WorldWideScience

Sample records for agonist tzp-101 accelerates

  1. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis

    DEFF Research Database (Denmark)

    Ejskjaer, N; Vestergaard, E T; Hellström, P M;

    2009-01-01

    microg/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine...... between TZP-101 and placebo. CONCLUSIONS: This proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying....... responses. RESULTS: Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and > or =29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0...

  2. Accelerated molecular dynamics simulations of the octopamine receptor using GPUs: discovery of an alternate agonist-binding position.

    Science.gov (United States)

    Kastner, Kevin W; Izaguirre, Jesús A

    2016-10-01

    Octopamine receptors (OARs) perform key biological functions in invertebrates, making this class of G-protein coupled receptors (GPCRs) worth considering for insecticide development. However, no crystal structures and very little research exists for OARs. Furthermore, GPCRs are large proteins, are suspended in a lipid bilayer, and are activated on the millisecond timescale, all of which make conventional molecular dynamics (MD) simulations infeasible, even if run on large supercomputers. However, accelerated Molecular Dynamics (aMD) simulations can reduce this timescale to even hundreds of nanoseconds, while running the simulations on graphics processing units (GPUs) would enable even small clusters of GPUs to have processing power equivalent to hundreds of CPUs. Our results show that aMD simulations run on GPUs can successfully obtain the active and inactive state conformations of a GPCR on this reduced timescale. Furthermore, we discovered a potential alternate active-state agonist-binding position in the octopamine receptor which has yet to be observed and may be a novel GPCR agonist-binding position. These results demonstrate that a complex biological system with an activation process on the millisecond timescale can be successfully simulated on the nanosecond timescale using a simple computing system consisting of a small number of GPUs. Proteins 2016; 84:1480-1489. © 2016 Wiley Periodicals, Inc.

  3. Accelerated molecular dynamics simulations of the octopamine receptor using GPUs: discovery of an alternate agonist-binding position.

    Science.gov (United States)

    Kastner, Kevin W; Izaguirre, Jesús A

    2016-10-01

    Octopamine receptors (OARs) perform key biological functions in invertebrates, making this class of G-protein coupled receptors (GPCRs) worth considering for insecticide development. However, no crystal structures and very little research exists for OARs. Furthermore, GPCRs are large proteins, are suspended in a lipid bilayer, and are activated on the millisecond timescale, all of which make conventional molecular dynamics (MD) simulations infeasible, even if run on large supercomputers. However, accelerated Molecular Dynamics (aMD) simulations can reduce this timescale to even hundreds of nanoseconds, while running the simulations on graphics processing units (GPUs) would enable even small clusters of GPUs to have processing power equivalent to hundreds of CPUs. Our results show that aMD simulations run on GPUs can successfully obtain the active and inactive state conformations of a GPCR on this reduced timescale. Furthermore, we discovered a potential alternate active-state agonist-binding position in the octopamine receptor which has yet to be observed and may be a novel GPCR agonist-binding position. These results demonstrate that a complex biological system with an activation process on the millisecond timescale can be successfully simulated on the nanosecond timescale using a simple computing system consisting of a small number of GPUs. Proteins 2016; 84:1480-1489. © 2016 Wiley Periodicals, Inc. PMID:27318014

  4. Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

    Science.gov (United States)

    Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

    2014-07-15

    DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation.

  5. Wound Healing Is Accelerated by Agonists of Adenosine A2 (Gα s-linked) Receptors

    OpenAIRE

    Montesinos, M. Carmen; Gadangi, Pratap; Longaker, Michael; Sung, Joanne; Levine, Jamie; Nilsen, Diana; Reibman, Joan; Min LI; Jiang, Chuan-Kui; Hirschhorn, Rochelle; Recht, Phoebe A.; Ostad, Edward; Levin, Richard I.; Cronstein, Bruce N.

    1997-01-01

    The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the Gαs-linked adenosine receptors on the cells o...

  6. Age-related expression of sigma1 receptors and antidepressant efficacy of a selective agonist in the senescence-accelerated (SAM) mouse.

    Science.gov (United States)

    Phan, Vân-Ly; Miyamoto, Yoshiaki; Nabeshima, Toshitaka; Maurice, Tangui

    2005-02-15

    The sigma1 receptor is a unique intracellular receptor whose activation results in an efficient modulation of several neurotransmitter responses. Its role as a target for the rapid nongenomic effects of neuro(active)steroids and the age-related diminutions in steroid levels suggested that targeting the sigma1 receptor might allow alleviation of age-related neuronal dysfunctions. We examined here the expression and behavioral efficacy of sigma1 receptors in the senescence-accelerated (SAM) mouse model. The sigma1 receptor mRNA expression was measured by using comparative RT-PCR in the olfactory bulb, hippocampus, hypothalamus, cortex, or cerebellum of senescence-prone SAMP/8 and senescence-resistant SAMR/1 control animals. No difference was observed between substrains in 6-, 9-, and 12-month-old (m.o.) mice. The sigma1 protein expression was analyzed by using immunohistochemical techniques. Labeling was intense in the olfactory bulb, hippocampus, hypothalamus, and midbrain of both SAMR/1 and SAMP/8 mice, and the distribution appeared unchanged in 6-, 9-, and 12-m.o. animals. The receptor's in vivo availability was examined by using in vivo [3H](+)-SKF-10,047 binding. No age-related difference was observed in the olfactory bulb, hippocampus, hypothalamus, cortex, cerebellum, and brainstem of 6- or 12-m.o. SAMR/1 or SAMP/8 mice. The antidepressant efficacy of the selective agonist igmesine was examined in the forced-swimming test. The compound decreased significantly the immobility duration at 60 mg/kg in 6- and 12-m.o. SAMR/1 and in 6-m.o. SAMP/8 mice. In 12-m.o. SAMP/8 mice, the drug efficacy was facilitated; a significant effect was measured at 30 mg/kg. Decreased neurosteroid levels, particularly of progesterone, were seen in 12-m.o. SAMP/8 mice that might explain the enhanced efficacy of igmesine. Preserved sigma1 receptor expression and enhanced behavioral efficacy of sigma1 agonists were measured in SAM animals, confirming the therapeutic opportunities for

  7. Accelerator

    International Nuclear Information System (INIS)

    The invention claims equipment for stabilizing the position of the front covers of the accelerator chamber in cyclic accelerators which significantly increases accelerator reliability. For stabilizing, it uses hydraulic cushions placed between the electromagnet pole pieces and the front chamber covers. The top and the bottom cushions are hydraulically connected. The cushions are disconnected and removed from the hydraulic line using valves. (J.P.)

  8. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...

  9. A natural history of "agonist".

    Science.gov (United States)

    Russo, Ruth

    2002-01-01

    This paper constructs a brief history of the biochemical term agonist by exploring the multiple meanings of the root agôn in ancient Greek literature and describing how agonist first appeared in the scientific literature of the 20th century in the context of neurophysiologists' debates about the existence and properties of cellular receptors. While the narrow scientific definition of agonist may appear colorless and dead when compared with the web of allusions spun by the ancient Greek agôn, the scientific power and creativity of agonist actually resides precisely in its exact, restricted meaning for biomedical researchers.

  10. EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing

    Institute of Scientific and Technical Information of China (English)

    Guang-Liang Jiang; Wha Bin Im; Yariv Donde; Larry A Wheeler

    2009-01-01

    AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacininduced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro , the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis. CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and indomethacin-aggravated gastric ulcers, via promoting proliferation and survival of mucous epithelial cells.

  11. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  12. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide and...... liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  13. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide...... and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  14. GnRH agonist triggering

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2013-01-01

    The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages...... triggering concept should be challenged and that the GnRHa trigger is the way to move forward with thoughtful consideration of the needs, safety and comfort of our patients. Routinely, human chorionic gonadotrophin (HCG) is used to induce ovulation in fertility treatments. This approach deviates...... significantly from physiology and often results in insufficient hormonal support in early pregnancy and in ovarian hyperstimulation syndrome (OHSS). An alternative approach is to use a gonadotrophin-releasing hormone (GnRH) agonist which allows a more physiological trigger of ovulation and, most importantly...

  15. Linear Accelerators

    CERN Document Server

    Vretenar, M

    2014-01-01

    The main features of radio-frequency linear accelerators are introduced, reviewing the different types of accelerating structures and presenting the main characteristics aspects of linac beam dynamics.

  16. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

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

    2015-01-01

    antagonists and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  17. Effect of β3-adrenergic agonists on alveolar fluid clearance in hypoxic rat lungs

    Institute of Scientific and Technical Information of China (English)

    LI Nai-jing; LI Wei; HE Ping; GU Xiu; LI Sheng-qi

    2010-01-01

    Background Recent research suggests that β_2-adrenergic agonists increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether β_3-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of β_3 -adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved.Methods Hypoxic rats were exposed to 10% oxygen. BRL-37344 (β_3-adrenergic agonist) or CGP-12177 (selective β_3-adrenergic agonist) alone or combined with β receptor antagonists, sodium channel blockers, or Na~+/K~+-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content (TLW) and AFC were measured.Results AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride (a Na~+ channel blocker) and ouabain (a Na~+/K~+-ATPase inhibitor) by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177.Conclusions These findings suggest that (β3-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

  18. Future accelerators (?)

    Energy Technology Data Exchange (ETDEWEB)

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  19. β2-agonist therapy in lung disease.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  20. Accelerating Value Creation with Accelerators

    DEFF Research Database (Denmark)

    Jonsson, Eythor Ivar

    2015-01-01

    accelerator programs. Microsoft runs accelerators in seven different countries. Accelerators have grown out of the infancy stage and are now an accepted approach to develop new ventures based on cutting-edge technology like the internet of things, mobile technology, big data and virtual reality. It is also...... with the traditional audit and legal universes and industries are examples of emerging potentials both from a research and business point of view to exploit and explore further. The accelerator approach may therefore be an Idea Watch to consider, no matter which industry you are in, because in essence accelerators...

  1. Laser accelerator

    OpenAIRE

    Vigil, Ricardo

    2014-01-01

    Approved for public release; distribution is unlimited In 1979,W. B. Colson and S. K. Ride proposed a new kind of electron accelerator using a uniform magnetic field in combination with a circularly-polarized laser field. A key concept is to couple the oscillating electric field to the electron’s motion so that acceleration is sustained. This dissertation investigates the performance of the proposed laser accelerator using modern high powered lasers and mag-netic fields that are significan...

  2. 短期促性腺激素释放激素拟似物促进青春期雌性大鼠的线性生长%Short-term long-acting gonadotropin-releasing hormone agonist accelerates longitudinal growth in female rats during puberty

    Institute of Scientific and Technical Information of China (English)

    马华梅; 李燕虹; 苏喆; 杜敏联; 黄婷婷; 赖峰; 黄莲芳

    2008-01-01

    目的 探讨短期(4周)促性腺激素释放激素拟似物(GnRHa)对青春期雌性大鼠生长的影响及机制.方法 40只3周龄雌鼠按随机区组设计分为GnRHa处理组(Gn组)、雌激素替代组(E2组)、对照组、卵巢切除组(OVX组)以及基线对照组.Gn组和E2组注射曲普瑞林,每2周1次,共2次;E2组在第2次曲普瑞林注射后每日注射E2共11d;OVX组在实验开始时予卵巢切除.除基线对照组外,所有鼠均在实验结束前9天和2天分别注射盐酸土霉素和钙黄绿素使其在骨表面形成荧光标记.比较4周后4组大鼠的体格生长指标、血胰岛素样生长因子(IGF)-I及IGF结合蛋白(IGFBP)-3浓度、肝脏生长激素受体(GHR)、IGF-I及IGFBP-3mRNA水平、胫骨生长板IGF-I及IGF-I受体(IGF-IR)水平、软骨细胞增殖度等.结果 4周的GnRHa注射达到"性腺切除"效应,Gn组的体重、身长、胫骨长度、生长板参数、纵向生长速率、软骨细胞增殖率均较对照组增加(P<0.05或P<0.01),E2组则与对照组相近.4组的血清IGF-I及IGFBP-3水平、肝脏IGF-I及IGFBP-3mRNA、生长板IGF-I及IGF-IR水平差异无统计学意义.Gn组和OVX组的肝脏GHR mRNA的表达均低于对照组,E2组则与对照组相仿.结论 GnRHa通过抑制雌激素的分泌、间接促进生长板软骨细胞增殖度和抑制生长板老化而促进青春期雌鼠的线性生长,其促生长效应不依赖于IGF-I/IGFBP-3的内分泌机制,也不依赖于生长板IGF-I/IGF-IR的改变.%Objective To investigate the possible mechanism of the effect of short-term gonadotropin-re-leasing hormone agonist(GnRHa)on linear growth in female pubertal rats. Methods Forty 3-week-old female rats were randomly divided into 5 groups(n=8 each). One group was sacrificed as base-line control. Group OVX was operated for ovariectomy at the beginning of experiment. Group Gn and group E2 each received two intramuscu-lar injections of 2.5mg·kg-1 triptorelin 2 weeks apart, and group E2

  3. Metabotropic glutamate receptor agonists modify the pyloric output of the crustacean stomatogastric ganglion.

    Science.gov (United States)

    Pérez-Acevedo, Nivia L; Krenz, Wulf D

    2005-11-16

    We have studied the effects of groups I, II, and III metabotropic glutamate receptor (mGluR) agonists and antagonists on pyloric activity in the stomatogastric ganglion (STG) of the Caribbean spiny lobster Panulirus argus. We have found that agonists for all three groups of mGluRs modify the pyloric output. The group I agonist, l-quisqualic acid (l-QA), activated the pyloric central pattern generator (CPG). When the pyloric rhythm was partially suppressed by sucrose-block of input fibers in the stomatogastric nerve (stn), l-QA accelerated the rhythmic activity. In addition, the number of spike discharges was increased in pyloric motoneurons: pyloric (PY), and lateral pyloric (LP). In completely blocked preparations, a slow pyloric rhythm was initiated by l-QA. Groups II and III agonists exerted an inhibitory effect on pyloric activity. The group II agonist, (2S,1'S,2'S)-2-(Carboxycyclopropyl)glycine (L-CCG-I), decreased both the frequency of the pyloric rhythm and the number of spike discharges in the motoneurons: ventricular dilator (VD), PY, and LP. The effects of L-CCG-I were dose-dependent. The group III agonist, l-(+)-2-Amino-4-phosphonobutyric acid (l-AP4), slightly decreased the frequency of the pyloric rhythm and suppressed spike discharges in the VD neuron. All effects of mGluR agonists were reversible. The effect of l-QA was blocked by the broad spectrum mGluR antagonist (S)-Methyl-4-carboxyphenylglycine (MCPG). The inhibitory effect of L-CCG-I was prevented by MCPG and by the group II/III mGluR antagonist (RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG), and was partially blocked by the group II mGluR antagonist (RS)-1-amino-5-phosphonoindan-1-carboxylic acid (APICA). The inhibitory effect of l-AP4 was blocked by MPPG and partially blocked by APICA. PMID:16256086

  4. Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy

    OpenAIRE

    Jakubík, J; Janíčková, H; El-Fakahany, EE; Doležal, V

    2011-01-01

    BACKGROUND AND PURPOSE Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5′-γ−thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M2 muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. EXPERIMENTAL APPROACH Filtration and scintillation proximity ass...

  5. PPAR Agonists and Cardiovascular Disease in Diabetes.

    Science.gov (United States)

    Calkin, Anna C; Thomas, Merlin C

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARalpha agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARgamma agonists, and more recently dual PPARalpha/gamma coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARgamma receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  6. PPAR Agonists and Cardiovascular Disease in Diabetes

    Directory of Open Access Journals (Sweden)

    Anna C. Calkin

    2008-01-01

    Full Text Available Peroxisome proliferators activated receptors (PPARs are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR agonists, and more recently dual PPAR/ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  7. Dihydrocodeine / Agonists for Alcohol Dependents

    Directory of Open Access Journals (Sweden)

    Albrecht eUlmer

    2012-03-01

    Full Text Available Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients.Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC to 102 heavily alcohol addict-ed patients, later, also Buprenorphine, Clomethiazole (>6 weeks, Baclofen and in one case Amphetamine, each on individual indication. This paper focuses on the data with DH, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC-treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-step scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details.Conclusions: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around ¼ of the patients already. Many further

  8. LIBO accelerates

    CERN Multimedia

    2002-01-01

    The prototype module of LIBO, a linear accelerator project designed for cancer therapy, has passed its first proton-beam acceleration test. In parallel a new version - LIBO-30 - is being developed, which promises to open up even more interesting avenues.

  9. beta2-Agonists at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  10. FXR agonist activity of conformationally constrained analogs of GW 4064

    Energy Technology Data Exchange (ETDEWEB)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  11. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  12. Exploring prospects of β3-adrenoceptor agonists and inverse agonists for colon mobility control

    Directory of Open Access Journals (Sweden)

    Maria Grazia Perrone

    2013-07-01

    Full Text Available Inverse agonists are useful active ingredient of drugs clinically used to treat diseases mainly involving receptors endowed with non-endogenous agonist induced activity (constitutive or basal activity. SP-1e and SP-1g are the first two potent and highly selective β3-adrenoceptor inverse agonists [EC50=181 nM (IA=- 64% and 136 nM (IA=-73%, respectively], which their peculiar activity seems due to the absolute configurations of the two stereogenic centres present in each molecule. Rat proximal colon motility measurements allowed their further pharmacological characterization and pA2 values determination by Schild analysis (7.89 and 8.16, respectively. The purpose of our work is a further characterization of our novel β3-adrenoceptor agonists (SP-1a-d, SP-1f,1h and inverse agonists (SP-1e and SP-1g on rat proximal colon motility and a confirmation of their inverse agonist nature in a more complex system like the functional test on rat proximal colon. Male Wistar rats segment of the proximal colon were placed in organ baths containing Krebs solution. Muscle tension was recorded isotonically. Cumulative β3-AR agonists doses experiments were performed for each test compound: isoprenaline, BRL37344, SP-1a-d, SP-1f and SP-1h were dissolved in Krebs. The EC50 values of each agonists and pA2 of inverse agonists were determined. SP- 1a-d, SP-1f and SP-1h in rat colon have a muscle relaxing effect thus confirming their partial agonist activity found in CHO-K1 cell line. SP-1e and SP-1g behaved as antagonists with pA2 values of 7.89 and 8.16, respectively. In conclusion, experiments carried out by using isolated rat proximal colon allowed us to determine the pA2 values of the two β3-AR inverse agonists and add knowledge on the behavior of a novel set of compounds and their possible value as agents useful whenever is necessary to also control the colon motility.

  13. Accelerator operations

    International Nuclear Information System (INIS)

    This section is concerned with the operation of both the tandem-linac system and the Dynamitron, two accelerators that are used for entirely different research. Developmental activities associated with the tandem and the Dynamitron are also treated here, but developmental activities associated with the superconducting linac are covered separately because this work is a program of technology development in its own right

  14. Advanced accelerators

    International Nuclear Information System (INIS)

    This report discusses the suitability of four novel particle acceleration technologies for multi-TeV particle physics machines: laser driven linear accelerators (linac), plasma beat-wave devices, plasma wakefield devices, and switched power and cavity wakefield linacs. The report begins with the derivation of beam parameters practical for multi-TeV devices. Electromagnetic field breakdown of materials is reviewed. The two-beam accelerator scheme for using a free electron laser as the driver is discussed. The options recommended and the conclusions reached reflect the importance of cost. We recommend that more effort be invested in achieving a self-consistent range of TeV accelerator design parameters. Beat-wave devices have promise for 1-100 GeV applications and, while not directly scalable to TeV designs, the current generation of ideas are encouraging for the TeV regime. In particular, surfatrons, finite-angle optical mixing devices, plasma grating accelerator, and the Raman forward cascade schemes all deserve more complete analysis. The exploitation of standard linac geometry operated in an unconventional mode is in a phase of rapid evolution. While conceptual projects abound, there are no complete designs. We recommend that a fraction of sponsored research be devoted to this approach. Wakefield devices offer a great deal of potential; trades among their benefits and constraints are derived and discussed herein. The study of field limitation processes has received inadequate attention; this limits experiment designers. The costs of future experiments are such that investment in understanding these processes is prudent. 34 refs., 12 figs., 3 tabs

  15. KEKB accelerator

    International Nuclear Information System (INIS)

    KEKB, the B-Factory at High Energy Accelerator Research Organization (KEK) recently achieved the luminosity of 1 x 1034 cm-2s-1. This luminosity is two orders higher than the world's level at 1990 when the design of KEKB started. This unprecedented result was made possible by KEKB's innovative design and technology in three aspects - beam focusing optics, high current storage, and beam - beam interaction. Now KEKB is leading the luminosity frontier of the colliders in the world. (author)

  16. Recent advances in the discovery of alpha1-adrenoceptor agonists.

    Science.gov (United States)

    Bishop, Michael J

    2007-01-01

    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  17. Accelerating networks

    International Nuclear Information System (INIS)

    Evolving out-of-equilibrium networks have been under intense scrutiny recently. In many real-world settings the number of links added per new node is not constant but depends on the time at which the node is introduced in the system. This simple idea gives rise to the concept of accelerating networks, for which we review an existing definition and-after finding it somewhat constrictive-offer a new definition. The new definition provided here views network acceleration as a time dependent property of a given system as opposed to being a property of the specific algorithm applied to grow the network. The definition also covers both unweighted and weighted networks. As time-stamped network data becomes increasingly available, the proposed measures may be easily applied to such empirical datasets. As a simple case study we apply the concepts to study the evolution of three different instances of Wikipedia, namely, those in English, German, and Japanese, and find that the networks undergo different acceleration regimes in their evolution

  18. Signal Use by Octopuses in Agonistic Interactions.

    Science.gov (United States)

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-01

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID:26832440

  19. Accelerators and the Accelerator Community

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  20. accelerating cavity

    CERN Multimedia

    On the inside of the cavitytThere is a layer of niobium. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment.

  1. Impact of the AT(2) receptor agonist C21 on blood pressure and beyond

    DEFF Research Database (Denmark)

    Foulquier, Sébastien; Steckelings, Ulrike Muscha; Unger, Thomas

    2012-01-01

    It is now widely accepted that the angiotensin AT(2) receptor (AT(2)R) plays an important protective role during pathophysiologic conditions, acting as a repair system. The development of the first selective nonpeptide AT(2)R agonist C21 accelerated our understanding of AT(2)R-mediated protective...... signaling and actions. This article reviews the impact of C21 on blood pressure in normotensive and hypertensive animal models. Although C21 does not act as a classical antihypertensive drug, it could be useful in preventing hypertension-induced vascular and other end organ damages via anti-apoptotic, anti...

  2. GLP-1 agonists for type 2 diabetes

    DEFF Research Database (Denmark)

    Jespersen, Maria J; Knop, Filip K; Christensen, Mikkel

    2013-01-01

    Within recent years, glucagon-like peptide 1 receptor agonists (GLP-1-RA) have emerged as a new treatment option for type 2 diabetes. The GLP-1-RA are administered subcutaneously and differ substantially in pharmacokinetic profiles. AREAS COVERED: This review describes the pharmacokinetics...... and legal documents in the form of assessment reports from the European Medicines Agency and the United States Food and Drug Administration. EXPERT OPINION: GLP-1-based therapy combines several unique mechanisms of action and have the potential to gain widespread use in the fight against diabetes...

  3. Strategies for designing synthetic immune agonists.

    Science.gov (United States)

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  4. Unique interaction pattern for a functionally biased ghrelin receptor agonist

    DEFF Research Database (Denmark)

    Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.;

    2011-01-01

    Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers co...

  5. Highly Potent, Chemically Stable Quorum Sensing Agonists for Vibrio Cholerae

    OpenAIRE

    Perez, Lark J; Karagounis, Theodora K.; Hurley, Amanda; Bassler, Bonnie L.; Semmelhack, Martin F.

    2013-01-01

    In the Vibrio cholerae pathogen, initiation of bacterial quorum sensing pathways serves to suppress virulence. We describe herein a potent and chemically stable small molecule agonist of V. cholerae quorum sensing, which was identified through rational drug design based on the native quorum sensing signal. This novel agonist may serve as a useful lead compound for the control of virulence in V. cholerae.

  6. The importance of β2-agonists in myocardial infarction

    DEFF Research Database (Denmark)

    Rørth, Rasmus; Fosbøl, Emil L; Mogensen, Ulrik M;

    2015-01-01

    PURPOSE: β2-Agonists are widely used for relief of respiratory symptoms. Studies so far have reported conflicting results regarding use of β2-agonists and risk of myocardial infarction (MI). Yet, coronary angiographical data and longitudinal outcomes data are sparse and could help explain...

  7. Combining GLP-1 receptor agonists with insulin

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Vilsbøll, T

    2013-01-01

    physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose......Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among......, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic...

  8. Linear Accelerator (LINAC)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Linear Accelerator A linear accelerator (LINAC) customizes high energy x-rays to ... ensured? What is this equipment used for? A linear accelerator (LINAC) is the device most commonly used ...

  9. Toll-like receptor 2 agonists inhibit human fibrocyte differentiation

    Directory of Open Access Journals (Sweden)

    Maharjan Anu S

    2010-11-01

    Full Text Available Abstract Background In healing wounds, some monocytes enter the wound and differentiate into fibroblast-like cells called fibrocytes. Since Toll-like receptors (TLRs are present on monocytes, and pathogens that can infect a wound have and/or release TLR agonists, we examined whether TLR agonists affect fibrocyte differentiation. Results When human peripheral blood mononuclear cells (PBMCs were cultured with TLR3, TLR4, TLR5, TLR7, TLR8 or TLR9 agonists, there was no significant effect on fibrocyte differentiation, even though enhanced extracellular tumor necrosis factor (TNF-α accumulation and/or increased cell surface CD86 or major histocompatibility complex (MHC class II levels were observed. However, all TLR2 agonists tested inhibited fibrocyte differentiation without any significant effect on cell survival. Adding TLR2 agonists to purified monocytes had no effect on fibrocyte differentiation. However, some TLR2 agonists caused PBMCs to secrete a factor that inhibits the differentiation of purified monocytes into fibrocytes. This factor is not interferon (IFN-α, IFN-γ, interleukin (IL-12, aggregated immunoglobulin G (IgG or serum amyloid P (SAP, factors known to inhibit fibrocyte differentiation. TLR2 agonist-treated PBMCs secrete low levels of IL-6, TNF-α, IFN-γ, granulocyte colony-stimulating factor and tumor growth factor β1, but combinations of these factors had no effect on fibrocyte differentiation from purified monocytes. Conclusions Our results indicate that TLR2 agonists indirectly inhibit fibrocyte differentiation and that, for some TLR2 agonists, this inhibition involves other cell types in the PBMC population secreting an unknown factor that inhibits fibrocyte differentiation. Together, these data suggest that the presence of some bacterial signals can inhibit fibrocyte differentiation and may thus slow wound closure.

  10. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper. PMID:23686524

  11. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    Science.gov (United States)

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. PMID:20579229

  12. Agonist Replacement for Stimulant Dependence: A Review of Clinical Research

    OpenAIRE

    Stoops, William W.; Rush, Craig R.

    2013-01-01

    Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and clinical trials to determine whether agonist replacement therapy is a viable strategy for managing cocaine and/or amphetamine use disorders. The extant literature suggests that ago...

  13. Identification of M-CSF agonists and antagonists

    Science.gov (United States)

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  14. Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Jennifer G. Robinson

    2008-01-01

    Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

  15. 2014 CERN Accelerator Schools: Plasma Wake Acceleration

    CERN Multimedia

    2014-01-01

    A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

  16. The direction of acceleration

    Science.gov (United States)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  17. Glucocorticoids and beta-adrenergic-receptor agonists: their combined effect on fetal rabbit lung surfactant.

    Science.gov (United States)

    Ekelund, L; Enhorning, G

    1985-08-15

    In a previous study on pregnant rabbits (Am J Obstet Gynecol 1983; 147:437) we found that a prolonged infusion of the beta 2-adrenergic-receptor agonist terbutaline would first cause a release of fetal pulmonary surfactant, so that more was available in the airways. However, the airway fluid then contained less surfactant, indicating a depletion of stores. Since terbutaline is often used in high doses as a tocolytic agent, surfactant depletion could be a serious side effect. With further studies on rabbits, we wanted to test the hypothesis that with an accelerated surfactant synthesis, achieved with glucocorticoids, the increased release, evoked with the terbutaline, would never cause a depletion of the surfactant stores. Our results supported this hypothesis. Betamethasone, administered to the pregnant doe on the twenty-sixth and twenty-seventh days of gestation, 0.1 mg/kg, increased compliance of the fetal lungs, and more phospholipid phosphorus could be lavaged from the airways. These effects were further increased when, following steroid administration, the doe was infused with terbutaline. Depletion of the surfactant stores was never seen when betamethasone was given prior to the beta-adrenergic-receptor agonist. PMID:3839627

  18. San Francisco Accelerator Conference

    International Nuclear Information System (INIS)

    'Where are today's challenges in accelerator physics?' was the theme of the open session at the San Francisco meeting, the largest ever gathering of accelerator physicists and engineers

  19. Improved plasma accelerator

    Science.gov (United States)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  20. Standing wave linear accelerator

    International Nuclear Information System (INIS)

    Consideration is being given to standing wave linear accelerator containing generator, phase shifter, two accelerating resonator sections, charged particle injector and waveguide bridge. Its first arm is oined up with generator via the phase shifter, the second and the third ones-with accelerating sections and the fourth one - with HF-power absorber. HF-power absorber represents a section of circular diaphragmatic wavequide with transformer with input wave and intrawaveguide output load located between injector and the first accelerating section. The section possesses holes in side walls lying on accelerator axis. The distances between centers of the last cell of the fast accelerating section and the first cell of the second accelerating sectiOn equal (2n+3)lambda/4, where n=1, 2, 3..., lambda - wave length of generator. The suggested system enables to improve by one order spectral characteristics of accelerators as compared to the prototype in which magnetrons are used as generator

  1. Accelerator Technology Division

    Science.gov (United States)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  2. High Energy Particle Accelerators

    CERN Multimedia

    Audio Productions, Inc, New York

    1960-01-01

    Film about the different particle accelerators in the US. Nuclear research in the US has developed into a broad and well-balanced program.Tour of accelerator installations, accelerator development work now in progress and a number of typical experiments with high energy particles. Brookhaven, Cosmotron. Univ. Calif. Berkeley, Bevatron. Anti-proton experiment. Negative k meson experiment. Bubble chambers. A section on an electron accelerator. Projection of new accelerators. Princeton/Penn. build proton synchrotron. Argonne National Lab. Brookhaven, PS construction. Cambridge Electron Accelerator; Harvard/MIT. SLAC studying a linear accelerator. Other research at Madison, Wisconsin, Fixed Field Alternate Gradient Focusing. (FFAG) Oakridge, Tenn., cyclotron. Two-beam machine. Comments : Interesting overview of high energy particle accelerators installations in the US in these early years. .

  3. Are Dopamine Agonists Neuroprotective in Parkinson′s Disease?

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Dopamine (DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson′s disease (PD) and in PD patient with levodopa (L-DOPA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer′s disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinical trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as 18 F-L-DOPA PET and 123 I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.``

  4. Are Dopamine Agonists Neuroprotective in Parkinson‘s disease?

    Institute of Scientific and Technical Information of China (English)

    乐卫东; Jank.J

    2002-01-01

    Dopamine(DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson's disease(PD) and in PD patient with levodopa(L-DO-PA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoylasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer's disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinal trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as18F-L-DOPA PET and123I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.

  5. Maximal Acceleration Is Nonrotating

    OpenAIRE

    Page, Don N.

    1997-01-01

    In a stationary axisymmetric spacetime, the angular velocity of a stationary observer that Fermi-Walker transports its acceleration vector is also the angular velocity that locally extremizes the magnitude of the acceleration of such an observer, and conversely if the spacetime is also symmetric under reversing both t and phi together. Thus a congruence of Nonrotating Acceleration Worldlines (NAW) is equivalent to a Stationary Congruence Accelerating Locally Extremely (SCALE). These congruenc...

  6. A Solid state accelerator

    International Nuclear Information System (INIS)

    We present a solid state accelerator concept utilizing particle acceleration along crystal channels by longitudinal electron plasma waves in a metal. Acceleration gradients of order 100 GV/cm are theoretically possible, but channeling radiation limits the maximum attainable energy to 105 TeV for protons. Beam dechanneling due to multiple scattering is substantially reduced by the high acceleration gradient. Plasma wave dissipation and generation in metals are also discussed

  7. Applications of particle accelerators

    International Nuclear Information System (INIS)

    Particle accelerators are now widely used in a variety of applications for scientific research, applied physics, medicine, industrial processing, while possible utilisation in power engineering is envisaged. Earlier presentations of this subject, given at previous CERN Accelerator School sessions have been updated with papers contributed to the first European Conference on Accelerators in Applied Research and Technology (ECAART) held in September 1989 in Frankfurt and to the Second European Particle Accelerator Conference in Nice in June 1990. (orig.)

  8. Accelerators at school

    International Nuclear Information System (INIS)

    Latest subject covered by the CERN Accelerator School was 'Applied Geodesy of Particle Accelerators', which attracted an impressive number of outside participants to CERN for a week in April. Since the forerunners of today's particle accelerators were demonstrated over 50 years ago, the positioning of accelerator components has progressed from the laboratory bench-top to tunnels tens of kilometres long. Despite this phenomenal growth in size, sub-millimetre accuracy is still required

  9. Acceleration: It's Elementary

    Science.gov (United States)

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  10. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

    Introduction to accelerator physics The CERN Accelerator School: Introduction to Accelerator Physics, which should have taken place in Istanbul, Turkey, later this year has now been relocated to Budapest, Hungary.  Further details regarding the new hotel and dates will be made available as soon as possible on a new Indico site at the end of May.

  11. Accelerators and Dinosaurs

    CERN Document Server

    Turner, Michael Stanley

    2003-01-01

    Using naturally occuring particles on which to research might have made accelerators become extinct. But in fact, results from astrophysics have made accelerator physics even more important. Not only are accelerators used in hospitals but they are also being used to understand nature's inner workings by searching for Higgs bosons, CP violation, neutrino mass and dark matter (2 pages)

  12. Far field acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail.

  13. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists.

    Science.gov (United States)

    Harmon, Jennifer L; Wills, Lauren P; McOmish, Caitlin E; Demireva, Elena Y; Gingrich, Jay A; Beeson, Craig C; Schnellmann, Rick G

    2016-04-01

    In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP

  14. Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    glycine-free or a glycine-bound subunit. Agonist-free subunits were created by incorporating T204A and R65K mutations, which disrupted glycine binding to both (+) and (-) subunit interfaces. In heteromeric receptors comprising wild-type and R65K,T204A,R271C triple-mutant subunits, the fluorescence...... response exhibited a drastically reduced glycine sensitivity relative to the current response. Two conclusions can be drawn from this. First, because the labeled glycine-free subunits were activated by glycine binding to neighboring wild-type subunits, our results provide evidence for a cooperative...... activation mechanism. However, because the fluorescent label on glycine-free subunits does not reflect movements at the channel gate, we conclude that glycine binding also produces a local non-concerted conformational change that is not essential for receptor activation....

  15. Direct Laser Acceleration in Laser Wakefield Accelerators

    OpenAIRE

    Shaw, Jessica

    2016-01-01

    In this dissertation, the direct laser acceleration (DLA) of ionization-injected electrons in a laser wakefield accelerator (LWFA) operating in the quasi-blowout regime has been investigated through experiment and simulation. In the blowout regime of LWFA, the radiation pressure of an intense laser pulse can push a majority of the plasma electrons out and around the main body of the pulse. The expelled plasma electrons feel the electrostatic field of the relatively-stationary ions and are t...

  16. The Accelerator Reliability Forum

    CERN Document Server

    Lüdeke, Andreas; Giachino, R

    2014-01-01

    A high reliability is a very important goal for most particle accelerators. The biennial Accelerator Reliability Workshop covers topics related to the design and operation of particle accelerators with a high reliability. In order to optimize the over-all reliability of an accelerator one needs to gather information on the reliability of many different subsystems. While a biennial workshop can serve as a platform for the exchange of such information, the authors aimed to provide a further channel to allow for a more timely communication: the Particle Accelerator Reliability Forum [1]. This contribution will describe the forum and advertise it’s usage in the community.

  17. Induction linear accelerators

    Science.gov (United States)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typicallymarriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  18. Principles of agonist recognition in Cys-loop receptors

    Directory of Open Access Journals (Sweden)

    Timothy eLynagh

    2014-04-01

    Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

  19. The GABAB receptor agonist, baclofen, contributes to three distinct varieties of amnesia in the human brain - A detailed case report.

    Science.gov (United States)

    Zeman, Adam; Hoefeijzers, Serge; Milton, Fraser; Dewar, Michaela; Carr, Melanie; Streatfield, Claire

    2016-01-01

    We describe a patient in whom long-term, therapeutic infusion of the selective gamma-amino-butyric acid type B (GABAB) receptor agonist, baclofen, into the cerebrospinal fluid (CSF) gave rise to three distinct varieties of memory impairment: i) repeated, short periods of severe global amnesia, ii) accelerated long-term forgetting (ALF), evident over intervals of days and iii) a loss of established autobiographical memories. This pattern of impairment has been reported in patients with temporal lobe epilepsy (TLE), in particular the subtype of Transient Epileptic Amnesia (TEA). The amnesic episodes and accelerated forgetting remitted on withdrawal of baclofen, while the autobiographical amnesia (AbA) persisted. This exceptional case highlights the occurrence of 'non-standard' forms of human amnesia, reflecting the biological complexity of memory processes. It suggests a role for GABAB signalling in the modulation of human memory over multiple time-scales and hints at its involvement in 'epileptic amnesia'. PMID:26599496

  20. Particle-accelerator decommissioning

    International Nuclear Information System (INIS)

    Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given

  1. Particle-accelerator decommissioning

    Energy Technology Data Exchange (ETDEWEB)

    Opelka, J.H.; Mundis, R.L.; Marmer, G.J.; Peterson, J.M.; Siskind, B.; Kikta, M.J.

