength and independence through ownership and control via reserved powers. Today, as new relations are established with other providers, a presence is required that relies more on the ability to influence. Sponsorship in canon law entails a relation to the threefold mission and ministry of the church: to teach, to sanctify, and to serve God's people. Undoubtedly, health care fits in among these elements of ecclesial service. It has generally been held that for a work to be identified as "Catholic," it must, in one way or another, be related to a juridic person in the church, such as a diocese, a religious institute, one of the institute's provinces, or even one of its established houses (canon 634). There could also be situations in which no formal juridical person is involved and yet the work is considered to be "Catholic." Lately, new entities established specifically for sponsorship purposes have been recognized either by bishops or by the Holy See. These entities, usually known as "public juridic persons" (but sometimes also called "foundations") assume the sponsorship responsibilities previously assumed by a religious institute (or one of its parts) or a diocese. In some instances, these entities also assume all the ownership and property rights previously held by the original institute or diocese. PMID:17274574

  3. Denominator function for canonical SU(3) tensor operators

    International Nuclear Information System (INIS)

    The definition of a canonical unit SU(3) tensor operator is given in terms of its characteristic null space as determined by group-theoretic properties of the intertwining number. This definition is shown to imply the canonical splitting conditions used in earlier work for the explicit and unique (up to +- phases) construction of all SU(3) WCG coefficients (Wigner--Clebsch--Gordan). Using this construction, an explicit SU(3)-invariant denominator function characterizing completely the canonically defined WCG coefficients is obtained. It is shown that this denominator function (squared) is a product of linear factors which may be obtained explicitly from the characteristic null space times a ratio of polynomials. These polynomials, denoted G/sup t//sub q/, are defined over three (shift) parameters and three barycentric coordinates. The properties of these polynomials (hence, of the corresponding invariant denominator function) are developed in detail: These include a derivation of their degree, symmetries, and zeros. The symmetries are those induced on the shift parameters and barycentric coordinates by the transformations of a 3 x 3 array under row interchange, column interchange, and transposition (the group of 72 operations leaving a 3 x 3 determinant invariant). Remarkably, the zeros of the general G/sup t//sub q/ polynomial are in position and multiplicity exactly those of the SU(3) weight space associated with irreducible representation [q-1,t-1,0]. The results obtained are an essential step in the derivation of a fully explicit and comprehensible algebraic expression for all SU(3) WCG coefficients

  4. Canonical commutation relations - historical aspect and new results

    International Nuclear Information System (INIS)

    The aim of the paper is to describe the historical aspects of the canonical commutation relations (CCR) and to analyse the new results. The CCR are the algebraic structure (Heisenberg algebra) on the basis of quantum mechanics and quantum field theory. The following results are discussed: the Weyl form of CCR, Von Neumann's uniqueness theorem, regularity conditions, CCR representation in standard and Weyl forms, CCR in an indefinite metric space, class of CCR regular representations and CCR in the case of infinite number of degrees of freedom

  5. A canonical correlation analysis of intelligence and executive functioning.

    Science.gov (United States)

    Davis, Andrew S; Pierson, Eric E; Finch, W Holmes

    2011-01-01

    Executive functioning is one of the most researched and debated topics in neuropsychology. Although neuropsychologists routinely consider executive functioning and intelligence in their assessment process, more information is needed regarding the relationship between these constructs. This study reports the results of a canonical correlation study between the most widely used measure of adult intelligence, the Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III; Wechsler, 1997), and the Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001). The results suggest that, despite considerable shared variability, the measures of executive functioning maintain unique variance that is not encapsulated in the construct of global intelligence. PMID:21390902

  6. The canonical structure of maximally extended supergravity in three dimensions

    International Nuclear Information System (INIS)

    The algebra of local and rigid symmetries of N = 16 supergravity in three dimensions is discussed in detail. The conserved charges associated with the rigid E8 symmetry are constructed and shown to be physical observables in that they weakly commute with all constraints. The phase space variables, which render the constraints polynomial, are identified; they are related to the variables used in the SO(1,2) x SO(16)-invariant reformulation of d = 11 supergravity. This indicates that Ashtekar's approach to canonical gravity can be generalized to higher dimensions if suitable matter degrees of freedom are added to gravity. (orig.)

  7. The canonical structure of maximally extended supergravity in three dimensions

    International Nuclear Information System (INIS)

    The algebra of local and rigid symmetries of N = 16 supergravity in three dimensions is discussed in detail. The conserved charges associated with the rigid E8 symmetry are constructed and shown to be physical observables in that they weakly commute with all constraints. The phase-space variables, which render the constraints polynomial, are identified; they are related to the variables used in the SO(1,2)xSO(16)-invariant reformulation of d = 11 supergravity. This indicates that Ashtekar's approach to canonical gravity can be generalized to higher dimensions if suitable matter degrees of freedom are added to gravity. (orig.)

  8. Two channel paraunitary filter banks based on linear canonical transform

    CERN Document Server

    Shinde, Sudarshan

    2009-01-01

    In this paper a two channel paraunitary filter bank is proposed, which is based on linear canonical transform, instead of discrete Fourier transform. Input-output relation for such a filter bank are derived in terms of polyphase matrices and modulation matrices. It is shown that like conventional filter banks, the LCT based paraunitary filter banks need only one filter to be designed and rest of the filters can be obtained from it. It is also shown that LCT based paraunitary filter banks can be designed by using conventional power-symmetric filter design in Fourier domain.

  9. Log canonical thresholds on varieties with bounded singularities

    CERN Document Server

    de Fernex, Tommaso; Mustata, Mircea

    2010-01-01

    We consider pairs (X,A), where X is a variety with klt singularities and A is a formal product of ideals on X with exponents in a fixed set that satisfies the Descending Chain Condition. We also assume that X has (formally) bounded singularities, in the sense that it is, formally locally, a subvariety in a fixed affine space defined by equations of bounded degree. We prove in this context a conjecture of Shokurov, predicting that the set of log canonical thresholds for such pairs satisfies the Ascending Chain Condition.

