42 CFR 422.752 - Basis for imposing intermediate sanctions and civil money penalties.

Science.gov (United States)

2010-10-01

... money penalties. 422.752 Section 422.752 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Sanctions § 422.752 Basis for imposing intermediate sanctions and civil money penalties. (a) All... sanctions at 422.750(a)(1) and (a)(3). (c) Civil Money Penalties. (1) CMS. In addition to, or in place of...

Cannabinoid receptor CB2 modulates axon guidance

DEFF Research Database (Denmark)

Duff, Gabriel; Argaw, Anteneh; Cecyre, Bruno

2013-01-01

on axon guidance. These effects are specific to CB2R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced morphological changes observed at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted...... CB2R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R....

Electrochemical Impedance Spectroscopy Of Metal Alloys

Science.gov (United States)

Macdowell, L. G.; Calle, L. M.

1993-01-01

Report describes use of electrochemical impedance spectroscopy (EIS) to investigate resistances of 19 alloys to corrosion under conditions similar to those of corrosive, chloride-laden seaside environment of Space Transportation System launch site. Alloys investigated: Hastelloy C-4, C-22, C-276, and B-2; Inconel(R) 600, 625, and 825; Inco(R) G-3; Monel 400; Zirconium 702; Stainless Steel 304L, 304LN, 316L, 317L, and 904L; 20Cb-3; 7Mo+N; ES2205; and Ferralium 255. Results suggest electrochemical impedance spectroscopy used to predict corrosion performances of metal alloys.

48 CFR 752.226-1 - Determination of status as disadvantaged enterprise.

Science.gov (United States)

2010-10-01

... by socially and economically disadvantaged individuals means management and daily business are... individuals; and (ii) Has its management and daily business controlled by one or more such individuals. (7... disadvantaged enterprise. 752.226-1 Section 752.226-1 Federal Acquisition Regulations System AGENCY FOR...

Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

Directory of Open Access Journals (Sweden)

Shuxian Jiang

2007-07-01

Full Text Available Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.The cannabinoid receptor type 1 (CB1 and cannabinoid receptor type 2 (CB2 are members of the G-protein coupled receptor (GPCR family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Delta(9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists.This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell

48 CFR 752.219-8 - Utilization of small business concerns and small disadvantaged business concerns.

Science.gov (United States)

2010-10-01

... business concerns and small disadvantaged business concerns. 752.219-8 Section 752.219-8 Federal... AND CONTRACT CLAUSES Texts of Provisions and Clauses 752.219-8 Utilization of small business concerns and small disadvantaged business concerns. The Foreign Assistance Act calls for USAID to give small...

Expression Analysis of CB2-GFP BAC Transgenic Mice.

Science.gov (United States)

Schmöle, Anne-Caroline; Lundt, Ramona; Gennequin, Benjamin; Schrage, Hanna; Beins, Eva; Krämer, Alexandra; Zimmer, Till; Limmer, Andreas; Zimmer, Andreas; Otte, David-Marian

2015-01-01

The endocannabinoid system (ECS) is a retrograde messenger system, consisting of lipid signaling molecules that bind to at least two G-protein-coupled receptors, Cannabinoid receptor 1 and 2 (CB1 and 2). As CB2 is primarily expressed on immune cells such as B cells, T cells, macrophages, dendritic cells, and microglia, it is of great interest how CB2 contributes to immune cell development and function in health and disease. Here, understanding the mechanisms of CB2 involvement in immune-cell function as well as the trafficking and regulation of CB2 expressing cells are crucial issues. Up to now, CB2 antibodies produce unclear results, especially those targeting the murine protein. Therefore, we have generated BAC transgenic GFP reporter mice (CB2-GFPTg) to trace CB2 expression in vitro and in situ. Those mice express GFP under the CB2 promoter and display GFP expression paralleling CB2 expression on the transcript level in spleen, thymus and brain tissue. Furthermore, by using fluorescence techniques we show that the major sources for GFP-CB2 expression are B cells in spleen and blood and microglia in the brain. This novel CB2-GFP transgenic reporter mouse line represents a powerful resource to study CB2 expression in different cell types. Furthermore, it could be used for analyzing CB2-mediated mobilization and trafficking of immune cells as well as studying the fate of recruited immune cells in models of acute and chronic inflammation.

Expression Analysis of CB2-GFP BAC Transgenic Mice.

Directory of Open Access Journals (Sweden)

Anne-Caroline Schmöle

Full Text Available The endocannabinoid system (ECS is a retrograde messenger system, consisting of lipid signaling molecules that bind to at least two G-protein-coupled receptors, Cannabinoid receptor 1 and 2 (CB1 and 2. As CB2 is primarily expressed on immune cells such as B cells, T cells, macrophages, dendritic cells, and microglia, it is of great interest how CB2 contributes to immune cell development and function in health and disease. Here, understanding the mechanisms of CB2 involvement in immune-cell function as well as the trafficking and regulation of CB2 expressing cells are crucial issues. Up to now, CB2 antibodies produce unclear results, especially those targeting the murine protein. Therefore, we have generated BAC transgenic GFP reporter mice (CB2-GFPTg to trace CB2 expression in vitro and in situ. Those mice express GFP under the CB2 promoter and display GFP expression paralleling CB2 expression on the transcript level in spleen, thymus and brain tissue. Furthermore, by using fluorescence techniques we show that the major sources for GFP-CB2 expression are B cells in spleen and blood and microglia in the brain. This novel CB2-GFP transgenic reporter mouse line represents a powerful resource to study CB2 expression in different cell types. Furthermore, it could be used for analyzing CB2-mediated mobilization and trafficking of immune cells as well as studying the fate of recruited immune cells in models of acute and chronic inflammation.