    1979-12-01

    Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given.

  2. Synthesis of Selective A3 and M1 Receptor Agonists

    OpenAIRE

    Snee, Stephen

    2011-01-01

    Detailed within this thesis is the synthesis of three A1 agonists which were designed by Muscagen using computational studies. The agonists are derived from condensation of the modified adenosine: (4S,6R)-6-(6-chloro-9H-purin-9-yl)-N,2,2-trimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide with novel heterocyclic primary amines.The amines 5-(aminomethyl)-N,N-diethyl-7-methyloxazolo[4,5-b]pyridin-2-amine, 5-(1-aminoethyl)-N,N,7-trimethyloxazolo[4,5-b]pyridin-2-amine and 5-(1-aminoethyl)-N,...

  3. An introduction to acceleration mechanisms

    International Nuclear Information System (INIS)

    This paper discusses the acceleration of charged particles by electromagnetic fields, i.e., by fields that are produced by the motion of other charged particles driven by some power source. The mechanisms that are discussed include: Ponderamotive Forces, Acceleration, Plasma Beat Wave Acceleration, Inverse Free Electron Laser Acceleration, Inverse Cerenkov Acceleration, Gravity Acceleration, 2D Linac Acceleration and Conventional Iris Loaded Linac Structure Acceleration

  4. Accelerator reliability workshop

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, L.; Duru, Ph.; Koch, J.M.; Revol, J.L.; Van Vaerenbergh, P.; Volpe, A.M.; Clugnet, K.; Dely, A.; Goodhew, D

    2002-07-01

    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop.

  5. Switched Matrix Accelerator

    International Nuclear Information System (INIS)

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium

  6. Accelerator and radiation physics

    CERN Document Server

    Basu, Samita; Nandy, Maitreyee

    2013-01-01

    "Accelerator and radiation physics" encompasses radiation shielding design and strategies for hadron therapy accelerators, neutron facilities and laser based accelerators. A fascinating article describes detailed transport theory and its application to radiation transport. Detailed information on planning and design of a very high energy proton accelerator can be obtained from the article on radiological safety of J-PARC. Besides safety for proton accelerators, the book provides information on radiological safety issues for electron synchrotron and prevention and preparedness for radiological emergencies. Different methods for neutron dosimetry including LET based monitoring, time of flight spectrometry, track detectors are documented alongwith newly measured experimental data on radiation interaction with dyes, polymers, bones and other materials. Design of deuteron accelerator, shielding in beam line hutches in synchrotron and 14 MeV neutron generator, various radiation detection methods, their characteriza...

  7. Leaky Fermi accelerators

    CERN Document Server

    Shah, Kushal; Rom-Kedar, Vered; Turaev, Dmitry

    2015-01-01

    A Fermi accelerator is a billiard with oscillating walls. A leaky accelerator interacts with an environment of an ideal gas at equilibrium by exchange of particles through a small hole on its boundary. Such interaction may heat the gas: we estimate the net energy flow through the hole under the assumption that the particles inside the billiard do not collide with each other and remain in the accelerator for sufficiently long time. The heat production is found to depend strongly on the type of the Fermi accelerator. An ergodic accelerator, i.e. one which has a single ergodic component, produces a weaker energy flow than a multi-component accelerator. Specifically, in the ergodic case the energy gain is independent of the hole size, whereas in the multi-component case the energy flow may be significantly increased by shrinking the hole size.

  8. Nuclear physics accelerator facilities

    International Nuclear Information System (INIS)

    This paper describes many of the nuclear physics heavy-ion accelerator facilities in the US and the research programs being conducted. The accelerators described are: Argonne National Laboratory--ATLAS; Brookhaven National Laboratory--Tandem/AGS Heavy Ion Facility; Brookhaven National Laboratory--Relativistic Heavy Ion Collider (RHIC) (Proposed); Continuous Electron Beam Accelerator Facility; Lawrence Berkeley Laboratory--Bevalac; Lawrence Berkeley Laboratory--88-Inch Cyclotron; Los Alamos National Laboratory--Clinton P. Anderson Meson Physics Facility (LAMPF); Massachusetts Institute of Technology--Bates Linear Accelerator Center; Oak Ridge National Laboratory--Holifield Heavy Ion Research Facility; Oak Ridge National Laboratory--Oak Ridge Electron Linear Accelerator; Stanford Linear Accelerator Center--Nuclear Physics Injector; Texas AandM University--Texas AandM Cyclotron; Triangle Universities Nuclear Laboratory (TUNL); University of Washington--Tandem/Superconducting Booster; and Yale University--Tandem Van de Graaff

  9. Accelerator reliability workshop

    International Nuclear Information System (INIS)

    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop

  10. High Gradient Accelerator Research

    Energy Technology Data Exchange (ETDEWEB)

    Temkin, Richard [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Physics. Plasma Science and Fusion Center

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  11. High Gradient Accelerator Research

    Energy Technology Data Exchange (ETDEWEB)

    Temkin, Richard [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Physics. Plasma Science and Fusion Center

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low power microwave cold test and high power, high gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  12. Partial Agonists Activate PPARgamma Using a Helix 12 Independent Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Bruning, J.B.; Chalmers, M.J.; Prasad, S.; Bushby, S.A.; Kamenecka, T.A.; He, Y.; Nettles, K.W.; Griffin, P.R.

    2009-05-28

    Binding to helix 12 of the ligand-binding domain of PPAR{gamma} is required for full agonist activity. Previously, the degree of stabilization of the activation function 2 (AF-2) surface was thought to correlate with the degree of agonism and transactivation. To examine this mechanism, we probed structural dynamics of PPAR{gamma} with agonists that induced graded transcriptional responses. Here we present crystal structures and amide H/D exchange (HDX) kinetics for six of these complexes. Amide HDX revealed each ligand induced unique changes to the dynamics of the ligand-binding domain (LBD). Full agonists stabilized helix 12, whereas intermediate and partial agonists did not at all, and rather differentially stabilized other regions of the binding pocket. The gradient of PPAR{gamma} transactivation cannot be accounted for solely through changes to the dynamics of AF-2. Thus, our understanding of allosteric signaling must be extended beyond the idea of a dynamic helix 12 acting as a molecular switch.

  13. Innovations in agonist maintenance treatment of opioid-dependent patients

    NARCIS (Netherlands)

    C. Haasen; W. van den Brink

    2006-01-01

    Purpose of review To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. Recent findings The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid depe

  14. Synthetic RORγt Agonists Enhance Protective Immunity.

    Science.gov (United States)

    Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Doebelin, Christelle; Garcia-Ordonez, Ruben D; Novick, Scott J; Kuruvilla, Dana S; Kamenecka, Theodore M; Griffin, Patrick R

    2016-04-15

    The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer. PMID:26785144

  15. Systemic cancer immunotherapy with Toll-like receptor 7 agonists

    Science.gov (United States)

    Hotz, Christian; Bourquin, Carole

    2012-01-01

    Toll-like receptor (TLR) 7 agonists represent a promising strategy for the immunotherapy of cancer. We have recently investigated the influence of TLR tolerance on the efficacy of systemic tumor treatment with TLR7 ligands. We propose that considering the kinetics of receptor sensitivity highly improves the outcome of cancer immunotherapy. PMID:22720251

  16. The emerging therapeutic roles of κ-opioid agonists.

    Science.gov (United States)

    Jones, Mark R; Kaye, Alan D; Kaye, Aaron J; Urman, Richard D

    2016-01-01

    The current practice of μ-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the μ-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established μ-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents.

  17. Glucagon-like peptide 1 receptor agonist (GLP-1 RA)

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Tine Willum; Goetze, Jens Peter;

    2015-01-01

    AIMS: In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim...

  18. Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian;

    2012-01-01

    FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metaboli...

  19. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    DEFF Research Database (Denmark)

    Goadsby, P J; Hoskin, K L; Storer, R J;

    2002-01-01

    There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperit......There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg...... from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS...... 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion...

  20. Accelerator Modeling with MATLAB Accelerator Toolbox

    International Nuclear Information System (INIS)

    This paper introduces Accelerator Toolbox (AT)--a collection of tools to model storage rings and beam transport lines in the MATLAB environment. The objective is to illustrate the flexibility and efficiency of the AT-MATLAB framework. The paper discusses three examples of problems that are analyzed frequently in connection with ring-based synchrotron light sources

  1. Angular velocities, angular accelerations, and coriolis accelerations

    Science.gov (United States)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  2. Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists.

    Science.gov (United States)

    Gilmore, John L; Sheppeck, James E; Wang, Jim; Dhar, T G Murali; Cavallaro, Cullen; Doweyko, Arthur M; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Nadler, Steven G; Dodd, John H; Somerville, John E; Barrish, Joel C

    2013-10-01

    SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. PMID:23916594

  3. β-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review

    OpenAIRE

    Tabner, Andrew John; Johnson, Graham David; Fakis, Apostolos; Surtees, Jane; Lennon, Robert Iain

    2016-01-01

    Objectives To determine whether β-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature. Setting Adult emergency departments or acute assessment units. Participants Human participants with proven or suspected renal colic. Interventions β-adrenoreceptor agonists. Outcome measures Primary: level of pain at 30 min following administration of the β-agonist. Secondary: level of pain at various time points following β-agonist ad...

  4. Racetrack linear accelerators

    International Nuclear Information System (INIS)

    An improved recirculating electron beam linear accelerator of the racetrack type is described. The system comprises a beam path of four straight legs with four Pretzel bending magnets at the end of each leg to direct the beam into the next leg of the beam path. At least one of the beam path legs includes a linear accelerator. (UK)

  5. COLLECTIVE-FIELD ACCELERATION

    Energy Technology Data Exchange (ETDEWEB)

    Sessler, Andrew M.

    1969-07-04

    Diverse methods proposed for the acceleration of particles by means of collective fields are reviewed. A survey is made of the various currently active experimental programs devoted to investigating collective acceleration, and the present status of the research is briefly noted.

  6. KEK digital accelerator

    Science.gov (United States)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  7. Asia honours accelerator physicists

    CERN Multimedia

    2010-01-01

    "Steve Meyers of Cern and Jie Wei of Beijing's Tsinghua University are the first recipients of a new prize for particle physics. The pair were honoured for their contributions to numerous particle-accelerator projects - including Cern's Large Hadron Collider - by the Asian Committee for Future Accelerators (ACFA)..." (1 paragraph)

  8. Accelerators for energy production

    International Nuclear Information System (INIS)

    A tremendous progress of accelerators for these several decades, has been motivated mainly by the research on subnuclear physics. The culmination in high energy accelerators might be SSC, 20 TeV collider in USA, probably the ultimate accelerator being built with the conventional principle. The technology cultivated and integrated for the accelerator development, can now stably offer the high power beam which could be used for the energy problems. The Inertial Confinement Fusion (ICF) with high current, 10 kA and short pulse, 20 ns heavy ion beam (HIB) of mass number ∼200, would be the most promising application of accelerators for energy production. In this scenario, the fuel containing D-T mixture, will be compressed to the high temperature, ∼10 keV and to the high density state, ∼1000 times the solid density with the pressure of ablative plasma or thermal X ray produced by bombarding of high power HIB. The efficiency, beam power/electric power for accelerator, and the repetition rate of HIB accelerators could be most suitable for the energy production. In the present paper, the outline of HIB ICF (HIF) is presented emphasizing the key issues of high current heavy ion accelerator system. (author)

  9. Accelerators Beyond The Tevatron?

    Energy Technology Data Exchange (ETDEWEB)

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  10. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans;

    1999-01-01

    , whereas IP-10 and stromal cell-derived factor-1alpha surprisingly acted as inverse agonists. These peptides had similar pharmacological properties with regard to enhancing or inhibiting, respectively, the stimulatory effect of ORF-74 on NIH-3T3 cell proliferation. Construction of a high affinity zinc...... as demonstrated by the effect of Zn2+ on the metal ion site-engineered receptor....

  11. Maximal Acceleration Is Nonrotating

    CERN Document Server

    Page, D N

    1998-01-01

    In a stationary axisymmetric spacetime, the angular velocity of a stationary observer that Fermi-Walker transports its acceleration vector is also the angular velocity that locally extremizes the magnitude of the acceleration of such an observer, and conversely if the spacetime is also symmetric under reversing both t and phi together. Thus a congruence of Nonrotating Acceleration Worldlines (NAW) is equivalent to a Stationary Congruence Accelerating Locally Extremely (SCALE). These congruences are defined completely locally, unlike the case of Zero Angular Momentum Observers (ZAMOs), which requires knowledge around a symmetry axis. The SCALE subcase of a Stationary Congruence Accelerating Maximally (SCAM) is made up of stationary worldlines that may be considered to be locally most nearly at rest in a stationary axisymmetric gravitational field. Formulas for the angular velocity and other properties of the SCALEs are given explicitly on a generalization of an equatorial plane, infinitesimally near a symmetry...

  12. Linear induction accelerator

    International Nuclear Information System (INIS)

    This paper examines a new layout for the injector and accelerating sectins of a linear induction accelerator. The sections are combined in a single housing: an induction system with a current-pulse generator based on double strip shaping lines laid over ferromagnetic cores; a multichannel spark discharger with forced current division among channels; and a system for core demagnetization and electron-beam formation and transport. The results of formation of an electron beam in the injector system and its acceleration in the first accelerating section of the accelerator for injection of beams with energies of 0.2-0.4 MeV, currents of 1-2 kA, and pulse durations of 60 nsec are given

  13. Collinear wake field acceleration

    International Nuclear Information System (INIS)

    In the Voss-Weiland scheme of wake field acceleration a high current, ring-shaped driving bunch is used to accelerate a low current beam following along on axis. In such a structure, the transformer ratio, i.e., the ratio of maximum voltage that can be gained by the on-axis beam and the voltage lost by the driving beam, can be large. In contrast, it has been observed that for an arrangement in which driving and driven bunches follow the same path, and where the current distribution of both bunches is gaussian, the transformer ratio is not normally greater than two. This paper explores some of the possibilities and limitations of a collinear acceleration scheme. In addition to its application to wake field acceleration in structures, this study is also of interest for the understanding of the plasma wake field accelerator. 11 refs., 4 figs

  14. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    Energy Technology Data Exchange (ETDEWEB)

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  15. The miniature accelerator

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    The image that most people have of CERN is of its enormous accelerators and their capacity to accelerate particles to extremely high energies. But thanks to some cutting-edge studies on beam dynamics and radiofrequency technology, along with innovative construction techniques, teams at CERN have now created the first module of a brand-new accelerator, which will be just 2 metres long. The potential uses of this miniature accelerator will include deployment in hospitals for the production of medical isotopes and the treatment of cancer. It’s a real David-and-Goliath story.   Serge Mathot, in charge of the construction of the "mini-RFQ", pictured with the first of the four modules that will make up the miniature accelerator. The miniature accelerator consists of a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains around the world, from the smallest to the largest. The LHC is designed to produce very high-intensity beams ...

  16. Large electrostatic accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  17. Accelerator programme at CAT

    International Nuclear Information System (INIS)

    The Accelerator Programme at the Centre for Advanced Technology (CAT), Indore, has very broad based concept under which all types of accelerators are to be taken up for design and fabrication. This centre will be housing a wide variety of accelerators to serve as a common facility for the universities, national laboratories in addition to laboratories under the Department of Atomic Energy. In the first phase of the programme, a series of electron accelerators are designed and fabricated. They are synchrotron radiation sources of 450 MeV (INDUS-I) and of 2 GeV (INDUS-II), microtron upto energy of 20 MeV, linear accelerator upto 20 MeV, and DC Accelerator for industrial irradiation upto 750 KeV and 20 KW. A proton accelerator of 300 MeV with 20 MeV linac injector is also designed. CAT is also developing a strong base for support technologies like ultra high vacuum, radio frequency and microwaves, DC pulsed and superconducting magnets, power supplies and controls etc. These technologies are very useful for other industrial applications also. To develop user groups to utilise INDUS-II synchrotron radiation source, a batch production of rotating Anode X-ray generators with power supplies has been initiated. So also, the sputter ion pumps, electron guns, turbo molecular pumps are brought into batch production. (author)

  18. Collective ion acceleration

    International Nuclear Information System (INIS)

    Progress achieved in the understanding and development of collective ion acceleration is presented. Extensive analytic and computational studies of slow cyclotron wave growth on an electron beam in a helix amplifier were performed. Research included precise determination of linear coupling between beam and helix, suppression of undesired transients and end effects, and two-dimensional simulations of wave growth in physically realizable systems. Electrostatic well depths produced exceed requirements for the Autoresonant Ion Acceleration feasibility experiment. Acceleration of test ions to modest energies in the troughs of such waves was also demonstrated. Smaller efforts were devoted to alternative acceleration mechanisms. Langmuir wave phase velocity in Converging Guide Acceleration was calculated as a function of the ratio of electron beam current to space-charge limiting current. A new collective acceleration approach, in which cyclotron wave phase velocity is varied by modulation of electron beam voltage, is proposed. Acceleration by traveling Virtual Cathode or Localized Pinch was considered, but appears less promising. In support of this research, fundamental investigations of beam propagation in evacuated waveguides, of nonneutral beam linear eigenmodes, and of beam stability were carried out. Several computer programs were developed or enhanced. Plans for future work are discussed

  19. Accelerator Toolbox for MATLAB

    International Nuclear Information System (INIS)

    This paper introduces Accelerator Toolbox (AT)--a collection of tools to model particle accelerators and beam transport lines in the MATLAB environment. At SSRL, it has become the modeling code of choice for the ongoing design and future operation of the SPEAR 3 synchrotron light source. AT was designed to take advantage of power and simplicity of MATLAB--commercially developed environment for technical computing and visualization. Many examples in this paper illustrate the advantages of the AT approach and contrast it with existing accelerator code frameworks

  20. Hadron accelerators in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Amaldi, U. [European Organization for Nuclear Research (CERN), Geneva (Switzerland). Accelerator School; Silari, M. [Consiglio Nazionale delle Ricerche, Milan (Italy)

    1996-12-31

    The application of hadron accelerators (protons and light ions) in cancer therapy is discussed. After a brief introduction on the rationale for the use of heavy charged particles in radiation therapy, a discussion is given on accelerator technology and beam delivery systems. Next, existing and planned facilities are briefly reviewed. The Italian Hadron-therapy Project is then described in some detail, with reference ro both the National Centre for Oncological Hadron-therapy and the design of different types of compact proton accelerators aimed at introducing proton therapy in a large umber of hospitals. (author) 28 refs.

  1. Confronting Twin Paradox Acceleration

    Science.gov (United States)

    Murphy, Thomas W.

    2016-05-01

    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  2. Entropic accelerating universe

    Energy Technology Data Exchange (ETDEWEB)

    Easson, Damien A., E-mail: easson@asu.ed [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa, Chiba 277-8568 (Japan); Department of Physics and School of Earth and Space Exploration and Beyond Center, Arizona State University, Phoenix, AZ 85287-1504 (United States); Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106-4030 (United States); Frampton, Paul H., E-mail: frampton@physics.unc.ed [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa, Chiba 277-8568 (Japan); Department of Physics and Astronomy, University of North Carolina, Chapel Hill, NC 27599 (United States); Smoot, George F., E-mail: gfsmoot@lbl.go [Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa, Chiba 277-8568 (Japan); Lawrence Berkeley National Lab, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Physics Department, University of California, Berkeley, CA 94720 (United States); Institute for the Early Universe, Ewha Womans University and Advanced Academy, Seoul (Korea, Republic of); Chaire Blaise Pascale, Universite Paris Denis Diderot, Paris (France)

    2011-01-31

    To accommodate the observed accelerated expansion of the universe, one popular idea is to invoke a driving term in the Friedmann-Lemaitre equation of dark energy which must then comprise 70% of the present cosmological energy density. We propose an alternative interpretation which takes into account the entropy and temperature intrinsic to the horizon of the universe due to the information holographically stored there. Dark energy is thereby obviated and the acceleration is due to an entropic force naturally arising from the information storage on the horizon surface screen. We consider an additional quantitative approach inspired by surface terms in general relativity and show that this leads to the entropic accelerating universe.

  3. ACCELERATORS: School prizes

    International Nuclear Information System (INIS)

    Dedicated to its goal of encouraging scientists and students to work in the field of particle accelerators, the US Particle Accelerator School (operating since 1981) has switched to a new format. Starting this year, it will offer in alternate years basic accelerator physics plus advanced subjects in both university and symposium styles over four weeks. Expanding the school from two to four weeks gives additional flexibility, and undergraduate participation should be encouraged by university credits being offered for particular courses. In the intervening years, the school will organize six-day topical courses

  4. Auroral electron acceleration

    International Nuclear Information System (INIS)

    Two theories of auroral electron acceleration are discussed. Part 1 examines the currently widely held view that the acceleration is an ordered process in a quasi-static electric field. It is suggested that, although there are many factors seeming to support this theory, the major qualifications and uncertainties that have been identified combine to cast serious doubt over its validity. Part 2 is devoted to a relatively new interpretation in terms of stochastic acceleration in turbulent electric fields. This second theory, which appears to account readily for most known features of the electron distribution function, is considered to provide a more promising approach to this central question in magnetospheric plasma physics. (author)

  5. The particle accelerator

    International Nuclear Information System (INIS)

    As the Palais de la Decouverte (in Paris) is the sole scientific vulgarization establishment in the world to operate an actual particle accelerator able to provoke different types of nuclear reactions, the author recalls some historical aspects of the concerned department since the creation of the 'Radioactivity - Atom synthesis' department in 1937. He recalls the experiments which were then performed, the installation of the particle accelerator in 1964 and its renewal. He describes what's going on in this accelerator. He gives an overview of the difficulties faced after it has been decided to move it, of the works which had to be performed, and of radiation protection measures

  6. PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available Synthetic peroxisome proliferator-activated receptor (PPAR agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate and a PPARγ agonist (rosiglitazone on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3 and decreased monocyte chemoattractant protein-1 (Mcp1 expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM, we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/- BMDM resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/- BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists.

  7. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    Science.gov (United States)

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

  8. PPAR GAMMA AGONISTS: AN EFFECTIVE STRATEGY FOR CANCER TREATMENT

    Directory of Open Access Journals (Sweden)

    Divya G.S

    2013-10-01

    Full Text Available PPAR-γ regulates cellular differentiation, development and metabolism. They play these essential roles by functioning as transcription factors regulating the expression of genes. The PPARs mainly are of three types α, β and γ. The PPAR-γ expressed in three forms γ1, γ2 and γ3 present in different tissues. When PPAR binds its ligand, transcription of target gene is increased or decreased. Tzds were able to induce cell differentiation and apoptosis or inhibit cell proliferation both in vitro and in vivo. However, widespread use of thiazolidinediones (TZDs, the clinically used synthetic PPAR gamma agonists, has been limited by adverse effects. So in this review we are suggesting some new molecules other than thiazolidine diones which can act as potential anticancer agents, after explaining the mechanism of action of PPAR-γ agonists as anticancer agents especially thiazolidinediones.

  9. Grooming, rank, and agonistic support in tufted capuchin monkeys.

    Science.gov (United States)

    Schino, Gabriele; Di Giuseppe, Francesca; Visalberghi, Elisabetta

    2009-02-01

    Studies investigating the relation between allogrooming and social rank in capuchin monkeys (genus Cebus) have yielded inconsistent results. In this study, we investigated the relation between grooming, agonistic support, aggression and social rank in a captive group of tufted capuchin monkeys (C. apella). Differently from most previous studies, we based our analyses on a relatively large database and studied a group with known genealogical relationships. Tufted capuchin females did not exchange grooming for rank-related benefits such as agonistic support or reduced aggression. Coherently with this picture, they did not groom up the hierarchy and did not compete for accessing high-ranking grooming partners. It is suggested that a small group size, coupled with a strong kin bias, may make the exchange of grooming for rank-related benefits impossible or unprofitable, thus eliminating the advantages of grooming up the hierarchy. We provide several possible explanations for the heterogeneity of results across capuchin studies that have addressed similar questions.

  10. SPS accelerating cavity

    CERN Multimedia

    1983-01-01

    See photo 8202397: View towards the downstream end of one of the SPS accelerating cavities (200 MHz, travelling wave structure). See 7603195 and 8011289 for more details, 7411032 for the travelling wave structure, and also 8104138.

  11. SPS accelerating cavity

    CERN Multimedia

    1983-01-01

    View towards the downstream end of one of the SPS accelerating cavities (200 MHz, travelling wave structure). See 7603195 and 8011289 for more details, 7411032 for the travelling wave structure, and also 8104138.

  12. Rejuvenating CERN's Accelerators

    CERN Multimedia

    2004-01-01

    In the coming years and especially in 2005, CERN's accelerators are going to receive an extensive renovation programme to ensure they will perform reliably and effectively when the LHC comes into service.

  13. Dimension Driven Accelerating Universe

    CERN Document Server

    Chatterjee, S

    2009-01-01

    The current acceleration of the universe leads us to investigate higher dimensional gravity theory, which is able to explain acceleration from a theoretical view point without the need of introducing dark energy by hand. We argue that the terms containing higher dimensional metric coefficients produce an extra negative pressure that apparently drives an acceleration of the 3D space, tempting us to suggest that the accelerating universe seems to act as a window to the existence of extra spatial dimensions. Interesting to point out that in this case our cosmology apparently mimics the well known quintessence scenario fuelled by a generalised Chaplygin-type of fluid where a smooth transition from a dust dominated model to a de Sitter like one takes place. Correspondence to models generated by a tachyonic form of matter is also briefly discussed.

  14. Revisiting Caianiello's Maximal Acceleration

    OpenAIRE

    Papini, G.

    2003-01-01

    A quantum mechanical limit on the speed of orthogonality evolution justifies the last remaining assumption in Caianiello's derivation of the maximal acceleration. The limit is perfectly compatible with the behaviour of superconductors of the first type.

  15. Joint International Accelerator School

    CERN Multimedia

    CERN Accelerator School

    2014-01-01

    The CERN and US Particle Accelerator Schools recently organised a Joint International Accelerator School on Beam Loss and Accelerator Protection, held at the Hyatt Regency Hotel, Newport Beach, California, USA from 5-14 November 2014. This Joint School was the 13th in a series of such schools, which started in 1985 and also involves the accelerator communities in Japan and Russia.   Photo courtesy of Alfonse Pham, Michigan State University.   The school attracted 58 participants representing 22 different nationalities, with around half from Europe and the other half from Asia and the Americas. The programme comprised 26 lectures, each of 90 minutes, and 13 hours of case study. The students were given homework each day and had an opportunity to sit a final exam, which counted towards university credit. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and quality of their lectures. Initial dis...

  16. Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

    OpenAIRE

    Hayley Patricia Ellis; Kathreena Mary Kurian

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral...

  17. Alternation of Agonists and Antagonists During Turtle Hindlimb Motor Rhythms

    OpenAIRE

    Stein, Paul S.G.

    2010-01-01

    In a variety of vertebrates, including turtle, many classical and contemporary studies of spinal cord neuronal networks generating rhythmic motor behaviors emphasize a Reciprocal Model with alternation of agonists and antagonists, alternation of excitatory and inhibitory postsynaptic potentials, and reciprocal inhibition. Some studies of spinal cord neuronal networks, including those in turtle during scratch motor rhythms, describe a Balanced Model with concurrent excitatory and inhibitory po...

  18. Melatonin agonists for treatment of sleep and depressive disorders

    OpenAIRE

    Pandi-Perumal, Seithikurippu R.; Brown, Gregory M.; Daniel P. Cardinali; Venkataramanujan Srinivasan

    2011-01-01

    Melatonin the hormone secreted by the pineal gland has been effective in improving sleep both in normal sleepers and insomniacs and has been used successfully in treating sleep and circadian rhythm sleep disorders. The lack of consistency in the reports published by the authors is attributed to the differential bioavailabilty and short half-life of melatonin. Sleep disturbances are also prominent features of depressive disorders. To overcome this problem, melatonergic agonists with sleep prom...

  19. Pharmacophore-driven identification of PPARγ agonists from natural sources

    DEFF Research Database (Denmark)

    Petersen, R. K.; Christensen, Kathrine Bisgaard; Assimopoulou, A. N.;

    2011-01-01

    In a search for more effective and safe anti-diabetic compounds, we developed a pharmacophore model based on partial agonists of PPARγ. The model was used for the virtual screening of the Chinese Natural Product Database (CNPD), a library of plant-derived natural products primarily used in folk...... at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery....

  20. Discriminative learning occasioned by the administration of a dopamine agonist

    OpenAIRE

    Keller, Sabine; Delius, Juan

    2001-01-01

    Rationale: The repeated administration of psychostimulants usually brings about a progressive increment of the behavioral responses that they induce. We examined to what extent this sensitization is due to an associative learning process. Objectives: The dopamine agonist apomorphine elicits stereotyped pecking in pigeons, a response that increases with successive intramuscular injections. We tested whether this sensitized pecking would be discriminatively directed at environmental stimuli tha...

  1. Beta-adrenergic agonists as additive in beef cattle

    Directory of Open Access Journals (Sweden)

    Marcelo Vedovatto

    2014-10-01

    Full Text Available The agonists receptor beta-adrenergic (β-AA are present in virtually all types of mammalian cells and are stimulated by catecholamines (epinephrine and norepinephrine produced by the organism itself. The β-AA agonists are synthetic substances with similar structure to these amines. When provided in the diet they alter the body composition of animals, affecting the distribution of nutrients toward to protein deposition, and decreasing lipogenesis. Although the mechanisms of action are not fully understood, these may cause morphological and physiological changes such as increased blood flow decrease in plasma insulin, decreased lipogenesis, and muscle hypertrophy mainly in type II fibers. We also observed changes in motility and secretions grastointestinal tract, beyond the direct influence on the rumen bacteria, altering the digestibility of the diet. The β-AA agonists released in some countries for use in beef cattle are ractopamine hydrochloride and zilpaterol hydrochloride. According to literature data, the inclusion of these additives in the diet of feedlot cattle has been associated with an increase infeed efficiency with the increase in daily weight gain and with equal or lower feed intake. Carcass characteristics improvement was verified in carcass weight, and increased loin eye area, but with the possibility to decrease the subcutaneous fat thickness and marbling. Reviews in sensory panel of meat from animals consuming β-AA agonists showed decreased tenderness and juiciness. Thus β-AA improve performance and carcass characteristics, but more studies are needed to confirm whether they have negative influence on the organoleptic characteristics of the meat.

  2. A symmetrical rail accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Igenbergs, E. (Technische Univ. Muenchen, Lehrstuhl fuer Raumfahrttechnik, Richard-Wagner-Strasse 18, 8000 Muenchen 2 (DE))

    1991-01-01

    This paper reports on the symmetrical rail accelerator that has four rails, which are arranged symmetrically around the bore. The opposite rails have the same polarity and the adjacent rails the opposite polarity. In this configuration the radial force acting upon the individual rails is significantly smaller than in a conventional 2-rail configuration and a plasma armature is focussed towards the axis of the barrel. Experimental results indicate a higher efficiency compared to a conventional rail accelerator.

  3. Advanced Accelerator Concepts

    International Nuclear Information System (INIS)

    This conference proceedings represent the results of theThird Advanced Accelerator Concepts Workshop held in PortJefferson, New York. The workshop was sponsored by the U.S.Department of Energy, the Office of Navel Research and BrookhavenNational Laboratory. The purpose was to assess new techniques forproduction of ultra-high gradient acceleration and to addressengineering issues in achieving this goal. There are eighty-onepapers collected in the proceedings and all have been abstractedfor the database

  4. CEBAF Accelerator Achievements

    International Nuclear Information System (INIS)

    In the past decade, nuclear physics users of Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) have benefited from accelerator physics advances and machine improvements. As of early 2011, CEBAF operates routinely at 6 GeV, with a 12 GeV upgrade underway. This article reports highlights of CEBAF's scientific and technological evolution in the areas of cryomodule refurbishment, RF control, polarized source development, beam transport for parity experiments, magnets and hysteresis handling, beam breakup, and helium refrigerator operational optimization.

  5. Accelerating Cosmologies from Compactification

    CERN Document Server

    Townsend, P K; Townsend, Paul K.; Wohlfarth, Mattias N.R.

    2003-01-01

    A solution of the (4+n)-dimensional vacuum Einstein equations is found for which spacetime is compactified on a compact hyperbolic manifold of time-varying volume to a flat four-dimensional FLRW cosmology undergoing accelerated expansion in Einstein conformal frame. This shows that the `no-go' theorem forbidding acceleration in `standard' (time-independent) compactifications of string/M-theory does not apply to `cosmological' (time-dependent) hyperbolic compactifications.

  6. Designing reliability into accelerators

    International Nuclear Information System (INIS)

    Future accelerators will have to provide a high degree of reliability. Quality must be designed in right from the beginning and must remain a central theme throughout the project. The problem is similar to the problems facing US industry today, and examples of the successful application of quality engineering will be given. Different aspects of an accelerator project will be addressed: Concept, Design, Motivation, Management Techniques, and Fault Diagnosis. The importance of creating and maintaining a coherent team will be stressed

  7. Accelerated cyclic corrosion tests

    OpenAIRE

    Prošek T.

    2016-01-01

    Accelerated corrosion testing is indispensable for material selection, quality control and both initial and residual life time prediction for bare and painted metallic, polymeric, adhesive and other materials in atmospheric exposure conditions. The best known Neutral Salt Spray (NSS) test provides unrealistic conditions and poor correlation to exposures in atmosphere. Modern cyclic accelerated corrosion tests include intermittent salt spray, wet and dry phases and eventually other technical p...

  8. Accelerating News Issue 2

    CERN Document Server

    Kahle, K; Wildner, E

    2012-01-01

    In this summer issue we look at how developments in collimator materials could have applications in aerospace and beyond, and how Polish researchers are harnessing accelerators for medical and industrial uses. We see how the LHC luminosity upgrade is linking with European industry and US researchers, and how the neutrino oscillation community is progressing. We find out the mid-term status of TIARA-PP and how it is mapping European accelerator education resources.

  9. Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Hayley Patricia Ellis

    2014-03-01

    Full Text Available Glioblastoma Multiforme (GBM is the most common primary intrinsic CNS tumour and has an extremely poor overall survival, despite advances in neurosurgery, chemotherapy and radiation therapy. There has been interesting preliminary evidence suggesting that patients receiving the group of anti-diabetic drugs known as PPARγ (Peroxisome proliferator-activated receptor gamma agonists have a lower incidence of glioma. The nuclear hormone receptor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists, as Pioglitazone and Rosiglitazone are only FDA-approved for use in treatment of type-2 diabetes. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of high grade glioma. We introduce the PPARγ pathway, PPARγ gene and its products and examine recent research in glioblastoma.

  10. Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.

    Science.gov (United States)

    Lin, Hsiang-Ru; Chou, Tsung-Hsien; Huang, Din-Wen; Chen, Ih-Sheng

    2014-09-01

    Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one-hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists. PMID:25127166

  11. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  12. Dopamine agonist activity of EMD 23,448

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G.E.; Pettibone, D.J. (Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology)

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

  13. Suppression of atherosclerosis by synthetic REV-ERB agonist

    International Nuclear Information System (INIS)

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization

  14. Emerging strategies for exploiting cannabinoid receptor agonists as medicines.

    Science.gov (United States)

    Pertwee, Roger G

    2009-02-01

    Medicines that activate cannabinoid CB(1) and CB(2) receptor are already in the clinic. These are Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol) and Sativex (Delta(9)-tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol can also be prescribed to stimulate appetite, while Sativex is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB(2) receptors; or (v) 'multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. PMID:19226257

  15. Nuclear physics accelerator facilities

    International Nuclear Information System (INIS)

    Brief descriptions are given of DOE and Nuclear Physics program operated and sponsored accelerator facilities. Specific facilities covered are the Argonne Tandem/Linac Accelerator System, the Tandem/AGS Heavy Ion Facility at Brookhaven National Laboratory, the proposed Continuous Beam Accelerator at Newport News, Virginia, the Triangle Universities Nuclear Laboratory at Duke University, the Bevalac and the SuperHILAC at Lawrence Berkeley Laboratory, the 88-Inch Cyclotron at Lawrence Berkeley Laboratory, the Clinton P. Anderson Meson Physics Facility at Los Alamos National Laboratory, the Bates Linear Accelerator Center at Massachusetts Institute of Technology, the Holifield Heavy Ion Research Facility at Oak Ridge National Laboratory, the Nuclear Physics Injector at Stanford Linear Accelerator Center, the Texas A and M Cyclotrons, the Tandem/Superconducting Booster Accelerator at the University of Washington and the Tandem Van de Graaff at the A.W. Wright Nuclear Structure Laboratory of Yale University. Included are acquisition cost, research programs, program accomplishments, future directions, and operating parameters of each facility

  16. Accelerators for America's Future

    Science.gov (United States)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  17. Diffusive Shock Acceleration and Reconnection Acceleration Processes

    Science.gov (United States)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; Le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.; Cummings, A.; Stone, E.; Decker, R.

    2015-12-01

    Shock waves, as shown by simulations and observations, can generate high levels of downstream vortical turbulence, including magnetic islands. We consider a combination of diffusive shock acceleration (DSA) and downstream magnetic-island-reconnection-related processes as an energization mechanism for charged particles. Observations of electron and ion distributions downstream of interplanetary shocks and the heliospheric termination shock (HTS) are frequently inconsistent with the predictions of classical DSA. We utilize a recently developed transport theory for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets. Particle energization associated with the anti-reconnection electric field, a consequence of magnetic island merging, and magnetic island contraction, are considered. For the former only, we find that (i) the spectrum is a hard power law in particle speed, and (ii) the downstream solution is constant. For downstream plasmoid contraction only, (i) the accelerated spectrum is a hard power law in particle speed; (ii) the particle intensity for a given energy peaks downstream of the shock, and the distance to the peak location increases with increasing particle energy, and (iii) the particle intensity amplification for a particular particle energy, f(x,c/{c}0)/f(0,c/{c}0), is not 1, as predicted by DSA, but increases with increasing particle energy. The general solution combines both the reconnection-induced electric field and plasmoid contraction. The observed energetic particle intensity profile observed by Voyager 2 downstream of the HTS appears to support a particle acceleration mechanism that combines both DSA and magnetic-island-reconnection-related processes.