  10. Canonical formulation and conserved charges of double field theory

    CERN Document Server

    Naseer, Usman

    2015-01-01

    We provide the canonical formulation of double field theory. It is shown that this dynamics is subject to primary and secondary constraints. The Poisson bracket algebra of secondary constraints is shown to close on-shell according to the C-bracket. A systematic way of writing boundary integrals in doubled geometry is given. By including appropriate boundary terms in the double field theory Hamiltonian, expressions for conserved energy and momentum of an asymptotically flat doubled space-time are obtained and applied to a number of solutions.

  11. El canon literario mexicano en Los detectives salvajes

    Directory of Open Access Journals (Sweden)

    Carmen de Mora

    2015-02-01

    Full Text Available En el presente artículo se examina el canon personal de Bolaño en Los detectives salvajes acerca de la literatura mexicana, a partir de la intertextualidad entendida como un rasgo característico de la narrativa postmoderna del autor. Para ello se han tenido en cuenta tanto las citas explícitas que aparecen en la novela como algunas citas implícitas fundamentales. A través del análisis de las mismas se pretende demostrar que para entender el alcance de esta obra es preciso enfrentarse a su escritura en palimpsesto.

  12. Canonical description of a second-order achromat

    Energy Technology Data Exchange (ETDEWEB)

    Kheifets, S.A.; Fieguth, T.H.; Ruth, R.D.

    1988-03-01

    Charged particle motion in second-order magnetic optical achromat is described using a canonical perturbation theory. Necessary and sufficient conditions for the existence of such a device are presented. Given these conditions, the second-order matrix elements at the end of the achromat are found explicity. It is shown that all geometric matrix elements are equal to zero and all chromatic matrix elements are either also equal to zero or proportional to the corresponding chromaticity. Thus all second-order matrix elements vanish simultaneously when the two chromaticities are made to be equal to zero 13 refs., 1 tab.

  13. Two channel paraunitary filter banks based on linear canonical transform

    OpenAIRE

    Shinde, Sudarshan

    2009-01-01

    In this paper a two channel paraunitary filter bank is proposed, which is based on linear canonical transform, instead of discrete Fourier transform. Input-output relation for such a filter bank are derived in terms of polyphase matrices and modulation matrices. It is shown that like conventional filter banks, the LCT based paraunitary filter banks need only one filter to be designed and rest of the filters can be obtained from it. It is also shown that LCT based paraunitary filter banks can ...

  14. [Interaction of Ag+ ions with ribonucleotides of canonical bases].

    Science.gov (United States)

    Sorokin, V A; Valeev, V A; Gladchenko, G O; Sysa, I V; Degtiar, M V; Volchok, I V; Blagoĭ, Iu P

    1999-01-01

    The interaction of Ag+ ions with ribonucleotides of canonical bases in aqueous solution was studied by differential UV spectroscopy. Atoms coordinating silver ions (N7, O6 of guanosine 5'-monophosphate, N3, O2 of cytidine 5'-monophosphate, N7, N1, N3 of adenosine 5'-monophosphate and N3 of uridine 5'-monophosphate) and the binding constants characterizing the formation of appropriate complexes were determined. The differences in the relative affinity of Ag+ ions for the atoms of nucleotide bases correlate with the potential on them. PMID:10418671

  15. Alternative representation of the linear canonical integral transform.

    Science.gov (United States)

    Alieva, Tatiana; Bastiaans, Martin J

    2005-12-15

    Starting with the Iwasawa-type decomposition of a first-order optical system (or ABCD system) as a cascade of a lens, a magnifier, and an orthosymplectic system (a system that is both symplectic and orthogonal), a further decomposition of the orthosymplectic system in the form of a separable fractional Fourier transformer embedded between two spatial-coordinate rotators is proposed. The resulting decomposition of the entire first-order optical system then shows a physically attractive representation of the linear canonical integral transformation, which, in contrast to Collins integral, is valid for any ray transformation matrix. PMID:16389812

  16. Communication: Generalized canonical purification for density matrix minimization

    Science.gov (United States)

    Truflandier, Lionel A.; Dianzinga, Rivo M.; Bowler, David R.

    2016-03-01

    A Lagrangian formulation for the constrained search for the N-representable one-particle density matrix based on the McWeeny idempotency error minimization is proposed, which converges systematically to the ground state. A closed form of the canonical purification is derived for which no a posteriori adjustment on the trace of the density matrix is needed. The relationship with comparable methods is discussed, showing their possible generalization through the hole-particle duality. The appealing simplicity of this self-consistent recursion relation along with its low computational complexity could prove useful as an alternative to diagonalization in solving dense and sparse matrix eigenvalue problems.

  17. Canonical stability in terms of singularity index for algebraic threefolds

    OpenAIRE

    Chen, Meng

    2000-01-01

    Let X be a projective 3-fold with at most Q-factorial terminal singularities on which K_X is nef and big. Suppose the canonical index r(X)>1. For any positive integer m, it is interesting to consider the base point freeness and birationality of the divisor mK_X. For example, we know the following results: (1) the system |5rK_X| is base point free (Ein-Lazarsfeld-Lee); (2) |mK_X| gives a birational map for all m>4r+2 (M. Hanamura). This article aims to present a better result in direction (2)....

  18. Current commutator anomalies and chiral anomalies in the canonical formalism

    International Nuclear Information System (INIS)

    Without recourse to the Bjorken-Johnson-Low (BJL) method, current-current and current-electric-field commutator anomalies are evaluated in chiral gauge theories in two- and four-dimensional spacetime with the help of a gauge covariant regularization method. The results are consistent with previous analyses through the BJL method, and partially confirmed Faddeev's conjecture on the commutator anomalies of the Gauss law constraint operators within the canonical formalism. The chiral anomalies of the current divergence are derived from these commutator anomalies in the Weyl gauge where current-electric-field commutator anomalies play important roles

  19. Currents, charges, and canonical structure of pseudodual chiral models

    International Nuclear Information System (INIS)

    We discuss the pseudodual chiral model to illustrate a class of two-dimensional theories which have an infinite number of conservation laws but allow particle production, at variance with naive expectations. We describe the symmetries of the pseudodual model, both local and nonlocal, as transmutations of the symmetries of the usual chiral model. We refine the conventional algorithm to more efficiently produce the nonlocal symmetries of the model, and we discuss the complete local current algebra for the pseudodual theory. We also exhibit the canonical transformation which connects the usual chiral model to its fully equivalent dual, further distinguishing the pseudodual theory

  20. Canonical energy and hairy AdS black holes

    Science.gov (United States)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2016-08-01

    We propose the modified version of the canonical energy which was introduced originally by Hollands and Wald. Our construction depends only on the Euler-Lagrange expression of the system and thus is independent of the ambiguity in the Lagrangian. After some comments on our construction, we briefly mention on the relevance of our construction to the boundary information metric in the context of the AdS/CFT correspondence. We also study the stability of three-dimensional hairy extremal black holes by using our construction.