48 CFR 752.225-9 - Buy American Act-Trade Agreements Act-Balance of Payments Program.

Science.gov (United States)

2010-10-01

... CLAUSES Texts of Provisions and Clauses 752.225-9 Buy American Act—Trade Agreements Act—Balance of... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Buy American Act-Trade Agreements Act-Balance of Payments Program. 752.225-9 Section 752.225-9 Federal Acquisition Regulations...

Loss of cannabinoid receptor CB1 induces preterm birth.

Directory of Open Access Journals (Sweden)

Haibin Wang

2008-10-01

Full Text Available Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in

Stress corrosion cracking of several high strength ferrous and nickel alloys

Science.gov (United States)

Nelson, E. E.

1971-01-01

The stress corrosion cracking resistance of several high strength ferrous and nickel base alloys has been determined in a sodium chloride solution. Results indicate that under these test conditions Multiphase MP35N, Unitemp L605, Inconel 718, Carpenter 20Cb and 20Cb-3 are highly resistant to stress corrosion cracking. AISI 410 and 431 stainless steels, 18 Ni maraging steel (250 grade) and AISI 4130 steel are susceptible to stress corrosion cracking under some conditions.

5 CFR 752.101 - Principal statutory requirements.

Science.gov (United States)

2010-01-01

... Section 752.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... (a) Under regulations prescribed by the Office of Personnel Management, an employee may be suspended... affidavits and other documentary evidence in support of the answer; (3) be represented by an attorney or...

Phenotype-gene: 752 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 752 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u3ria224u928i abnormal for trait of behavior...a224u16055636i abnormal for trait of behavioral quality in organ named stamen dur

5 CFR 752.501 - Principal statutory requirements.

Science.gov (United States)

2010-01-01

... Section 752.501 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... Personnel Management, an agency may take an action covered by this subchapter against an employee only for... answer orally and in writing and to furnish affidavits and other documentary evidence in support of the...

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

Science.gov (United States)

Gaffal, E; Cron, M; Glodde, N; Tüting, T

2013-08-01

∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors and relevance for Alzheimer's disease and levodopa-induced dyskinesia.

Science.gov (United States)

Navarro, Gemma; Borroto-Escuela, Dasiel; Angelats, Edgar; Etayo, Íñigo; Reyes-Resina, Irene; Pulido-Salgado, Marta; Rodríguez-Pérez, Ana I; Canela, Enric I; Saura, Josep; Lanciego, José Luis; Labandeira-García, José Luis; Saura, Carlos A; Fuxe, Kjell; Franco, Rafael

2018-01-01

Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB 1 and CB 2 receptors, which may form heteromeric complexes (CB 1 -CB 2 Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB 1 and circa 20 fold for CB 2 ), whereas receptor levels were similar for CB 1 and markedly upregulated for CB 2 ; CB 1 -CB 2 Hets were also upregulated. Unlike in resting cells, CB 2 receptors became robustly coupled to G i in activated cells, in which CB 1 -CB 2 Hets mediated a potentiation effect. Hence, resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß 1-42 ). Microglial activation markers were detected in the striatum of a Parkinson's disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APP Sw,Ind ) mice, a transgenic Alzheimer's disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APP Sw,Ind and in cells from control animals activated using LPS plus IFN-γ. Expression of CB 1 -CB 2 Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment. In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB 1 -CB 2 Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB 1 -CB 2 heteroreceptor complex in activated microglia have potential as targets in the

The role of CB1 receptors in psychostimulant addiction

NARCIS (Netherlands)

Wiskerke, J.; Pattij, T.; Schoffelmeer, A.N.M.; de Vries, T.J.

2008-01-01

Recent studies have implicated the endocannabinoid (eCB) system in the neuronal mechanisms underlying substance dependence. Here, we review results of studies using cannabinoid receptor subtype 1 (CB1) knockout mice as well as CB1 antagonists to elucidate the role of this neurotransmitter system in

Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

Science.gov (United States)

Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

2007-01-01

Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

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Ken Soderstrom

2017-10-01

Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

Vibrational spectra and structure of icosahedral anion of monocarba-closo-dodecaborane [CB11H12]- and its nido-derivative: [CB10H13]-

International Nuclear Information System (INIS)

Kononova, E.G.; Bukalov, S.S.; Lejtes, L.A.; Lysenko, K.A.; Ol'shevskaya, V.A.