  18. Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

    DEFF Research Database (Denmark)

    Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek;

    2009-01-01

    secretagogue GHRP-6) plus four nonpeptide agonists-the original benzolactam L-692,429 [3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5-yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamide], the spiroindoline sulfonamide MK-677 [N-[1(R)-1, 2-dihydro-1-ethanesulfonylspiro-3H...

  19. Problems of normative strenght and critique within the concept of agonistic participation: Towards the complementarity of agonistic and participatory democracy

    Directory of Open Access Journals (Sweden)

    Đorđević Biljana

    2014-01-01

    Full Text Available In this article I argue that there are grounds for considering agonistic democracy and participatory democracy complementarity in order to institutionalize agonism which has thus far lacked an elaborate articulation of its institutional dimension. The two democratic theories share a commitment toward widening the scope of the political as a way of inclusion of citizens and their subsequent political subjectivation and empowerment. Furthermore, there are authors on both sides who think democracy does not need foundations. Agonistic participation and contestation, on the one hand, and the broadening and strengthening of various sectors of political participation, on the other, both open up new possibilities for critique and change, but also create new risks. Building on a redefinition of agonisitic participation, I aim to attenuate an objection that agonism is normatively weak in terms of lacking resources to motivate citizens and justify their critique of practices of domination and oppression. The article concludes that we need to embrace agonistic participation as a means towards the development of democratic political judgement, as there are no other guarantees, i.e. secure foundations, for our ability to distinguish between democratic and non-democratic agon. [Projekat Ministarstva nauke Republike Srbije, br. 47026: Konstitucionalizam i vladavina prava u izgradnji nacionalne države - slučaj Srbije

  20. The treatment of Parkinson's disease with dopamine agonists

    Directory of Open Access Journals (Sweden)

    Frank, Wilhelm

    2008-06-01

    Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

  1. Small type accelerator. Try for accelerator driven system

    CERN Document Server

    Mori, Y

    2003-01-01

    FFAG (Fixed-field alternating gradient) accelerator for accelerator driven subcritical reactor, which aims to change from long-lived radioactive waste to short-lived radioactivity, is introduced. It is ring accelerator. The performance needed is proton as accelerator particle, 10MW (total) beam power, about 1GeV beam energy, >30% power efficiency and continuous beam. The feature of FFAG accelerator is constant magnetic field. PoP (Proof-of-principle)-FFAG accelerator, radial type, was run at first in Japan in 2000. The excursion is about some ten cm. In principle, beam can be injected and extracted at any place of ring. The 'multi-fish' acceleration can accelerate beams to 100% duty by repeating acceleration. 150MeV-FFAG accelerator has been started since 2001. It tried to practical use, for example, treatment of cancer. (S.Y.)

  2. The effects of agonists of ionotropic GABA(A) and metabotropic GABA(B) receptors on learning.

    Science.gov (United States)

    Zyablitseva, Evgeniya A; Kositsyn, Nikolay S; Shul'gina, Galina I

    2009-05-01

    The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABA(A) and metabotropic GABA(B) receptors and 2) gaboxadol a selective agonist of ionotropic GABA(A) receptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABA(B) receptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABA(A) and GABA(B) receptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes. PMID:19476215

  3. Accelerating nondiffracting beams

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Shaohui; Li, Manman; Yao, Baoli, E-mail: yaobl@opt.ac.cn; Yu, Xianghua; Lei, Ming; Dan, Dan; Yang, Yanlong; Min, Junwei; Peng, Tong

    2015-06-05

    We present a set of beams which combine the properties of accelerating beams and (conventional) diffraction-free beams. These beams can travel along a desired trajectory while keeping an approximately invariant transverse profile, which may be (higher-order) Bessel-, Mathieu- or parabolic-nondiffracting-like beams, depending on the initial complex amplitude distribution. A possible application of these beams presented here may be found in optical trapping field. For example, a higher-order Bessel-like beam, which has a hollow (transverse) pattern, is suitable for guiding low-refractive-index or metal particles along a curve. - Highlights: • A set of beams having arbitrary trajectories of accelerating and nondiffracting behaviors are generalized and presented. • Bessel-like accelerating beams are generalized to the higher-order (hollow) version. • Mathieu-like accelerating beams and parabolic-nondiffracting-like accelerating beams are presented. • A possible application of these beams may be found in optical trapping and guiding of particles.

  4. Dielectric laser accelerators

    Science.gov (United States)

    England, R. Joel; Noble, Robert J.; Bane, Karl; Dowell, David H.; Ng, Cho-Kuen; Spencer, James E.; Tantawi, Sami; Wu, Ziran; Byer, Robert L.; Peralta, Edgar; Soong, Ken; Chang, Chia-Ming; Montazeri, Behnam; Wolf, Stephen J.; Cowan, Benjamin; Dawson, Jay; Gai, Wei; Hommelhoff, Peter; Huang, Yen-Chieh; Jing, Chunguang; McGuinness, Christopher; Palmer, Robert B.; Naranjo, Brian; Rosenzweig, James; Travish, Gil; Mizrahi, Amit; Schachter, Levi; Sears, Christopher; Werner, Gregory R.; Yoder, Rodney B.

    2014-10-01

    The use of infrared lasers to power optical-scale lithographically fabricated particle accelerators is a developing area of research that has garnered increasing interest in recent years. The physics and technology of this approach is reviewed, which is referred to as dielectric laser acceleration (DLA). In the DLA scheme operating at typical laser pulse lengths of 0.1 to 1 ps, the laser damage fluences for robust dielectric materials correspond to peak surface electric fields in the GV /m regime. The corresponding accelerating field enhancement represents a potential reduction in active length of the accelerator between 1 and 2 orders of magnitude. Power sources for DLA-based accelerators (lasers) are less costly than microwave sources (klystrons) for equivalent average power levels due to wider availability and private sector investment. Because of the high laser-to-particle coupling efficiency, required pulse energies are consistent with tabletop microJoule class lasers. Combined with the very high (MHz) repetition rates these lasers can provide, the DLA approach appears promising for a variety of applications, including future high-energy physics colliders, compact light sources, and portable medical scanners and radiative therapy machines.

  5. Plasma-based accelerator structures

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Carl B.

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  6. Plasma-based accelerator structures

    International Nuclear Information System (INIS)

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas

  7. Infusions of alpha-2 noradrenergic agonists and antagonists into the amygdala: effects on kindling.

    Science.gov (United States)

    Pelletier, M R; Corcoran, M E

    1993-12-31

    We reported previously that activation of alpha-2 adrenoceptors with infusions of clonidine into the amygdala/pyriform region is sufficient to retard kindling. To characterize further the involvement in kindling of alpha-2 receptors in the amygdala/pyriform, we exposed rats to unilateral intraamygdaloid infusions of a variety of noradrenergic drugs followed by either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Infusions and electrical stimulation were administered once every 48 h. The prophylactic effects of clonidine were blocked by simultaneous infusion of idazoxan, an alpha-2 adrenergic antagonist, which suggests strongly that these effects were produced at an alpha-2 receptor. Intraamygdaloid infusions of xylazine, another alpha-2 agonist, also significantly retarded low-frequency kindling. Unexpectedly, intraamygdaloid infusions of the alpha-2 antagonists idazoxan, yohimbine, and SK&F 104856 failed to accelerate kindling. Infusion of the alpha-1 antagonist corynanthine also failed to affect kindling. We propose that the alpha-2 adrenoceptors in the amygdala/pyriform region contribute to the prophylactic effects of systemically administered clonidine and that the facilitation of kindling observed after systemic administration of alpha-2 antagonists may be due to blockade of alpha-2 adrenoceptors outside of the amygdala/pyriform region.

  8. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice.

    Science.gov (United States)

    Kitaoka, Kazuyoshi; Shimizu, Noriyuki; Ono, Koji; Chikahisa, Sachiko; Nakagomi, Madoka; Shudo, Koichi; Ishimura, Kazunori; Séi, Hiroyoshi; Yoshizaki, Kazuo

    2013-09-01

    The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8). Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aβ), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice; their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aβ levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway. PMID:23624141

  9. Superconducting accelerator magnet design

    International Nuclear Information System (INIS)

    Superconducting dipoles, quadrupoles and correction magnets are necessary to achieve the high magnetic fields required for big accelerators presently in construction or in the design phase. Different designs of superconducting accelerator magnets are described and the designs chosen at the big accelerator laboratories are presented. The most frequently used cosθ coil configuration is discussed in detail. Approaches for calculating the magnetic field quality including coil end fields are presented. Design details of the cables, coils, mechanical structures, yokes, helium vessels and cryostats including thermal radiation shields and support structures used in superconducting magnets are given. Necessary material properties are mentioned. Finally, the main results of magnetic field measurements and quench statistics are presented. (orig.)

  10. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut

    2007-01-01

    Particle Accelerator Physics is an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. Part I gathers the basic tools, recalling the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part II is an extensive primer in beam dynamics, followed in Part III by the introduction and description of the main beam parameters. Part IV is devoted to the treatment of perturbations in beam dynamics. Part V discusses the details of charged particle accleration. Part VI and Part VII introduce the more advanced topics of coupled beam dynamics and the description of very intense beams. Part VIII is an exhaustive treatment of radiation from accelerated charges and introduces important sources of coherent radiation such as synchrotrons and free-electron lasers. Part IX collects the appendices gathering useful mathematical and physical formulae, parameters and units. Solutions to many end-of-chapter problems are give...

  11. Superconducting Accelerator Magnets

    CERN Document Server

    Mess, K H; Wolff, S

    1996-01-01

    The main topic of the book are the superconducting dipole and quadrupole magnets needed in high-energy accelerators and storage rings for protons, antiprotons or heavy ions. The basic principles of low-temperature superconductivity are outlined with special emphasis on the effects which are relevant for accelerator magnets. Properties and fabrication methods of practical superconductors are described. Analytical methods for field calculation and multipole expansion are presented for coils without and with iron yoke. The effect of yoke saturation and geometric distortions on field quality is studied. Persistent magnetization currents in the superconductor and eddy currents the copper part of the cable are analyzed in detail and their influence on field quality and magnet performance is investigated. Superconductor stability, quench origins and propagation and magnet protection are addressed. Some important concepts of accelerator physics are introduced which are needed to appreciate the demanding requirements ...

  12. Uniform Acceleration in General Relativity

    CERN Document Server

    Friedman, Yaakov

    2016-01-01

    We extend de la Fuente and Romero's defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  13. Nuclear Physics accelerator facilities

    International Nuclear Information System (INIS)

    The Nuclear Physics program requires the existence and effective operation of large and complex accelerator facilities. These facilities provide the variety of projectile beams upon which virtually all experimental nuclear research depends. Their capability determine which experiments can be performed and which cannot. Seven existing accelerator facilities are operated by the Nuclear Physics program as national facilities. These are made available to all the Nation's scientists on the basis of scientific merit and technical feasibility of proposals. The national facilities are the Clinton P. Anderson Meson Physics Facility (LAMPF) at Los Alamos National Laboratory; the Bates Linear Accelerator Center at Massachusetts Institute of Technology; the Bevalac at Lawrence Berkeley Laboratory; the Tandem/AGS Heavy Ion Facility at Brookhaven National Laboratory; the ATLAS facility at Argonne National Laboratory; the 88-Inch Cyclotron at Lawrence Berkeley Laboratory; the Holifield Heavy Ion Research Facility at Oak Ridge National Laboratory. The Nuclear Physics Injector at the Stanford Linear Accelerator Center (SLAC) enables the SLAC facility to provide a limited amount of beam time for nuclear physics research on the same basis as the other national facilities. To complement the national facilities, the Nuclear Physics program supports on-campus accelerators at Duke University, Texas A and M University, the University of Washington, and Yale University. The facility at Duke University, called the Triangle Universities Nuclear Laboratory (TUNL), is jointly staffed by Duke University, North Carolina State University, and the University of North Carolina. These accelerators are operated primarily for the research use of the local university faculty, junior scientists, and graduate students

  14. Microelectromechanical acceleration-sensing apparatus

    Science.gov (United States)

    Lee, Robb M.; Shul, Randy J.; Polosky, Marc A.; Hoke, Darren A.; Vernon, George E.

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  15. Studies of accelerated compact toruses

    International Nuclear Information System (INIS)

    In an earlier publication we considered acceleration of plasma rings (Compact Torus). Several possible accelerator configurations were suggested and the possibility of focusing the accelerated rings was discussed. In this paper we consider one scheme, acceleration of a ring between coaxial electrodes by a B/sub theta/ field as in a coaxial rail-gun. If the electrodes are conical, a ring accelerated towards the apex of the cone undergoes self-similar compression (focusing) during acceleration. Because the allowable acceleration force, F/sub a/ = kappaU/sub m//R where (kappa -2, the accelerating distance for conical electrodes is considerably shortened over that required for coaxial electrodes. In either case, however, since the accelerating flux can expand as the ring moves, most of the accelerating field energy can be converted into kinetic energy of the ring leading to high efficiency

  16. Intermittent Sea Level Acceleration

    OpenAIRE

    Olivieri, M.; Istituto Nazionale di Geofisica e Vulcanologia, Sezione Bologna, Bologna, Italia; Spada, G.; Dipartimento di Scienze di Base e Fondamenti, Università di Urbino Carlo Bo, Urbino

    2013-01-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea{level acceleration for the last 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, con firm the existence of a global sea level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0:01 mm/yr2. However, di fferently from previous studies, we discuss how change points or ...

  17. Seismic surveying and accelerators

    International Nuclear Information System (INIS)

    The paper deals with an investigation into the impact of earth vibrations on charged particle beams in modern colliders. It is ascertained that the displacement of accelerator magnetic elements from the perfect position results in the excitation of betatron oscillations and distortion of particle orbit position. The results of experimental investigations into seismic noises are presented for ASR, SSC, DESY and KEK. The rms orbit displacement in accelerators is estimated relying on the law of earth diffusion motion, according to which the variance of relative displacements is proportional to the distance between these points and time of observation. 6 refs., 3 figs., 2 tabs

  18. High intensity hadron accelerators

    International Nuclear Information System (INIS)

    This rapporteur report consists mainly of two parts. Part I is an abridged review of the status of all High Intensity Hadron Accelerator projects in the world in semi-tabulated form for quick reference and comparison. Part II is a brief discussion of the salient features of the different technologies involved. The discussion is based mainly on my personal experiences and opinions, tempered, I hope, by the discussions I participated in in the various parallel sessions of the workshop. In addition, appended at the end is my evaluation and expression of the merits of high intensity hadron accelerators as research facilities for nuclear and particle physics

  19. Identification of human dopamine receptors agonists from Chinese herbs

    Institute of Scientific and Technical Information of China (English)

    Yi-lin ZHANG; Hai-qing ZHANG; Xiao-yu LIU; Shi-neng HUA; Lu-bing ZHOU; Jun YU; Xue-hai TAN

    2007-01-01

    Aim: To find human dopamine receptors, especially D1-like receptor specific ago-nists from Chinese herbs as potential antihypertension drug leads. Methods: Two D1-like receptor cell lines carrying a β-lactamase reporter gene, and a D2 receptor cell line coexpressing a promiscuous G protein G15 were constructed using HEK293 cells. A natural compound library made from fractionated samples of herbal ex-tracts was used for high-throughput screening (HTS) against one of the cell lines,HEK/D5R/CRE-blax. The interested hits were evaluated for their activities against various dopamine receptors. Results: Fourteen hits were identified from primary screening, of which 2 of the better hit samples, HD0522 and HD0059, were selected for further material and activity analysis, and to obtain 2 compounds that ap-peared as 2 single peaks in HPLC, HD0522H01 and HD0059H01. HD0059H01 could activate D1, D2, and D5 receptors, with EC50 values of 2.28 μg/mL, 0.85 μg/mL, and 1.41 μg/mL, respectively. HD0522H01 could only activate D1R and D5R with EC50 values of 2.95 μg/mL and 8.38 μg/mL. Conclusion: We established cell-based assays for 3 different human dopamine receptors and identified specific agonists HD0522H01 and HD0059H01 through HTS. The specific agonist to D1-like receptors, HD0522H01, may become a new natural product-based drug lead for antihypertension treatment.

  20. Agonist binding to high-affinity dopamine sites

    Energy Technology Data Exchange (ETDEWEB)

    Tedesco, J.L.

    1985-01-01

    The authors have characterized the dopamine D/sub 3/ site and its binding requirements. The dopamine D/sub 3/ site in calf caudate crude homogenate has a site density of 214-230 fmoles/mg. protein by both /sup 3/H-apomorphine (/sup 3/H-AOP) and /sup 3/H-dopamine (/sup 3/H-DA) Scatchard analysis of specific binding (SB). Stereospecific subsets of /sup 3/H-APO and /sup 3/H-DA sites were defined by the use of agonist and antagonist enantiomer-pairs as a rigorous test for D/sub 3/ site heterogeneity. IC/sub 50/ values for both /sup 3/H-APO and /sup 3/H-DA SB sites were assessed for 55 agonist ligands and an excellent correlation was obtained. The authors conclude that both /sup 3/H-ligands label the same D/sub 3/ site. The D/sub 3/ site affinities of 105 dopamine-agonist ligands, in particular 2-aminotetralins,, aporphines and flexible dopamine analogues were measured. Low D/sub 3/-site affinities of N-quaternary analogues confirm the need for a lone pair. Subadditivity of substituents' effects in semi-flexible DA analogues confirms their postulate that sidechain conformation is the critical determinant of affinity. They conclude that there are at least two high-affinity ligand conformations of the DA sidechain pharmacophore. These binding requirements are presented as two interface-Geometry tetrahedral models of the double H-bond interface between the D/sub 3/ site and the ideal ligand.

  1. AG-4:A NICOTINIC AGONIST ENDOWED WITH ANTIAMNESIC PROPERTIES

    OpenAIRE

    Ghelardini, C; Galeotti, N; Di Cesare Mannelli, L.; S. Dei; F. GUALTIERI; Bartolini, A.

    2000-01-01

    The effect of the nicotinic agonist AG-4 on memory processes was evaluated in the mouse passive avoidance test. AG-4 (100 mg per mouse icv) prevented amnesia induced by scopolamine (1.5 mg kg–1 ip), mecamylamine (20 mg kg–1 ip), and dihydro-b-erythroidine (10 mg per mouse icv). In the same experimental conditions, AG-4 (100 mg per mouse icv) also prevented baclofen (2 mg kg–1 ip), clonidine (0.125 mg kg–1 ip), and diphenhydramine (20 mg kg–1 ip) amnesia in mice. AG-4 exerted an an...

  2. Discovery of a potent and selective GPR120 agonist.

    Science.gov (United States)

    Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel; Milligan, Graeme; Ulven, Trond

    2012-05-10

    GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist.

  3. Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine.

    Science.gov (United States)

    Simeon, D; Hollander, E; Stein, D J; DeCaria, C; Cohen, L J; Saoud, J B; Islam, N; Hwang, M

    1995-09-29

    Sixty-seven subjects, including normal volunteers and patients with obsessive-compulsive disorder, social phobia, and borderline personality disorder, received ratings of depersonalization after double-blind, placebo-controlled challenges with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge with m-CPP induced depersonalization significantly more than did placebo. Subjects who became depersonalized did not differ in age, sex, or diagnosis from those who did not experience depersonalization. There was a significant correlation between the induction of depersonalization and increase in panic, but not nervousness, anxiety, sadness, depression, or drowsiness. This report suggests that serotonergic dysregulation may in part underlie depersonalization.

  4. Narrow SAR in odorant sensing Orco receptor agonists.

    Science.gov (United States)

    Romaine, Ian M; Taylor, Robert W; Saidu, Samsudeen P; Kim, Kwangho; Sulikowski, Gary A; Zwiebel, Laurence J; Waterson, Alex G

    2014-06-15

    The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure-activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a 'mix-and-match' strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification. PMID:24813736

  5. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

    Energy Technology Data Exchange (ETDEWEB)

    Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Parks, Derek J.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

  6. Discovery of potent and selective nonsteroidal indazolyl amide glucocorticoid receptor agonists.

    Science.gov (United States)

    Sheppeck, James E; Gilmore, John L; Xiao, Hai-Yun; Dhar, T G Murali; Nirschl, David; Doweyko, Arthur M; Sack, Jack S; Corbett, Martin J; Malley, Mary F; Gougoutas, Jack Z; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Dodd, John H; Nadler, Steven G; Somerville, John E; Barrish, Joel C

    2013-10-01

    Modification of a phenolic lead structure based on lessons learned from increasing the potency of steroidal glucocorticoid agonists lead to the discovery of exceptionally potent, nonsteroidal, indazole GR agonists. SAR was developed to achieve good selectivity against other nuclear hormone receptors with the ultimate goal of achieving a dissociated GR agonist as measured by human in vitro assays. The specific interactions by which this class of compounds inhibits GR was elucidated by solving an X-ray co-crystal structure. PMID:23953070

  7. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    OpenAIRE

    Cowen, P. J.; Grahame-Smith, D.G.; Green, A R; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-meth...

  8. SPS accelerating cavity

    CERN Multimedia

    1983-01-01

    See photo 8302397: View from the downstream end of one of the SPS accelerating cavities (200 MHz, travelling wave structure). See 7603195 and 8011289 for more details, 7411032 for the travelling wave structure, and also 8104138. Giacomo Primadei stands on the left.

  9. The CERN accelerator complex

    CERN Multimedia

    Haffner, Julie

    2013-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  10. Hamburg Accelerator Conference

    International Nuclear Information System (INIS)

    From 20-24 July, Hamburg welcomed the Fifteenth International Conference on High Energy Accelerators (HEACC). A natural highlight was the recent commissioning success of the HERA electron-proton collider at Hamburg's DESY Laboratory and its first high energy electron-proton collision data. This gave the meeting the feel of a family event celebrating a newborn

  11. The CERN accelerator complex

    CERN Multimedia

    Christiane Lefèvre

    2008-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  12. The CERN accelerator complex

    CERN Multimedia

    De Melis, Cinzia

    2016-01-01

    The LHC is the last ring (dark blue line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  13. The Bevalac accelerator

    International Nuclear Information System (INIS)

    Presented are the characteristics of the Bevatron and SuperHilac heavy ion accelerators in a very general manner. Some aspects of their application in the field of biological medicine and some of the interesting results obtained in experiments on nuclear physics are mentioned. (Author). 20 refs, 2 figs, 2 tabs

  14. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

      Introduction to accelerator physics This course will take place in Istanbul, Turkey, from 18 to 30 September 2016. It is now open for registration, and further information can be found here: http://cas.web.cern.ch/cas/Turkey-2016/Turkey-advert.html

  15. SPS accelerating cavity

    CERN Multimedia

    1980-01-01

    One of the SPS acceleration cavities (200 MHz, travelling wave structure). On the ceiling one sees the coaxial transmission line which feeds the power from the amplifier, located in a surface building above, to the upstream end of the cavity. See 7603195 for more details, 7411032 for the travelling wave structure, and also 8104138, 8302397.

  16. Accelerators in the sky

    International Nuclear Information System (INIS)

    The author surveys the large body of evidence showing that there are very efficient mechanisms capable of accelerating particles to high energies under very different astrophysical conditions. The circumstances whereby huge amounts of relativistic and ultrarelativistic particles such as one finds in a) cosmic rays, b) supernova remnants and c) radio galaxies and quasars are produced are considered. (Auth.)

  17. Prospects for Accelerator Technology

    Science.gov (United States)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  18. Heavy ion accelerator GANIL

    International Nuclear Information System (INIS)

    This article presents GANIL, a large national heavy ion accelerator. The broad problems of nuclear physics, atomic physics, astrophysics and physics of condensed media which can be approached and studied with this machine are discussed first, after which the final construction project is described. The project comprises a circular injector, a separated sector cyclotron up beam stripper, and a second separated cyclotron downstream

  19. Superconducting traveling wave accelerators

    International Nuclear Information System (INIS)

    This note considers the applicability of superconductivity to traveling wave accelerators. Unlike CW operation of a superconducting standing wave or circulating wave accelerator section, which requires improvement factors (superconductor conductivity divided by copper conductivity) of about 106 in order to be of practical use, a SUperconducting TRaveling wave Accelerator, SUTRA, operating in the pulsed mode requires improvement factors as low as about 103, which are attainable with niobium or lead at 4.2K, the temperature of liquid helium at atmospheric pressure. Changing from a copper traveling wave accelerator to SUTRA achieves the following. (1) For a given gradient SUTRA reduces the peak and average power requirements typically by a factor of 2. (2) SUTRA reduces the peak power still further because it enables us to increase the filling time and thus trade pulse width for gradient. (3) SUTRA makes possible a reasonably long section at higher frequencies. (4) SUTRA makes possible recirculation without additional rf average power. 8 references, 6 figures, 1 table

  20. SPS accelerating cavity

    CERN Multimedia

    CERN PhotoLab

    1981-01-01

    One of the SPS accelerating cavities (200 MHz, travelling wave structure). The power that is fed into the upstream end of the cavity is extracted at the downstream end and sent into a dump load. See 7603195 for more details, 7411032 for the travelling wave structure, and also 8011289, 8302397.

  1. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

    Introduction to accelerator physics This course will take place in Budapest, Hungary, from 2 to 14 October 2016. It is now open for registration and further information can be found at: http://cas.web.cern.ch/cas/Hungary2016/Hungary-advert.html and http://indico.cern.ch/event/532397/.

  2. Menopause accelerates biological aging.

    Science.gov (United States)

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  3. Long-acting beta(2)-agonists in management of childhood asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

  4. Structure and function of an irreversible agonist-β(2) adrenoceptor complex

    DEFF Research Database (Denmark)

    Rosenbaum, Daniel M; Zhang, Cheng; Lyons, Joseph A;

    2011-01-01

    G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs, the molecular basis for agonist binding...... and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered...

  5. Dopamine agonist-induced substance addiction: the next piece of the puzzle.

    Science.gov (United States)

    Evans, Andrew

    2011-02-01

    Traditional antiparkinson treatment strategies strive to balance the antiparkinson effects of dopaminergic drugs with the avoidance of motor response complications. Dopamine agonists have an established role in delaying the emergence of motor response complications or reducing motor "off" periods. The recent recognition of a range of "behavioural addictions" that are linked to dopamine agonist use has highlighted the role of dopamine in brain reward function and addiction disorders in general. Dopamine agonists have now even been linked occasionally to new substance addictions. The challenge now for the Parkinsonologist is to also balance the net benefits of using dopamine agonists for their motor effects with avoiding the harm from behavioural compulsions. PMID:20980151

  6. Structural complexes of the agonist, inverse agonist and antagonist bound C5a receptor: insights into pharmacology and signaling.

    Science.gov (United States)

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-04-26

    The C5a receptor (C5aR) is a pharmacologically important G-protein coupled receptor (GPCR) that interacts with (h)C5a, by recruiting both the "orthosteric" sites (site1 at the N-terminus and site2 at the ECS, extra cellular surface) on C5aR in a two site-binding model. However, the complex pharmacological landscape and the distinguishing chemistry operating either at the "orthosteric" site1 or at the functionally important "orthosteric" site2 of C5aR are still not clear, which greatly limits the understanding of C5aR pharmacology. One of the major bottlenecks is the lack of an experimental structure or a refined model structure of C5aR with appropriately defined active sites. The study attempts to understand the pharmacology at the "orthosteric" site2 of C5aR rationally by generating a highly refined full-blown model structure of C5aR through advanced molecular modeling techniques, and further subjecting it to automated docking and molecular dynamics (MD) studies in the POPC bilayer. The first series of structural complexes of C5aR respectively bound to a linear native peptide agonist ((h)C5a-CT), a small molecule inverse agonist (NDT) and a cyclic peptide antagonist (PMX53) are reported, apparently establishing the unique pharmacological landscape of the "orthosteric" site2, which also illustrates an energetically distinct but coherent competitive chemistry ("cation-π" vs. "π-π" interactions) involved in distinguishing the established ligands known for targeting the "orthosteric" site2 of C5aR. Over a total of 1 μs molecular dynamics (MD) simulation in the POPC bilayer, it is evidenced that while the agonist prefers a "cation-π" interaction, the inverse agonist prefers a "cogwheel/L-shaped" interaction in contrast to the "edge-to-face/T-shaped" type π-π interactions demonstrated by the antagonist by engaging the F275(7.28) of the C5aR. In the absence of a NMR or crystallographically guided model structure of C5aR, the computational model complexes not only

  7. Toll-Like Receptor 9 Agonists for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Davide Melisi

    2014-08-01

    Full Text Available The immune system has acquired increasing importance as a key player in cancer maintenance and growth. Thus, modulating anti-tumor immune mediators has become an attractive strategy for cancer treatment. Toll-like receptors (TLRs have gradually emerged as potential targets of newer immunotherapies. TLR-9 is preferentially expressed on endosome membranes of B-cells and plasmacytoid dendritic cells (pDC and is known for its ability to stimulate specific immune reactions through the activation of inflammation-like innate responses. Several synthetic CpG oligonucleotides (ODNs have been developed as TLR-9 agonists with the aim of enhancing cancer immune surveillance. In many preclinical models, CpG ODNs were found to suppress tumor growth and proliferation both in monotherapy and in addition to chemotherapies or target therapies. TLR-9 agonists have been also tested in several clinical trials in patients with solid tumors. These agents showed good tolerability and usually met activity endpoints in early phase trials. However, they have not yet been demonstrated to significantly impact survival, neither as single agent treatments, nor in combination with chemotherapies or cancer vaccines. Further investigations in larger prospective studies are required.

  8. Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

    Science.gov (United States)

    Galle-Treger, Lauriane; Suzuki, Yuzo; Patel, Nisheel; Sankaranarayanan, Ishwarya; Aron, Jennifer L.; Maazi, Hadi; Chen, Lin; Akbari, Omid

    2016-01-01

    Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β. Additionally, the specific α7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that α7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma. PMID:27752043

  9. Cariprazine:New dopamine biased agonist for neuropsychiatric disorders.

    Science.gov (United States)

    De Deurwaerdère, P

    2016-02-01

    Cariprazine (RGH-188, MP-214, Vraylar[TM]) is a new dopamine receptor ligand developed for the treatment of several neuropsychiatric diseases including schizophrenia and bipolar disorders. Cariprazine displays higher affinity at dopamine D3 receptors and a similar affinity at D2 and 5-HT2B receptors. At variance with some atypical antipsychotics, its affinity at 5-HT1A, 5-HT2A and histamine H1 receptors is modest compared with its three main targets. Cariprazine could correspond to a biased agonist at dopamine receptors, displaying either antagonist or partial agonist properties depending on the signaling pathways linked to D2/D3 receptors. The compound crosses the blood-brain barrier, as revealed by positron emission tomography and pharmacokinetic studies in various species. Two main metabolites result mainly from the activity of CYP34A and display properties similar to those of the parent drug. Behavioral data report that cariprazine is efficacious in animal models addressing positive, negative and cognitive symptoms of schizophrenia with no extrapyramidal side effects. In September 2015, the FDA approved the use of cariprazine for the treatment of schizophrenia and type I bipolar disorder. The efficacy of cariprazine in other neuropsychiatric diseases is currently being evaluated in preclinical and clinical studies. Side effects have been observed in humans, including extrapyramidal side effects and akathisia of mild to moderate intensity. PMID:27092339

  10. How does agonistic behaviour differ in albino and pigmented fish?

    Science.gov (United States)

    Horký, Pavel; Wackermannová, Marie

    2016-01-01

    In addition to hypopigmentation of the skin and red iris colouration, albino animals also display distinct physiological and behavioural alterations. However, information on the social interactions of albino animals is rare and has mostly been limited to specially bred strains of albino rodents and animals from unique environments in caves. Differentiating between the effects of albinism and domestication on behaviour in rodents can be difficult, and social behaviour in cave fish changes according to species-specific adaptations to conditions of permanent darkness. The agonistic behaviours of albino offspring of pigmented parents have yet to be described. In this study, we observed agonistic behaviour in albino and pigmented juvenile Silurus glanis catfish. We found that the total number of aggressive interactions was lower in albinos than in pigmented catfish. The distance between conspecifics was also analysed, and albinos showed a tendency towards greater separation from their same-coloured conspecifics compared with pigmented catfish. These results demonstrate that albinism can be associated with lower aggressiveness and with reduced shoaling behaviour preference, as demonstrated by a tendency towards greater separation of albinos from conspecifics. PMID:27114883

  11. Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

    Science.gov (United States)

    Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

    2010-01-01

    For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists. PMID:19832688

  12. Accelerator mass spectrometry programme at Mumbai pelletron accelerator facility

    International Nuclear Information System (INIS)

    The Accelerator Mass Spectrometry (AMS) programme and the related developments based on the Mumbai Pelletron accelerator are described. The initial results of the measurement of the ratio, 36Cl / Cl in water samples are presented. (author)

  13. Accelerator research studies

    International Nuclear Information System (INIS)

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under contract number AC05-85ER40216-8, is currently in the third year of its three-year funding cycle. This Renewal Proposal requests DOE support for the next three-year period from June 1, 1991 to May 31, 1994. It documents the progress made during the past year and outlines the proposed research program for the next three years. The program consisted of the following three tasks: Task A, ''Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams,'' Task B, ''Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams,'' Task C, ''Study of a Gyroklystron High-Power Microwave Source for Linear Colliders.'' These tasks will be discussed in this paper

  14. Accelerator research studies

    International Nuclear Information System (INIS)

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the first year of a three-year funding cycle. The program consists of the following three tasks: TASK A, Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams, TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams; TASK C, Study of a Gyroklystron High-power Microwave Source for Linear Colliders. In this report we document the progress that has been made during the past year for each of the three tasks

  15. Accelerated Parallel Texture Optimization

    Institute of Scientific and Technical Information of China (English)

    Hao-Da Huang; Xin Tong; Wen-Cheng Wang

    2007-01-01

    Texture optimization is a texture synthesis method that can efficiently reproduce various features of exemplar textures. However, its slow synthesis speed limits its usage in many interactive or real time applications. In this paper, we propose a parallel texture optimization algorithm to run on GPUs. In our algorithm, k-coherence search and principle component analysis (PCA) are used for hardware acceleration, and two acceleration techniques are further developed to speed up our GPU-based texture optimization. With a reasonable precomputation cost, the online synthesis speed of our algorithm is 4000+ times faster than that of the original texture optimization algorithm and thus our algorithm is capable of interactive applications. The advantages of the new scheme are demonstrated by applying it to interactive editing of flow-guided synthesis.

  16. Hardware Accelerated Simulated Radiography

    Energy Technology Data Exchange (ETDEWEB)

    Laney, D; Callahan, S; Max, N; Silva, C; Langer, S; Frank, R

    2005-04-12

    We present the application of hardware accelerated volume rendering algorithms to the simulation of radiographs as an aid to scientists designing experiments, validating simulation codes, and understanding experimental data. The techniques presented take advantage of 32 bit floating point texture capabilities to obtain validated solutions to the radiative transport equation for X-rays. An unsorted hexahedron projection algorithm is presented for curvilinear hexahedra that produces simulated radiographs in the absorption-only regime. A sorted tetrahedral projection algorithm is presented that simulates radiographs of emissive materials. We apply the tetrahedral projection algorithm to the simulation of experimental diagnostics for inertial confinement fusion experiments on a laser at the University of Rochester. We show that the hardware accelerated solution is faster than the current technique used by scientists.

  17. Accelerating QDP++ using GPUs

    CERN Document Server

    Winter, Frank

    2011-01-01

    Graphic Processing Units (GPUs) are getting increasingly important as target architectures in scientific High Performance Computing (HPC). NVIDIA established CUDA as a parallel computing architecture controlling and making use of the compute power of GPUs. CUDA provides sufficient support for C++ language elements to enable the Expression Template (ET) technique in the device memory domain. QDP++ is a C++ vector class library suited for quantum field theory which provides vector data types and expressions and forms the basis of the lattice QCD software suite Chroma. In this work accelerating QDP++ expression evaluation to a GPU was successfully implemented leveraging the ET technique and using Just-In-Time (JIT) compilation. The Portable Expression Template Engine (PETE) and the C API for CUDA kernel arguments were used to build the bridge between host and device memory domains. This provides the possibility to accelerate Chroma routines to a GPU which are typically not subject to special optimisation. As an ...

  18. Accelerator research studies

    International Nuclear Information System (INIS)

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the second year of a three-year funding cycle. The program consists of the following three tasks: TASK A, ''Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams,'' (P.I., M. Reiser); TASK B, ''Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams,'' (Co-P.I.'s, W.W. Destler, M. Reiser, M.J. Rhee, and C.D. Striffler); TASK C, ''Study of a Gyroklystron High-Power Microwave Source for Linear Colliders,'' (Co-P.I.'s, V.L. Granatstein, W. Lawson, M. Reiser, and C.D. Striffler). In this report we document the progress that has been made during the past year for each of the three tasks

  19. accelerating cavity from LEP

    CERN Multimedia

    This is an accelerating cavity from LEP, with a layer of niobium on the inside. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment. These challenging requirements pushed European industry to new achievements. 256 of these cavities are now used in LEP to double the energy of the particle beams.