  1. The canonical ring of a 3-connected curve

    CERN Document Server

    Franciosi, Marco

    2011-01-01

    Let C be a Gorenstein curve which is either reduced or contained in a smooth algebraic surface. We show that the canonical ring R(C, \\omega_C)=\\oplus_{k \\geq 0} H^0(C, \\omega_C^k) is generated in degree 1 if C is 3-connected and not (honestly) hyperelliptic; we show moreover that R(C, L)=\\oplus_{k \\geq 0} H^0(C,L^k) is generated in degree 1 if C is reduced and L is an invertible sheaf such that deg L_{|B} \\geq 2p_a(B)+1 for every subcurve B \\subset C.

  2. Tsh receptor

    OpenAIRE

    Frauman, Albert

    2013-01-01

    The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage ...

  3. Families of canonically polarized manifolds over log Fano varieties

    CERN Document Server

    Lohmann, Daniel

    2011-01-01

    Let (X,D) be a dlt pair, where X is a normal projective variety. Let S denote the support of the rounddown of D, and K the canonical divisor of X. We show that any smooth family of canonically polarized varieties over X\\S is isotrivial if the divisor -(K+D) is ample. This result extends results of Viehweg-Zuo and Kebekus-Kovacs. To prove this result we show that any extremal ray of the moving cone is generated by a family of curves, and these curves are contracted after a certain run of the minimal model program. In the log Fano case, this generalizes a theorem by Araujo from the klt to the dlt case. In order to run the minimal model program, we have to switch to a Q-factorialization of X. As Q-factorializations are generally not unique, we use flops to pass from one Q-factorialization to another, proving the existence of a Q-factorialization suitable for our purposes.

  4. Canonical RNA Pseudoknot Structures with Arc Length $\\geq 4$

    CERN Document Server

    Reidys, Christian M; Zhao, Albus Y Y

    2010-01-01

    In this paper, we compute the generating function of the arguably most important target class of folding algorithms into RNA pseudoknot structures. This class consists of $k$-noncrossing, canonical RNA structures having minimum arc length four and generalizes directly the canonical secondary structures, studied by Schuster {\\it et al.} \\cite{Schuster:98}. The combinatorics of this class is important since, in analogy to the case of secondary structures, generic properties of genotype phenotype maps into RNA pseudoknot structures, like shape space covering \\cite{Schuster:94} and neutral networks \\cite{Reidys:97a} are a result of the combinatorics and not of the particulars of energy parameters. Let ${\\sf Q}_k(n)$ denote the number of these structures over $n$ vertices. We derive exact enumeration results as well as the asymptotic formula ${\\sf Q}_k(n)\\sim c_k n^{-(k-1)^2-\\frac{k-1}{2}}(\\gamma_{\\theta,k})^{-n}$ for $k=3, ..., 9$ and derive a new proof of Schuster's result, ${\\sf Q}_2(n)\\sim 1.4848\\, n^{-3/2}\\,1...

  5. The gauge-invariant canonical energy-momentum tensor

    Directory of Open Access Journals (Sweden)

    Lorcé Cédric

    2016-01-01

    Full Text Available The canonical energy-momentum tensor is often considered as a purely academic object because of its gauge dependence. However, it has recently been realized that canonical quantities can in fact be defined in a gauge-invariant way provided that strict locality is abandoned, the non-local aspect being dictacted in high-energy physics by the factorization theorems. Using the general techniques for the parametrization of non-local parton correlators, we provide for the first time a complete parametrization of the energy-momentum tensor (generalizing the purely local parametrizations of Ji and Bakker-Leader-Trueman used for the kinetic energy-momentum tensor and identify explicitly the parts accessible from measurable two-parton distribution functions (TMDs and GPDs. As by-products, we confirm the absence of model-independent relations between TMDs and parton orbital angular momentum, recover in a much simpler way the Burkardt sum rule and derive three similar new sum rules expressing the conservation of transverse momentum.

  6. The gauge-invariant canonical energy-momentum tensor

    Science.gov (United States)

    Lorcé, Cédric

    2016-03-01

    The canonical energy-momentum tensor is often considered as a purely academic object because of its gauge dependence. However, it has recently been realized that canonical quantities can in fact be defined in a gauge-invariant way provided that strict locality is abandoned, the non-local aspect being dictacted in high-energy physics by the factorization theorems. Using the general techniques for the parametrization of non-local parton correlators, we provide for the first time a complete parametrization of the energy-momentum tensor (generalizing the purely local parametrizations of Ji and Bakker-Leader-Trueman used for the kinetic energy-momentum tensor) and identify explicitly the parts accessible from measurable two-parton distribution functions (TMDs and GPDs). As by-products, we confirm the absence of model-independent relations between TMDs and parton orbital angular momentum, recover in a much simpler way the Burkardt sum rule and derive three similar new sum rules expressing the conservation of transverse momentum.

  7. The gauge-invariant canonical energy-momentum tensor

    CERN Document Server

    Lorcé, Cédric

    2016-01-01

    The canonical energy-momentum tensor is often considered as a purely academic object because of its gauge dependence. However, it has recently been realized that canonical quantities can in fact be defined in a gauge-invariant way provided that strict locality is abandoned, the non-local aspect being dictacted in high-energy physics by the factorization theorems. Using the general techniques for the parametrization of non-local parton correlators, we provide for the first time a complete parametrization of the energy-momentum tensor (generalizing the purely local parametrizations of Ji and Bakker-Leader-Trueman used for the kinetic energy-momentum tensor) and identify explicitly the parts accessible from measurable two-parton distribution functions (TMDs and GPDs). As by-products, we confirm the absence of model-independent relations between TMDs and parton orbital angular momentum, recover in a much simpler way the Burkardt sum rule and derive three similar new sum rules expressing the conservation of transv...