  20. Accelerator research studies

    International Nuclear Information System (INIS)

    This progress report for the Accelerator Research Studies program at the University of Maryland covers the second year (June 1, 1989 to May 31, 1990) of the current three-year contract period from June 1, 1988 to May 31, 1991, funded by the Department of Energy under Contract No. AC05-85ER40216. The research program is divided into three separate tasks, as follows: the study of Transport and Longitudinal Compression of Intense, High-Brightness Beams; the study of Collective Ion Acceleration by Intense Electron Beams and Pulse-Powered Plasma Focus; the study of Microwave Sources and Parameter Scaling for High-Frequency Linacs. This report consists of three sections in which the progress for each task is documented separately. An introduction and synopsis is presented at the beginning of the progress report for each task

  1. NEW ACCELERATION METHODS

    Energy Technology Data Exchange (ETDEWEB)

    Sessler, A.M.

    1984-07-01

    But a glance at the Livingston chart, Fig. 1, of accelerator particle energy as a function of time shows that the energy has steadily, exponentially, increased. Equally significant is the fact that this increase is the envelope of diverse technologies. If one is to stay on, or even near, the Livingston curve in future years then new acceleration techniques need to be developed. What are the new acceleration methods? In these two lectures I would like to sketch some of these new ideas. I am well aware that they will probably not result in high energy accelerators within this or the next decade, but conversely, it is likely that these ideas will form the basis for the accelerators of the next century. Anyway, the ideas are stimulating and suffice to show that accelerator physicists are not just 'engineers', but genuine scientists deserving to be welcomed into the company of high energy physicists. I believe that outsiders will find this field surprisingly fertile and, certainly fun. To put it more personally, I very much enjoy working in this field and lecturing on it. There are a number of review articles which should be consulted for references to the original literature. In addition there are three books on the subject. Given this material, I feel free to not completely reference the material in the remainder of this article; consultation of the review articles and books will be adequate as an introduction to the literature for references abound (hundreds are given). At last, by way of introduction, I should like to quote from the end of Ref. 2 for I think the remarks made there are most germane. Remember that the talk was addressed to accelerator physicists: 'Finally, it is often said, I think by physicists who are not well-informed, that accelerator builders have used up their capital and now are bereft of ideas, and as a result, high energy physics will eventually--rather soon, in fact--come to a halt. After all, one can't build too many

  2. RFQ accelerator development

    International Nuclear Information System (INIS)

    Radio frequency quadrupole (RFQ) accelerators have established themselves as highly efficient and potential tools for delivering intense beams of the order of 100 mA or more. They are being employed as injectors to high energy machines used for basic sciences, spallation neutron sources, fusion devices and accelerator breeders. They have also made their mark as neutron generators, ion implanters, x-ray generators, etc. Realising the importance of this programme, Bhabha Atomic Research Centre initiated a totally indigenous effort to develop RFQs for the light as well as heavy ion beams. A low power RFQ for the proton and deuteron beams is already in the final phase of commissioning. (author). 30 refs., 14 figs., 2 tabs

  3. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut

    2015-01-01

    This book by Helmut Wiedemann is a well-established, classic text, providing an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. The present 4th edition has been significantly revised, updated and expanded. The newly conceived Part I is an elementary introduction to the subject matter for undergraduate students. Part II gathers the basic tools in preparation of a more advanced treatment, summarizing the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part III is an extensive primer in beam dynamics, followed, in Part IV, by an introduction and description of the main beam parameters and including a new chapter on beam emittance and lattice design. Part V is devoted to the treatment of perturbations in beam dynamics. Part VI then discusses the details of charged particle acceleration. Parts VII and VIII introduce the more advanced topics of coupled beam dynamics and describe very intense bea...

  4. Accelerators for Cancer Therapy

    Science.gov (United States)

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  5. Particle acceleration by pulsars

    International Nuclear Information System (INIS)

    The evidence that pulsars accelerate relativistic particles is reviewed, with emphasis on the γ-ray observations. The current state of knowledge of acceleration in strong waves is summarized, with emphasis on the inability of consistent theories to accelerate very high energy particles without converting too much energy into high energy photons. The state of viable models for pair creation by pulsars is summarized, with the conclusion that pulsars very likely lose rotational energy in winds instead of in superluminous strong waves. The relation of the pair creation models to γ-ray observations and to soft X-ray observations of pulsars is outlined, with the conclusion that energetically viable models may exist, but none have yet yielded useful agreement with the extant data. Some paths for overcoming present problems are discussed. The relation of the favored models to cosmic rays is discussed. It is pointed out that the pairs made by the models may have observable consequences for observation of positrons in the local cosmic ray flux and for observations of the 511 keV line from the interstellar medium. Another new point is that asymmetry of plasma supply from at least one of the models may qualitatively explain the gross asymmetry of the X-ray emission from the Crab nebula. It is also argued that acceleration of cosmic ray nuclei by pulsars, while energetically possible, can occur only at the boundary of the bubbles blown by the pulsars, if the cosmic ray composition is to be anything like that of the known source spectrum

  6. GPU accelerated face detection

    OpenAIRE

    Mäkelä, J.

    2013-01-01

    Graphics processing units have massive parallel processing capabilities, and there is a growing interest in utilizing them for generic computing. One area of interest is computationally heavy computer vision algorithms, such as face detection and recognition. Face detection is used in a variety of applications, for example the autofocus on cameras, face and emotion recognition, and access control. In this thesis, the face detection algorithm was accelerated with GPU using OpenCL. The goal was...

  7. Accelerator Experiments for Astrophysics

    OpenAIRE

    Ng, Johnny S. T.

    2003-01-01

    Many recent discoveries in astrophysics involve phenomena that are highly complex. Carefully designed experiments, together with sophisticated computer simulations, are required to gain insights into the underlying physics. We show that particle accelerators are unique tools in this area of research, by providing precision calibration data and by creating extreme experimental conditions relevant for astrophysics. In this paper we discuss laboratory experiments that can be carried out at the S...

  8. Compact pulsed accelerator

    International Nuclear Information System (INIS)

    The formation of fast pulses from a current charged transmission line and opening switch is described. By employing a plasma focus as an opening switch and diode in the prototype device, a proton beam of peak energy 250 keV is produced. The time integrated energy spectrum of the beam is constructed from a Thomson spectrograph. Applications of this device as an inexpensive and portable charged particle accelerator are discussed. 7 refs., 5 figs., 1 tab

  9. Laser plasma accelerators

    OpenAIRE

    Malka, V.

    2012-01-01

    Research activities on laser plasma accelerators are paved by many significant breakthroughs. This review article provides an opportunity to show the incredible evolution of this field of research which has, in record time, allowed physicists to produce high quality electron beams at the GeV level using compact laser systems. I will show the scientific path that led us to explore different injection schemes and to produce stable, high peak current and high quality electron beams with control ...

  10. LEP copper accelerating cavities

    CERN Multimedia

    Laurent Guiraud

    1999-01-01

    These copper cavities were used to generate the radio frequency electric field that was used to accelerate electrons and positrons around the 27-km Large Electron-Positron (LEP) collider at CERN, which ran from 1989 to 2000. The copper cavities were gradually replaced from 1996 with new superconducting cavities allowing the collision energy to rise from 90 GeV to 200 GeV by mid-1999.

  11. Accelerated plate tectonics.

    Science.gov (United States)

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  12. Future Accelerator Magnet Needs

    CERN Document Server

    Devred, Arnaud; Yamamoto, A

    2005-01-01

    Superconducting magnet technology is continually evolving in order to meet the demanding needs of new accelerators and to provide necessary upgrades for existing machines. A variety of designs are now under development, including high fields and gradients, rapid cycling and novel coil configurations. This paper presents a summary of R&D programs in the EU, Japan and the USA. A performance comparison between NbTi and Nb3Sn along with fabrication and cost issues are also discussed.

  13. Shock accelerated vortex ring

    CERN Document Server

    Haehn, N; Oakley, J; Anderson, M; Rothamer, D; Bonazza, R

    2009-01-01

    The interaction of a shock wave with a spherical density inhomogeneity leads to the development of a vortex ring through the impulsive deposition of baroclinic vorticity. The present fluid dynamics videos display this phenomenon and were experimentally investigated at the Wisconsin Shock Tube Laboratory's (WiSTL) 9.2 m, downward firing shock tube. The tube has a square internal cross-section (0.25 m x 0.25 m) with multiple fused silica windows for optical access. The spherical soap bubble is generated by means of a pneumatically retracted injector and released into free-fall 200 ms prior to initial shock acceleration. The downward moving, M = 2.07 shock wave impulsively accelerates the bubble and reflects off the tube end wall. The reflected shock wave re-accelerates the bubble (reshock), which has now developed into a vortex ring, depositing additional vorticity. In the absence of any flow disturbances, the flow behind the reflected shock wave is stationary. As a result, any observed motion of the vortex rin...

  14. Accelerated Profile HMM Searches.

    Directory of Open Access Journals (Sweden)

    Sean R Eddy

    2011-10-01

    Full Text Available Profile hidden Markov models (profile HMMs and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches.

  15. Optimizing accelerator technology

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    A new EU-funded research and training network, oPAC, is bringing together 22 universities, research centres and industry partners to optimize particle accelerator technology. CERN is one of the network’s main partners and will host 5 early-stage researchers in the BE department.   A diamond detector that will be used for novel beam diagnostics applications in the oPAC project based at CIVIDEC. (Image courtesy of CIVIDEC.) As one of the largest Marie Curie Initial Training Networks ever funded by the EU – to the tune of €6 million – oPAC extends well beyond the particle physics community. “Accelerator physics has become integral to research in almost every scientific discipline – be it biology and life science, medicine, geology and material science, or fundamental physics,” explains Carsten P. Welsch, oPAC co-ordinator based at the University of Liverpool. “By optimizing the operation of accelerators, all of these...

  16. Accelerated GLAS exposure station

    International Nuclear Information System (INIS)

    The Geoscience Laser Altimeter System (GLAS) is being developed by NASA/GSFC to measure the dynamics of the ice sheet mass balance, land, and cloud and atmospheric properties. An instrument altimetric resolution of 10 cm per shot is required. The laser transmitter will be a diode pumped, Q-switched, Nd:YAG laser producing 1064 nm, 100 mJ, 4 ns pulses at 40 Hz repetition rate in a TEM∞ mode. A minimum lifetime goal of 2 billion shots is required per laser transmitter. The performance of the GLAS laser can be limited by physical damage to the optical components caused by the interaction of intense laser energy with the optical coatings and substrates. Very little data exists describing the effects of long duration laser exposure, of 4 ns pulses, on an optical component. An Accelerated GLAS Exposure Station (AGES) is being developed which will autonomously operate and monitor the GLAS laser at an accelerated rate of 500 Hz. The effects of a large number of laser shots will be recorded. Parameters to be monitored include: laser power, pulsewidth, beam size, laser diode drive current and power, Q-switch drive voltage, temperature, and humidity. For comparison, one set of AGES-sister optical components will be used in the non-accelerated GLAS laser and another will be evaluated by a commercial optical damage test facility

  17. Linac transport and acceleration

    International Nuclear Information System (INIS)

    The acceleration of intense bunches maintaining high brightness is limited both by single-particle effects, e.g., misalignments, injection errors, and rf-steering, and collective phenomena, where the effects of the longitudinal and transverse wakefield on particles within a single bunch are the most severe. The working group has considered both problems and potentials of linac acceleration from ∼50 MeV to 1 GeV for free electron laser (FEL) applications, as well as from a few Gev to 1 TeV for linear colliders. The outlook for free electron lasers is bright: no fundamental problems seem to arise in the acceleration of peak currents in excess of 100 A with small emittance and low momentum spread. The situation of linear colliders is more complex and more difficult. Two examples, one operating at 11.4 GHz, the other at 30 GHz, are used to illustrate some of the difficulties and the exceedingly tight tolerances required. Both examples are based on round beams, and thus neither benefit from the advantages of flat beams nor address the increased care required in transporting beams of very small emittance in one plane. The working group acknowledges, but did not explore, promising concepts for colliders based on RF superconductivity

  18. Acceleration during magnetic reconnection

    Energy Technology Data Exchange (ETDEWEB)

    Beresnyak, Andrey [Los Alamos National Laboratory; Li, Hui [Los Alamos National Laboratory

    2015-07-16

    The presentation begins with colorful depictions of solar x-ray flares and references to pulsar phenomena. Plasma reconnection is complex, could be x-point dominated or turbulent, field lines could break due to either resistivity or non-ideal effects, such as electron pressure anisotropy. Electron acceleration is sometimes observed, and sometimes not. One way to study this complex problem is to have many examples of the process (reconnection) and compare them; the other way is to simplify and come to something robust. Ideal MHD (E=0) turbulence driven by magnetic energy is assumed, and the first-order acceleration is sought. It is found that dissipation in big (length >100 ion skin depths) current sheets is universal and independent on microscopic resistivity and the mean imposed field; particles are regularly accelerated while experiencing curvature drift in flows driven by magnetic tension. One example of such flow is spontaneous reconnection. This explains hot electrons with a power-law tail in solar flares, as well as ultrashort time variability in some astrophysical sources.

  19. Laser driven particle acceleration

    International Nuclear Information System (INIS)

    This dissertation summarizes the last ten years of research at the Laboratory of Applied Optics on laser-plasma based electron acceleration. The main result consists of the development and study of a relativistic electron source with unique properties: high energy (100-300 MeV) in short distances (few millimeters), mono-energetic, ultra-short (few fs), stable and tunable. The manuscript describes the steps that led to understanding the physics, and then mastering it in order to produce this new electron source. Non linear propagation of the laser pulse in the plasma is first presented, with phenomena such as non linear wakefield excitation, relativistic and ponderomotive self-focusing in the short pulse regime, self-compression. Acceleration and injection of electrons are then reviewed from a theoretical perspective. Experimental demonstrations of self-injection in the bubble regime and then colliding pulse injection are then presented. These experiments were among the first to produce monoenergetic, high quality, stable and tunable electron beams from a laser-plasma accelerator. The last two chapters are dedicated to the characterization of the electron beam using transition radiation and to its applications to gamma radiography and radiotherapy. Finally, the perspectives of this research are presented in the conclusion. Scaling laws are used to determine the parameters that the electron beams will reach using peta-watt laser systems currently under construction. (author)

  20. Berkeley Proton Linear Accelerator

    Science.gov (United States)

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  1. CESR Test Accelerator

    CERN Document Server

    Rubin, David L

    2013-01-01

    The Cornell Electron Storage Ring (CESR) was reconfigured in 2008 as a test accelerator to investigate the physics of ultra-low emittance damping rings. During the approximately 40 days/year available for dedicated operation as a test accelerator, specialized instrumentation is used to measure growth and mitigation of the electron cloud, emittance growth due to electron cloud, intra-beam scattering, and ions, and single and multi-bunch instabilities generated by collective effects. The flexibility of the CESR guide field optics and the integration of accelerator modeling codes with the control system have made possible an extraordinary range of experiments. Findings at CesrTA with respect to electron cloud effects, emittance tuning techniques, and beam instrumentation for measuring electron cloud, beam sizes, and beam positions are the basis for much of the design of the ILC damping rings as documented in the ILC-Technical Design Report. The program has allowed the Cornell group to cultivate the kind of talen...

  2. Laser-driven electron accelerators

    International Nuclear Information System (INIS)

    The following possibilities are discussed: inverse free electron laser (wiggler accelerator); inverse Cerenkov effect; plasma accelerator; dielectric tube; and grating linac. Of these, the grating acceleraton is considered the most attractive alternative

  3. Electron accelerators for environmental protection

    International Nuclear Information System (INIS)

    The primary objective of this publication is to provide information suitable for electron accelerators implementation in facilities applying radiation technology for environmental protection. It should be noticed that radiation processing has been successfully used in the fields of crosslinking polymer curing and medical products sterilization for more than 40 years. Practical application of radiation technology today extends on SO2 and NOx removal from the flue gas (one of major power intensive radiation processing), destruction and removal of organic chemicals from water, decreasing bacteria content in the irradiated sludge and waste water. On the other hand the increased awareness of environmental pollution hazards and more stringent waste regulations in many countries may open stronger support for environmentally oriented technologies. This publication provides an evaluation of electron accelerators capabilities in respect of environmental applications where technological and economical criteria are now well defined. In order to determine the potential of electron accelerators, the literature data were examined as well visits and meetings with various accelerator manufacturers were performed by the author. Experience of the author in accelerator facilities construction and exploitation including those which were used for environmental protection are significant part of this publication. The principle of accelerator action was described in Chapter 1. Early development, accelerator classification and fields of accelerators application were included to this chapter as well. Details of accelerator construction was described in Chapter 2 to illustrate physical capability of accelerators to perform the function of ionizing radiation source. Electron beam extraction devices, under beam equipment, electron beam parameters and measuring methods were characterized in this chapter as well. Present studies of accelerator technology was described in Chapter 3, where direct

  4. Accelerating in de Sitter spacetimes

    CERN Document Server

    Cotaescu, Ion I

    2014-01-01

    We propose a definition of uniform accelerated frames in de Sitter spacetimes exploiting the Nachtmann group theoretical method of introducing coordinates on these manifolds. Requiring the transformation between the static frame and the accelerated one to depend continuously on acceleration in order to recover the well-known Rindler approach in the flat limit, we obtain a result with a reasonable physical meaning.

  5. Concerns with beta2-agonists in pediatric asthma - a clinical perspective

    NARCIS (Netherlands)

    Kersten, Elin T G; Koppelman, Gerard H; Thio, Bernard J

    2016-01-01

    Beta2-adrenoreceptor agonists (β2-agonists) are extensively used in the treatment of childhood asthma. However, there have been concerns regarding their adverse effects and safety. In 2005, the FDA commissioned a "Black Box Warning" communicating the potential for an increased risk for serious asthm

  6. Major drawbacks and additional benefits of agonist trigger--not ovarian hyperstimulation syndrome related

    DEFF Research Database (Denmark)

    Shapiro, Bruce S; Andersen, Claus Yding

    2015-01-01

    . The agonist trigger might alter other paradigms as well, such as making oocyte donation more efficient per stimulation by virtually eliminating follicular-phase cycle cancellation, coasting, and premature triggering. There are both corresponding potential benefits and drawbacks of using the agonist trigger...

  7. Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

    Directory of Open Access Journals (Sweden)

    Min Gao

    Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

  8. Synthesis of urea acetates as potential PPARα/γ,dual agonists

    Institute of Scientific and Technical Information of China (English)

    Chang Yan Zhao; Chang Qing Shi; Yuan Wei Chen

    2008-01-01

    In the quest for novel PPARα/γ dual agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia,we designed and synthesized a series of urea acetates as potential PPARα/γ dual agonists.The structure of the target compounds,intermediates were characterized by 1H NMR,HRMS.

  9. The dopamine D1 receptor agonist SKF-82958 effectively increases eye blinking count in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Kiyoshi, Akihiko; Murai, Takeshi; Nakako, Tomokazu; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Ogi, Yuji; Ikeda, Kazuhito

    2016-03-01

    Eye blinking is a spontaneous behavior observed in all mammals, and has been used as a well-established clinical indicator for dopamine production in neuropsychiatric disorders, including Parkinson's disease and Tourette syndrome [1,2]. Pharmacological studies in humans and non-human primates have shown that dopamine agonists/antagonists increase/decrease eye blinking rate. Common marmosets (Callithrix jacchus) have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field due to their more developed prefrontal cortex than rodents, easy handling compare to other non-human primates, and requirement for small amounts of test drugs. In this study, we evaluated the effects of dopamine D1-4 receptors agonists on eye blinking in common marmosets. Our results show that the dopamine D1 receptor agonist SKF-82958 and the non-selective dopamine receptor agonist apomorphine significantly increased common marmosets eye blinking count, whereas the dopamine D2 agonist (+)-PHNO and the dopamine D3 receptor agonist (+)-PD-128907 produced somnolence in common marmosets resulting in a decrease in eye blinking count. The dopamine D4 receptor agonists PD-168077 and A-41297 had no effect on common marmosets' eye blinking count. Finally, the dopamine D1 receptor antagonist SCH 39166 completely blocked apomorphine-induced increase in eye blinking count. These results indicate that eye blinking in common marmosets may be a useful tool for in vivo screening of novel dopamine D1 receptor agonists as antipsychotics. PMID:26675887

  10. The interplay between agonistic character displacement and reproductive interference in rubyspot damselflies (Hetaerina spp.)

    OpenAIRE

    Drury, Jonathan

    2014-01-01

    Aggressive interactions between species are common despite being relatively understudied. Agonistic character displacement (ACD) theory makes predictions about how selection should act on traits that mediate the occurrence of interspecific aggressive interactions. Previous research on rubyspot damseflies (Hetaerina spp.) documented several cases of divergent agonistic character displacement acting on wing coloration and competitor recognition to diminish wasteful interspecific aggression. How...

  11. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu...

  12. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Angelica Maria Garzon

    2015-08-01

    Full Text Available Most children with immune thrombocytopenia (ITP will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data is emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long term safety issues that need to be considered when using these agents

  13. N-methyl-D-aspartic acid receptor agonists

    DEFF Research Database (Denmark)

    Madsen, U; Frydenvang, Karla Andrea; Ebert, B;

    1996-01-01

    (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

  14. Locomotion induced by ventral tegmental microinjections of a nicotinic agonist.

    Science.gov (United States)

    Museo, E; Wise, R A

    1990-03-01

    Bilateral microinjections of the nicotinic agonist cytisine (0.1, 1 or 10 nanomoles per side) into the ventral tegmental area increased locomotor activity. This increase in locomotion was antagonized by mecamylamine (2 mg/kg, IP), a nicotinic antagonist that readily crosses the blood-brain barrier, and by pimozide (0.3 mg/kg, IP), a central dopaminergic antagonist. Hexamethonium (2 mg/kg, IP), a nicotinic antagonist that, unlike mecamylamine, does not cross the blood-brain barrier, had no effect; this suggests that mecamylamine's attenuation of cytisine-induced locomotor activity resulted from a blockade of central and not peripheral nicotinic receptors. The data support the notion that nicotinic and dopaminergic substrates interact at the level of the VTA to produce increases in locomotor activity.

  15. Recent advances in the development of farnesoid X receptor agonists.

    Science.gov (United States)

    Ali, Ahmad H; Carey, Elizabeth J; Lindor, Keith D

    2015-01-01

    Farnesoid X receptors (FXRs) are nuclear hormone receptors expressed in high amounts in body tissues that participate in bilirubin metabolism including the liver, intestines, and kidneys. Bile acids (BAs) are the natural ligands of the FXRs. FXRs regulate the expression of the gene encoding for cholesterol 7 alpha-hydroxylase, which is the rate-limiting enzyme in BA synthesis. In addition, FXRs play a critical role in carbohydrate and lipid metabolism and regulation of insulin sensitivity. FXRs also modulate live growth and regeneration during liver injury. Preclinical studies have shown that FXR activation protects against cholestasis-induced liver injury. Moreover, FXR activation protects against fatty liver injury in animal models of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and improved hyperlipidemia, glucose intolerance, and insulin sensitivity. Obeticholic acid (OCA), a 6α-ethyl derivative of the natural human BA chenodeoxycholic acid (CDCA) is the first-in-class selective FXR agonist that is ~100-fold more potent than CDCA. Preliminary human clinical trials have shown that OCA is safe and effective. In a phase II clinical trial, administration of OCA was well-tolerated, increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type II diabetes mellitus and NAFLD. In two clinical trials of OCA in patients with primary biliary cirrhosis (PBC), a progressive cholestatic liver disease, OCA significantly reduced serum alkaline phosphatase (ALP) levels, an important disease marker that correlates well with clinical outcomes of patients with PBC. Together, these studies suggest that FXR agonists could potentially be used as therapeutic tools in patients suffering from nonalcoholic fatty and cholestatic liver diseases. Larger and Longer-term studies are currently ongoing. PMID:25705637

  16. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Directory of Open Access Journals (Sweden)

    Guido eFrank

    2014-11-01

    Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  17. Could dopamine agonists aid in drug development for anorexia nervosa?

    Science.gov (United States)

    Frank, Guido K W

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

  18. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    Science.gov (United States)

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  19. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.

    Science.gov (United States)

    DeVree, Brian T; Mahoney, Jacob P; Vélez-Ruiz, Gisselle A; Rasmussen, Soren G F; Kuszak, Adam J; Edwald, Elin; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A; Pardon, Els; Steyaert, Jan; Kobilka, Brian K; Sunahara, Roger K

    2016-07-01

    G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the β2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID:27362234

  20. APT accelerator. Topical report

    International Nuclear Information System (INIS)

    The Accelerator Production of Tritium (APT) project, sponsored by Department of Energy Defense Programs (DOE/DP), involves the preconceptual design of an accelerator system to produce tritium for the nation's stockpile of nuclear weapons. Tritium is an isotope of hydrogen used in nuclear weapons, and must be replenished because of radioactive decay (its half-life is approximately 12 years). Because the annual production requirements for tritium has greatly decreased since the end of the Cold War, an alternative approach to reactors for tritium production, based on a linear accelerator, is now being seriously considered. The annual tritium requirement at the time this study was undertaken (1992-1993) was 3/8 that of the 1988 goal, usually stated as 3/8-Goal. Continued reduction in the number of weapons in the stockpile has led to a revised (lower) production requirement today (March, 1995). The production requirement needed to maintain the reduced stockpile, as stated in the recent Nuclear Posture Review (summer 1994) is approximately 3/16-Goal, half the previous level. The Nuclear Posture Review also requires that the production plant be designed to accomodate a production increase (surge) to 3/8-Goal capability within five years, to allow recovery from a possible extended outage of the tritium plant. A multi-laboratory team, collaborating with several industrial partners, has developed a preconceptual APT design for the 3/8-Goal, operating at 75% capacity. The team has presented APT as a promising alternative to the reactor concepts proposed for Complex-21. Given the requirements of a reduced weapons stockpile, APT offers both significant safety, environmental, and production-fexibility advantages in comparison with reactor systems, and the prospect of successful development in time to meet the US defense requirements of the 21st Century

  1. VLHC accelerator physics

    Energy Technology Data Exchange (ETDEWEB)

    Michael Blaskiewicz et al.

    2001-11-01

    A six-month design study for a future high energy hadron collider was initiated by the Fermilab director in October 2000. The request was to study a staged approach where a large circumference tunnel is built that initially would house a low field ({approx}2 T) collider with center-of-mass energy greater than 30 TeV and a peak (initial) luminosity of 10{sup 34} cm{sup -2}s{sup -1}. The tunnel was to be scoped, however, to support a future upgrade to a center-of-mass energy greater than 150 TeV with a peak luminosity of 2 x 10{sup 34} cm{sup -2} sec{sup -1} using high field ({approx} 10 T) superconducting magnet technology. In a collaboration with Brookhaven National Laboratory and Lawrence Berkeley National Laboratory, a report of the Design Study was produced by Fermilab in June 2001. 1 The Design Study focused on a Stage 1, 20 x 20 TeV collider using a 2-in-1 transmission line magnet and leads to a Stage 2, 87.5 x 87.5 TeV collider using 10 T Nb{sub 3}Sn magnet technology. The article that follows is a compilation of accelerator physics designs and computational results which contributed to the Design Study. Many of the parameters found in this report evolved during the study, and thus slight differences between this text and the Design Study report can be found. The present text, however, presents the major accelerator physics issues of the Very Large Hadron Collider as examined by the Design Study collaboration and provides a basis for discussion and further studies of VLHC accelerator parameters and design philosophies.

  2. APT accelerator. Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, G.; Rusthoi, D. [comp.] [ed.

    1995-03-01

    The Accelerator Production of Tritium (APT) project, sponsored by Department of Energy Defense Programs (DOE/DP), involves the preconceptual design of an accelerator system to produce tritium for the nation`s stockpile of nuclear weapons. Tritium is an isotope of hydrogen used in nuclear weapons, and must be replenished because of radioactive decay (its half-life is approximately 12 years). Because the annual production requirements for tritium has greatly decreased since the end of the Cold War, an alternative approach to reactors for tritium production, based on a linear accelerator, is now being seriously considered. The annual tritium requirement at the time this study was undertaken (1992-1993) was 3/8 that of the 1988 goal, usually stated as 3/8-Goal. Continued reduction in the number of weapons in the stockpile has led to a revised (lower) production requirement today (March, 1995). The production requirement needed to maintain the reduced stockpile, as stated in the recent Nuclear Posture Review (summer 1994) is approximately 3/16-Goal, half the previous level. The Nuclear Posture Review also requires that the production plant be designed to accomodate a production increase (surge) to 3/8-Goal capability within five years, to allow recovery from a possible extended outage of the tritium plant. A multi-laboratory team, collaborating with several industrial partners, has developed a preconceptual APT design for the 3/8-Goal, operating at 75% capacity. The team has presented APT as a promising alternative to the reactor concepts proposed for Complex-21. Given the requirements of a reduced weapons stockpile, APT offers both significant safety, environmental, and production-fexibility advantages in comparison with reactor systems, and the prospect of successful development in time to meet the US defense requirements of the 21st Century.

  3. 2014 CERN Accelerator Schools

    CERN Multimedia

    2014-01-01

    A specialised school on Power Converters will be held in Baden, Switzerland, from 7 to 14 May 2014. Please note that the deadline for applications is 7 FEBRUARY 2014. A course on Introduction to Accelerator Physics will be held in Prague, Czech Republic, from 31 August to 12 September 2014. Applications are now open for this school; the application deadline is 25 APRIL 2014. Further information on these schools and other CAS events can be found on the CAS website and on the Indico page. For further information please contact Barbara.strasser@cern.ch

  4. Accelerating abelian gauge dynamics

    CERN Document Server

    Adler, Stephen Louis

    1991-01-01

    In this paper, we suggest a new acceleration method for Abelian gauge theories based on linear transformations to variables which weight all length scales equally. We measure the autocorrelation time for the Polyakov loop and the plaquette at β=1.0 in the U(1) gauge theory in four dimensions, for the new method and for standard Metropolis updates. We find a dramatic improvement for the new method over the Metropolis method. Computing the critical exponent z for the new method remains an important open issue.

  5. Accelerated Innovation Pilot

    Science.gov (United States)

    Davis, Jeffrey

    2012-01-01

    Opportunities: I. Engage NASA team (examples) a) Research and technology calls . provide suggestions to AES, HRP, OCT. b) Use NASA@Work to solicit other ideas; (possibly before R+D calls). II. Stimulate collaboration (examples) a) NHHPC. b) Wharton Mack Center for Technological Innovation (Feb 2013). c) International ] DLR ] :envihab (July 2013). d) Accelerated research models . NSF, Myelin Repair Foundation. III. Engage public Prizes (open platform: InnoCentive, yet2.com, NTL; Rice Business Plan, etc.) IV. Use same methods to engage STEM.

  6. Hardware Accelerated Power Estimation

    CERN Document Server

    Coburn, Joel; Raghunathan, Anand

    2011-01-01

    In this paper, we present power emulation, a novel design paradigm that utilizes hardware acceleration for the purpose of fast power estimation. Power emulation is based on the observation that the functions necessary for power estimation (power model evaluation, aggregation, etc.) can be implemented as hardware circuits. Therefore, we can enhance any given design with "power estimation hardware", map it to a prototyping platform, and exercise it with any given test stimuli to obtain power consumption estimates. Our empirical studies with industrial designs reveal that power emulation can achieve significant speedups (10X to 500X) over state-of-the-art commercial register-transfer level (RTL) power estimation tools.

  7. Medical applications of accelerators

    CERN Document Server

    Rossi, Sandro

    1998-01-01

    At Present, about five thousands accelerators are devoted to biomedical applications. They are mainly used in radiotherapy, research and medical radioisotopes production. In this framework oncological hadron-therapy deserves particular attention since it represents a field in rapid evolution thanks to the joint efforts of laboratories with long experiences in particle physics. It is the case of CERN where the design of an optimised synchrotron for medical applications has been pursued. These lectures present these activities with particular attention to the new developments which are scientifically interesting and/or economically promising.

  8. Acceleration without Temperature

    CERN Document Server

    Doria, Alaric

    2015-01-01

    We show that while some non-uniformly accelerating observers (NUAOs) do indeed see a Bose-Einstein distribution of particles for the expectation value of the number operator in the Minkowski vacuum state, the density matrix is non-thermal and therefore a definition of temperature is not warranted. This is due to the fact that our NUAOs do not see event horizons in the spacetime. More specifically, the Minkowski vacuum state is perceived by our NUAOs as a single-mode squeezed state as opposed to the two-mode squeezed state characteristic of uniformly accelerating observers. Both single and two-mode squeezed states are pure quantum states; however, tracing over degrees of freedom in one of the modes of the two-mode squeezed state reduces the pure density matrix to a thermal density matrix. It is this property in the two-mode squeezed state that allows one to consistently define a temperature. In the single-mode case, an equivalent tracing is neither required nor available.

  9. Accelerator School Success

    CERN Document Server

    2004-01-01

    Accelerator specialists don't grow on trees: training them is the job of the CERN Accelerator School (CAS). Group photo during visit to the Daresbury Laboratory. CAS and the CCLRC Daresbury Laboratory jointly organised a specialised school on Power Converters in Warrington, England from 12-18 May 2004. The last CAS Power Converter course was in 1990, so there was plenty of ground to cover. The challenging programme proposed a review of the state of the art and the latest developments in the field, including 30 hours of tuition. The school also included a visit to the CCLRC Daresbury laboratory, a one-day excursion to Liverpool and Chester and a themed (Welsh medieval) dinner at the school's closure. A record attendance of 91 students of more than 20 different nationalities included not only participants from Europe and North America but also from Armenia, Taiwan, India, Turkey, Iran and for the first time, fee-paying students from China and Australia. European industry showed a welcome and solid interest in...

  10. 2014 Joint International Accelerator School: Beam Loss and Accelerator Protection

    CERN Document Server

    JAS - Joint US-CERN-Japan-Russia Accelerator School

    2016-01-01

    Many particle accelerators operate with very high beam power and very high energy stored in particle beams as well as in magnet systems. In the future, the beam power in high intensity accelerators will further increase. The protection of the accelerator equipment from the consequences of uncontrolled release of the energy is essential. This was the motivation for organizing a first school on beam losses and accelerator protection (in general referred to as machine protection). During the school the methods and technologies to identify, mitigate, monitor and manage the technical risks associated with the operation of accelerators with high-power beams or subsystems with large stored energy were presented. At the completion of the school the participants should have been able to understand the physical phenomena that can damage machine subsystems or interrupt operations and to analyze an accelerator facility to produce a register of technical risks and the corresponding risk mitigation and management strategie...

  11. Accelerator Technology: Geodesy and Alignment for Particle Accelerators

    CERN Document Server

    Missiaen, D

    2013-01-01

    This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the the Section '8.9 Geodesy and Alignment for Particle Accelerators' of the Chapter '8 Accelerator Technology' with the content: 8.9 Geodesy and Alignment for Particle Accelerators 8.9.1 Introduction 8.9.2 Reference and Co-ordinate Systems 8.9.3 Definition of the Beam Line on the Accelerator Site 8.9.4 Geodetic Network 8.9.5 Tunnel Preliminary Works 8.9.6 The Alignment References 8.9.7 Alignment of Accelerator Components 8.9.8 Permanent Monitoring and Remote Alignment of Low Beta Quadrupoles 8.9.9 Alignment of Detector Components

  12. Acceleration in Linear and Circular Motion

    Science.gov (United States)

    Kellington, S. H.; Docherty, W.

    1975-01-01

    Describes the construction of a simple accelerometer and explains its use in demonstrating acceleration, deceleration, constant speed, measurement of acceleration, acceleration and the inclined plane and angular and radial acceleration. (GS)

  13. Investigation on laser accelerators. Plasma beat wave accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Akihiko; Miyamoto, Yasuaki; Hagiwara, Masayoshi; Suzuki, Mitsutoshi; Sudo, Osamu [Power Reactor and Nuclear Fuel Development Corp., Tokai, Ibaraki (Japan). Tokai Works

    1998-04-01

    Laser accelerator technology has characteristics of high energy, compact, short pulse and high luminescence{center_dot}low emittance. This means potential many applications in wide ranges of fields as well as high energy and nuclear physics. High power short laser pulses are injected to a plasma in the typical example of laser accelerators. Large electric fields are induced in the plasma. Electrons in the plasma are accelerated with the ponderomotive force of the electric field. The principles of interaction on beat wave, wakefield accelerators, inverse free electron laser and inverse Cherenkov radiation are briefly introduced. The overview of plasma beat wave accelerator study is briefly described on the programs at Chalk River Laboratories(Canada), UCLA(USA), Osaka Univ. (Japan) and Ecole Polytechnique (France). Issues of the plasma beat wave accelerator are discussed from the viewpoint of application. Existing laser technologies of CO{sub 2}, YAG and YFL are available for the present day accelerator technology. An acceleration length of beat wave interaction is limited due to its phase condition. Ideas on multi-staged acceleration using the phasing plasma fiber are introduced. (Y. Tanaka)

  14. CAS CERN Accelerator School: Advanced accelerator physics. Proceedings. Vol. 1

    International Nuclear Information System (INIS)

    This advanced course on general accelerator physics is the second of the biennial series given by the CERN Accelerator School and follows on from the first basic course given at Gif-sur-Yvette, Paris, in 1984. Stress is placed on the mathematical tools of Hamiltonian mechanics and the Vlasov and Fokker-Planck equations, which are widely used in accelerator theory. The main topics treated in this present work include: nonlinear resonances, chromaticity, motion in longitudinal phase space, growth and control of longitudinal and transverse beam emittance, space-charge effects and polarization. The seminar programme treats some specific accelerator techniques, devices, projects and future possibilities. (orig.)

  15. CERN Accelerator School: Registration open for Advanced Accelerator Physics course

    CERN Multimedia

    2015-01-01

    Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of accelerator physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

  16. CERN Accelerator School: Registration open for Advanced Accelerator Physics course

    CERN Multimedia

    2015-01-01

    Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of Accelerator Physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

  17. CAS CERN Accelerator School: Advanced accelerator physics. Proceedings. Vol. 2

    International Nuclear Information System (INIS)

    This advanced course on general accelerator physics is the second of the biennial series given by the CERN Accelerator School and follows on from the first basic course given at Gif-sur-Yvette, Paris, in 1984. Stress is placed on the mathematical tools of Hamiltonian mechanics and the Vlasov and Fokker-Planck equations, which are widely used in accelerator theory. The main topics treated in this present work include: nonlinear resonances, chromaticity, motion in longitudinal phase space, growth and control of longitudinal and transverse beam emittance, space-charge effects and polarization. The seminar programme treats some specific accelerator techniques, devices, projects and future possibilities. (orig.)

  18. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    International Nuclear Information System (INIS)

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC50 values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50 = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other

  19. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  20. Binding Mode of Insulin Receptor and Agonist Peptide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two α subunits with a molecular weight of 135 kD and twoβ subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular α subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the α subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide.We employed the extracellular domain (PDBID: 1IGR) of the insulin-like growth factor-1 receptor (IGF-1 R ) as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides.Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small

  1. Lectures in accelerator theory

    International Nuclear Information System (INIS)

    Lecture I deals with the behavior of particles in the nonlinear field arising from the electromagnetic interaction of colliding beams. The case treated, that of counter-rotating proton beams crossing each other at a non-zero angle, has the simple feature that the force between the beam is one dimensional. In lecture II, an analysis of the development of traveling waves on particle beams is presented. The situation studied is that of a uniform beam current in a circular accelerator and the excitation for the coherent motion is induced by the resistivity of the vacuum chamber wall. Finally, in lecture III, a description of the current accumulation process used at the proton storage rings at CERN (The ISR) is given. Particle pulses of rather low average current are injected and stored along the length and width of the vacuum chamber. The efficiency is very high and large currents (over 40 amperes) have been achieved

  2. Accelerator vacuum system elements

    International Nuclear Information System (INIS)

    Some elements of vacuum systems are investigated. Considerable attention has been given to the investigation into peculiarities in pumping out of a ionoguide for transportation of an accelerated charged particles beam the spread of which often attains a considerable length. The number of pumps over the ionoguide length is experimentally determined. It is shown that as a result of ionoguide warm-up the pumping out time is considerably reduced maximum permissible pressure is decreased by two orders and lesser rate of pump pumping out is required. The investigations have shown that when operating the ionoguide there is no necessity in setting up seals between the ionoguide and magnetodischarged pump. The causes of the phenomenon in which the pressure near the pump is greater than in the end of the ionoguide, are impurities carried in by the pump into the ionoguide volume and the pumping out capacity of the pressure converter

  3. ACCELERATING NANO-TECHNOLOGICAL

    DEFF Research Database (Denmark)

    Jensen, Jens Stissing; Koch, Christian

    2007-01-01

    By viewing the construction industry as a technological innovation system (TIS) this paper discusses possible initiatives to accelerate nanotechnological innovations. The point of departure is a recent report on the application of nano-technology in the Danish construction industry, which concludes...... of the system are furthermore poorly equipped at identifying potentials within high-tech areas. In order to exploit the potentials of nano-technology it is thus argued that an alternative TIS needs to be established. Initiatives should identify and support “incubation rooms” or marked niches in order...... for the different elements of the TIS to evolve. This could involve nano-visioning including scenarios of future technological applications and industrial dynamics....

  4. Testing Gravity on Accelerators

    CERN Document Server

    Kalaydzhyan, Tigran

    2016-01-01

    Weak equivalence principle (WEP) is one of the cornerstones of the modern theories of gravity, stating that the trajectory of a freely falling test body is independent of its internal structure and composition. Even though WEP is known to be valid for the normal matter with a high precision, it has never been experimentally confirmed for relativistic matter and antimatter. We make an attempt to constrain possible deviations from WEP utilizing the modern accelerator technologies. We analyze the (absence of) vacuum Cherenkov radiation, photon decay, anomalous synchrotron losses and the Compton spectra to put limits on the isotropic Lorentz violation and further convert them to the constraints on the difference between the gravitational and inertial masses of the relativistic electrons/positrons. Our main result is the 0.1% limit on the mentioned difference.

  5. Self-accelerated Universe

    CERN Document Server

    Kosyakov, B P

    2005-01-01

    It is widely believed that the large redshifts for distant supernovae are explained by the vacuum energy dominance, or, in other words, by the cosmological constant in Einstein's equations, which is responsible for the anti-gravitation effect. A tacit assumption is that particles move along a geodesic for the background metric. This is in the same spirit as the consensus regarding the uniform Galilean motion of a free electron. However, there is a runaway solution to the Lorentz--Dirac equation governing the behavior of a radiating electron, in addition to the Galilean solution. Likewise, a runaway solution to the entire system of equations, both gravitation and matter equations of motion including, may provide an alternative explanation for the accelerated expansion of the Universe, without recourse to the hypothetic cosmological constant.

  6. The entangled accelerating universe

    CERN Document Server

    González-Díaz, Pedro F

    2009-01-01

    Using the known result that the nucleation of baby universes in correlated pairs is equivalent to spacetime squeezing, we show in this letter that there exists a T-duality symmetry between two-dimensional warp drives, which are physically expressible as localized de Sitter little universes, and two dimensional Tolman-Hawking and Gidding-Strominger baby universes respectively correlated in pairs, so that the creation of warp drives is also equivalent to spacetime squeezing. Perhaps more importantly, it has been also seen that the nucleation of warp drives entails a violation of the Bell's inequalities, and hence the phenomena of quantum entanglement, complementarity and wave function collapse. These results are generalized to the case of any dynamically accelerating universe filled with dark or phantom energy whose creation is also physically equivalent to spacetime squeezing and to the violation of the Bell's inequalities, so that the universe we are living in should be governed by essential sharp quantum the...

  7. SPS accelerating cavity

    CERN Multimedia

    1976-01-01

    The SPS started up with 2 accelerating cavities (each consisting of 5 tank sections) in LSS3. They have a 200 MHz travelling wave structure (see 7411032 and 7802190) and 750 kW of power is fed to each of the cavities from a 1 MW tetrode power amplifier, located in a surface building above, via a coaxial transmission line. Clemens Zettler, builder of the SPS RF system, is standing at the side of one of the cavities. In 1978 and 1979 another 2 cavities were added and entered service in 1980. These were part of the intensity improvement programme and served well for the new role of the SPS as proton-antiproton collider. See also 7411032, 8011289, 8104138, 8302397.

  8. Accelerator Technology for the Mankind

    CERN Document Server

    Sultansoy, S

    2006-01-01

    Particle accelerators technology is one of the generic technologies which is locomotive of the development in almost all fields of science and technology. According to the U.S. Department of Energy: "Accelerators underpin every activity of the Office of Science and, increasingly, of the entire scientific enterprise. From biology to medicine, from materials to metallurgy, from elementary particles to the cosmos, accelerators provide the microscopic information that forms the basis for scientific understanding and applications. The combination of ground and satellite based observatories and particle accelerators will advance our understanding of our world, our galaxy, our universe, and ourselves." Because of this, accelerator technology should become widespread all over the world. Existing situation shows that a large portion of the world, namely the South and Mid-East, is poor on the accelerator technology. UNESCO has recognized this deficit and started SESAME project in Mid-East, namely Jordan. Turkic Acceler...

  9. Electrostatic accelerators fundamentals and applications

    CERN Document Server

    2005-01-01

    Electrostatic accelerators are an important and widespread subgroup within the broad spectrum of modern, large particle acceleration devices. They are specifically designed for applications that require high-quality ion beams in terms of energy stability and emittance at comparatively low energies (a few MeV). Their ability to accelerate virtually any kind of ion over a continuously tunable range of energies make them a highly versatile tool for investigations in many research fields including, but not limited to, atomic and nuclear spectroscopy, heavy ion reactions, accelerator mass spectroscopy as well as ion-beam analysis and modification. The book is divided into three parts. The first part concisely introduces the field of accelerator technology and techniques that emphasize their major modern applications. The second part treats the electrostatic accelerator per se: its construction and operational principles as well as its maintenance. The third part covers all relevant applications in which electrosta...

  10. Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Grube; Frølund, Bente Flensborg; Kehler, Jan;

    2011-01-01

    A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor...... yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess...

  11. Accelerating Universe and Event Horizon

    OpenAIRE

    He, Xiao-Gang(INPAC, SKLPPC and Department of Physics, Shanghai Jiao Tong University, Shanghai, China)

    2001-01-01

    It has been argued in the literature that if a universe is expanding with an accelerating rate indefinitely, it presents a challenge to string theories due to the existence of event horizons. We study the fate of a currently accelerating universe. We show that the universe will continue to accelerate indefinitely if the parameter $\\omega = p/\\rho$ of the equation of state is a constant, no matter how many different types of energy (matter, radiation, quintessence, cosmological constant and et...

  12. Project X: Accelerator Reference Design

    CERN Document Server

    Holmes, S D; Chase, B; Gollwitzer, K; Johnson, D; Kaducak, M; Klebaner, A; Kourbanis, I; Lebedev, V; Leveling, A; Li, D; Nagaitsev, S; Ostroumov, P; Pasquinelli, R; Patrick, J; Prost, L; Scarpine, V; Shemyakin, A; Solyak, N; Steimel, J; Yakovlev, V; Zwaska, R

    2013-01-01

    Part 1 of "Project X: Accelerator Reference Design, Physics Opportunities, Broader Impacts". Part 1 contains the volume Preface and a description of the conceptual design for a high-intensity proton accelerator facility being developed to support a world-leading program of Intensity Frontier physics over the next two decades at Fermilab. Subjects covered include performance goals, the accelerator physics design, and the technological basis for such a facility.

  13. Stationary plasma accelerator - ATON engine

    International Nuclear Information System (INIS)

    The principles of a stationary plasma accelerator (engine) with closed electron drift are described. The accelerator has record integral characteristics. A method for analysis of operating process features in the integral characteristics is proposed. Results are presented of local measurements of the plasma parameters in the accelerator channel and in the leaving plasma jet Main attention is paid to determination of the part of twice ionized ions in the plasma flow

  14. Accelerator control systems in China

    International Nuclear Information System (INIS)

    Three accelerator facilities were built in the past few years, the 2.8 GeV electron positron collider BEPC, the heavy ion SSC cyclotron accelerator HIRFL and the 800 MeV synchrotron radiation storage ring HESYRL. Aimed at different research areas, they represent a new generation of accelerator in China. This report describes the design philosophy, the structure, performance as well as future improvements of the control systems of the these facilities. (author)

  15. Accelerator science in medical physics

    OpenAIRE

    Peach, K.; Wilson, P.; Jones, B

    2011-01-01

    The use of cyclotrons and synchrotrons to accelerate charged particles in hospital settings for the purpose of cancer therapy is increasing. Consequently, there is a growing demand from medical physicists, radiographers, physicians and oncologists for articles that explain the basic physical concepts of these technologies. There are unique advantages and disadvantages to all methods of acceleration. Several promising alternative methods of accelerating particles also have to be considered sin...

  16. Superposed-laser electron acceleration

    International Nuclear Information System (INIS)

    A new mechanism is proposed for electron acceleration by using two superposed laser beams in vacuum. In this mechanism, an electron is accelerated by the longitudinal component of the wave electric field in the overlapped region of two laser beams. Single-particle computations and analytical works are performed in order to demonstrate the viability. These results show that the electron can be accelerated well in this proposed mechanism. (author)

  17. Accelerators for research and applications

    International Nuclear Information System (INIS)

    The newest particle accelerators are almost always built for extending the frontiers of research, at the cutting edge of science and technology. Once these machines are operating and these technologies mature, new applications are always found, many of which touch our lives in profound ways. The evolution of accelerator technologies will be discussed, with descriptions of accelerator types and characteristics. The wide range of applications of accelerators will be discussed, in fields such as nuclear science, medicine, astrophysics and space-sciences, power generation, airport security, materials processing and microcircuit fabrication. 13 figs

  18. Maximal acceleration and radiative processes

    OpenAIRE

    Papini, Giorgio

    2015-01-01

    We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass $m$ has the upper limit $\\mathcal{A}_m=2mc^3/\\hbar$. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to $\\mathcal{A}_m$ and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws du...

  19. Thomas Precession by Uniform Acceleration

    CERN Document Server

    Pardy, Miroslav

    2015-01-01

    We determine the nonlinear transformations between coordinate systems which are mutually in a constant symmetrical accelerated motion. The maximal acceleration limit follows from the kinematical origin and it is an analogue of the maximal velocity in special relativity. We derive the dependence of mass, length, time, Doppler effect, Cherenkov effect and transition radiation angle on acceleration as an analogue phenomena in special theory of relativity. The last application of our method is the Thomas precession by uniform acceleration with the possible role in the modern physics and cosmology. The comparison of derived results with other relativistic methods is necessary.

  20. Superconducting Radiofrequency (SRF) Acceleration Technology

    Data.gov (United States)

    Federal Laboratory Consortium — SRF cavities enable accelerators to increase particle beam energy levels while minimizing the use of electrical power by all but eliminating electrical resistance....

  1. Therapeutic applications of TRAIL receptor agonists in cancer and beyond.

    Science.gov (United States)

    Amarante-Mendes, Gustavo P; Griffith, Thomas S

    2015-11-01

    TRAIL/Apo-2L is a member of the TNF superfamily first described as an apoptosis-inducing cytokine in 1995. Similar to TNF and Fas ligand, TRAIL induces apoptosis in caspase-dependent manner following TRAIL death receptor trimerization. Because tumor cells were shown to be particularly sensitive to this cytokine while normal cells/tissues proved to be resistant along with being able to synthesize and release TRAIL, it was rapidly appreciated that TRAIL likely served as one of our major physiologic weapons against cancer. In line with this, a number of research laboratories and pharmaceutical companies have attempted to exploit the ability of TRAIL to kill cancer cells by developing recombinant forms of TRAIL or TRAIL receptor agonists (e.g., receptor-specific mAb) for therapeutic purposes. In this review article we will describe the biochemical pathways used by TRAIL to induce different cell death programs. We will also summarize the clinical trials related to this pathway and discuss possible novel uses of TRAIL-related therapies. In recent years, the physiological importance of TRAIL has expanded beyond being a tumoricidal molecule to one critical for a number of clinical settings - ranging from infectious disease and autoimmunity to cardiovascular anomalies. We will also highlight some of these conditions where modulation of the TRAIL/TRAIL receptor system may be targeted in the future. PMID:26343199

  2. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

    Directory of Open Access Journals (Sweden)

    Paul Fredrickson

    2014-01-01

    Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

  3. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  4. Agonists and Antagonists of TGF-β Family Ligands.

    Science.gov (United States)

    Chang, Chenbei

    2016-08-01

    The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

  5. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  6. CAS CERN Accelerator School: Second general accelerator physics course

    International Nuclear Information System (INIS)

    The course on general accelerator physics given at Aarhus is basically a repeat of that organised by the CERN Accelerator School at Gif-sur-Yvette, Paris in September 1984 and whose proceedings were published as CERN Yellow Report 85-19 (1985). However, the opportunity was taken to improve or extend certain subjects while introducing new ones and it is these which are included in the present proceedings. The lectures treated here include accelerator optics, insertions, image and space charge forces, neutralisation, diagnostics and intra-beam scattering while the seminar programme includes a number of specialised accelerator topics. Reports on a separate series of seminars organised by the University of Aarhus, Denmark, and devoted to advanced technology arising from general accelerator physics are also included, as well as errata to CERN 85-19. (orig.)

  7. CAS CERN Accelerator School superconductivity in particle accelerators

    International Nuclear Information System (INIS)

    One of the objectives of the CERN Accelerator School is to run courses on specialised topics in the particle accelerator field. The present volume contains the proceedings of one such course, this time organized in conjunction with the Deutsches Elektronen Synchrotron (DESY) on the subject of superconductivity in particle accelerators. This course reflects the very considerable progress made over the last few years in the use of the technology for the magnet and radio-frequency systems of many large and small accelerators already in use or nearing completion, while also taking account of the development work now going on for future machines. The lectures cover the theory of superconductivity, cryogenics and accelerator magnets and cavities, while the seminars include superfluidity, superconductors, special magnets and the prospects for high-temperature superconductors. (orig.)

  8. Dopamine Agonist in Treatment of ADHD with Restless Legs Syndrome and ODD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-05-01

    Full Text Available A 6-year-old male with attention deficit hyperactivity disorder who responded poorly to methylphenidate (MPH was benefited following treatment with the dopamine agonist ropinirole, in a report from the Hopital Robert Debre, Paris, France.

  9. Lepidozenolide from the liverwort Lepidozia fauriana acts as a farnesoid X receptor agonist.

    Science.gov (United States)

    Lin, Hsiang-Ru

    2015-01-01

    Lepidozenolide is a sesquiterpenoid isolated from the liverwort Lepidozia fauriana and its possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and hyperglycemia. In this study, whether lepidozenolide may act as a FXR agonist was determined. Indeed, in mammalian one-hybrid and transient transfection reporter assays, lepidozenolide transactivated FXR to modulate promoter action including GAL4, CYP7A1, and PLTP promoters in a dose-dependent manner, while it exhibited slightly less agonistic activity than chenodeoxycholic acid, an endogenous FXR agonist. Through the molecular modeling docking studies lepidozenolide was shown to bind to FXR ligand binding pocket fairly well. All these results indicate that lepidozenolide acts as a FXR agonist. PMID:25315435

  10. Synthesis of 2-(Benzodioxol-2-yl)acetic Acids as PPARδ Agonists

    Institute of Scientific and Technical Information of China (English)

    Jian Lei KANG; Zhi Bing ZHENG; Dan QIN; Li Li WANG; Song LI

    2006-01-01

    A new series of compounds, 2-(benzodioxol-2-yl)acetic acids, have been synthesized. Their structures were confirmed by MS and 1H-NMR. The preliminary pharmacological screening showed that these compounds exhibited potent human PPARδ agonist activities.

  11. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

    Science.gov (United States)

    Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

    2013-01-01

    This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

  12. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    YonglianSun; JonathanH.Chen; YangxinFu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  13. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    Yonglian Sun; Jonathan H.Chen; Yangxin Fu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  14. Differential effects of beta-adrenoceptor partial agonists in patients with postural hypotension

    DEFF Research Database (Denmark)

    Mehlsen, J; Stadeager, C; Trap-Jensen, J

    1993-01-01

    The central haemodynamic effects of pindolol and xamoterol have been investigated in patients with postural hypotension. Pindolol is a non-selective beta-adrenoceptor partial agonist, whereas xamoterol is beta 1-selective and possesses a higher degree of agonist activity. The study comprised 16.......min-1 and LVEF from 0.57 to 0.52, and reduced mean arterial blood pressure from 103 mm Hg to 93 mm Hg. Xamoterol showed beta-adrenoceptor agonistic effects in the supine position through increments in heart rate from 72 to 90 beats.min-1 and LVEF from 0.58 to 0.66, and raised mean arterial blood...... pressure from 108 to 123 mm Hg. It is concluded that the degree of agonist activity of a beta-adrenergic agent is of importance if it is given to a patient with postural hypotension....

  15. The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis

    OpenAIRE

    Nicole A. Hofmann; Yang, Jiang; Trauger, Sunia A.; Nakayama, Hironao; Huang, Lan; Strunk, Dirk; Moses, Marsha A.; Klagsbrun, Michael; Bischoff, Joyce; Graier, Wolfgang F

    2015-01-01

    Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Experimental Approach Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo ch...

  16. Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells

    OpenAIRE

    Yamasaki, M.; Masgrau, R.; Morgan, A. J.; Churchill, G. C.; Patel, S.; Ashcroft, S. J. H.; Galione, A

    2004-01-01

    How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle seleetion") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively...

  17. Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

    2008-01-01

    A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

  18. A comparison of agonist-specific coupling of cloned human α2-adrenoceptor subtypes

    OpenAIRE

    Rudling, Jane E; Richardson, Jo; Evans, Peter D.

    2000-01-01

    The agonist-specific coupling properties of the three cloned human α2-adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and (±)-meta-octopamine as agonists.Noradrenaline can couple the receptor to both the inhibition and stimulation of forskolin-stimulated cyclic AMP production in all three receptor subtypes, with the relative strength of the coupling to the pathways varying for each of the receptor subtyp...

  19. Perioperative use of selective alpha-2 agonists and antagonists in small animals

    OpenAIRE

    Lemke, Kip A.

    2004-01-01

    Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardi...

  20. PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

    OpenAIRE

    Silswal, Neerupma; Parelkar, Nikhil K; Michael J. Wacker; Badr, Mostafa; Andresen, Jon

    2012-01-01

    We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPAR α ) agonists using isolated mouse aortas and middle cerebral arteries (MCAs). The PPAR α agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPAR α deficient mice demonstrated that responses were also ...

  1. Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature

    OpenAIRE

    Lute, Beth; Jou, William; Lateef, Dalya M.; Goldgof, Margalit; Xiao, Cuiying; Piñol, Ramón A.; Kravitz, Alexxai V.; Miller, Nicole R.; Huang, Yuning George; Girardet, Clemence; Butler, Andrew A.; Gavrilova, Oksana; Reitman, Marc L.

    2014-01-01

    The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r) mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia tha...

  2. Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity

    OpenAIRE

    Jordi Riba; Krämer, Ulrike M.; Marcus Heldmann; Sylvia Richter; Münte, Thomas F.

    2008-01-01

    The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefo...

  3. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Scott K.; Washburn, David G.; Frazee, James S.; Madauss, Kevin P.; Hoang, Tram H.; Lapinski, Leahann; Grygielko, Eugene T.; Glace, Lindsay E.; Trizna, Walter; Williams, Shawn P.; Duraiswami, Chaya; Bray, Jeffrey D.; Laping, Nicholas J.; (GSKNC); (GSKPA)

    2010-09-03

    Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

  4. Lack of Cocaine-Like Discriminative-Stimulus Effects of σ Receptor Agonists in Rats

    OpenAIRE

    Hiranita, Takato; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L.

    2011-01-01

    Previous studies demonstrated effectiveness of selective sigma-receptor (σR) agonists (DTG, PRE-084) as reinforcers in rats trained to self-administer cocaine. Like cocaine, these drugs increased nucleus accumbens shell dopamine levels, and effects of DTG, but not PRE-084, on dopamine appeared to be mediated by σRs. Additionally, σR antagonists blocked self-administration of σR agonists, but were inactive against reinforcing and neurochemical effects of cocaine. Thus pharmacologically distinc...

  5. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors

    OpenAIRE

    Ginj, Mihaela; Zhang, Hanwen; Waser, Beatrice; Cescato, Renzo; Wild, Damian; Wang, Xuejuan; Erchegyi, Judit; Rivier, Jean; Mäcke, Helmut R.; Reubi, Jean Claude

    2006-01-01

    Targeting neuroendocrine tumors expressing somatostatin receptor subtypes (sst) with radiolabeled somatostatin agonists is an established diagnostic and therapeutic approach in oncology. While agonists readily internalize into tumor cells, permitting accumulation of radioactivity, radiolabeled antagonists do not, and they have not been considered for tumor targeting. The macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to two potent somatostatin...

  6. Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.

    Science.gov (United States)

    Deng, Guanghui; Meng, Qinghua; Liu, Qian; Xu, Xuesong; Xu, Qiongfeng; Ren, Feng; Guo, Taylor B; Lu, Hongtao; Xiang, Jia-Ning; Elliott, John D; Lin, Xichen

    2012-06-15

    A novel series of benzoxazole-derived S1P(1) agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P(1) agonist (over S1P(3)) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.

  7. PPAR agonists regulate brain gene expression: Relationship to their effects on ethanol consumption

    OpenAIRE

    Ferguson, Laura B.; Most, Dana; Yuri A Blednov; Harris, R. Adron

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We teste...

  8. SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist.

    Science.gov (United States)

    Sard, Howard; Kumaran, Govindaraj; Morency, Cynthia; Roth, Bryan L; Toth, Beth Ann; He, Ping; Shuster, Louis

    2005-10-15

    An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications for drug discovery.

  9. Evaluation of the beta 2 adrenoceptor agonist/antagonist activity of formoterol and salmeterol.

    OpenAIRE

    Grove, A.; Lipworth, B J

    1996-01-01

    BACKGROUND: Salmeterol and formoterol have a lower intrinsic activity at beta 2 receptors than isoprenaline in human bronchus in vitro. The aim of the present study was to evaluate in vivo the beta 2 agonist/antagonist activity of salmeterol and formoterol at rest with low endogenous adrenergic tone, on exercise with raised endogenous adrenergic tone, and in the presence of fenoterol, an exogenous full beta 2 receptor agonist. METHODS: Eight normal subjects were randomised to receive single d...

  10. Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Hancox Robert J

    2005-09-01

    Full Text Available Abstract Background Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. Methods Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 μg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 μg (cumulative dose was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. Results The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68% lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001. Conclusion The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

  11. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis.

    OpenAIRE

    Dekkers, O. M.; Lagro, J.; Burman, P; J. O. Jorgensen; Romijn, J.A.; A M Pereira

    2010-01-01

    CONTEXT: Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia. However, the optimal treatment strategy and treatment duration is not clear in all details. OBJECTIVE: The aim of the study was to assess the effect of dopamine agonist withdrawal in patients with idiopathic hyperprolactinemia and prolactinomas. DATA SOURCES: PubMed, the Cochrane Library, the Web of Science, and EMBASE were searched electronically. No restriction was made wi...

  12. Inhibition of glucagon secretion by GLP-1 agonists and DPP4 inhibitors

    DEFF Research Database (Denmark)

    Hansen, Morten; Juul Hare, Kristine; Holst, Jens Juul;

    2011-01-01

    with emphasis on their glucagon-lowering effects. Finally, we review available glucagon data from current clinical studies on incretin-based treatment modalities (dipeptidyl peptidase 4 [DPP4] inhibitors and GLP-1 receptor agonists). Most of these studies suggest that both DPP4 inhibitors and GLP-1 receptor...... agonists lower fasting and postprandial plasma glucagon, and recent data suggest that these effects contribute importantly to the glucose-lowering effect of these treatments....

  13. COMPASS Accelerator Design Technical Overview

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Emilio; Dolgashev, Valery; Tantawi, Sami; Neilson, Jeff; /SLAC

    2016-03-14

    This report is a survey of technical options for generating a MeV-class accelerator for space based science applications. The survey was performed focusing on the primary technical requirements of the accelerator in the context of a satellite environment with its unique challenges of limited electrical power (PE), thermal isolation, dimensions, payload requirement and electrical isolation.

  14. Correct and efficient accelerator programming

    OpenAIRE

    Cohen, Albert; Donaldson, Alistair F.; Huisman, Marieke; Katoen, Joost-Pieter

    2013-01-01

    This report documents the program and the outcomes of Dagstuhl Seminar 13142 “Correct and Efficient Accelerator Programming”. The aim of this Dagstuhl seminar was to bring together researchers from various sub-disciplines of computer science to brainstorm and discuss the theoretical foundations, design and implementation of techniques and tools for correct and efficient accelerator programming.

  15. Software for virtual accelerator designing

    International Nuclear Information System (INIS)

    The article discusses appropriate technologies for software implementation of the Virtual Accelerator. The Virtual Accelerator is considered as a set of services and tools enabling transparent execution of computational software for modeling beam dynamics in accelerators on distributed computing resources. Distributed storage and information processing facilities utilized by the Virtual Accelerator make use of the Service-Oriented Architecture (SOA) according to a cloud computing paradigm. Control system tool-kits (such as EPICS, TANGO), computing modules (including high-performance computing), realization of the GUI with existing frameworks and visualization of the data are discussed in the paper. The presented research consists of software analysis for realization of interaction between all levels of the Virtual Accelerator and some samples of middle-ware implementation. A set of the servers and clusters at St.-Petersburg State University form the infrastructure of the computing environment for Virtual Accelerator design. Usage of component-oriented technology for realization of Virtual Accelerator levels interaction is proposed. The article concludes with an overview and substantiation of a choice of technologies that will be used for design and implementation of the Virtual Accelerator. (authors)

  16. Shadows of a maximal acceleration

    OpenAIRE

    Papini, G.

    2002-01-01

    A quantum mechanical upper limit on the value of particle accelerations, or maximal acceleration (MA), is applied to compact stars. A few MA fermions are at most present in canonical white dwarfs and neutron stars. They drastically alter a star's stability conditions.

  17. Shadows of a maximal acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Papini, G

    2002-12-16

    A quantum mechanical upper limit on the value of particle accelerations, or maximal acceleration (MA), is applied to compact stars. A few MA fermions are at most present in canonical white dwarfs and neutron stars. They drastically alter a star's stability conditions.

  18. Lorentz contraction and accelerated systems

    OpenAIRE

    Tartaglia, Angelo; Ruggiero, Matteo Luca

    2003-01-01

    The paper discusses the problem of the Lorentz contraction in accelerated systems, in the context of the special theory of relativity. Equal proper accelerations along different world lines are considered, showing the differences arising when the world lines correspond to physically connected or disconnected objects. In all cases the special theory of relativity proves to be completely self-consistent

  19. Thomas Edison Accelerated Elementary School.

    Science.gov (United States)

    Levin, Henry M.; Chasin, Gene

    This paper describes early outcomes of a Sacramento, California, elementary school that participated in the Accelerated Schools Project. The school, which serves many minority and poor students, began training for the project in 1992. Accelerated Schools were designed to advance the learning rate of students through a gifted and talented approach,…

  20. New directions in linear accelerators

    International Nuclear Information System (INIS)

    Current work on linear particle accelerators is placed in historical and physics contexts, and applications driving the state of the art are discussed. Future needs and the ways they may force development are outlined in terms of exciting R and D challenges presented to today's accelerator designers. 23 references, 7 figures

  1. Accelerator technology for the mankind

    International Nuclear Information System (INIS)

    Full text: Particle accelerators technology is one of the generic technologies which is locomotive of the development in almost all fields of science and technology. According to the U. S. Department of Energy: Accelerators underpin every activity of the Office of Science and, increasingly, of the entire scientific enterprise. From biology to medicine, from materials to metallurgy, from elementary particles to the cosmos, accelerators provide the microscopic information that forms the basis for scientific understanding and applications. The combination of ground and satellite based observatories and particle accelerators will advance our understanding of our world, our galaxy, our universe, and ourselves. Because of this, accelerator technology should become widespread all over the world. Existing situation shows that a large portion of the world, namely the South and Mid-East, is poor on the accelerator technology. UNESCO has recognized this deficit and started SESAME project in Mid-East, namely Jordan. Turkic Accelerator Complex (TAC) project is more comprehensive and ambitious project, from the point of view of it includes light sources, particle physics experiments and proton and secondary beam applications. At this stage, TAC project includes: Linac-ring type charm factory; Synchrotron light source based on positron ring; Free electron laser based on electron linac; GeV scale proton accelerator; TAC-Test Facility

  2. Analysis of Accelerated Gossip Algorithms

    NARCIS (Netherlands)

    Liu, J.; Anderson, B.D.O.; Cao, M.; Morse, A.S.

    2009-01-01

    This paper investigates accelerated gossip algorithms for distributed computations in networks where shift-registers are utilized at each node. By using tools from matrix analysis, we prove the existence of the desired acceleration and establish the fastest rate of convergence in expectation for two

  3. The entangled accelerating universe

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Diaz, Pedro F. [Colina de los Chopos, Instituto de Fisica Fundamental, Consejo Superior de Investigaciones Cientificas, Serrano 121, 28006 Madrid (Spain); Estacion Ecologica de Biocosmologia, Pedro de Alvarado, 14, 06411-Medellin (Spain)], E-mail: p.gonzalezdiaz@imaff.cfmac.csic.es; Robles-Perez, Salvador [Colina de los Chopos, Instituto de Fisica Fundamental, Consejo Superior de Investigaciones Cientificas, Serrano 121, 28006 Madrid (Spain); Estacion Ecologica de Biocosmologia, Pedro de Alvarado, 14, 06411-Medellin (Spain)

    2009-08-31

    Using the known result that the nucleation of baby universes in correlated pairs is equivalent to spacetime squeezing, we show in this Letter that there exists a T-duality symmetry between two-dimensional warp drives, which are physically expressible as localized de Sitter little universes, and two-dimensional Tolman-Hawking and Gidding-Strominger baby universes respectively correlated in pairs, so that the creation of warp drives is also equivalent to spacetime squeezing. Perhaps more importantly, it has been also seen that the nucleation of warp drives entails a violation of the Bell's inequalities, and hence the phenomena of quantum entanglement, complementarity and wave function collapse. These results are generalized to the case of any dynamically accelerating universe filled with dark or phantom energy whose creation is also physically equivalent to spacetime squeezing and to the violation of the Bell's inequalities, so that the universe we are living in should be governed by essential sharp quantum theory laws and must be a quantum entangled system.

  4. Actinides, accelerators and erosion

    Science.gov (United States)

    Tims, S. G.; Fifield, L. K.

    2012-10-01

    Fallout isotopes can be used as artificial tracers of soil erosion and sediment accumulation. The most commonly used isotope to date has been 137Cs. Concentrations of 137Cs are, however, significantly lower in the Southern Hemisphere, and furthermore have now declined to 35% of original values due to radioactive decay. As a consequence the future utility of 137Cs is limited in Australia, with many erosion applications becoming untenable within the next 20 years, and there is a need to replace it with another tracer. Plutonium could fill this role, and has the advantages that there were six times as many atoms of Pu as of 137Cs in fallout, and any loss to decay has been negligible due to the long half-lives of the plutonium isotopes. Uranium-236 is another long-lived fallout isotope with significant potential for exploitation as a tracer of soil and sediment movement. Uranium is expected to be more mobile in soils than plutonium (or caesium), and hence the 236U/Pu ratio will vary with soil depth, and so could provide an independent measure of the amount of soil loss. In this paper we discuss accelerator based ultra-sensitive measurements of plutonium and 236U isotopes and their advantages over 137Cs as tracers of soil erosion and sediment movement.

  5. EXOTIC MAGNETS FOR ACCELERATORS.

    Energy Technology Data Exchange (ETDEWEB)

    WANDERER, P.

    2005-09-18

    Over the last few years, several novel magnet designs have been introduced to meet the requirements of new, high performance accelerators and beam lines. For example, the FAIR project at GSI requires superconducting magnets ramped at high rates ({approx} 4 T/s) in order to achieve the design intensity. Magnets for the RIA and FAIR projects and for the next generation of LHC interaction regions will need to withstand high doses of radiation. Helical magnets are required to maintain and control the polarization of high energy protons at RHIC. In other cases, novel magnets have been designed in response to limited budgets and space. For example, it is planned to use combined function superconducting magnets for the 50 GeV proton transport line at J-PARC to satisfy both budget and performance requirements. Novel coil winding methods have been developed for short, large aperture magnets such as those used in the insertion region upgrade at BEPC. This paper will highlight the novel features of these exotic magnets.

  6. Is Global Warming Accelerating?

    Science.gov (United States)

    Shukla, J.; Delsole, T. M.; Tippett, M. K.

    2009-12-01

    A global pattern that fluctuates naturally on decadal time scales is identified in climate simulations and observations. This newly discovered component, called the Global Multidecadal Oscillation (GMO), is related to the Atlantic Meridional Oscillation and shown to account for a substantial fraction of decadal fluctuations in the observed global average sea surface temperature. IPCC-class climate models generally underestimate the variance of the GMO, and hence underestimate the decadal fluctuations due to this component of natural variability. Decomposing observed sea surface temperature into a component due to anthropogenic and natural radiative forcing plus the GMO, reveals that most multidecadal fluctuations in the observed global average sea surface temperature can be accounted for by these two components alone. The fact that the GMO varies naturally on multidecadal time scales implies that it can be predicted with some skill on decadal time scales, which provides a scientific rationale for decadal predictions. Furthermore, the GMO is shown to account for about half of the warming in the last 25 years and hence a substantial fraction of the recent acceleration in the rate of increase in global average sea surface temperature. Nevertheless, in terms of the global average “well-observed” sea surface temperature, the GMO can account for only about 0.1° C in transient, decadal-scale fluctuations, not the century-long 1° C warming that has been observed during the twentieth century.

  7. Accelerating quantum universe

    CERN Document Server

    Kuzmichev, V E

    2007-01-01

    The exactly solvable quantum model of the homogeneous, isotropic and closed universe filled with a uniform scalar field and a perfect fluid which defines a reference frame is considered. The equations of the model are reduced to the form which allows a direct comparison between them and the equations of the Einstein classical theory of gravity. It is shown that matter in the universe has a component in a form of a condensate of massive zero-momentum excitation quanta of oscillations of a primordial scalar field which behaves as an antigravitating medium. The theory predicts an accelerating expansion of the universe even if the vacuum energy density vanishes. An antigravitating effect of a condensate has a purely quantum nature. It is ensured by quantum transitions between close states of the universe with different masses of a condensate. It is shown that in a state with large quantum numbers (in semi-classical approximation) the universe has to look effectively like spatially flat with a deceleration paramet...

  8. EXHIBITION: Accelerated Particles

    CERN Document Server

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  9. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  10. The entangled accelerating universe

    International Nuclear Information System (INIS)

    Using the known result that the nucleation of baby universes in correlated pairs is equivalent to spacetime squeezing, we show in this Letter that there exists a T-duality symmetry between two-dimensional warp drives, which are physically expressible as localized de Sitter little universes, and two-dimensional Tolman-Hawking and Gidding-Strominger baby universes respectively correlated in pairs, so that the creation of warp drives is also equivalent to spacetime squeezing. Perhaps more importantly, it has been also seen that the nucleation of warp drives entails a violation of the Bell's inequalities, and hence the phenomena of quantum entanglement, complementarity and wave function collapse. These results are generalized to the case of any dynamically accelerating universe filled with dark or phantom energy whose creation is also physically equivalent to spacetime squeezing and to the violation of the Bell's inequalities, so that the universe we are living in should be governed by essential sharp quantum theory laws and must be a quantum entangled system.