  8. Nonbijective canonical transformations and applications to some dynamical systems

    International Nuclear Information System (INIS)

    A first part is devoted to a presentation of a simplified formalism concerning non-bijective canonical transformations and to an interpretation of some of them in the framework on the theory of Lie algebras. In particular, the well-known Levi-Civita and Kustaanheimo-Stiefel transformations are generalized to the non-compact case and to the dimensions 2, 4 and 8. The differential and geometrical properties of the so-called Hurwitz transformations as well as their interpretation in terms of Lie algebras under constraints are given. A second part is concerned with the application of certain non-bijective canonical transformations (and in particular the Kustaanheimo-Stiefel transformation) to some dynamical systems of interest in theoretical and in chemical physics. The applications concern especially hydrogenoid systems, free or embedded in static and uniform electromagnetic fields, and systems presenting a line of singularity (as the Hartmann system, the Aharonov-Bohm system, and the dyonium system). The Kustaanheimo-Stiefel transformation allows to convert the Schroedinger equations for the later systems into Schroedinger equations for oscillators (harmonic, anharmonic, non-harmonic) in 2 or 4 dimensions

  9. Deformed special relativity and deformed symmetries in a canonical framework

    International Nuclear Information System (INIS)

    In this paper we have studied the nature of kinematical and dynamical laws in κ-Minkowski spacetime from a new perspective: the canonical phase space approach. We discuss a particular form of κ-Minkowski phase space algebra that yields the κ-extended finite Lorentz transformations derived in [D. Kimberly, J. Magueijo, and J. Medeiros, Phys. Rev. D 70, 084007 (2004).]. This is a particular form of a deformed special relativity model that admits a modified energy-momentum dispersion law as well as noncommutative κ-Minkowski phase space. We show that this system can be completely mapped to a set of phase space variables that obey canonical (and not κ-Minkowski) phase space algebra and special relativity Lorentz transformation (and not κ-extended Lorentz transformation). The complete set of deformed symmetry generators are constructed that obeys an unmodified closed algebra but induce deformations in the symmetry transformations of the physical κ-Minkowski phase space variables. Furthermore, we demonstrate the usefulness and simplicity of this approach through a number of phenomenological applications both in classical and quantum mechanics. We also construct a Lagrangian for the κ-particle

  10. A Nonlinear GMRES Optimization Algorithm for Canonical Tensor Decomposition

    CERN Document Server

    De Sterck, Hans

    2011-01-01

    A new algorithm is presented for computing a canonical rank-R tensor approximation that has minimal distance to a given tensor in the Frobenius norm, where the canonical rank-R tensor consists of the sum of R rank-one components. Each iteration of the method consists of three steps. In the first step, a tentative new iterate is generated by a stand-alone one-step process, for which we use alternating least squares (ALS). In the second step, an accelerated iterate is generated by a nonlinear generalized minimal residual (GMRES) approach, recombining previous iterates in an optimal way, and essentially using the stand-alone one-step process as a preconditioner. In particular, the nonlinear extension of GMRES is used that was proposed by Washio and Oosterlee in [ETNA Vol. 15 (2003), pp. 165-185] for nonlinear partial differential equation problems. In the third step, a line search is performed for globalization. The resulting nonlinear GMRES (N-GMRES) optimization algorithm is applied to dense and sparse tensor ...

  11. Biodegradation of tetramethylammonium hydroxide (TMAH) in completely autotrophic nitrogen removal over nitrite (CANON) process.

    Science.gov (United States)

    Chen, Shen-Yi; Lu, Li-An; Lin, Jih-Gaw

    2016-06-01

    This study conducted a completely autotrophic nitrogen removal over nitrite (CANON) process in a continuous anoxic upflow bioreactor to treat synthetic wastewater with TMAH (tetramethylammonium hydroxide) ranging from 200 to 1000mg/L. The intermediates were analyzed for understanding the metabolic pathway of TMAH biodegradation in CANON process. In addition, (15)N-labeled TMAH was used as the substrate in a batch anoxic bioreactor to confirm that TMAH was converted to nitrogen gas in CANON process. The results indicated that TMAH was almost completely biodegraded in CANON system at different influent TMAH concentrations of 200, 500, and 1000mg/L. The average removal efficiencies of total nitrogen were higher than 90% during the experiments. Trimethylamine (TMA) and methylamine (MA) were found to be the main biodegradation intermediates of TMAH in CANON process. The production of nitrogen gas with (15)N-labeled during the batch anaerobic bioreactor indicated that CANON process successfully converted TMAH into nitrogen gas. PMID:26879202

  12. Workshop on Radio Transients

    Science.gov (United States)

    Croft, Steve; Gaensler, Bryan

    2012-04-01

    abstract-type="normal">SummaryWe are entering a new era in the study of variable and transient radio sources. This workshop discussed the instruments and the strategies employed to study those sources, how they are identified and classified, how results from different surveys can be compared, and how radio observations tie in with those at other wavelengths. The emphasis was on learning what common ground there is between the plethora of on-going projects, how methods and code can be shared, and how best practices regarding survey strategy could be adopted. The workshop featured the four topics below. Each topic commenced with a fairly brief introductory talk, which then developed into discussion. By way of preparation, participants had been invited to upload and discuss one slide per topic to a wiki ahead of the workshop. 1. Telescopes, instrumentation and survey strategy. New radio facilities and on-going projects (including upgrades) are both studying the variability of the radio sky, and searching for transients. The discussion first centred on the status of those facilities, and on projects with a time-domain focus, both ongoing and planned, before turning to factors driving choices of instrumentation, such as phased array versus single pixel feeds, the field of view, spatial and time resolution, frequency and bandwidth, depth, area, and cadence of the surveys. 2. Detection, pipelines, and classification. The workshop debated (a) the factors that influence decisions to study variability in the (u,v) plane, in images, or in catalogues, (b) whether, and how much, pipeline code could potentially be shared between one project and another, and which software packages are best for different approaches, (c) how data are stored and later accessed, and (d) how transients and variables are defined and classified. 3. Statistics, interpretation, and synthesis. It then discussed how (i) the choice of facility and strategy and (ii) detection and classification schemes