  11. LHC Dipoles Accelerate

    CERN Multimedia

    2001-01-01

    Andrezej Siemko (left), Peter Sievers (centre), and Lucio Rossi (right), have the exciting challenge of preparing and testing 2000 magnets for the LHC. The LHC is going to require a lot of powerful magnets by the time it begins operation in 2006. More specifically, it is going to need 130 special magnets, 400 quadrupoles, and a whopping 1250 dipoles! Preparing and testing these magnets for the conditions they will encounter in the LHC is not an easy task. But evaluation of the most recently received magnet, from the German company Noell, is showing that while the monumental task of receiving and testing nearly 2000 magnets is going to be exhausting, the goals are definitely attainable. At the moment and over the next year, pre-series magnets (the magnets that CERN uses to fine tune performance) are arriving slowly (90 in total will arrive), but by 2003 the rate of series magnet arrival will accelerate to 9 per week, that's over 450 in a single year! And working with these magnets when they arrive is tough. ...

  12. Pulsed Superconductivity Acceleration

    CERN Document Server

    Liepe, M

    2000-01-01

    The design of the proposed linear collider TESLA is based on 9-cell 1.3 GHz superconducting niobium cavities, operated in pulsed mode. Within the framework of an international collaboration the TESLA Test Facility (TTF) has been set up at DESY, providing the infrastructure for cavity R&D towards higher gradients. More than 60 nine-cell cavities were tested, accelerating gradients as high as 30 MV/m were measured. In the second production of TTF-cavities the average gradient was measured to be 24.7 MV/m. Two modules, each containing eight resonators, are presently used in the TTF-linac. These cavities are operated in pulsed mode: 0.8 ms constant gradient with up to 10 Hz repetitions rate. We will focus on two aspects: Firstly, the cavity fabrication and treatment is discussed, allowing to reach high gradients. Latest results of single cell cavities will be shown, going beyond 40 MV/m. Secondly, the pulsed mode operation of superconducting cavities is reviewed. This includes Lorentz force detuning, mechanic...

  13. SPS RF Accelerating Cavity

    CERN Multimedia

    1979-01-01

    This picture shows one of the 2 new cavities installed in 1978-1979. The main RF-system of the SPS comprises four cavities: two of 20 m length and two of 16.5 m length. They are all installed in one long straight section (LSS 3). These cavities are of the travelling-wave type operating at a centre frequency of 200.2 MHz. They are wideband, filling time about 700 ns and untuned. The power amplifiers, using tetrodes are installed in a surface building 200 m from the cavities. Initially only two cavities were installed, a third cavity was installed in 1978 and a forth one in 1979. The number of power amplifiers was also increased: to the first 2 MW plant a second 2 MW plant was added and by end 1979 there were 8 500 kW units combined in pairs to feed each of the 4 cavities with up to about 1 MW RF power, resulting in a total accelerating voltage of about 8 MV. See also 7412016X, 7412017X, 7411048X

  14. Actinides, accelerators and erosion

    Directory of Open Access Journals (Sweden)

    Fifield L.K.

    2012-10-01

    Full Text Available Fallout isotopes can be used as artificial tracers of soil erosion and sediment accumulation. The most commonly used isotope to date has been 137Cs. Concentrations of 137Cs are, however, significantly lower in the Southern Hemisphere, and furthermore have now declined to 35% of original values due to radioactive decay. As a consequence the future utility of 137Cs is limited in Australia, with many erosion applications becoming untenable within the next 20 years, and there is a need to replace it with another tracer. Plutonium could fill this role, and has the advantages that there were six times as many atoms of Pu as of 137Cs in fallout, and any loss to decay has been negligible due to the long half-lives of the plutonium isotopes. Uranium-236 is another long-lived fallout isotope with significant potential for exploitation as a tracer of soil and sediment movement. Uranium is expected to be more mobile in soils than plutonium (or caesium, and hence the 236U/Pu ratio will vary with soil depth, and so could provide an independent measure of the amount of soil loss. In this paper we discuss accelerator based ultra-sensitive measurements of plutonium and 236U isotopes and their advantages over 137Cs as tracers of soil erosion and sediment movement.

  15. Heavy ion accelerators at GSI

    International Nuclear Information System (INIS)

    The status of the Unilac heavy ion linear accelerator at GSI, Darmstadt is given. A schematic overall plan view of the Unilac is shown and its systems are described. List of isotopes and intensities accelerated at the Unilac is presented. The experimental possibilities at GSI should be considerably extended by a heavy ion synchrotron (SIS 18) in combination with an experimental storage ring (ESR). A prototype of the rf-accelerating system of the synchrotron has been built and tested. Prototypes for the quadrupole and dipole magnets for the ring are being constructed. The SIS 18 is desigmed for a maximum magnetic rigidity of 18Tm so that neon can be accelerated to 2 GeV/W and uranium to 1 GeV/u. The design allows also the acceleration of protons up to 4.5 GeV. The ESR permits to storage fully stripped uranium ions up to an energy of approximately R50 MeV/u

  16. Industrial accelerators and their applications

    CERN Document Server

    Hamm, Marianne E

    2012-01-01

    This unique new book is a comprehensive review of the many current industrial applications of particle accelerators, written by experts in each of these fields. Readers will gain a broad understanding of the principles of these applications, the extent to which they are employed, and the accelerator technology utilized. The book also serves as a thorough introduction to these fields for non-experts and laymen. Due to the increased interest in industrial applications, there is a growing interest among accelerator physicists and many other scientists worldwide in understanding how accelerators are used in various applications. The government agencies that fund scientific research with accelerators are also seeking more information on the many commercial applications that have been or can be developed with the technology developments they are funding. Many industries are also doing more research on how they can improve their products or processes using particle beams.

  17. Maximal acceleration and radiative processes

    CERN Document Server

    Papini, Giorgio

    2015-01-01

    We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass $m$ has the upper limit $\\mathcal{A}_m=2mc^3/\\hbar$. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to $\\mathcal{A}_m$ and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws due to the maximal acceleration with that for particles in gravitational fields, we find that the model of Caianiello allows, in principle, the use of charged particles as tools to distinguish inertial from gravitational fields locally.

  18. Maximal acceleration and radiative processes

    Science.gov (United States)

    Papini, Giorgio

    2015-08-01

    We derive the radiation characteristics of an accelerated, charged particle in a model due to Caianiello in which the proper acceleration of a particle of mass m has the upper limit 𝒜m = 2mc3/ℏ. We find two power laws, one applicable to lower accelerations, the other more suitable for accelerations closer to 𝒜m and to the related physical singularity in the Ricci scalar. Geometrical constraints and power spectra are also discussed. By comparing the power laws due to the maximal acceleration (MA) with that for particles in gravitational fields, we find that the model of Caianiello allows, in principle, the use of charged particles as tools to distinguish inertial from gravitational fields locally.

  19. The ISAC post-accelerator

    Science.gov (United States)

    Laxdal, R. E.; Marchetto, M.

    2014-01-01

    The acceleration chain of the ISAC facility boosts the energy of both radioactive and stable light and heavy ions for beam delivery to both a medium energy area in ISAC-I and a high energy area in ISAC-II. The post-accelerator comprises a 35.4 MHz RFQ to accelerate beams of A/q ≤ 30 from 2 keV/u to 150 keV/u and a post stripper, 106.1 MHz variable energy drift tube linac (DTL) to accelerate ions of A/q ≤ 6 to a final energy between 0.15 MeV/u to 1.5 MeV/u. A 40 MV superconducting linac further accelerates beam from 1.5 MeV/u to energies above the Coulomb barrier. All linacs operate cw to preserve beam intensity.

  20. Particle Acceleration in Astrophysical Sources

    CERN Document Server

    Amato, Elena

    2015-01-01

    Astrophysical sources are extremely efficient accelerators. Some sources emit photons up to multi-TeV energies, a signature of the presence, within them, of particles with energies much higher than those achievable with the largest accelerators on Earth. Even more compelling evidence comes from the study of Cosmic Rays, charged relativistic particles that reach the Earth with incredibly high energies: at the highest energy end of their spectrum, these subatomic particles are carrying a macroscopic energy, up to a few Joules. Here I will address the best candidate sources and mechanisms as cosmic particle accelerators. I will mainly focus on Galactic sources such as Supernova Remnants and Pulsar Wind Nebulae, which being close and bright, are the best studied among astrophysical accelerators. These sources are held responsible for most of the energy that is put in relativistic particles in the Universe, but they are not thought to accelerate particles up to the highest individual energies, $\\approx 10^{20}$ eV...

  1. Ion sources for electrostatic accelerators

    International Nuclear Information System (INIS)

    Maybe the most important part of an electrostatic accelerator system, and also often the most tricky part is the ion source. There has been a rapid growth in activity in ion-source research and development during the last two to three decades. Some of these developments have also been of benefit to electrostatic accelerator users. In this report some of the different types of ion sources used in electrostatic accelerators are described. The list is not complete but more an overview of some of the more commonly used sources. The description is divided into two groups; positive ion sources for single stage electrostatic accelerators and negative ion sources for two stages (i.e. tandem) accelerators

  2. Alpha1 receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    International Nuclear Information System (INIS)

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha1 receptor, were compared with the α1 selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, 45Ca influx, 45Ca efflux, and 32P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10-5M) were 53.8, 67.6 and 99.7% of the PE (10-5M) response respectively. These same partial agonists caused a stimulation of 45Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In 45Ca efflux studies, (a measure of the intracellular Ca+2 release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. 32P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after α1 receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate α receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle

  3. Alpha/sub 1/ receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wick, P.; Keung, A.; Deth, R.

    1986-03-01

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha/sub 1/ receptor, were compared with the ..cap alpha../sub 1/ selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, /sup 45/Ca influx, /sup 45/Ca efflux, and /sup 32/P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10/sup -5/M) were 53.8, 67.6 and 99.7% of the PE (10/sup -5/M) response respectively. These same partial agonists caused a stimulation of /sup 45/Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In /sup 45/Ca efflux studies, (a measure of the intracellular Ca/sup +2/ release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. /sup 32/P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after ..cap alpha../sub 1/ receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate ..cap alpha.. receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle.

  4. Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections

    Science.gov (United States)

    Mhashilkar, Amruta S.; Vankayala, Sai L.; Liu, Canhui; Kearns, Fiona; Mehrotra, Priyanka; Tzertzinis, George; Palli, Subba R.; Woodcock, H. Lee; Unnasch, Thomas R.

    2016-01-01

    Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. Conclusions The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites. PMID:27300294

  5. GLP-1 receptor agonists or DPP-4 inhibitors: how to guide the clinician?

    Science.gov (United States)

    Scheen, André J

    2013-12-01

    Pharmacological treatment of type 2 diabetes has been enriched during recent years, with the launch of incretin therapies targeting glucagon-like peptide-1 (GLP-1). Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). Although both pharmacological approaches target GLP-1, important differences exist concerning the mode of administration (subcutaneous injection versus oral ingestion), the efficacy (better with GLP-1 agonists), the effects on body weight and systolic blood pressure (diminution with agonists versus neutrality with gliptins), the tolerance profile (nausea and possibly vomiting with agonists) and the cost (higher with GLP-1 receptor agonists). Both agents may exert favourable cardiovascular effects. Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. However, this scheme is probably too restrictive and modalities of using incretins are numerous, in almost all stages of type 2 diabetes. Physicians may guide the pharmacological choice based on clinical characteristics, therapeutic goals and patient's preference.

  6. PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

    Directory of Open Access Journals (Sweden)

    Neerupma Silswal

    2012-01-01

    Full Text Available We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα agonists using isolated mouse aortas and middle cerebral arteries (MCAs. The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC, and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.

  7. Radiolabelled D2 agonists as prolactinoma imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Otto, C.A.

    1989-08-01

    During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB, like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of evaluation of quaternized mAChR ligands in the heart is included. In a limited series of such ligands, we have observed a single binding site and a difference in B{sub max} values: QNB competition studies yield larger B{sub max} values than studies with {sup 3}H-NMS. Progress in the synthesis of D{sub 2} agonists includes solving a synthetic problem and preparation of the cold'' analogue of N-0437 using procedures applicable to eventual synthesis with {sup 11}C-CH{sub 3}I. 2 refs., 5 figs., 1 tab.

  8. Velocity bunching in travelling wave accelerator with low acceleration gradient

    CERN Document Server

    Huang, Rui-Xuan; Li, Wei-Wei; Jia, Qi-Ka

    2013-01-01

    We present the analytical and simulated results concerning the influences of the acceleration gradient in the velocity bunching process, which is a bunch compression scheme that uses a traveling wave accelerating structure as a compressor. Our study shows that the bunch compression application with low acceleration gradient is more tolerant to phase jitter and more successful to obtain compressed electron beam with symmetrical longitudinal distribution and low energy spread. We also present a transverse emittance compensation scheme to compensate the emittance growth caused by the increasing of the space charge force in the compressing process that is easy to be adjusted for different compressing factors.

  9. Accelerated coffee pulp composting.

    Science.gov (United States)

    Sánchez, G; Olguín, E J; Mercado, G

    1999-02-01

    The effect of two abundant, easily available and very low-cost agro-industrial organic residues, i.e., filter cake from the sugar industry and poultry litter, on the composting stabilization time of coffee pulp and on the quality of the produced compost, was evaluated. Piles of one cubic meter were built and monitored within the facilities of a coffee processing plant in the Coatepec region of the State of Veracruz, Mexico. Manual aeration was carried out once a week. A longer thermophilic period (28 days) and a much lower C/N ratio (in the range of 6.9-9.1) were observed in the piles containing the amendments, as compared to the control pile containing only coffee pulp (14 days and a C/N ratio of 14.4, respectively). The maximum assimilation rate of the reducing sugars was 1.6 g kg-1 d-1 (from 7.5 to 5.3%) during the first two weeks when accelerators were present in the proportion of 20% filter cake plus 20% poultry litter, while they accumulated at a rate of 1.2 g kg-1 d-1 (from 7.4 to 9.13%) during the same period in the control pile. The best combination of amendments was 30% filter cake with 20% poultry litter, resulting in a final nitrogen content as high as 4.81%. The second best combination was 20% filter cake with 10% poultry litter, resulting in a compost which also contained a high level of total nitrogen (4.54%). It was concluded that the use of these two residues enhanced the composting process of coffee pulp, promoting a shorter stabilization period and yielding a higher quality of compost.

  10. Operation of the accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, R.C.; Batzka, B.; Billquist, P.J. [and others

    1995-08-01

    Fiscal Year 1994 was the first year of seven-day operation since ATLAS became a national user facility in 1985. ATLAS made the most of the opportunity this year by providing 5200 hours of beam on-target to the research program. A record number of 60 experiments were completed and the {open_quotes}facility reliability{close_quotes} remained near the 90% level. Seven-day operation was made possible with the addition to the staff of two operator positions providing single-operator coverage during the weekend period. The normally scheduled coverage was augmented by an on-call list of system experts who respond to emergencies with phone-in advice and return to the Laboratory when necessary. This staffing approach continues but we rearranged our staffing patterns so that we now have one cryogenics engineer working a shift pattern which includes 8-hour daily coverage during the weekend. ATLAS provided a beam mix to users consisting of 26 different isotopic species, 23% of which were for A>100 in FY 1994. Approximately 60% of the beam time was provided by the Positive Ion Injector, slightly less than the usage rate of FY 1993. Experiments using uranium or lead beams accounted for 16.4% of the total beam time. The ECR ion source and high-voltage platform functioned well throughout the year. A new technique for solid material production in the source was developed which uses a sputtering process wherein the sample of material placed near the plasma chamber wall is biased negatively. Plasma ions are accelerated into the sample and material is sputtered from the surface into the plasma. This technique is now used routinely for many elements. Runs of calcium, germanium, nickel, lead, tellurium, and uranium were carried out with this technique.

  11. Accelerating DSMC data extraction.

    Energy Technology Data Exchange (ETDEWEB)

    Gallis, Michail A.; Piekos, Edward Stanley

    2006-10-01

    In many direct simulation Monte Carlo (DSMC) simulations, the majority of computation time is consumed after the flowfield reaches a steady state. This situation occurs when the desired output quantities are small compared to the background fluctuations. For example, gas flows in many microelectromechanical systems (MEMS) have mean speeds more than two orders of magnitude smaller than the thermal speeds of the molecules themselves. The current solution to this problem is to collect sufficient samples to achieve the desired resolution. This can be an arduous process because the error is inversely proportional to the square root of the number of samples so we must, for example, quadruple the samples to cut the error in half. This work is intended to improve this situation by employing more advanced techniques, from fields other than solely statistics, for determining the output quantities. Our strategy centers on exploiting information neglected by current techniques, which collect moments in each cell without regard to one another, values in neighboring cells, nor their evolution in time. Unlike many previous acceleration techniques that modify the method itself, the techniques examined in this work strictly post-process so they may be applied to any DSMC code without affecting its fidelity or generality. Many potential methods are drawn from successful applications in a diverse range of areas, from ultrasound imaging to financial market analysis. The most promising methods exploit relationships between variables in space, which always exist in DSMC due to the absence of shocks. Disparate techniques were shown to produce similar error reductions, suggesting that the results shown in this report may be typical of what is possible using these methods. Sample count reduction factors of approximately three to five were found to be typical, although factors exceeding ten were shown on some variables under some techniques.

  12. Early administration of RS 67333, a specific 5-HT4 receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Patrizia eGiannoni

    2013-12-01

    Full Text Available Amyloid β (Aβ accumulation is considered the main culprit in the pathogenesis of Alzheimer's disease (AD. Recent studies suggest that decreasing Aβ production at very early stages of AD could be a promising strategy to slow down disease progression. Serotonin 5-HT4 receptor activation stimulates α-cleavage of the amyloid precursor protein (APP, leading to the release of the soluble and neurotrophic sAPPα fragment and thus precluding Aβ formation. Using the 5XFAD mouse model of AD that shows accelerated Aβ deposition, we investigated the effect of chronic treatments (treatment onset at different ages and different duration with the 5-HT4 receptor agonist RS 67333 during the asymptomatic phase of the disease. Chronic administration of RS 67333 decreased concomitantly the number of amyloid plaques and the level of Aβ species. Reduction of Aβ levels was accompanied by a striking decrease in hippocampal astrogliosis and microgliosis. RS 67333 also transiently increased sAPPα concentration in the cerebrospinal fluid and brain. Moreover, a specific 5-HT4 receptor antagonist (RS 39604 prevented the RS 67333-mediated reduction of the amyloid pathology. Finally, the novel object recognition test deficits of 5XFAD mice were reversed by chronic treatment with RS 67333. Collectively, these results strongly highlight this 5-HT4 receptor agonist as a promising disease modifying-agent for AD.

  13. "small ACCELERATORS" 24 May - 2 June 2005

    CERN Multimedia

    2005-01-01

    CERN Accelerator School and Kernfysisch Versneller Instituut (KVI) Groningen, the Netherlands announce a course on "Small Accelerators", Hotel Golden Tulip Drenthe, Zeegse, the Netherlands, 24 May - 2 June 2005. This specialised course is dedicated to the physics and the main applications of small accelerators. The course will review the different accelerator types as well as their specificities in terms of accelerator physics.

  14. Application of electron accelerator worldwide

    Energy Technology Data Exchange (ETDEWEB)

    Machi, Sueo [Japan Atomic Industrial Forum, Inc., Tokyo (Japan)

    2003-02-01

    Electron accelerator is an important radiation source for radiation technology, which covers broad fields such as industry, health care, food and environmental protection. There are about 1,000 electron accelerators for radiation processing worldwide. Electron accelerator has advantage over Co-60 irradiator in term of high dose rate and power, assurance of safety, and higher economic performance at larger volume of irradiation. Accelerator generating higher energy in the range of 10 MeV and high power electron beam is now commercially available. There is a trend to use high-energy electron accelerator replacing Co-60 in case of large through-put of medical products. Irradiated foods, in particular species, are on the commercial market in 35 countries. Electron accelerator is used efficiently and economically for production of new or modified polymeric materials through radiation-induced cross-linking, grafting and polymerization reaction. Another important application of electron beam is the curing of surface coatings in the manufacture of products. Electron accelerators of large capacity are used for cleaning exhaust gases in industrial scale. Economic feasibility studies of this electron beam process have shown that this technology is more cost effective than the conventional process. It should be noted that the conventional limestone process produce gypsum as a by-product, which cannot be used in some countries. By contrast, the by-product of the electron beam process is a valuable fertilizer. (Y. Tanaka)

  15. Application of electron accelerator worldwide

    International Nuclear Information System (INIS)

    Electron accelerator is an important radiation source for radiation technology, which covers broad fields such as industry, health care, food and environmental protection. There are about 1,000 electron accelerators for radiation processing worldwide. Electron accelerator has advantage over Co-60 irradiator in term of high dose rate and power, assurance of safety, and higher economic performance at larger volume of irradiation. Accelerator generating higher energy in the range of 10 MeV and high power electron beam is now commercially available. There is a trend to use high-energy electron accelerator replacing Co-60 in case of large through-put of medical products. Irradiated foods, in particular species, are on the commercial market in 35 countries. Electron accelerator is used efficiently and economically for production of new or modified polymeric materials through radiation-induced cross-linking, grafting and polymerization reaction. Another important application of electron beam is the curing of surface coatings in the manufacture of products. Electron accelerators of large capacity are used for cleaning exhaust gases in industrial scale. Economic feasibility studies of this electron beam process have shown that this technology is more cost effective than the conventional process. It should be noted that the conventional limestone process produce gypsum as a by-product, which cannot be used in some countries. By contrast, the by-product of the electron beam process is a valuable fertilizer. (Y. Tanaka)

  16. PROTON ACCELERATION AT OBLIQUE SHOCKS

    International Nuclear Information System (INIS)

    Acceleration at the shock waves propagating oblique to the magnetic field is studied using a recently developed theoretical/numerical model. The model assumes that resonant hydromagnetic wave-particle interaction is the most important physical mechanism relevant to motion and acceleration of particles as well as to excitation and damping of waves. The treatment of plasma and waves is self-consistent and time dependent. The model uses conservation laws and resonance conditions to find where waves will be generated or damped, and hence particles will be pitch-angle-scattered. The total distribution is included in the model and neither introduction of separate population of seed particles nor some ad hoc escape rate of accelerated particles is needed. Results of the study show agreement with diffusive shock acceleration models in the prediction of power spectra for accelerated particles in the upstream region. However, they also reveal the presence of spectral break in the high-energy part of the spectra. The role of the second-order Fermi-like acceleration at the initial stage of the acceleration is discussed. The test case used in the paper is based on ISEE-3 data collected for the shock of 1978 November 12.

  17. Proton Acceleration at Oblique Shocks

    Science.gov (United States)

    Galinsky, V. L.; Shevchenko, V. I.

    2011-06-01

    Acceleration at the shock waves propagating oblique to the magnetic field is studied using a recently developed theoretical/numerical model. The model assumes that resonant hydromagnetic wave-particle interaction is the most important physical mechanism relevant to motion and acceleration of particles as well as to excitation and damping of waves. The treatment of plasma and waves is self-consistent and time dependent. The model uses conservation laws and resonance conditions to find where waves will be generated or damped, and hence particles will be pitch-angle-scattered. The total distribution is included in the model and neither introduction of separate population of seed particles nor some ad hoc escape rate of accelerated particles is needed. Results of the study show agreement with diffusive shock acceleration models in the prediction of power spectra for accelerated particles in the upstream region. However, they also reveal the presence of spectral break in the high-energy part of the spectra. The role of the second-order Fermi-like acceleration at the initial stage of the acceleration is discussed. The test case used in the paper is based on ISEE-3 data collected for the shock of 1978 November 12.

  18. 2014 CERN Accelerator Schools: Beam Loss and Accelerator Protection

    CERN Multimedia

    2014-01-01

    The US-CERN-JAPAN-RUSSIA Joint International Accelerator School is organising a course on Beam Loss and Accelerator Protection to be held in Newport Beach, California, USA from 5-14 November, 2014.    This school is intended for physicists and engineers who are or may be engaged in the design, construction, and/or operation of accelerators with high power photon or particle beams and/or accelerator sub-systems with large stored energy. Application deadlines are 15 August and 4 September. Further information on this Joint School can be found at: http://cas.web.cern.ch/cas/JAS/Newport%20Beach%202014/NPBadvert.html http://indico.cern.ch/event/287647/ http://uspas.fnal.gov/programs/JAS/JAS14.shtml

  19. CAS CERN Accelerator School second advanced accelerator physics course

    International Nuclear Information System (INIS)

    The advanced course on general accelerator physics given in West Berlin closely followed that organised by the CERN Accelerator School at Oxford in September 1985 and whose proceedings were published as CERN Yellow Report 87-03 (1987). However, certain subjects were treated in a different way, improved or extended, while some new ones were introduced and it is all of these which are included in the present proceedings. The lectures include particle-photon interactions, high-brilliance lattices and single/multiple Touschek effect, while the seminars are on the major accelerators presently under construction or proposed for the near future, applications of synchrotron radiation, free-electron lasers, cosmic accelerators and crystal beams. Also included are errata, and addenda to some of the lectures, of CERN 87-03. (orig.)

  20. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    Directory of Open Access Journals (Sweden)

    Vadim I Krivokrysenko

    Full Text Available There are currently no approved medical radiation countermeasures (MRC to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01 absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05 effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

  1. The Radiological Research Accelerator Facility

    International Nuclear Information System (INIS)

    The Radiological Research Accelerator Facility (RARAF) is based on a 4-MV Van de Graaff accelerator, which is used to generate a variety of well-characterized radiation beams for research in radiobiology, radiological physics, and radiation chemistry. It is part of the Center for Radiological Research (CRR) -- formerly the Radiological Research Laboratory (RRL) -- of Columbia University, and its operation is supported as a National Facility by the US Department of Energy (DOE). Fifteen different experiments were run during these 12 months, approximately the same as the previous two years. Brief summaries of each experiment are included. Accelerator usage is summarized and development activities are discussed. 7 refs., 4 tabs

  2. Stochastic modeling of Lagrangian accelerations

    Science.gov (United States)

    Reynolds, Andy

    2002-11-01

    It is shown how Sawford's second-order Lagrangian stochastic model (Phys. Fluids A 3, 1577-1586, 1991) for fluid-particle accelerations can be combined with a model for the evolution of the dissipation rate (Pope and Chen, Phys. Fluids A 2, 1437-1449, 1990) to produce a Lagrangian stochastic model that is consistent with both the measured distribution of Lagrangian accelerations (La Porta et al., Nature 409, 1017-1019, 2001) and Kolmogorov's similarity theory. The later condition is found not to be satisfied when a constant dissipation rate is employed and consistency with prescribed acceleration statistics is enforced through fulfilment of a well-mixed condition.

  3. Particle acceleration in modified shocks

    International Nuclear Information System (INIS)

    Efficient particle acceleration in shocks must modify the shock structure with consequent changes in the particle acceleration. This effect is studied and analytic solutions are found describing the diffusive acceleration of particles with momentum independent diffusion coefficients in hyperbolic tangent type velocity transitions. If the input particle spectrum is a delta function, the shock smoothing replaces the truncated power-law downstream particle spectrum by a more complicated form, but one which has a power-law tail at high momenta. For a cold plasma this solution can be made completely self-consistent. Some problems associated with momentum dependent diffusion coefficients are discussed. (author)

  4. Electromagnetic acceleration of permanent magnets

    CERN Document Server

    Dolya, S N

    2015-01-01

    We consider the acceleration of the permanent magnets, consisting of neodymium iron boron by means of the running magnetic field gradient. It is shown that the specific magnetic moment per nucleon in neodymium iron boron is determined by the remained magnetization of the substance. The maximum accessable gradient of the magnetic field accelerating the permanent magnets is determined by the coercive force thirty kilogauss. For the neodymium iron boron magnets this gradient is equal to twenty kilogauss divided by one centimeter. The finite velocity of the magnets six kilometers per second, the length of acceleration is six hundred thirty-seven meters.

  5. The wake field acceleration mechanism

    International Nuclear Information System (INIS)

    The wake fields of dense bunches of relativistic electrons are used to accelerate secondary beams of positrons and electrons. The basic principle is the transformation of wake forces by means of geometric structures with different impedances at different locations. In such wake field transformers beams of a few GeV energy can accelerate secondary beams to ten times the energy of the driving particles. Two 50 GeV colliding beam linear accelerators based on this mechanism occupy less than 1300 meters total length. (orig.)

  6. New type of collective accelerator

    International Nuclear Information System (INIS)

    A collective accelerator based on magnetically confined plasma rings is described. Typical rings which have been produced and which have 10 kJ magnetic energy and 0.1 to 10 coulombs of nuclei are predicted to be accelerated magnetically to 10 MJ or higher in acceleration lengths of 100 m if the final power delivered to the ring is 1012 W. Applications are discussed of current drive in Tokamak fusion reactions, fueling and heating magnetic fusion reactors, transuranic element synthesis, and, for focused rings, a high energy density driver for inertial confinement fusion

  7. Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: a review.

    Science.gov (United States)

    Gobello, C

    2006-10-01

    Over the last 10 years, new drugs have been applied to canine reproduction, widening the spectrum of therapeutic possibilities for diseases that were previously surgically treated, and facilitating better control of the estrous cycle and fertility. Some are not approved for use in dogs; their use is experimental and further clinical trials are necessary. Dopamine agonists such as cabergoline, bromocriptine or metergoline are ergoderivative alkaloids that exert an anti-prolactinergic effect via stimulation of D2 pituitary receptors or inhibition of central serotoninergic ones. Their main indication is suppression of lactation. Anti-prolactinergic compounds have also been successfully used for pregnancy termination and shortening of interestrous intervals. Anti-progestins, (e.g. mifepristone and aglepristone) are synthetic steroids that bind with high affinity to progesterone (P4) receptors, preventing P4 from exerting its biological effects. Anti-progestins have been indicated in P4-dependent conditions, such as pregnancy termination, induction of parturition and the medical treatment of pyometra. Several groups of drugs have been described to have anti-androgenic properties through different mechanisms of action: progestins, receptor binding anti-androgens (e.g. flutamide), competitive enzyme inhibitors (e.g. finasteride), aromatase inhibitors, and GnRH agonists. Their main application is medical treatment of benign prostatic hyperplasia. Long-term release formulations of GnRH agonists (e.g. leuprolide or deslorelin acetate) postponed puberty and reversibly suppressed reproductive function in male and female dogs for periods exceeding 1 year. Anti-estrogens (e.g. clomiphene and tamoxifen citrate) are synthetic non-steroidal type I anti-estrogenic compounds that competitively block estrogen receptors with a combined antagonist-agonistic effect. In dogs, their action is more agonistic than antagonistic. PMID:16542717

  8. Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells.

    Science.gov (United States)

    Sharma, Pawan; Panebra, Alfredo; Pera, Tonio; Tiegs, Brian C; Hershfeld, Alena; Kenyon, Lawrence C; Deshpande, Deepak A

    2016-02-15

    Airway remodeling is a hallmark feature of asthma and chronic obstructive pulmonary disease. Clinical studies and animal models have demonstrated increased airway smooth muscle (ASM) mass, and ASM thickness is correlated with severity of the disease. Current medications control inflammation and reverse airway obstruction effectively but have limited effect on remodeling. Recently we identified the expression of bitter taste receptors (TAS2R) on ASM cells, and activation with known TAS2R agonists resulted in ASM relaxation and bronchodilation. These studies suggest that TAS2R can be used as new therapeutic targets in the treatment of obstructive lung diseases. To further establish their effectiveness, in this study we aimed to determine the effects of TAS2R agonists on ASM growth and promitogenic signaling. Pretreatment of healthy and asthmatic human ASM cells with TAS2R agonists resulted in a dose-dependent inhibition of ASM proliferation. The antimitogenic effect of TAS2R ligands was not dependent on activation of protein kinase A, protein kinase C, or high/intermediate-conductance calcium-activated K(+) channels. Immunoblot analyses revealed that TAS2R agonists inhibit growth factor-activated protein kinase B phosphorylation without affecting the availability of phosphatidylinositol 3,4,5-trisphosphate, suggesting TAS2R agonists block signaling downstream of phosphatidylinositol 3-kinase. Furthermore, the antimitogenic effect of TAS2R agonists involved inhibition of induced transcription factors (activator protein-1, signal transducer and activator of transcription-3, E2 factor, nuclear factor of activated T cells) and inhibition of expression of multiple cell cycle regulatory genes, suggesting a direct inhibition of cell cycle progression. Collectively, these findings establish the antimitogenic effect of TAS2R agonists and identify a novel class of receptors and signaling pathways that can be targeted to reduce or prevent airway remodeling as well as

  9. PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption.

    Science.gov (United States)

    Ferguson, Laura B; Most, Dana; Blednov, Yuri A; Harris, R Adron

    2014-11-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior. PMID:25036611

  10. Gonadotropin-releasing hormone agonist use in men without a cancer registry diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Kuo Yong-fang

    2008-07-01

    Full Text Available Abstract Background Use of gonadotropin-releasing hormone (GnRH agonists has become popular for virtually all stages of prostate cancer. We hypothesized that some men receive these agents after only a limited work-up for their cancer. Such cases may be missed by tumor registries, leading to underestimates of the total extent of GnRH agonist use. Methods We used linked Surveillance, Epidemiology and End-Results (SEER-Medicare data from 1993 through 2001 to identify GnRH agonist use in men with either a diagnosis of prostate cancer registered in SEER, or with a diagnosis of prostate cancer based only on Medicare claims (from the 5% control sample of Medicare beneficiaries residing in SEER areas without a registered diagnosis of cancer. The proportion of incident GnRH agonist users without a registry diagnosis of prostate cancer was calculated. Factors associated with lack of a registry diagnosis were examined in multivariable analyses. Results Of incident GnRH agonist users, 8.9% had no diagnosis of prostate cancer registered in SEER. In a multivariable logistic regression model, lack of a registry diagnosis of prostate cancer in GnRH agonist users was significantly more likely with increasing comorbidity, whereas it was less likely in men who had undergone either inpatient admission or procedures such as radical prostatectomy, prostate biopsy, or transurethral resection of the prostate. Conclusion Reliance solely on tumor registry data may underestimate the rate of GnRH agonist use in men with prostate cancer.

  11. Ascorbic acid enables reversible dopamine receptor /sup 3/H-agonist binding

    Energy Technology Data Exchange (ETDEWEB)

    Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

    1981-11-16

    The effects of ascorbic acid on dopaminergic /sup 3/H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the /sup 3/H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total /sup 3/H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable /sup 3/H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable /sup 3/H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of /sup 3/H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific /sup 3/H-agonist binding to dopamine receptors.

  12. Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Ming-Liang Zhang; Zuo-Jiong Gong

    2004-01-01

    dramatically compared with model group.CONCLUSION: PPARγ agonist pioglitazone greatly retards the progression of rat hepatic fibrosis induced by CCl4through inhibition of HSC activation and amelioration of hepatocyte necroinflammation in rats.

  13. Terahertz-driven linear electron acceleration

    CERN Document Server

    Nanni, Emilio Alessandro; Ravi, Koustuban; Fallahi, Arya; Moriena, Gustavo; Miller, R J Dwayne; Kärtner, Franz X

    2014-01-01

    The cost, size and availability of electron accelerators is dominated by the achievable accelerating gradient. Conventional high-brightness radio-frequency (RF) accelerating structures operate with 30-50 MeV/m gradients. Electron accelerators driven with optical or infrared sources have demonstrated accelerating gradients orders of magnitude above that achievable with conventional RF structures. However, laser-driven electron accelerators require intense sources and suffer from low bunch charge, sub-micron tolerances and sub-femtosecond timing requirements due to the short wavelength of operation. Here, we demonstrate the first linear acceleration of electrons with keV energy gain using optically-generated terahertz (THz) pulses. THz-driven accelerating structures enable high-gradient electron accelerators with simple accelerating structures, high repetition rates and significant charge per bunch. Increasing the operational frequency of accelerators into the THz band allows for greatly increased accelerating ...

  14. SNEAP 80: symposium of Northeastern Accelerator personnel

    International Nuclear Information System (INIS)

    Reports of operations are presented for twenty-seven facilities, along with reports on accelerators in progress, ion sources, insulating gases, charging systems, stripping foils, accelerating tubes, and upgraded accelerator systems

  15. SNEAP 80: symposium of Northeastern Accelerator personnel

    Energy Technology Data Exchange (ETDEWEB)

    Billen, J.H. (ed.)

    1980-01-01

    Reports of operations are presented for twenty-seven facilities, along with reports on accelerators in progress, ion sources, insulating gases, charging systems, stripping foils, accelerating tubes, and upgraded accelerator systems. (GHT)

  16. Accelerator technology working group summary

    International Nuclear Information System (INIS)

    A summary is presented of workshop deliberations on basic scaling, the economic viability of laser drive power for HEP accelerators, the availability of electron beam injectors for near-term experiments, and a few very general remarks on technology issues

  17. 1988 linear accelerator conference proceedings

    International Nuclear Information System (INIS)

    This report contains papers presented at the 1988 Linear Accelerator Conference. A few topics covered are beam dynamics; beam transport; superconducting components; free electron lasers; ion sources; and klystron research

  18. Accelerator and fusion research division

    International Nuclear Information System (INIS)

    This report contains brief discussions on research topics in the following area: Heavy-Ion Fusion Accelerator Research; Magnetic Fusion Energy; Advanced Light Source; Center for Beam Physics; Superconducting Magnets; and Bevalac Operations

  19. Accelerator structure work for NLC

    Energy Technology Data Exchange (ETDEWEB)

    Miller, R.H.; Adolphsen, C.; Bane, K.L.F.; Deruyter, H.; Farkas, Z.D.; Hoag, H.A.; Holtkamp, N.; Lavine, T.; Loew, G.A.; Nelson, E.M.; Palmer, R.B.; Paterson, J.M.; Ruth, R.D.; Thompson, K.A.; Vlieks, A.; Wang, J.W.; Wilson, P.B. [Stanford Linear Accelerator Center, Menlo Park, CA (United States); Gluckstern, R. [Maryland Univ., College Park, MD (United States); Ko, K.; Kroll, N. [Stanford Linear Accelerator Center, Menlo Park, CA (United States)]|[California Univ., San Diego, La Jolla, CA (United States). Dept. of Physics

    1992-07-01

    The NLC design achieves high luminosity with multiple bunches in each RF pulse. Acceleration of a train of bunches without emittance growth requires control of long range dipole wakefields. SLAC is pursuing a structure design which suppresses the effect of wakefields by varying the physical dimensions of successive cells of the disk-loaded traveling wave structure in a manner which spreads the frequencies of the higher mode while retaining the synchronism between the electrons and the accelerating mode. The wakefields of structures incorporating higher mode detuning have been measured at the Accelerator Test Facility at Argonne. Mechanical design and brazing techniques which avoid getting brazing alloy into the interior of the accelerator are being studied. A test facility for high-power testing of these structures is complete and high power testing has begun.