  13. The Rapid Transient Surveyor

    Science.gov (United States)

    Baranec, Christoph; Tonry, John; Wright, Shelley; Tully, R. Brent; Lu, Jessica R.; Takamiya, Marianne Y.; Hunter, Lisa

    2016-01-01

    The next decade of astronomy will be dominated by large area surveys (see the detailed discussion in the Astro-2010 Decadal survey and NRC's recent OIR System Report). Ground-based optical transient surveys, e.g., LSST, ZTF and ATLAS and space-based exoplanet, supernova, and lensing surveys such as TESS and WFIRST will join the Gaia all-sky astrometric survey in producing a flood of data that will enable leaps in our understanding of the universe. There is a critical need for further characterization of these discoveries through high angular resolution images, deeper images, spectra, or observations at different cadences or periods than the main surveys. Such follow-up characterization must be well matched to the particular surveys, and requires sufficient additional observing resources and time to cover the extensive number of targets.We describe plans for the Rapid Transient Surveyor (RTS), a permanently mounted, rapid-response, high-cadence facility for follow-up characterization of transient objects on the U. of Hawai'i 2.2-m telescope on Maunakea. RTS will comprise an improved robotic laser adaptive optics system, based on the prototype Robo-AO system (formerly at the Palomar 1.5-m and now at the Kitt Peak 2.2-m telescope), with simultaneous visible and near-infrared imagers as well as a near-infrared integral field spectrograph (R~100, λ = 850 - 1830 nm, 0.15″ spaxels, 8.7″×6.0″ FoV). RTS will achieve an acuity of ~0.07″ in visible wavelengths and factor of ~9, crucial for efficient near-infrared spectroscopy.RTS will allow us to map the dark matter distribution in the z < 0.1 local universe with ten times better accuracy and precision than previous experiments. ATLAS will discover several thousand SNIae per year, measuring SNIa peak brightness, and decline rates, while RTS will measure reddening by dust, confirm SN type and confirm redshifts of the host galaxies. This unique combination of automated detection and characterization of astrophysical

  14. Concept of canon in literary studies : critical debates 1970-2000.

    OpenAIRE

    Villa, Silvia Maria Teresa

    2012-01-01

    The present thesis focuses on the critical dialogues on the literary canon developed between 1970 and 2000 in the United States as a crucial juncture for the consolidation of the notion of canon as a scholarly subject matter within the field of literary studies. By taking stock of the abundance of scholarly contributions on the literary canon produced at this time, this thesis pursues two aims: first, it initiates a process of systematisation of the scholarly material on the ca...

  15. Generalized second law of thermodynamics for non-canonical scalar field model with corrected-entropy

    OpenAIRE

    Das, Sudipta; Debnath, Ujjal; Mamon, Abdulla Al

    2015-01-01

    In this work, we have considered a non-canonical scalar field dark energy model in the framework of flat FRW background. It has also been assumed that the dark matter sector interacts with the non-canonical dark energy sector through some interaction term. Using the solutions for this interacting non-canonical scalar field dark energy model, we have investigated the validity of generalized second law (GSL) of thermodynamics in various scenarios using first law and area law of thermodynamics. ...

  16. On the relation of canonical and covariant formulations of Loop Quantum Gravity

    OpenAIRE

    Zipfel, Antonia

    2015-01-01

    Loop Quantum Gravity (LQG) is a background independent approach towards a quantum theory of gravity that splits into a canonical and a covariant branch the latter of which is also often called spin foam model. The spin foam model can only be derived formally from a constrained BF-theory that is discretized prior to quantization so that the resulting quantum theory is not continuous while canonical LQG rests on a true representation of the continuum canonical commutation relations at the kinem...

  17. A Large and Phylogenetically Diverse Class of Type 1 Opsins Lacking a Canonical Retinal Binding Site.

    Science.gov (United States)

    Becker, Erin A; Yao, Andrew I; Seitzer, Phillip M; Kind, Tobias; Wang, Ting; Eigenheer, Rich; Shao, Katie S Y; Yarov-Yarovoy, Vladimir; Facciotti, Marc T

    2016-01-01

    Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1) and metazoan (type 2) opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs), of which metazoan type 2 opsins are a light-specific sub-clade. PMID:27327432

  18. A Large and Phylogenetically Diverse Class of Type 1 Opsins Lacking a Canonical Retinal Binding Site.

    Directory of Open Access Journals (Sweden)

    Erin A Becker

    Full Text Available Opsins are photosensitive proteins catalyzing light-dependent processes across the tree of life. For both microbial (type 1 and metazoan (type 2 opsins, photosensing depends upon covalent interaction between a retinal chromophore and a conserved lysine residue. Despite recent discoveries of potential opsin homologs lacking this residue, phylogenetic dispersal and functional significance of these abnormal sequences have not yet been investigated. We report discovery of a large group of putatively non-retinal binding opsins, present in a number of fungal and microbial genomes and comprising nearly 30% of opsins in the Halobacteriacea, a model clade for opsin photobiology. We report phylogenetic analyses, structural modeling, genomic context analysis and biochemistry, to describe the evolutionary relationship of these recently described proteins with other opsins, show that they are expressed and do not bind retinal in a canonical manner. Given these data, we propose a hypothesis that these abnormal opsin homologs may represent a novel family of sensory opsins which may be involved in taxis response to one or more non-light stimuli. If true, this finding would challenge our current understanding of microbial opsins as a light-specific sensory family, and provides a potential analogy with the highly diverse signaling capabilities of the eukaryotic G-protein coupled receptors (GPCRs, of which metazoan type 2 opsins are a light-specific sub-clade.

  19. A possible role for the canonical Wnt pathway in endocrine cell development in chicks

    International Nuclear Information System (INIS)

    Wnt signalling is involved in many developmental processes such as proliferation, differentiation, cell fate decisions, and morphogenesis. However, little is known about Wnt signalling during pancreas development. Multiple Wnt ligands and Frizzled receptors are expressed in the embryonic mouse pancreas, the surrounding mesenchyme, and have also been detected in the chicken endoderm during development. The aim of this study was to investigate the role of canonical Wnt signalling on endocrine cell development by use of the in ovo electroporation of the chicken endoderm. Overexpression with a constitutive active form of β-catenin in combination with Ngn3 resulted in reduced numbers of glucagon cells. dnLEF-1 or naked-1 did not alter endocrine cell differentiation when co-expressed with Ngn3, but dnLEF-1 appeared to have some potential for inhibiting delamination of Ngn3 cells. In addition, neuronal β-III-tubulin, which had previously been considered a specific marker for neuronal cells, was observed in the pancreas and was upregulated in the electroporated Ngn3 cells and thus may be a new endocrine marker in the chicken

  20. A non-canonical mechanism for Crm1-export cargo complex assembly.

    Science.gov (United States)

    Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

    2015-01-01

    The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. PMID:25895666

  1. The quantum general linear supergroup, canonical bases and Kazhdan-Lusztig polynomials

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Canonical bases of the tensor powers of the natural Uq(glm|n)-module V are constructed by adapting the work of Frenkel, Khovanov and Kirrilov to the quantum supergroup setting. This result is generalized in several directions. We first construct the canonical bases of the Z2-graded symmetric algebra of V and tensor powers of this superalgebra; then construct canonical bases for the superalgebra Oq(Mm|n) of a quantum (m, n) × (m, n)-supermatrix; and finally deduce from the latter result the canonical basis of every irreducible tensor module for Uq(glm|n) by applying a quantum analogue of the Borel-Weil construction.

  2. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. PMID:27341758

  3. Transient Black Hole Binaries

    CERN Document Server

    Belloni, T M

    2016-01-01

    The last two decades have seen a great improvement in our understand- ing of the complex phenomenology observed in transient black-hole binary systems, especially thanks to the activity of the Rossi X-Ray Timing Explorer satellite, com- plemented by observations from many other X-ray observatories and ground-based radio, optical and infrared facilities. Accretion alone cannot describe accurately the intricate behavior associated with black-hole transients and it is now clear that the role played by different kinds of (often massive) outflows seen at different phases of the outburst evolution of these systems is as fundamental as the one played by the accretion process itself. The spectral-timing states originally identified in the X-rays and fundamentally based on the observed effect of accretion, have acquired new importance as they now allow to describe within a coherent picture the phenomenology observed at other wave- length, where the effects of ejection processes are most evident. With a particular focu...

  4. 激活辣椒素受体是调控下颌下腺分泌的新途径%Activation of transient receptor potential vanilloid subtype 1 serves as a novel path-way to modulate secretion in submandibular gland

    Institute of Scientific and Technical Information of China (English)

    丛馨; 张艳; 俞光岩; 吴立玲

    2015-01-01

    SUMMARY Our work focused on the studies on the expression and function of transient receptor poten -tial vanilloid subtype 1 ( TRPV1) in the submandibular gland .By using reverse transcription-polymerase chain reaction ( RT-PCR ) , Western blotting , and immunofluorescence , our data demonstrated the expression and distribution characteristics of TRPV 1 in rabbit and human submandibular glands , as well as rat submandibular gland cell line SMG-C6.Furthermore, the possible intracellular signal molecules involved in the TRPV1-modulated saliva secretion were explored .Activation of TRPV1 increased the intracellular Ca2+concentration, upregulated the expression of aquaporin 5 (AQP5), the main transpor-ter that mediate water secretion through transcellular pathway , and led to AQP5 redistribution .Extracel-lular signal-regulated kinase 1/2 ( ERK1/2 ) was involved in the TRPV1-regulated AQP5 content. Besides, TRPV1 activation also modulated the expression , distribution, and function of tight junction protein, and increased paracellular permeability .ERK1/2 and myosin light chain 2 ( MLC2 ) were responsible for the regulation of TRPV1on tight junction properties.Taken together, our work suggested that TRPV1 was a potential target to promote saliva secretion , and activation of TRPV1 might provide a new and safe therapeutic strategy to ameliorate submandibular gland hypofunction .

  5. Theory of extreme correlations using canonical Fermions and path integrals

    International Nuclear Information System (INIS)

    The  t–J  model is studied using a novel and rigorous mapping of the Gutzwiller projected electrons, in terms of canonical electrons. The mapping has considerable similarity to the Dyson–Maleev transformation relating spin operators to canonical Bosons. This representation gives rise to a non Hermitian quantum theory, characterized by minimal redundancies. A path integral representation of the canonical theory is given. Using it, the salient results of the extremely correlated Fermi liquid (ECFL) theory, including the previously found Schwinger equations of motion, are easily rederived. Further, a transparent physical interpretation of the previously introduced auxiliary Greens function and the ‘caparison factor’, is obtained. The low energy electron spectral function in this theory, with a strong intrinsic asymmetry, is summarized in terms of a few expansion coefficients. These include an important emergent energy scale Δ0 that shrinks to zero on approaching the insulating state, thereby making it difficult to access the underlying very low energy Fermi liquid behavior. The scaled low frequency ECFL spectral function, related simply to the Fano line shape, has a peculiar energy dependence unlike that of a Lorentzian. The resulting energy dispersion obtained by maximization is a hybrid of a massive and a massless Dirac spectrum EQ∗∼γQ−√(Γ02+Q2), where the vanishing of Q, a momentum type variable, locates the kink minimum. Therefore the quasiparticle velocity interpolates between (γ∓1) over a width Γ0 on the two sides of Q=0, implying a kink there that strongly resembles a prominent low energy feature seen in angle resolved photoemission spectra (ARPES) of cuprate materials. We also propose novel ways of analyzing the ARPES data to isolate the predicted asymmetry between particle and hole excitations. -- Highlights: •Spectral function of the Extremely Correlated Fermi Liquid theory at low energy. •Electronic origin of low energy kinks in

  6. An unconventional canonical quantization of local field theories

    International Nuclear Information System (INIS)

    The conventional extension of the canonical quantization for the local field theories leads to serious mathematical and physical problems (ultraviolet catastrophes and instability of the vacuum). A new proposed method of this extension exploits maximally the principle of locality. Identical copies of the quantum counterparts of the classical mechanical system are placed at each points of a hyperspace of fixed time. The global system is synthetized by quantum statistical method. The argument of wave function, the field operator does not depend explicitely on the point of the space-time. In the perturbation theory the interaction Hamiltonian is now not global but local, thus the usual ultraviolet divergences do not appear. This formalism is an explicite example that the quantum dynamics of a system can be locally implemented, according to the physical measuring situation. (D. Gy.)