  20. Quantum aspects of accelerator optics

    OpenAIRE

    Khan, Sameen Ahmed

    1999-01-01

    Present understanding of accelerator optics is based mainly on classical mechanics and electrodynamics. In recent years quantum theory of charged-particle beam optics has been under development. In this paper the newly developed formalism is outlined.

  1. Electrodynamics acceleration of electrical dipoles

    CERN Document Server

    Dolya, S N

    2013-01-01

    This article considers the acceleration of electric dipoles consisting of thin metal plates and dielectric (barium titanate). The dipoles are of a cylindrical shape with a diameter of the cylinder two centimeters and length one centimeter. Capacity of the parallel-plate capacitor is three hundred picofarads and it is charged up to the voltage of two hundred eighty kilovolts. Pre-acceleration of the electric dipoles till velocity one kilometer per second is reached by the gas-dynamic method. The finite acceleration is produced in a spiral waveguide, where the pulse is travelling with voltage amplitude seven hundreds kilovolts and power one hundred twenty-five megawatts. This pulse travels via the spiral waveguide and accelerates the injected electric dipoles in the longitudinal direction till the finite velocity eight and a half kilometers per second over length seven hundred and seventy meters.

  2. drift tube for linear accelerator

    CERN Multimedia

    A drift tube from the Linac 1. This was the first tank of the linear accelerator Linac1, the injection system for the Proton Synchrotron, It ran for 34 years (1958 - 1992). Protons entered at the far end and were accelerated between the copper drift tubes by an oscillating electromagnetic field. The field flipped 200 million times a second (200 MHz) so the protons spent 5 nanoseconds crossing a drift tube and a gap. Moving down the tank, the tubes and gaps had to get longer as the protons gained speed. The tank accelerated protons from 500 KeV to 10 MeV. Linac1 was also used to accelerate deutrons and alpha particles for the Intersecting Storage Rings and oxygen and sulpher ions for the Super Proton Synchrotron heavy ion programme.

  3. Advanced Superconducting Test Accelerator (ASTA)

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Superconducting Test Accelerator (ASTA) facility will be based on upgrades to the existing NML pulsed SRF facility. ASTA is envisioned to contain 3 to...

  4. Prototype of industrial electrons accelerator

    International Nuclear Information System (INIS)

    The interest and the necessity of Mexico's industry in the use of irradiation process has been increased in the last years. As examples are the irradiation of combustion gases (elimination of NOx and SO2) and the polymer cross-linking between others. At present time at least twelve enterprises require immediately of them which have been contacted by electron accelerators suppliers of foreign countries. The first project step consisted in to identify the electrons accelerator type that in can be constructed in Mexico with the major number of possible equipment, instruments, components and acquisition materials local and useful for the major number of users. the characteristics of the accelerator prototype are: accelerator type transformer with multiple secondary insulated and rectifier circuits with a potential of 0.8 MV of voltage, the second step it consisted in an economic study that permitted to demonstrate the economic feasibility of its construction. (Author)

  5. Accelerating advanced-materials commercialization

    Science.gov (United States)

    Maine, Elicia; Seegopaul, Purnesh

    2016-05-01

    Long commercialization times, high capital costs and sustained uncertainty deter investment in innovation for advanced materials. With appropriate strategies, technology and market uncertainties can be reduced, and the commercialization of advanced materials accelerated.

  6. Particle accelerator; the Universe machine

    CERN Multimedia

    Yurkewicz, Katie

    2008-01-01

    "In summer 2008, scientists will switch on one of the largest machines in the world to search for the smallest of particle. CERN's Large Hadron Collider particle accelerator has the potential to chagne our understanding of the Universe."

  7. IGBT accelerated aging data set.

    Data.gov (United States)

    National Aeronautics and Space Administration — Preliminary data from thermal overstress accelerated aging using the aging and characterization system. The data set contains aging data from 6 devices, one device...

  8. Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2012-01-01

    Incretin-based therapies, which include the GLP-1 receptor agonists and DPP-4 inhibitors, use the antidiabetic properties of potentiating the GLP-1 receptor signalling via the regulation of insulin and glucagon secretion, inhibition of gastric emptying and suppression of appetite. Most physicians...... will start antidiabetic treatment with metformin, but adding a GLP-1 receptor agonist as the second drug seems to be optimal since more patients will reach an HbA1c below 7% than with a DPP-4 inhibitor or another oral antidiabetic agents and with minimal risk of hypoglycaemia. The GLP-1 receptor agonists...... are also more effective in weight and systolic blood pressure control than DPP-4 inhibitors. The side effects of the GLP-1 receptor agonists are primarily nausea and vomiting, which is less pronounced with the long acting agonists and often transient. A GLP-1 receptor agonist can be recommended before...

  9. Accelerated Development of Organizational Talent

    OpenAIRE

    Korotov, Konstantin

    2007-01-01

    This working paper explores the challenges of accelerated development of organizational talent. The meaning of the word "accelerated" is that such development takes place at a pace that is significantly higher than that of "traditional" development that allows an individual to learn the intricacies of the current job, observe incumbents in a higher level position (usually, one level up), practice elements of the boss' job when being delegated tasks, undergoing formal training, or benefiting f...

  10. Electron Cloud Effects in Accelerators

    OpenAIRE

    Furman, M.A.

    2014-01-01

    Abstract We present a brief summary of various aspects of the electron-cloud effect (ECE) in accelerators. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire ?ECLOUD? series [1?22]. In addition, the proceedings of the various flavors of Particle Accelerator Conferences [23] contain a large number of EC-related publications. The ICFA Beam Dynamics...

  11. Caianiello's maximal acceleration. Recent developments

    OpenAIRE

    Papini, G.

    2004-01-01

    A quantum mechanical upper limit on the value of particle accelerations is consistent with the behavior of a class of superconductors and well known particle decay rates. It also sets limits on the mass of the Higgs boson and affects the stability of compact stars. In particular, type-I superconductors in static conditions offer an example of a dynamics in which acceleration has an upper limit.

  12. Sequentially pulsed traveling wave accelerator

    Science.gov (United States)

    Caporaso, George J.; Nelson, Scott D.; Poole, Brian R.

    2009-08-18

    A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

  13. Particle accelerators and scientific culture

    International Nuclear Information System (INIS)

    A historical review of fifty years of physics around particle accelerators, from the first nuclear reactions produced by beams of artificially accelerated particles to the large multinational projects now under discussion. The aim is to show how our description of natural phenomena has been shaped by advances in theoretical understanding, the development of new techniques, and the characters of men. Large use has been made of quotations from many of the scientists involved. (Auth.)

  14. Particle accelerators and scientific culture

    International Nuclear Information System (INIS)

    A historical review of fifty years of physics around particle accelerators, from the first nuclear reactions produced by beams of artificially accelerated particles to the large multinational projects now under discussion. The aim is to show how the description of natural phenomena has been shaped by advances in theoretical understanding, the development of new techniques, and the characters of men. Large use has been made of quotations from many of the scientists involved. (Auth.)

  15. The Beta Tech electron accelerator

    International Nuclear Information System (INIS)

    After describing the background of the Swedish Electron Sterilization Centre, the proposed linear accelerator sterilization plant is outlined. The accelerator will produce electrons of energy 10 MeV and a beam power of 30 KW. The handling system, control and identification systems are also described. Documentation will be designed around a bar code system on line to a computer. The various uses of dosimetry in plant performance and process control are described. (U.K.)

  16. Dark Energy or local acceleration?

    CERN Document Server

    Feoli, Antonio

    2016-01-01

    We find that an observer with a suitable acceleration relative to the frame comoving whit the cosmic fluid, in the context of the FRW decelerating universe, measures the same cosmological redshift as the LambdaCDM model. The estimated value of this acceleration is beta = 1.4x10^-9m/s^2. The problem of a too high peculiar velocity can be solved assuming, for the observer, a sort of helical motion.

  17. The acceleration of galactic cosmic rays

    International Nuclear Information System (INIS)

    A number of acceleration mechanisms are discussed including stochastic acceleration, shock acceleration, laminar shock acceleration and acceleration by shocks in scattering media. The self-consistent problem is analysed and it is concluded that provided the cosmic rays are scattered effectively and provided energy losses are not too severe, they can be very efficiently accelerated by shock waves in the interstellar medium. (C.F.)

  18. Test accelerator for linear collider

    International Nuclear Information System (INIS)

    KEK has proposed to build Test Accelerator Facility (TAF) capable of producing a 2.5 GeV electron beam for the purpose of stimulating R ampersand D for linear collider in TeV region. The TAF consists of a 1.5 GeV S-band linear accelerator, 1.5 GeV damping ring and 1.0 GeV X-band linear accelerator. The TAF project will be carried forward in three phases. Through Phase-I and Phase-II, the S-band and X-band linacs will be constructed, and in Phase-III, the damping ring will be completed. The construction of TAF Phase-I has started, and the 0.2 GeV S-band injector linac has been almost completed. The Phase-I linac is composed of a 240 keV electron gun, subharmonic bunchers, prebunchers and traveling buncher followed by high-gradient accelerating structures. The SLAC 5045 klystrons are driven at 450 kV in order to obtain the rf-power of 100 MW in a 1 μs pulse duration. The rf-power from a pair of klystrons are combined into an accelerating structure. The accelerating gradient up to 100 MeV/m will be obtained in a 0.6 m long structure. 5 refs., 3 figs., 2 tabs

  19. Ponderomotive Acceleration by Relativistic Waves

    CERN Document Server

    Lau, Calvin; Yeh, Po-Chun; Luk, Onnie; McClenaghan, Joseph; Ebisuzaki, Toshikazu; Tajima, Toshiki

    2014-01-01

    In the extreme high intensity regime of electromagnetic (EM) waves in plasma, the acceleration process is found to be dominated by the ponderomotive acceleration (PA). While the wakefields driven by the ponderomotive force of the relativistic intensity EM waves are important, they may be overtaken by the PA itself in the extreme high intensity regime when the dimensionless vector potential $a_0$ of the EM waves far exceeds unity. The energy gain by this regime (in 1D) is shown to be (approximately) proportional to $a_0^2$. Before reaching this extreme regime, the coexistence of the PA and the wakefield acceleration (WA) is observed where the wave structures driven by the wakefields show the phenomenon of multiple and folded wave-breakings. Investigated are various signatures of the acceleration processes such as the dependence on the mass ratio for the energy gain as well as the energy spectral features. The relevance to high energy cosmic ray acceleration and to the relativistic laser acceleration is conside...

  20. High-Intensity Proton Accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Jay L. Hirshfield

    2011-12-27

    Analysis is presented for an eight-cavity proton cyclotron accelerator that could have advantages as compared with other accelerators because of its potentially high acceleration gradient. The high gradient is possible since protons orbit in a sequence of TE111 rotating mode cavities of equally diminishing frequencies with path lengths during acceleration that greatly exceed the cavity lengths. As the cavities operate at sequential harmonics of a basic repetition frequency, phase synchronism can be maintained over a relatively wide injection phase window without undue beam emittance growth. It is shown that use of radial vanes can allow cavity designs with significantly smaller radii, as compared with simple cylindrical cavities. Preliminary beam transport studies show that acceptable extraction and focusing of a proton beam after cyclic motion in this accelerator should be possible. Progress is also reported on design and tests of a four-cavity electron counterpart accelerator for experiments to study effects on beam quality arising from variations injection phase window width. This device is powered by four 500-MW pulsed amplifiers at 1500, 1800, 2100, and 2400 MHz that provide phase synchronous outputs, since they are driven from a with harmonics derived from a phase-locked 300 MHz source.

  1. Vacuum Brazing of Accelerator Components

    International Nuclear Information System (INIS)

    Commonly used materials for accelerator components are those which are vacuum compatible and thermally conductive. Stainless steel, aluminum and copper are common among them. Stainless steel is a poor heat conductor and not very common in use where good thermal conductivity is required. Aluminum and copper and their alloys meet the above requirements and are frequently used for the above purpose. The accelerator components made of aluminum and its alloys using welding process have become a common practice now a days. It is mandatory to use copper and its other grades in RF devices required for accelerators. Beam line and Front End components of the accelerators are fabricated from stainless steel and OFHC copper. Fabrication of components made of copper using welding process is very difficult and in most of the cases it is impossible. Fabrication and joining in such cases is possible using brazing process especially under vacuum and inert gas atmosphere. Several accelerator components have been vacuum brazed for Indus projects at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore using vacuum brazing facility available at RRCAT, Indore. This paper presents details regarding development of the above mentioned high value and strategic components/assemblies. It will include basics required for vacuum brazing, details of vacuum brazing facility, joint design, fixturing of the jobs, selection of filler alloys, optimization of brazing parameters so as to obtain high quality brazed joints, brief description of vacuum brazed accelerator components etc.

  2. Exercise as an Adjunct Treatment for Opiate Agonist Treatment: Review of the Current Research and Implementation Strategies

    OpenAIRE

    Weinstock, Jeremiah; Wadeson, Heather K.; VanHeest, Jaci L.

    2012-01-01

    Opiate dependence is a significant public health concern linked to poor quality of life, co-morbid psychiatric disorders, and high costs to society. Current opiate agonist treatments are an effective but limited intervention. Adjunctive interventions could improve and augment opiate agonist treatment outcomes, including drug abstinence, quality of life, and physical health. This article reviews exercise as an adjunctive intervention for opiate agonist treatment, especially in regards to impro...

  3. Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.

    Science.gov (United States)

    Scott, Caitlin E; Ahn, Kwang H; Graf, Steven T; Goddard, William A; Kendall, Debra A; Abrol, Ravinder

    2016-01-25

    Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives. This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions. We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization. This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.

  4. Effects of glucagon-like peptide-1 receptor agonists on renal function

    Institute of Scientific and Technical Information of China (English)

    Theodosios; D; Filippatos; Moses; S; Elisaf

    2013-01-01

    Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.

  5. Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

    Science.gov (United States)

    Sun, Yiyi; Zang, Zhihe; Zhong, Ling; Wu, Min; Su, Qing; Gao, Xiurong; Zan, Wang; Lin, Dong; Zhao, Yan; Zhang, Zhonglin

    2013-01-01

    Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases. PMID:23691032

  6. Dissociated nonsteroidal glucocorticoid receptor modulators; discovery of the agonist trigger in a tetrahydronaphthalene-benzoxazine series.

    Science.gov (United States)

    Barker, Mike; Clackers, Margaret; Copley, Royston; Demaine, Derek A; Humphreys, Davina; Inglis, Graham G A; Johnston, Michael J; Jones, Haydn T; Haase, Michael V; House, David; Loiseau, Richard; Nisbet, Lesley; Pacquet, Francois; Skone, Philip A; Shanahan, Stephen E; Tape, Dan; Vinader, Victoria M; Washington, Melanie; Uings, Iain; Upton, Richard; McLay, Iain M; Macdonald, Simon J F

    2006-07-13

    The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described. PMID:16821781

  7. Evidence for air movement signals in the agonistic behaviour of a nocturnal arachnid (order Amblypygi.

    Directory of Open Access Journals (Sweden)

    Roger D Santer

    Full Text Available Many arthropods possess filiform hair sensilla (termed trichobothria in arachnids, which are extremely sensitive detectors of medium particle displacement. Electrophysiological evidence in some taxa suggests that these sensilla can detect air particle displacements resulting from intraspecific communication signals. However, it has not yet been shown for any species that the air particle displacements detected by the filiform hairs are themselves perceived as a 'signal' (i.e. that individuals make behavioural decisions based upon the responses of these organs to the displays of conspecifics. We investigate the agonistic behaviour of the whip spider Phrynus marginemaculatus and the role of its trichobothria in receiving agonistic signals. Whip spiders have extremely elongated 'antenniform' first legs, which they vibrate close to their opponents during agonistic interactions, inducing air movements that excite their opponents' trichobothria. We find that ablation of the trichobothria causes significant increases in: (I contest duration, and (II the probability of contest escalation past aggressive displays to physical fighting. Therefore, in the absence of air movement-sensitive sensilla, contest assessment is impaired. This suggests that whip spiders exploit true air movement signals during agonistic interactions, and that these are received by the trichobothria. Furthermore, these results indicate that, in whip spiders, such signals help mitigate the cost of agonistic interaction.

  8. Evolution of the Bifunctional Lead μ Agonist / δ Antagonist Containing the Dmt-Tic Opioid Pharmacophore.

    Science.gov (United States)

    Balboni, Gianfranco; Salvadori, Severo; Trapella, Claudio; Knapp, Brian I; Bidlack, Jean M; Lazarus, Lawrence H; Peng, Xuemei; Neumeyer, John L

    2010-02-17

    Based on a renewed importance recently attributed to bi- or multifunctional opioids, we report the synthesis and pharmacological evaluation of some analogues derived from our lead μ agonist / δ antagonist, H-Dmt-Tic-Gly-NH-Bzl. Our previous studies focused on the importance of the C-teminal benzyl function in the induction of such bifunctional activity. The introduction of some substituents in the para position of the phenyl ring (-Cl, -CH(3), partially -NO(2), inactive -NH(2)) was found to give a more potent μ agonist / antagonist effect associated with a relatively unmodified δ antagonist activity (pA(2) = 8.28-9.02). Increasing the steric hindrance of the benzyl group (using diphenylmethyl and tetrahydroisoquinoline functionalities) substantially maintained the μ agonist and δ antagonist activities of the lead compound. Finally and quite unexpectedly D-Tic2, considered as a wrong opioid message now; inserted into the reference compound in lieu of L-Tic, provided a μ agonist / δ agonist better than our reference ligand (H-Dmt-Tic-Gly-NH-Ph) and was endowed with the same pharmacological profile.

  9. Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

    Directory of Open Access Journals (Sweden)

    Martin B. Oleksiewicz

    2008-01-01

    Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

  10. Reconstitution of high-affinity opioid agonist binding in brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Remmers, A.E.; Medzihradsky, F. (Univ. of Michigan Medical School, Ann Arbor (United States))

    1991-03-15

    In synaptosomal membranes from rat brain cortex, the {mu} selective agonist ({sup 3}H)dihydromorphine in the absence of sodium, and the nonselective antagonist ({sup 3}H)naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with K{sub d} values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 {mu}M guanosine 5{prime}-({gamma}-thio)triphosphate (GTP({gamma}S)) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP({gamma}-{sup 35}S) binding sites by 90% and low K{sub m}, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP({gamma}S) was diminished. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low K{sub m} GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor - guanine nucleotide binding protein complex.

  11. Modulation Effect of Peroxisome Proliferator-Activated Receptor Agonists on Lipid Droplet Proteins in Liver.

    Science.gov (United States)

    Zhu, Yun-Xia; Zhang, Ming-Liang; Zhong, Yuan; Wang, Chen; Jia, Wei-Ping

    2016-01-01

    Peroxisome proliferator-activated receptor (PPAR) agonists are used for treating hyperglycemia and type 2 diabetes. However, the mechanism of action of these agonists is still under investigation. The lipid droplet-associated proteins FSP27/CIDEC and LSDP5, regulated directly by PPARγ and PPARα, are associated with hepatic steatosis and insulin sensitivity. Here, we evaluated the expression levels of FSP27/CIDEC and LSDP5 and the regulation of these proteins by consumption of a high-fat diet (HFD) or administration of PPAR agonists. Mice with diet-induced obesity were treated with the PPARγ or PPARα agonist, pioglitazone or fenofibrate, respectively. Liver tissues from db/db diabetic mice and human were also collected. Interestingly, FSP27/CIEDC was expressed in mouse and human livers and was upregulated in obese C57BL/6J mice. Fenofibrate treatment decreased hepatic triglyceride (TG) content and FSP27/CIDEC protein expression in mice fed an HFD diet. In mice, LSDP5 was not detected, even in the context of insulin resistance or treatment with PPAR agonists. However, LSDP5 was highly expressed in humans, with elevated expression observed in the fatty liver. We concluded that fenofibrate greatly decreased hepatic TG content and FSP27/CIDEC protein expression in mice fed an HFD, suggesting a potential regulatory role for fenofibrate in the amelioration of hepatic steatosis.

  12. Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

    Directory of Open Access Journals (Sweden)

    Yiyi Sun

    Full Text Available Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (--arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

  13. Identification of PPARgamma partial agonists of natural origin (I: development of a virtual screening procedure and in vitro validation.

    Directory of Open Access Journals (Sweden)

    Laura Guasch

    Full Text Available BACKGROUND: Although there are successful examples of the discovery of new PPARγ agonists, it has recently been of great interest to identify new PPARγ partial agonists that do not present the adverse side effects caused by PPARγ full agonists. Consequently, the goal of this work was to design, apply and validate a virtual screening workflow to identify novel PPARγ partial agonists among natural products. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a virtual screening procedure based on structure-based pharmacophore construction, protein-ligand docking and electrostatic/shape similarity to discover novel scaffolds of PPARγ partial agonists. From an initial set of 89,165 natural products and natural product derivatives, 135 compounds were identified as potential PPARγ partial agonists with good ADME properties. Ten compounds that represent ten new chemical scaffolds for PPARγ partial agonists were selected for in vitro biological testing, but two of them were not assayed due to solubility problems. Five out of the remaining eight compounds were confirmed as PPARγ partial agonists: they bind to PPARγ, do not or only moderately stimulate the transactivation activity of PPARγ, do not induce adipogenesis of preadipocyte cells and stimulate the insulin-induced glucose uptake of adipocytes. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that our virtual screening protocol was successful in identifying novel scaffolds for PPARγ partial agonists.

  14. Accelerator and electrodynamics capability review

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Kevin W [Los Alamos National Laboratory

    2010-01-01

    Los Alamos National Laboratory (LANL) uses capability reviews to assess the science, technology and engineering (STE) quality and institutional integration and to advise Laboratory Management on the current and future health of the STE. Capability reviews address the STE integration that LANL uses to meet mission requirements. The Capability Review Committees serve a dual role of providing assessment of the Laboratory's technical contributions and integration towards its missions and providing advice to Laboratory Management. The assessments and advice are documented in reports prepared by the Capability Review Committees that are delivered to the Director and to the Principal Associate Director for Science, Technology and Engineering (PADSTE). Laboratory Management will use this report for STE assessment and planning. LANL has defined fifteen STE capabilities. Electrodynamics and Accelerators is one of the seven STE capabilities that LANL Management (Director, PADSTE, technical Associate Directors) has identified for review in Fiscal Year (FY) 2010. Accelerators and electrodynamics at LANL comprise a blend of large-scale facilities and innovative small-scale research with a growing focus on national security applications. This review is organized into five topical areas: (1) Free Electron Lasers; (2) Linear Accelerator Science and Technology; (3) Advanced Electromagnetics; (4) Next Generation Accelerator Concepts; and (5) National Security Accelerator Applications. The focus is on innovative technology with an emphasis on applications relevant to Laboratory mission. The role of Laboratory Directed Research and Development (LDRD) in support of accelerators/electrodynamics will be discussed. The review provides an opportunity for interaction with early career staff. Program sponsors and customers will provide their input on the value of the accelerator and electrodynamics capability to the Laboratory mission.

  15. Plasma Beat-Wave Acceleration

    Science.gov (United States)

    Clayton, Christopher E.

    2002-04-01

    Among all the advanced accelerator concepts that use lasers as the power source, most of the effort to date has been with the idea of using a laser pulse to excite a accelerating mode in a plasma. Within this area, there are a variety of approaches for creating the accelerating mode, as indicated by the other talks in this session. What is common to these approaches is the physics of how a laser pulse pushes on plasma electrons to organize electron-density perturbations, the sources of the ultra-high (> GeV/M) accelerating gradients. It is the "ponderomotive force", proportional to the local gradient of the of the laser intensity, that pushes plasma electrons forward (on the leading edge of the pulse) and backwards (on the trailing edge) which leads to harmonic motion of the electrons. As the laser pulse moves through the plasma at group velocity Vg c, the oscillating electrons show up macroscopically as a plasma mode or wave with frequency w equal to the plasma frequency and k = w/Vg. For short laser pulses, this is the Laser Wakefield Accelerator (LWFA) concept. Closely related is the Plasma Beat-Wave Acceleration (PBWA) concept. Here, the laser pulse that perturbs the plasma is composed of two closely-spaced frequencies that "beat", i.e., periodically constructively and destructively interfere, forming an electromagnetic beat wave. One can visualize this as a train of short pulses. If this beating frequency is set to the plasma frequency, then each pulse in the train will reinforce the density perturbation caused by the previous pulse. The principal advantage of multiple pulses driving up the plasma wave as opposed to a single pulse is in efficiency, allowing for the production of relatively large diameter (more 1-D like) accelerating modes. In this talk I will discuss past, current and planned PBWA experiments which are taking place at UCLA, RAL in England, and LULI in France.

  16. CAS Accelerator Physics (RF for Accelerators) in Denmark

    CERN Multimedia

    Barbara Strasser

    2010-01-01

    The CERN Accelerator School (CAS) and Aarhus University jointly organised a specialised course on RF for Accelerators, at the Ebeltoft Strand Hotel, Denmark from 8 to 17 June 2010.   Caption The challenging programme focused on the introduction of the underlying theory, the study and the performance of the different components involved in RF systems, the RF gymnastics and RF measurements and diagnostics. This academic part was supplemented with three afternoons dedicated to practical hands-on exercises. The school was very successful, with 100 participants representing 25 nationalities. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and excellent quality of their lectures. In addition to the academic programme, the participants were able to visit a small industrial exhibition organised by Aarhus University and take part in a one-day excursion consisting of a visit of the accelerators operated ...

  17. The Accelerator Markup Language and the Universal Accelerator Parser

    Energy Technology Data Exchange (ETDEWEB)

    Sagan, D.; Forster, M.; /Cornell U., LNS; Bates, D.A.; /LBL, Berkeley; Wolski, A.; /Liverpool U. /Cockcroft Inst. Accel. Sci. Tech.; Schmidt, F.; /CERN; Walker, N.J.; /DESY; Larrieu, T.; Roblin, Y.; /Jefferson Lab; Pelaia, T.; /Oak Ridge; Tenenbaum, P.; Woodley, M.; /SLAC; Reiche, S.; /UCLA

    2006-10-06

    A major obstacle to collaboration on accelerator projects has been the sharing of lattice description files between modeling codes. To address this problem, a lattice description format called Accelerator Markup Language (AML) has been created. AML is based upon the standard eXtensible Markup Language (XML) format; this provides the flexibility for AML to be easily extended to satisfy changing requirements. In conjunction with AML, a software library, called the Universal Accelerator Parser (UAP), is being developed to speed the integration of AML into any program. The UAP is structured to make it relatively straightforward (by giving appropriate specifications) to read and write lattice files in any format. This will allow programs that use the UAP code to read a variety of different file formats. Additionally, this will greatly simplify conversion of files from one format to another. Currently, besides AML, the UAP supports the MAD lattice format.

  18. Accelerator mass spectrometry programme at BARC-TIFR pelletron accelerator

    International Nuclear Information System (INIS)

    Accelerator based mass spectrometry (ABMs) is an ultra sensitive means of counting individual atoms having sufficiently long half life and available in small amount. The 14 U D Pelletron Accelerator is an ideal machine to carry out ABMs studies with heavy isotopes like 36Cl and 129I. Cosmogenic radio isotope 36Cl is widely being detected using ABMs as it has got applications in ground water research, radioactive waste management, atmospheric 36Cl transport mechanism studies of Arctic Alpine ice core etc. As a part of the ongoing ABMs programme at 14UD Pelletron Accelerator Facility at Mumbai, a segmented gas detector developed for identification of 36Cl was tested for performance. Recently a beam chopper required for this measurement has been developed. Further progress made in this programme is discussed in this paper. (author)

  19. CAS CERN Accelerator School third general accelerator physics course

    International Nuclear Information System (INIS)

    The general course on accelerator physics given in Salamanca, Spain, closely followed those organised by the CERN Accelerator School at Gif-sur-Yvette, Paris in 1984, and at Aarhus, Denmark in 1986 and whose proceedings were published as CERN Yellow Reports 85-19 (1985) and 87-10 (1987) respectively. However, certain topics were treated in a different way, improved or extended, while some new ones were introduced and it is all of these which are included in the present proceedings. The lectures include beam-cooling concepts, Liouville's theorem and emittance, emittance dilution in transfer lines, weak-betatron coupling, diagnostics, while the seminars are on positron and electron sources, linac structures and the LEP L3 experiment, together with industrial aspects of particle accelerators. Also included are errata and addenda to the Yellow Reports mentioned above. (orig.)

  20. CAS CERN Accelerator School: Fourth general accelerator physics course

    International Nuclear Information System (INIS)

    The fourth CERN Accelerator School (CAS) basic course on General Accelerator Physics was given at KFA, Juelich, from 17 to 28 September 1990. Its syllabus was based on the previous similar courses held at Gif-sur-Yvette in 1984, Aarhus 1986, and Salamanca 1988, and whose proceedings were published as CERN Reports 85-19, 87-10, and 89-05, respectively. However, certain topics were treated in a different way, improved or extended, while new subjects were introduced. All of these appear in the present proceedings, which include lectures or seminars on the history and applications of accelerators, phase space and emittance, chromaticity, beam-beam effects, synchrotron radiation, radiation damping, tune measurement, transition, electron cooling, the designs of superconducting magnets, ring lattices, conventional RF cavities and ring RF systems, and an introduction to cyclotrons. (orig.)

  1. CAS CERN Accelerator School. Third advanced accelerator physics course

    International Nuclear Information System (INIS)

    The third version of the CERN Accelerator School's (CAS) advanced course on General Accelerator Physics was given at Uppsala University from 18-29 September, 1989. Its syllabus was based on the previous courses held in Oxford, 1985 and Berlin, 1987 whose proceedings were published as CERN Yellow Reports 87-03 and 89-01 respectively. However, the opportunity was taken to emphasize the physics of small accelerators and storage rings, to present some topics in new ways, and to introduce new seminars. Thus the lectures contained in the present volume include chromaticity, dynamic aperture, kinetic theory, Landau damping, ion-trapping, Schottky noise, laser cooling and small ring lattice problems while the seminars include interpretation of numerical tracking, internal targets and living with radiation. (orig.)

  2. Search for new type of PPARγ agonist-like anti-diabetic compounds from medicinal plants.

    Science.gov (United States)

    Matsuda, Hisashi; Nakamura, Seikou; Yoshikawa, Masayuki

    2014-01-01

    Potent ligands of peroxisome proliferator-activated receptor γ (PPARγ) such as thiazolidinediones (pioglitazone, troglitazone, etc.) improve insulin sensitivity by increasing the levels of adiponectin, an important adipocytokine associated with insulin sensitivity in adipose tissue. Several constituents from medicinal plants were recently reported to show PPARγ agonist-like activity in 3T3-L1 cells, but did not show agonistic activity at the receptor site different from thiazolidinediones. Our recent studies on PPARγ agonist-like constituents, such as hydrangenol and hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii, piperlonguminine and retrofractamide A from the fruit of Piper chaba, and tetramethylkaempferol and pentamethylquercetin from the rhizomes of Kaempferia parviflora, are reviewed. PMID:24882400

  3. Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    matter, metabolizable energy and digestible protein was of the same magnitude for all groups. The beta-agonist had no significant effect on protein digestibility and metabolizability of energy, but daily live weight gain was significantly higher in the treated bulls. The utilization of digested protein......Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644......,969) treated animals (Group 2 and 3). Beta-agonist supplementation was 5 and 10 mg/d in Group 2 and 3 respectively in Section A and 10 and 20 mg/d in Section B. Measurements were performed by means of nitrogen and carbon balances and with use of indirect calorimetry. In each section the mean intake of dry...

  4. Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in CNS neurons

    Science.gov (United States)

    Zheng, F.; Gallagher, J. P.

    1992-01-01

    We have previously reported that, in the rat dorsolateral septal nucleus (DLSN), metabotropic glutamate receptor (met-GluR) agonists evoked a slow depolarization accompanied by an increase in membrane conductance and burst firing. We have speculated that the burst firing elicited by met-GluR agonists may be due to activation or enhancement of a non-specific cation current, which exists in some DLSN neurons. Now we report that a slow afterdepolarization (sADP) mediated by a non-specific cation current was potentiated by both 1S,3R-ACPD and quisqualate. In addition, met-GluR agonists unmask a sADP in DLSN neurons which did not show a sADP under control conditions. Our data suggest that a non-specific cation current can be potentiated by activation of the met-GluR.

  5. Diverging mechanisms of activation of chemokine receptors revealed by novel chemokine agonists.

    Directory of Open Access Journals (Sweden)

    Jose Sarmiento

    Full Text Available CXCL8/interleukin-8 is a pro-inflammatory chemokine that triggers pleiotropic responses, including inflammation, angiogenesis, wound healing and tumorigenesis. We engineered the first selective CXCR1 agonists on the basis of residue substitutions in the conserved ELR triad and CXC motif of CXCL8. Our data reveal that the molecular mechanisms of activation of CXCR1 and CXCR2 are distinct: the N-loop of CXCL8 is the major determinant for CXCR1 activation, whereas the N-terminus of CXCL8 (ELR and CXC is essential for CXCR2 activation. We also found that activation of CXCR1 cross-desensitized CXCR2 responses in human neutrophils co-expressing both receptors, indicating that these novel CXCR1 agonists represent a new class of anti-inflammatory agents. Further, these selective CXCR1 agonists will aid at elucidating the functional significance of CXCR1 in vivo under pathophysiological conditions.

  6. Chronic exposure to a beta 2-adrenoceptor agonist increases the airway response to methacholine.

    Science.gov (United States)

    Witt-Enderby, P A; Yamamura, H I; Halonen, M; Palmer, J D; Bloom, J W

    1993-09-01

    Scheduled chronic administration of beta 2-adrenoceptor agonist bronchodilators in patients with asthma recently has been reported to be associated with a worsening of symptoms and an increase in bronchial responsiveness. We wanted to determine whether a 28-day in vivo exposure to albuterol (beta 2-adrenoceptor agonist) altered the response of rabbit airways to the cholinergic agonist methacholine. We found, using in vitro tissue bath techniques, that in mainstem bronchi from rabbits given a 28-day exposure to albuterol, maximum contraction to methacholine was increased in the albuterol-treated group (control group = 1.10 +/- 0.11 g vs. treated group = 1.50 +/- 0.13 g, P airway smooth muscle to methacholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7901034

  7. Xamoterol, a new selective beta-1-adrenoceptor partial agonist, in the treatment of postural hypotension

    DEFF Research Database (Denmark)

    Mehlsen, J; Trap-Jensen, J

    1986-01-01

    Three patients severely disabled from postural hypotension were treated with xamoterol, a selective beta-1-adrenoceptor antagonist with a high degree of partial agonist activity. Oral treatment (200 mg b.i.d.) was chosen on the basis of the effects of acute intravenous administration of xamoterol...... and pindolol, a non-selective beta-adrenoceptor antagonist with partial agonist activity. In these patients pindolol had a predominantly antagonist effect, whereas xamoterol had a predominantly agonist effect after intravenous administration. Oral treatment was carried out with placebo control in a single......, supine). During the placebo period (2 weeks) heart rate decreased to pretreatment levels and mean blood pressure was reduced by only 14 mmHg. The patients reported substantial improvement in their condition during active medication. Xamoterol seems to be a useful alternative in the treatment of postural...

  8. PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes.

    Directory of Open Access Journals (Sweden)

    Saravanan Kanakasabai

    Full Text Available Neural stem cells (NSCs are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS. Peroxisome proliferator-activated receptor gamma (PPARγ is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture. We found that in vitro culture of mouse NSCs in neurobasal medium with B27 in the presence of epidermal growth factor (EGF and basic fibroblast growth factor (bFGF induced their growth and expansion as neurospheres. Addition of all-trans retinoic acid (ATRA and PPARγ agonist ciglitazone or 15-Deoxy-Δ(12,14-Prostaglandin J(2 (15d-PGJ2 resulted in a dose-dependent inhibition of cell viability and proliferation of NSCs in culture. Interestingly, NSCs cultured with PPARγ agonists, but not ATRA, showed significant increase in oligodendrocyte precursor-specific O4 and NG2 reactivity with a reduction in NSC marker nestin, in 3-7 days. In vitro treatment with PPARγ agonists and ATRA also induced modest increase in the expression of neuronal β-III tubulin and astrocyte-specific GFAP in NSCs in 3-7 days. Further analyses showed that PPARγ agonists and ATRA induced significant alterations in the expression of many stemness and differentiation genes associated with neuro-glial differentiation in NSCs. These findings highlight the influence of PPARγ agonists in promoting neuro-glial differentiation of NSCs and its significance in the treatment of neurodegenerative diseases.

  9. Ligand-based receptor tyrosine kinase partial agonists: New paradigm for cancer drug discovery?

    Science.gov (United States)

    Riese, David J.

    2010-01-01

    Introduction Receptor tyrosine kinases (RTKs) are validated targets for oncology drug discovery and several RTK antagonists have been approved for the treatment of human malignancies. Nonetheless, the discovery and development of RTK antagonists has lagged behind the discovery and development of agents that target G-protein coupled receptors. In part, this is because it has been difficult to discover analogs of naturally-occurring RTK agonists that function as antagonists. Areas covered Here we describe ligands of ErbB receptors that function as partial agonists for these receptors, thereby enabling these ligands to antagonize the activity of full agonists for these receptors. We provide insights into the mechanisms by which these ligands function as antagonists. We discuss how information concerning these mechanisms can be translated into screens for novel small molecule- and antibody-based antagonists of ErbB receptors and how such antagonists hold great potential as targeted cancer chemotherapeutics. Expert opinion While there have been a number of important key findings into this field, the identification of the structural basis of ligand functional specificity is still of the greatest importance. While it is true that, with some notable exceptions, peptide hormones and growth factors have not proven to be good platforms for oncology drug discovery; addressing the fundamental issues of antagonistic partial agonists for receptor tyrosine kinases has the potential to steer oncology drug discovery in new directions. Mechanism based approaches are now emerging to enable the discovery of RTK partial agonists that may antagonize both agonist-dependent and –independent RTK signaling and may hold tremendous promise as targeted cancer chemotherapeutics. PMID:21532939

  10. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    Energy Technology Data Exchange (ETDEWEB)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland); Erchegyi, Judit; Rivier, Jean E. [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States)

    2010-08-15

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst{sub 1}-sst{sub 5}) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst{sub 2} and sst{sub 3} internalization in vitro in HEK293 cells stably expressing the human sst{sub 2} or sst{sub 3} receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst{sub 2} internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst{sub 3} internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst{sub 3} receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  11. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    International Nuclear Information System (INIS)

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst1-sst5) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst2 and sst3 internalization in vitro in HEK293 cells stably expressing the human sst2 or sst3 receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst2 internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst3 internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst3 receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  12. Industrial Electron Accelerators Type ILU

    CERN Document Server

    Auslender, Vadim; Cheskidov, Vladimir; Faktorovich, Boris; Gorbunov, Vladimir; Gornakov, Igor; Nekhaev, V E; Panfilov, Alexander; Sidorov, Alexander; Tkachenko, Vadim; Tuvik, Alfred; Voronin, Leonid

    2005-01-01

    The report describes the electron accelerators of ILU series covering the energy range from 0.5 to 5 MeV with beam power up to 50 kW. The pulse linear accelerators type ILU are developed since 1970 in Budker institute of Nuclear Physics and are supplied to the industry. The ILU machines are purposed for wide application in various technological processes and designed for long continuous and round-the-clock work in industrial conditions. A principle of acceleration of electrons in the gap of HF resonator is used in the ILU machines. The HF resonator has toroidal form. The electron gun is placed in one of the protruding electrodes forming the accelerating gap of the resonator. The resonator is fed from HF autogenerator realized on the industrial triode, the feedback signal is given from the resonator. The absence of outer beam injection and usage of self-excited HF generator simplify the design of accelerator and ensure its reliable operation.

  13. A variable acceleration calibration system

    Science.gov (United States)

    Johnson, Thomas H.

    2011-12-01

    A variable acceleration calibration system that applies loads using gravitational and centripetal acceleration serves as an alternative, efficient and cost effective method for calibrating internal wind tunnel force balances. Two proof-of-concept variable acceleration calibration systems are designed, fabricated and tested. The NASA UT-36 force balance served as the test balance for the calibration experiments. The variable acceleration calibration systems are shown to be capable of performing three component calibration experiments with an approximate applied load error on the order of 1% of the full scale calibration loads. Sources of error are indentified using experimental design methods and a propagation of uncertainty analysis. Three types of uncertainty are indentified for the systems and are attributed to prediction error, calibration error and pure error. Angular velocity uncertainty is shown to be the largest indentified source of prediction error. The calibration uncertainties using a production variable acceleration based system are shown to be potentially equivalent to current methods. The production quality system can be realized using lighter materials and a more precise instrumentation. Further research is needed to account for balance deflection, forcing effects due to vibration, and large tare loads. A gyroscope measurement technique is shown to be capable of resolving the balance deflection angle calculation. Long term research objectives include a demonstration of a six degree of freedom calibration, and a large capacity balance calibration.

  14. Beam dynamics for induction accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward P., E-mail: eplee@lbl.gov

    2014-01-01

    An induction linac uses pulsed power that is applied directly, without any intervening resonant cavities, to accelerate a charged particle pulse. This approach can accommodate a large multiple-beam focusing lattice capable of transporting a large total beam current with a long pulse duration, which may be compressed while accelerating as well as afterward. The mean accelerating gradient is relatively low (less than about 1.5 MV/m), but the potential efficiency of energy transfer can be large up to about 50%. A multiple-beam induction linac is therefore a natural candidate accelerator for a heavy ion fusion (HIF) driver. However, the accelerated beams must meet stringent requirements on occupied phase space volume in order to be focused accurately and with small radius onto the fusion target. Dynamical considerations in the beam injector and linac, as well as in the final compression, final focus, and the fusion chamber, determine the quality of the driver beams as they approach the target. Requirements and tolerances derived from beam dynamics strongly influence the linac configuration and component design. After a summary of dynamical considerations, two major topics are addressed here: transportable current limits, which determine the choice of focal system for the linac, and longitudinal control of the beams, which are potentially destabilized by their interaction with the pulsed power system.

  15. Synergistic teratogenic effects induced by retinoids in mice by coadministration of a RARalpha- or RARgamma-selective agonist with a RXR-selective agonist.

    Science.gov (United States)

    Elmazar, M M; Rühl, R; Nau, H

    2001-01-01

    To study the interaction of retinoid-induced limb defects and cleft palate on day 11 of gestation, a RXR-selective agonist (AGN191701, an arylpropenyl-thiophene-carboxylic acid derivative, 20 mg/kg orally) was coadministered with a RARalpha-agonist (Am580, an arylcarboxamidobenzoic acid derivative, 5 mg/kg orally) to NMRI mice. AGN191701 was neither fetotoxic nor teratogenic at the dose used but potentiated Am580-induced limb defects and cleft palate and prevented Am580-induced fetal weight retardation. These results suggest that Am580-induced limb defects and probably cleft palate on day 11 of gestation may be mediated via RARalpha-RXR heterodimerization, particularly in the absence of toxicokinetic interactions. AGN191701 was also coadministered with a RARgamma-agonist (CD437, an adamantyl-hydroxyphenyl naphthoic acid derivative, 15 mg/kg orally) on days 8 and 11 of gestation to investigate which CD437-induced defects are mediated via RARgamma-RXR heterodimerization. On day 8 of gestation, AGN191701 potentiated CD437-induced embryolethality, exencephaly, spina bifida aperta, cleft palate, and tail defects, as well as visceral and skeletal defects, but not micrognathia. On day 11 of gestation, the incidence of CD437-induced cleft palate and limb defects was also potentiated when coadministered with the RXR agonist. These results suggest that synergistic teratogenic effects can be induced by coadministration of two receptor-selective retinoids, indicating the importance of RARalpha-RXR and RARgamma-RXR heterodimers in producing structural defects during organogenesis.

  16. Discovery of biaryls as RORγ inverse agonists by using structure-based design.

    Science.gov (United States)

    Enyedy, Istvan J; Powell, Noel A; Caravella, Justin; van Vloten, Kurt; Chao, Jianhua; Banerjee, Daliya; Marcotte, Douglas; Silvian, Laura; McKenzie, Andres; Hong, Victor Sukbong; Fontenot, Jason D

    2016-05-15

    RORγ plays a critical role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including T cells, γδ T cells, and innate lymphoid cells. RORγ-mediated inflammation has been linked to susceptibility to Crohn's disease, arthritis, and psoriasis. Thus inverse agonists of RORγ have the potential of modulating inflammation. Our goal was to optimize two RORγ inverse agonists: T0901317 from literature and 1 that we obtained from internal screening. We used information from internal X-ray structures to design two libraries that led to a new biaryl series. PMID:27080181

  17. Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists.

    Science.gov (United States)

    Yang, Bingwei V; Weinstein, David S; Doweyko, Lidia M; Gong, Hua; Vaccaro, Wayne; Huynh, Tram; Xiao, Hai-Yun; Doweyko, Arthur M; McKay, Lorraine; Holloway, Deborah A; Somerville, John E; Habte, Sium; Cunningham, Mark; McMahon, Michele; Townsend, Robert; Shuster, David; Dodd, John H; Nadler, Steven G; Barrish, Joel C

    2010-12-01

    A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed. PMID:21073190

  18. High specific activity tritium labelling of some sigma-1 receptor agonists

    International Nuclear Information System (INIS)

    The high specific activity tritiation of (+)-SKF-10,047 (1) and N,N-dimethyltryptamine (4) is described. [N-allyl-3H] (+)-SKF-10,047 (3) was prepared by Lindlar catalyst tritiation of (+)-N-propargylnormetazocine (2) and [N-methyl-3H] N,N-dimethyltryptamine (6) was synthesized by the alkylation of N-methyltryptamine (5) with [3H] methyl iodide. Both sigma-1 synthetic agonist 3 and endogenous agonist 6 have been useful in studying this receptor. (author)

  19. Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats

    OpenAIRE

    Ali, Quaisar; Patel, Sanket; Hussain, Tahir

    2015-01-01

    High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1 mg·kg−1·day−1, oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependen...

  20. Dopamine agonist increases risk taking but blunts reward-related brain activity.

    Directory of Open Access Journals (Sweden)

    Jordi Riba

    Full Text Available The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

  1. Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine alpha4beta2 receptors

    DEFF Research Database (Denmark)

    Rohde, Line Aagot Hede; Ahring, Philip Kiær; Jensen, Marianne Lerbech;

    2012-01-01

    The a4ß2 subtype of the nicotinic acetylcholine receptor (nAChR) has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of a4ß2 agonists is lacking....... Using binding experiments, electrophysiology and X-ray crystallography we have investigated a consecutive series of five prototypical pyridine-containing agonists derived from 1-(pyridin-3-yl)-1,4-diazepane. A correlation between binding affinities at a4ß2 and the acetylcholine binding protein from...

  2. Stereostructure-activity studies on agonists at the AMPA and kainate subtypes of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Johansen, Tommy N; Greenwood, Jeremy R; Frydenvang, Karla Andrea;

    2003-01-01

    -methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of ionotropic Glu receptors in the presence or absence of an agonist has provided important information about ligand-receptor interaction mechanisms. The availability of these binding domain crystal structures has formed the basis for rational...... design of ligands, especially for the AMPA and kainate subtypes of ionotropic Glu receptors. This mini-review will focus on structure-activity relationships on AMPA and kainate receptor agonists with special emphasis on stereochemical and three-dimensional aspects....

  3. Quantitative phosphoproteomics dissection of 7TM receptor signaling using full and biased agonists

    DEFF Research Database (Denmark)

    Christensen, Gitte Lund; Kelstrup, Christian; Lyngsø, Christina;

    2010-01-01

    performed a global quantitative phosphoproteomics analysis of the AT1R signaling network. We analyzed ligand-stimulated SILAC cells by high-resolution mass spectrometry (LTQ Orbitrap MS) and compared the phosphoproteomes of the AT1R agonist Angiotensin II and the biased agonist SII Angiotensin II, which...... only activates the Gaq protein-independent signaling.e quantified more than ten thousand phosphorylation sites of which 1183 were regulated by Angiotensin II or its analogue SII Angiotensin II. 36% of the AT1R regulated phosphorylations were regulated by SII Angiotensin II. Analysis of phosphorylation...

  4. Find novel dual-agonist drugs for treating type 2 diabetes by means of cheminformatics

    Directory of Open Access Journals (Sweden)

    Liu L

    2013-04-01

    Full Text Available Lei Liu,1 Ying Ma,2 Run-Ling Wang,2 Wei-Ren Xu,3 Shu-Qing Wang,2,5 Kuo-Chen Chou4,5 1PET/CT Center, General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 3Tianjin Institute of Pharmaceutical Research (TIPR, Tianjin, People’s Republic of China; 4Center of Excellence in Genomic Medicine Research (CEGMR, King Abdulaziz University, Jeddah, Saudi Arabia; 5Gordon Life Science Institute, Belmont, MA, USA Abstract: The high prevalence of type 2 diabetes mellitus in the world as well as the increasing reports about the adverse side effects of the existing diabetes treatment drugs have made developing new and effective drugs against the disease a very high priority. In this study, we report ten novel compounds found by targeting peroxisome proliferator-activated receptors (PPARs using virtual screening and core hopping approaches. PPARs have drawn increasing attention for developing novel drugs to treat diabetes due to their unique functions in regulating glucose, lipid, and cholesterol metabolism. The reported compounds are featured with dual functions, and hence belong to the category of dual agonists. Compared with the single PPAR agonists, the dual PPAR agonists, formed by combining the lipid benefit of PPARα agonists (such as fibrates and the glycemic advantages of the PPARγ agonists (such as thiazolidinediones, are much more powerful in treating diabetes because they can enhance metabolic effects while minimizing the side effects. This was observed in the studies on molecular dynamics simulations, as well as on absorption, distribution, metabolism, and excretion, that these novel dual agonists not only possessed the same function as ragaglitazar (an investigational drug developed by Novo Nordisk for treating type

  5. Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain

    OpenAIRE

    Gutierrez, Tannia; Crystal, Jonathon D.; Zvonok, Alexander M.; Makriyannis, Alexandros; Hohmann, Andrea G.

    2011-01-01

    Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB2 agonist to attenuate a neuropathic pain state. Self-medication of the CB2 agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal threshol...

  6. Agonists of fibroblast growth factor receptor induce neurite outgrowth and survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Li, Shizhong; Christensen, Claus; Køhler, Lene B;

    2009-01-01

    Fibroblast growth factor receptor (FGFR) signaling is pivotal in the regulation of neurogenesis, neuronal differentiation and survival, and synaptic plasticity both during development and in adulthood. In order to develop low molecular weight agonists of FGFR, seven peptides, termed hexafins...... phosphorylation, indicating that hexafins act as partial agonists. Hexafin2, 3, 8, 10, and 17 (but not 1 or 9) induced neurite outgrowth from cerebellar granule neurons (CGNs), an effect that was abolished by two inhibitors of FGFR, SU5402 and inositol hexaphosphate (IP6) and a diacylglycerol lipase inhibitor...

  7. Accelerator Technology Division annual report, FY 1989

    Energy Technology Data Exchange (ETDEWEB)

    1990-06-01

    This paper discusses: accelerator physics and special projects; experiments and injectors; magnetic optics and beam diagnostics; accelerator design and engineering; radio-frequency technology; accelerator theory and simulation; free-electron laser technology; accelerator controls and automation; and high power microwave sources and effects.

  8. 38 CFR 9.14 - Accelerated Benefits.

    Science.gov (United States)

    2010-07-01

    ...' GROUP LIFE INSURANCE AND VETERANS' GROUP LIFE INSURANCE § 9.14 Accelerated Benefits. (a) What is an Accelerated Benefit? An Accelerated Benefit is a payment of a portion of your Servicemembers' Group Life...? ____ Yes__ No__ The patient applied for an accelerated benefit under his/her government life...

  9. Accelerator Technology Division annual report, FY 1989

    International Nuclear Information System (INIS)

    This paper discusses: accelerator physics and special projects; experiments and injectors; magnetic optics and beam diagnostics; accelerator design and engineering; radio-frequency technology; accelerator theory and simulation; free-electron laser technology; accelerator controls and automation; and high power microwave sources and effects

  10. Non-linear eye movements during visual-vestibular interaction under body oscillation with step-mode lateral linear acceleration.

    Science.gov (United States)

    Mori, Shigeo; Katayama, Naomi

    2005-02-01

    We investigated visual-vestibular interactions in normal humans, where a constant speed of optokinetic stimulation was combined with whole body oscillation of lateral linear acceleration (10 m stroke). The acceleration mode was not sinusoidal, but rectangular (step). The pure optokinetic reflex (reference OKR) and the OKR under combined stimulation (combined OKR) were induced by a random-dot pattern projected onto a hemispherical dome-screen affixed to a chair on a linear accelerator. The translational vestibulo-ocular reflex (tVOR) was determined separately in the dark during acceleration-step oscillation. Since the tVOR was masked by the OKR under combined stimulation, the interaction was assessed as changes in combined-OKR velocity at two segments of opposing acceleration; in other words, tVOR directions identical to (agonistic) and opposite to (antagonistic) the OKR direction. When a moderate optokinetic stimulus-speed of 40 deg/s was combined with a moderate acceleration of 0.3 G (3.0 m/s2) as in Experiment 1 (N=10), the combined-OKR velocity always increased during the agonistic condition, and the motion of the visual pattern was perceived as slow and clear in this segment. On the other hand, during the antagonistic condition, the combined-OKR velocity either remained unchanged or increased moderately, and the motion of the visual pattern was sensed as fast and unclear. Notably, in most subjects, the velocity difference in combined-OKR between the agonistic and antagonistic conditions was around the value of the tVOR velocity. In five of the ten subjects who completed an additional test session with the acceleration level increased from 0.3 to 0.5 G (4.9 m/s2), similar findings were maintained individually, suggesting independent behavior of tVOR. Therefore, we hypothesized that the interaction could be direction-selective; in other words, both tVOR and OKR are additive during the agonistic condition, but tVOR is suppressed during the antagonistic condition

  11. Heavy ion toroidal collective accelerator

    International Nuclear Information System (INIS)

    Experiments on HIPAC at Maxwell Laboratories have shown that almost all of the confined electrons are trapped and do not go around the torus. A toroidal electric field produces a negligible toroidal electron current. An ion accelerator where electrons are magnetically contained and their space charge contains ions is considered. A toroidal electric field of suitable magnitude can be applied so that it accelerates all of the ions but does not accelerate most of the electrons. This is possible if the magnetic moment of electrons μsub(e) > μsub(i)/Z, where μsub(i) is the ion magnetic moment and Z is the charge of the ion. Ions would be contained by the electron space-charge electric field E, for energies up to ZeER/2 approximately 100 GeV where Z = 60, E = 107 V/cm and the major radius of the torus is R = 3.3 metres. (author)

  12. Superconducting magnet technology for accelerators

    International Nuclear Information System (INIS)

    A review article on superconducting magnets for accelerators should first answer the question, why superconductivity. The answer revolves around two pivotal facts: (1) fields in the range of 2 T to 10 T can be achieved; and (2) the operating cost can be less than conventional magnets. The relative importance of these two factors depends on the accelerator. In the case where an upgrade of an accelerator at an existing facility is planned, the ability to obtain fields higher than conventional magnets leads directly to an increase in machine energy for the given tunnel. In the case of a new facility, both factors must be balanced for the most economical machine. Ways to achieve this are discussed

  13. Virtual gap dielectric wall accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Caporaso, George James; Chen, Yu-Jiuan; Nelson, Scott; Sullivan, Jim; Hawkins, Steven A

    2013-11-05

    A virtual, moving accelerating gap is formed along an insulating tube in a dielectric wall accelerator (DWA) by locally controlling the conductivity of the tube. Localized voltage concentration is thus achieved by sequential activation of a variable resistive tube or stalk down the axis of an inductive voltage adder, producing a "virtual" traveling wave along the tube. The tube conductivity can be controlled at a desired location, which can be moved at a desired rate, by light illumination, or by photoconductive switches, or by other means. As a result, an impressed voltage along the tube appears predominantly over a local region, the virtual gap. By making the length of the tube large in comparison to the virtual gap length, the effective gain of the accelerator can be made very large.

  14. Relativistic shocks and particle acceleration

    International Nuclear Information System (INIS)

    In this paper, we investigate the fluid dynamics of relativistic shock waves, and use the results to calculate the spectral index of particles accelerated by the Fermi process in such shocks. We have calculated the distributions of Fermi-accelerated particles at shocks propagating into cold proton-electron plasma and also cold electron-positron plasma. We have considered two different power spectra for the scattering waves, and find, in contrast to the non-relativistic case, that the spectral index of the accelerated particles depends on the wave power spectrum. On the assumption of thermal equilibrium both upstream and downstream, we present some useful fits for the compression ratio of shocks propagating at arbitrary speeds into gas of any temperature. (author)

  15. Accelerator science in medical physics.

    Science.gov (United States)

    Peach, K; Wilson, P; Jones, B

    2011-12-01

    The use of cyclotrons and synchrotrons to accelerate charged particles in hospital settings for the purpose of cancer therapy is increasing. Consequently, there is a growing demand from medical physicists, radiographers, physicians and oncologists for articles that explain the basic physical concepts of these technologies. There are unique advantages and disadvantages to all methods of acceleration. Several promising alternative methods of accelerating particles also have to be considered since they will become increasingly available with time; however, there are still many technical problems with these that require solving. This article serves as an introduction to this complex area of physics, and will be of benefit to those engaged in cancer therapy, or who intend to acquire such technologies in the future. PMID:22374548

  16. Linear accelerator for radioisotope production

    Energy Technology Data Exchange (ETDEWEB)

    Hansborough, L.D.; Hamm, R.W.; Stovall, J.E.

    1982-02-01

    A 200- to 500-..mu..A source of 70- to 90-MeV protons would be a valuable asset to the nuclear medicine program. A linear accelerator (linac) can achieve this performance, and it can be extended to even higher energies and currents. Variable energy and current options are available. A 70-MeV linac is described, based on recent innovations in linear accelerator technology; it would be 27.3 m long and cost approx. $6 million. By operating the radio-frequency (rf) power system at a level necessary to produce a 500-..mu..A beam current, the cost of power deposited in the radioisotope-production target is comparable with existing cyclotrons. If the rf-power system is operated at full power, the same accelerator is capable of producing an 1140-..mu..A beam, and the cost per beam watt on the target is less than half that of comparable cyclotrons.

  17. Symposium on accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    None

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.

  18. Symposium on accelerator mass spectrometry

    International Nuclear Information System (INIS)

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base

  19. Niobium LEP 2 accelerating cavities

    CERN Multimedia

    An accelerating cavity from LEP. This could be cut open to show the layer of niobium on the inside. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment. These challenging requirements pushed European industry to new achievements. 256 of these cavities were used in an upgrade of the LEP accelerator to double the energy of the particle beams.

  20. The Radiological Research Accelerator Facility

    International Nuclear Information System (INIS)

    The Radiological Research Accelerator Facility (RARAF) is based on 4-MV Van de Graaff accelerator, which is used to generate a variety of well-characterized radiation beams for research in radiobiology, radiological physics, and radiation chemistry. It is part of the Center for Radiological Research (CRR) -- formerly the Radiological Research Laboratory (RRL) -- of Columbia University, and its operation is supported as a National Facility by the US Department of Energy (DOE). As such, RARAF is available to all potential users on an equal basis, and scientists outside the CRR are encouraged to submit proposals for experiments at RARAF. The operation of the Van de Graaff is supported by the DOE, but the research projects themselves must be supported separately. Brief summaries of research experiments are included. Accelerator usage is summarized and development activities are discussed. 8 refs., 8 tabs

  1. Developments in laser-driven plasma accelerators

    CERN Document Server

    Hooker, Simon Martin

    2014-01-01

    Laser-driven plasma accelerators provide acceleration gradients three orders of magnitude greater than conventional machines, offering the potential to shrink the length of accelerators by the same factor. To date, laser-acceleration of electron beams to particle energies comparable to those offered by synchrotron light sources has been demonstrated with plasma acceleration stages only a few centimetres long. This article describes the principles of operation of laser-driven plasma accelerators, and reviews their development from their proposal in 1979 to recent demonstrations. The potential applications of plasma accelerators are described and the challenges which must be overcome before they can become a practical tool are discussed.

  2. The Diffusive Shock Acceleration Myth

    Science.gov (United States)

    Gloeckler, G.; Fisk, L. A.

    2012-12-01

    It is generally accepted that diffusive shock acceleration (DSA) is the dominant mechanism for particle acceleration at shocks. This is despite the overwhelming observational evidence that is contrary to predictions of DSA models. For example, our most recent survey of hourly-averaged, spin-averaged proton distribution functions around 61 locally observed shocks in 2001 at 1 AU found that in 21 cases no particles were accelerated. Spectral indices (γ ) of suprathermal tails on the velocity distributions around the 40 shocks that did accelerate particles, showed none of the DSA-predicted correlations of γ with the shock compression ratio and the shock normal to magnetic field angle. Here we will present ACE/SWICS observations of three sets of 72 consecutive one-hour averaged velocity distributions (in each of 8 SWICS spin sectors). Each set includes passage of one or more shocks or strong compression regions. All spectra were properly transformed to the solar wind frame using the detailed, updated SWICS forward model, taking into account the hourly-averaged directions of the solar wind flow, the magnetic field and the ACE spin axis (http://www.srl.caltech.edu/ACE/ASC/). The suprathermal tails are observed to be a combination of locally accelerated and remote tails. The local tails are power laws. The remote tails are also power laws with rollovers at higher energies. When local tails are weak (as is the case especially upstream of strong shocks or compression regions) the remote tails also have a rollover at low energies due to modulation (transport effects). Among our main findings are that (1) the spectral indices of both the local and remote tails are -5 within the uncertainties of the measurements, as predicted by our pump acceleration mechanism, and (2) the velocity distributions are anisotropic with the perpendicular (to the magnetic field) pressure greater than the parallel pressure.

  3. Harmonic ratcheting for fast acceleration

    Science.gov (United States)

    Cook, N.; Brennan, J. M.; Peggs, S.

    2014-04-01

    A major challenge in the design of rf cavities for the acceleration of medium-energy charged ions is the need to rapidly sweep the radio frequency over a large range. From low-power medical synchrotrons to high-power accelerator driven subcritical reactor systems, and from fixed focus alternating gradient accelerators to rapid cycling synchrotrons, there is a strong need for more efficient, and faster, acceleration of protons and light ions in the semirelativistic range of hundreds of MeV/u. A conventional way to achieve a large, rapid frequency sweep (perhaps over a range of a factor of 6) is to use custom-designed ferrite-loaded cavities. Ferrite rings enable the precise tuning of the resonant frequency of a cavity, through the control of the incremental permeability that is possible by introducing a pseudoconstant azimuthal magnetic field. However, rapid changes over large permeability ranges incur anomalous behavior such as the "Q-loss" and "f-dot" loss phenomena that limit performance while requiring high bias currents. Notwithstanding the incomplete understanding of these phenomena, they can be ameliorated by introducing a "harmonic ratcheting" acceleration scheme in which two or more rf cavities take turns accelerating the beam—one turns on when the other turns off, at different harmonics—so that the radio frequency can be constrained to remain in a smaller range. Harmonic ratcheting also has straightforward performance advantages, depending on the particular parameter set at hand. In some typical cases it is possible to halve the length of the cavities, or to double the effective gap voltage, or to double the repetition rate. This paper discusses and quantifies the advantages of harmonic ratcheting in general. Simulation results for the particular case of a rapid cycling medical synchrotron ratcheting from harmonic number 9 to 2 show that stability and performance criteria are met even when realistic engineering details are taken into consideration.

  4. Electron accelerators for radiation sterilization

    International Nuclear Information System (INIS)

    Industrial radiation processes using high power electron accelerators are attractive because the throughput rates are very high and the treatment costs per unit of product are often competitive with more conventional chemical processes. The utilization of energy in e-beam processing is more efficient than typical thermal processing. The use of volatiles or toxic chemicals can be avoided. Strict temperature or moisture controls may not be needed. Irradiated materials are usable immediately after processing. These capabilities are unique in that beneficial changes can be induced rapidly in solid materials and preformed products. In recent years, e-beam accelerators have emerged as the preferred alternative for industrial processing as they offer advantages over isotope radiation sources, such as (a) increased public acceptance since the storage, transport and disposal of radioactive material is not an issue; (b) the ability to hook up with the manufacturing process for in-line processing; (c) higher dose rates resulting in high throughputs. During the 1980s and 1990s, accelerator manufacturers dramatically increased the beam power available for high energy equipment. This effort was directed primarily at meeting the demands of the sterilization industry. During this era, the perception that bigger (higher power, higher energy) was always better prevailed, since the operating and capital costs of accelerators did not increase with power and energy as fast as the throughput. High power was needed to maintain low unit costs for the treatment. During the late 1980s and early 1990s, advances in e-beam technology produced new high energy, high power e-beam accelerators suitable for use in sterilization on an industrial scale. These newer designs achieved high levels of reliability and proved to be competitive with gamma sterilization by 60Co and fumigation with EtO. In parallel, technological advances towards 'miniaturization' of accelerators also made it possible to

  5. Plasma-based and novel accelerators

    International Nuclear Information System (INIS)

    This publication is a collection of papers presented at Workshop on Plasma-Based and Novel Accelerators held at National Institute for Fusion Science, Nagoya, on December 19-20, 1991. Plasma-based accelerators are attracting considerable attention in these days a new, exciting field of plasma applications. The study gives rise to and spurs study of other unique accelerators like laser-based accelerators. The talks in the Workshop encompassed beat-wave accelerator (BWA), plasma wake field accelerator (PWFA), Vp x B accelerator, laser-based accelerators and some novel methods of acceleration. They also covered the topics such as FEL, cluster acceleration and plasma lens. Small scale experiments as those in universities have exhibited brilliant results while larger scale experiments like BWA in Institute of Laser Engineering, Osaka University, and PWFA in KEK start showing significant results as well. (J.P.N.)

  6. State of accelerator for therapy

    CERN Document Server

    Maruhashi, A

    2002-01-01

    21 facilities carry out particle radiotherapy in the world and 6 facilities will start in the next year. They are shown in the table. 6 facilities of them exist in Japan. Small accelerator for proton therapy is developed. The area of them becomes smaller than 100 m sup 2. 5 makers, form, kinds of accelerator, length of track, beam energy of them are shown. States of particle radiotherapy in 4 facilities in Japan are explained by the kinds of particle, energy, beam intensity, time structure and radiation room. The important problems are reconsideration of building and compact rotating gantry. The problems of radiotherapy are explained. (S.Y.)

  7. Centralized digital control of accelerators

    International Nuclear Information System (INIS)

    In contrasting the title of this paper with a second paper to be presented at this conference entitled Distributed Digital Control of Accelerators, a potential reader might be led to believe that this paper will focus on systems whose computing intelligence is centered in one or more computers in a centralized location. Instead, this paper will describe the architectural evolution of SLAC's computer based accelerator control systems with respect to the distribution of their intelligence. However, the use of the word centralized in the title is appropriate because these systems are based on the use of centralized large and computationally powerful processors that are typically supported by networks of smaller distributed processors

  8. OpenMP for Accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, J C; Stotzer, E J; Hart, A; de Supinski, B R

    2011-03-15

    OpenMP [13] is the dominant programming model for shared-memory parallelism in C, C++ and Fortran due to its easy-to-use directive-based style, portability and broad support by compiler vendors. Similar characteristics are needed for a programming model for devices such as GPUs and DSPs that are gaining popularity to accelerate compute-intensive application regions. This paper presents extensions to OpenMP that provide that programming model. Our results demonstrate that a high-level programming model can provide accelerated performance comparable to hand-coded implementations in CUDA.

  9. Seismic response of linear accelerators

    OpenAIRE

    Collette, Christophe; Artoos, Kurt; Guinchard, Michael; Hauviller, Claude

    2010-01-01

    This paper is divided into two parts. The first part presents recent measurements of ground motion in the LHC tunnel at CERN. From these measurements, an update of the ground motion model currently used in accelerator simulations is presented. It contains new features like a model of the lateral motion and the technical noise. In the second part, it is shown how this model can be used to evaluate the seismic response of a linear accelerator in the frequency domain. Then, the approach is valid...

  10. Geometric integration for particle accelerators

    International Nuclear Information System (INIS)

    This paper is a very personal view of the field of geometric integration in accelerator physics-a field where often work of the highest quality is buried in lost technical notes or even not published; one has only to think of Simon van der Meer Nobel prize work on stochastic cooling-unpublished in any refereed journal. So I reconstructed the relevant history of geometrical integration in accelerator physics as much as I could by talking to collaborators and using my own understanding of the field. The reader should not be too surprised if this account is somewhere between history, science and perhaps even fiction

  11. Channel guiding for advanced accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Milchberg, H.M. [Institute for Physical Science and Technology (United States); Durfee, C.G. III [Institute for Physical Science and Technology (United States); Antonsen, T.M. [Institute for Plasma Research, University of Maryland, College Park, Maryland, (United States) 20742; Mora, P. [Centre de Physique Theorique, Ecole Polytechnique, 91128 Palaiseau (France)

    1996-02-01

    The recent demonstration of optical guiding of high intensity laser pulses in plasma waveguides [C. G. Durfee III and H. M. Milchberg, Phys. Rev. Lett 71, 2409 (1993)] has opened the way to new advances in the development of compact laser-driven electron particle accelerators. We review plasma waveguide properties relevant to intense pulse guiding and electron acceleration and show that the shock driven channels described here are well suited for stabilization of a large class of laser-plasma instabilities deleterious to high intensity guiding over long distances. {copyright} {ital 1996 American Institute of Physics.}

  12. Calorimetry at industrial electron accelerators

    DEFF Research Database (Denmark)

    Miller, Arne; Kovacs, A.

    1985-01-01

    Calorimetry is a convenient way to measure doses at industrial electron accelerators, where high absorbed doses (1-100 kGy) are delivered at dose rates of 102-105 Gy s-1 or even higher. Water calorimeters have been used for this purpose for several years, but recently other materials such as grap......Calorimetry is a convenient way to measure doses at industrial electron accelerators, where high absorbed doses (1-100 kGy) are delivered at dose rates of 102-105 Gy s-1 or even higher. Water calorimeters have been used for this purpose for several years, but recently other materials...

  13. Electron Cloud Effects in Accelerators

    CERN Document Server

    Furman, M A

    2013-01-01

    We present a brief summary of various aspects of the electron-cloud effect (ECE) in accelerators. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire "ECLOUD" series [122]. In addition, the proceedings of the various flavors of Particle Accelerator Conferences [23] contain a large number of EC-related publications. The ICFA Beam Dynamics Newsletter series [24] contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC [25].

  14. Thermodynamics of Accelerating Black Holes

    CERN Document Server

    Appels, Michael; Kubiznak, David

    2016-01-01

    We address a long-standing problem of describing the thermodynamics of a charged accelerating black hole. We derive a standard first law of black hole thermodynamics, with the usual identification of entropy proportional to the area of the event horizon -- even though the event horizon contains a conical singularity. This result not only extends the applicability of black hole thermodynamics to realms previously not anticipated, it also opens a possibility for studying novel properties of an important class of exact radiative solutions of Einstein equations describing accelerated objects. We discuss the thermodynamic volume, stability and phase structure of these black holes.

  15. Electron Cloud Effects in Accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Furman, M.A.

    2012-11-30

    Abstract We present a brief summary of various aspects of the electron-cloud effect (ECE) in accelerators. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire ?ECLOUD? series [1?22]. In addition, the proceedings of the various flavors of Particle Accelerator Conferences [23] contain a large number of EC-related publications. The ICFA Beam Dynamics Newsletter series [24] contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC [25].

  16. Superconducting linear accelerator system for NSC

    Indian Academy of Sciences (India)

    P N Prakash; T S Datta; B P Ajith Kumar; J Antony; P Barua; J Chacko; A Choudhury; G K Chadhari; S Ghosh; S Kar; S A Krishnan; Manoj Kumar; Rajesh Kumar; A Mandal; D S Mathuria; R S Meena; R Mehta; K K Mistri; A Pandey; M V Suresh Babu; B K Sahu; A Sarkar; S S K Sonti; A Rai; S Venkatramanan; J Zacharias; R K Bhowmik; A Roy

    2002-11-01

    This paper reports the construction of a superconducting linear accelerator as a booster to the 15 UD Pelletron accelerator at Nuclear Science Centre, New Delhi. The LINAC will use superconducting niobium quarter wave resonators as the accelerating element. Construction of the linear accelerator has progressed sufficiently. Details of the entire accelerator system including the cryogenics facility, RF electronics development, facilities for fabricating niobium resonators indigenously, and present status of the project are presented.

  17. The use of anchored agonists of phagocytic receptors for cancer immunotherapy: B16-F10 murine melanoma model.

    Directory of Open Access Journals (Sweden)

    Tereza Janotová

    Full Text Available The application of the phagocytic receptor agonists in cancer immunotherapy was studied. Agonists (laminarin, molecules with terminal mannose, N-Formyl-methioninyl-leucyl-phenylalanine were firmly anchored to the tumor cell surface. When particular agonists of phagocytic receptors were used together with LPS (Toll-like receptor agonist, high synergy causing tumour shrinkage and a temporary or permanent disappearance was observed. Methods of anchoring phagocytic receptor agonists (charge interactions, anchoring based on hydrophobic chains, covalent bonds and various regimes of phagocytic agonist/LPS mixture applications were tested to achieve maximum therapeutic effect. Combinations of mannan/LPS and f-MLF/LPS (hydrophobic anchors in appropriate (pulse regimes resulted in an 80% and 60% recovery for mice, respectively. We propose that substantial synergy between agonists of phagocytic and Toll-like receptors (TLR is based on two events. The TLR ligand induces early and massive inflammatory infiltration of tumors. The effect of this cell infiltrate is directed towards tumor cells, bearing agonists of phagocytic receptors on their surface. The result of these processes was effective killing of tumor cells. This novel approach represents exploitation of innate immunity mechanisms for treating cancer.

  18. A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Hanek, Ariele P; Price, Kerry L;

    2011-01-01

    Cation-π interactions have been demonstrated to play a major role in agonist-binding in Cys-loop receptors. However, neither the aromatic amino acid contributing to this interaction nor its location is conserved among Cys-loop receptors. Likewise, it is not clear how many different agonists of a ...

  19. Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian;

    2013-01-01

    reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral...

  20. Differential Rho-kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D; Boterman, M; de Jong, AM; Hovens, Iris; Penninks, JM; Nelemans, SA; Meurs, H; Zaagsma, J

    2006-01-01

    1 In airway smooth muscle (ASM), full and partial muscarinic receptor agonists have been described to have large differences in their ability to induce signal transduction, including Ca2+-mobilization. Despite these differences, partial agonists are capable of inducing a submaximal to maximal ASM co