  7. Canonical formulation and path integral for local vacuum energy sequestering

    CERN Document Server

    Bufalo, R; Oksanen, M

    2016-01-01

    We establish the Hamiltonian analysis and the canonical path integral for a local formulation of vacuum energy sequestering. In particular, by considering the state of the universe as a superposition of vacuum states corresponding to different values of the cosmological and gravitational constants, the path integral is extended to include integrations over the cosmological and gravitational constants. The result is an extension of the Ng-van Dam form of the path integral of unimodular gravity. It is argued to imply a relation between the fraction of the most likely values of the gravitational and cosmological constants and the average values of the energy density and pressure of matter over spacetime. Finally, we construct and analyze a BRST-exact formulation of the theory, which can be considered as a topological field theory.

  8. Canonical Group Quantization, Rotation Generators and Quantum Indistinguishability

    CERN Document Server

    Benavides, C

    2008-01-01

    Using the method of canonical group quantization, we construct the angular momentum operators associated to configuration spaces with the topology of (i) a sphere and (ii) a projective plane. In the first case, the obtained angular momentum operators are the quantum version of Poincare's vector, i.e., the physically correct angular momentum operators for an electron coupled to the field of a magnetic monopole. In the second case, the obtained operators represent the angular momentum operators of a system of two indistinguishable spin zero quantum particles in three spatial dimensions. We explicitly show how our formalism relates to the one developed by Berry and Robbins. The relevance of the proposed formalism for an advance in our understanding of the spin-statistics connection in non-relativistic quantum mechanics is discussed.

  9. Paul Weiss and the genesis of canonical quantization

    Science.gov (United States)

    Rickles, Dean; Blum, Alexander

    2015-12-01

    This paper describes the life and work of a figure who, we argue, was of primary importance during the early years of field quantisation and (albeit more indirectly) quantum gravity. A student of Dirac and Born, he was interned in Canada during the second world war as an enemy alien and after his release never seemed to regain a good foothold in physics, identifying thereafter as a mathematician. He developed a general method of quantizing (linear and non-linear) field theories based on the parameters labelling an arbitrary hypersurface. This method (the `parameter formalism' often attributed to Dirac), though later discarded, was employed (and viewed at the time as an extremely important tool) by the leading figures associated with canonical quantum gravity: Dirac, Pirani and Schild, Bergmann, DeWitt, and others. We argue that he deserves wider recognition for this and other innovations.

  10. A Computer Program for a Canonical Problem in Underwater Shock

    Directory of Open Access Journals (Sweden)

    Thomas L. Geers

    1994-01-01

    Full Text Available Finite-element/boundary-element codes are widely used to analyze the response of marine structures to underwater explosions. An important step in verifying the correctness and accuracy of such codes is the comparison of code-generated results for canonical problems with corresponding analytical or semianalytical results. At the present time, such comparisons rely on hardcopy results presented in technical journals and reports. This article describes a computer program available from SAVIAC that produces user-selected numerical results for a step-wave-excited spherical shell submerged in and (optionally filled with an acoustic fluid. The method of solution employed in the program is based on classical expansion of the field quantities in generalized Fourier series in the meridional coordinate. Convergence of the series is enhanced by judicious application of modified Cesàro summation and partial closed-form solution.

  11. Canonical momenta indicators of financial markets and neocortical EEG

    CERN Document Server

    Ingber, L

    1996-01-01

    A paradigm of statistical mechanics of financial markets (SMFM) is fit to multivariate financial markets using Adaptive Simulated Annealing (ASA), a global optimization algorithm, to perform maximum likelihood fits of Lagrangians defined by path integrals of multivariate conditional probabilities. Canonical momenta are thereby derived and used as technical indicators in a recursive ASA optimization process to tune trading rules. These trading rules are then used on out-of-sample data, to demonstrate that they can profit from the SMFM model, to illustrate that these markets are likely not efficient. This methodology can be extended to other systems, e.g., electroencephalography. This approach to complex systems emphasizes the utility of blending an intuitive and powerful mathematical-physics formalism to generate indicators which are used by AI-type rule-based models of management.

  12. The Danish Reportive Passive as a Non-Canonical Passive

    DEFF Research Database (Denmark)

    Ørsnes, Bjarne

    Danish passive utterance and cognitive verbs allow a construction where the subject of an infinitival complement is raised: Peter siges at være bortrejst (‘Peter is said to be out of town’). Contrary to English, these verbs are not ECM-verbs or subject-to-object raising verbs in the active. The...... subject of the passive can never be construed as an object. These raising passives are termed Reportive Passives since they attribute a proposition to an (unknown) information source. Some analyses treat these passives as special constructions with an idiosyncratic semantics or even as grammaticalized...... evidentiality markers. I argue that they are fully compositional passives in Danish, but that they are non-canonical inasmuch as they raise an argument of an embedded predicate. I provide an account within the framework of Head-Driven Phrase Structure Grammar and I suggest that such passives are motivated in...

  13. Canonical approach to the closed string non-commutativity

    Directory of Open Access Journals (Sweden)

    Davidović Ljubica

    2014-01-01

    Full Text Available We consider the propagation of the closed bosonic string in the weakly curved background. We show that the closed string non-commutativity is essentially connected to the T-duality and nontrivial background. From the T-duality transformation laws, connecting the canonical variables of the original and T-dual theory, we find the structure of the Poisson brackets in the T-dual space corresponding to the fundamental Poisson brackets in the original theory. We find that the commutative original theory is equivalent to the non-commutative T-dual theory, in which Poisson brackets close on winding and momenta numbers and the coefficients are proportional to the background fluxes. [Projekat Ministarstva nauke Republike Srbije, br. 171031

  14. Recovery of spectral data using weighted canonical correlation regression

    Science.gov (United States)

    Eslahi, Niloofar; Amirshahi, Seyed Hossein; Agahian, Farnaz

    2009-05-01

    The weighted canonical correlation regression technique is employed for reconstruction of reflectance spectra of surface colors from the related XYZ tristimulus values of samples. Flexible input data based on applying certain weights to reflectance and colorimetric values of Munsell color chips has been implemented for each particular sample which belongs to Munsell or GretagMacbeth Colorchecker DC color samples. In fact, the colorimetric and spectrophotometric data of Munsell chips are selected as fundamental bases and the color difference values between the target and samples in Munsell dataset are chosen as a criterion for determination of weighting factors. The performance of the suggested method is evaluated in spectral reflectance reconstruction. The results show considerable improvements in terms of root mean square error (RMS) and goodness-of-fit coefficient (GFC) between the actual and reconstructed reflectance curves as well as CIELAB color difference values under illuminants A and TL84 for CIE1964 standard observer.

  15. On two mathematical problems of canonical quantization. IV

    International Nuclear Information System (INIS)

    A method for solving the problem of reconstructing a measure beginning with its logarithmic derivative is presented. The method completes that of solving the stochastic differential equation via Dirichlet forms proposed by S. Albeverio and M. Rockner. As a result one obtains the mathematical apparatus for the stochastic quantization. The apparatus is applied to prove the existence of the Feynman-Kac measure of the sine-Gordon and λφ2n/(1 + κ2φ2n)-models. A synthesis of both mathematical problems of canonical quantization is obtained in the form of a second-order martingale problem for vacuum noise. It is shown that in stochastic mechanics the martingale problem is an analog of Newton's second law and enables us to find the Nelson's stochastic trajectories without determining the wave functions. 33 refs

  16. Successive canonical transformation in model two-body electrodynamics

    International Nuclear Information System (INIS)

    The possibility is investigated of bypassing the no interaction theorum of Currie, Jordan and Sudarshan for direct action Lagrangians. Starting with the field theoretic description of a two-body electrodynamic problem, the field variable is solved for in terms of the particle variables, which paves the way to write an action-at-a-distance Hamiltonian for the problem. A suitable transformation is found which uncouples the field and the particle variables in the interaction up to order e2. It is shown that this transformation leaves the statement of Newton's 2nd law unchanged which also agrees with the standard results of electrodynamics. This allows for the identification of canonical variables for the proper action-at-a-distance problem. 19 references

  17. Successive canonical transformation in model two-body electrodynamics

    International Nuclear Information System (INIS)

    We investigate the possibility of bypassing the no-interaction theorem of Currie, Jordan, and Sudarshan for direct action Lagrangians. Starting with the field-theoretic description of a two-body electrodynamic problem, we solve for the field variables in terms of the particle variables, which paves the way to write an action-at-a-distance Hamiltonian for the problem. A suitable transformation is found which uncouples the field and the particle variables in the interaction up to order e2. It is shown that this transformation leaves the statement of Newton's second law unchanged which also agrees with the standard results of electrodynamics. This allows for the identification of canonical variables for the proper action-at-a-distance problem

  18. A NOVEL ALGORITHM FOR VOICE CONVERSION USING CANONICAL CORRELATION ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    Jian Zhihua; Yang Zhen

    2008-01-01

    A novel algorithm for voice conversion is proposed in this paper. The mapping function of spectral vectors of the source and target speakers is calculated by the Canonical Correlation Analysis(CCA) estimation based on Gaussian mixture models. Since the spectral envelope feature remains a majority of second order statistical information contained in speech after Linear Prediction Coding(LPC) analysis, the CCA method is more suitable for spectral conversion than Minimum Mean Square Error (MMSE) because CCA explicitly considers the variance of each component of the spectral vectors during conversion procedure. Both objective evaluations and subjective listening tests are conducted. The experimental results demonstrate that the proposed scheme can achieve better performance than the previous method which uses MMSE estimation criterion.

  19. Linking covariant and canonical LQG II: Spin foam projector

    CERN Document Server

    Thiemann, Thomas

    2013-01-01

    In a seminal paper, Kaminski, Kisielowski an Lewandowski for the first time extended the definition of spin foam models to arbitrary boundary graphs. This is a prerequisite in order to make contact to the canonical formulation of Loop Quantum Gravity (LQG) and allows to investigate the question whether any of the presently considered spin foam models yield a rigging map for any of the presently defined Hamiltonian constraint operators. The KKL extension cannot be described in terms of Group Field Theory (GFT) since arbitrary foams are involved while GFT is tied to simplicial complexes. Therefore one has to define the sum over spin foams with given boundary spin networks in an independent fashion using natural axioms, most importantly a gluing property for 2-complexes. These axioms are motivated by the requirement that spin foam amplitudes should define a rigging map (physical inner product) induced by the Hamiltonian constraint. This is achieved by constructing a spin foam operator based on abstract 2-complex...

  20. Improved confinement regimes within the transport model of canonical profiles

    International Nuclear Information System (INIS)

    The canonical profiles transport model is extended to describe various modes with improved confinement in tokamaks. A generalized profile consistency principle is proposed and a corresponding mathematical formalism is formulated. This formalism is used for the modelling of various regimes, such as H modes in DIII-D, JET and ASDEX, the hot ion mode and enhanced performance after pellet injection (PEP mode) in JET. This modelling, together with a known global scaling law, allowed the dependence of the internal model parameters on the plasma geometry and other physical variables to be established. This makes the model predictive. The approximate analytical criteria for the L → H and L → hot ion mode transitions are also obtained. (author). 32 refs, 30 figs