2003-01-01

Raman and IR spectra of cesium salts of monocarborane anions [closo-CB 11 H 12 ] - and [nido-CB 10 H 13 ] - were recorded, assignment of frequencies being provided. Quantum-chemical calculation of geometry of the closo-polyhedrons [B 12 H 12 ] 2- and [CB 11 H 12 ] - along with that of frequencies and forms of normal vibrations of the latter was made. Comparison of structural and spectral characteristics in the series of isoelectronic closo-polyhedrons [B 12 H 12 ] 2- , [CB 11 H 12 ] - and p-C 2 B 10 H 12 , as well as those of the closo- and nido structures, was made [ru

Cannabinoid-1 receptor (CB1R) blockers as medicines: beyond obesity and cardiometabolic disorders to substance abuse/drug addiction with CB1R neutral antagonists.

Science.gov (United States)

Janero, David R

2012-03-01

Addiction to chemical substances with abuse potential presents medical needs largely unsolved by extant therapeutic strategies. Signal transmission through the cannabinoid-1 receptor (CB1R) in the central nervous system (CNS) modulates neurotransmitters/neuronal pathways contributing to the rewarding properties and hedonic effects of certain nondrug stimuli (e.g., food) and many prototypical addictive drugs, promoting excessive intake and its pathological consequences. Typical CB1R antagonists/inverse agonists reduce the rewarding effects and normalize behavioral phenotypes associated with food and abused drugs, but carry an unacceptable adverse-event profile that may reflect, at least partly, their intrinsic ability to alter basal homeostatic CB1R signaling in the CNS and elicit a negative efficacy response. Alternatively, peripherally biased CB1R inverse agonists with limited CNS permeability and putative CB1R neutral antagonists expressing modest (if any) inverse-agonist efficacy are garnering attention for treating obesity and related cardiometabolic complications with a potentially enhanced benefit-to-risk profile. This mini-review calls attention to the proposition that CB1R neutral antagonists offer attractive opportunities for pharmacotherapeutic exploitation in the substance abuse/drug addiction space, whereas the restricted CNS accessibility of peripherally biased CB1R inverse agonists circumscribes their therapeutic utility for this indication. The unique preclinical pharmacology, efficacy profiles, and reduced adverse-event risk of CB1R neutral antagonists make them worthy of translational study for their potential therapeutic application beyond obesity/cardiometabolic disease to include substance-abuse/drug-addiction disorders.

A superplastic Al-Li-Cu-Mg-Zr powder alloy with high hardness and modulus

International Nuclear Information System (INIS)

Phillips, V.A.

1986-01-01

Structure/property studies were made on an experimental Al-3.18% Li-4.29% Cu-1.17% Mg-0.18% Zr powder alloy, which is of the low density/high modulus type. Alloy powder was made by the P and W/GPD rapid solidification rate (RSR) process, canned, and extruded to bar. The density was 2.458 x 10/sup 6/ g/m/sup 3/. The material was solution-treated, and aged at 149 0 C(300 0 F), 171 0 C(340 0 F), and 193 0 C(380 0 F), using hardness tests to determine the aging curves. Testpieces solution-treated at 516 0 C(961 0 F) showed an average yield strength (0.2% offset) of 43.3 ksi (299 MPa) and ultimate tensile strength of 50.0 ksi (345 MPa), with 1% elongation, which increased to 73.0 ksi (503 MPa) and 73.1 ksi (504 MPa), respectively, with only 0.2% elongation, on peak aging at 193 0 C(380 0 F), with a modulus of elasticity of 11.4 x 10/sup 6/ psi (78.3 GPa). Hardness values reached 90-92 R/sub B/ on aging at 149-193 0 C(300-380 0 F). The as-extruded alloy showed superplastic behavior at 400-500 0 C(752-932 0 F) with elongations of 80-185% on 25.6 mm, peaking at 450 0 C(842 0 F). An RSR Al-2.53% Li-2.82% Mn-0.02% Zr extruded allow showed only 18-23% elongation at 400-500 0 C(752-932 0 F)

Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

Science.gov (United States)

Khodadadi, M; Zendehdel, M; Baghbanzadeh, A; Babapour, V

2017-10-01

1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB 1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg). Experiments 2-4 were similar to Experiment 1 except birds were injected with either 6-OHDA (6-hydroxydopamine as dopamine synthesis inhibitor; 150 nmol), SCH23390 (D1 receptor antagonist; 5 nmol) and AMI-193 (D2 receptor antagonist; 5 nmol) instead of l-DOPA, respectively. Additionally, Experiments 5-8 followed the previous ones using the same dose of l-DOPA, 6-OHDA and dopamine antagonists except that birds were injected with CB65 (CB2 receptor agonist; 5 µg) instead of 2-AG. Coadministrations were at the same dose for each experiment. Cumulative feed intakes were measured until 120 min after each injection. 3. ICV administration of 6-OHDA and AMI-193 significantly attenuated 2-AG-induced hyperphagia. Interestingly, the hyperphagic effect of CB65 was significantly attenuated by administration of l-DOPA, whereas the administration of 6-OHDA and AMI-193 together amplified the hyperphagic effect of CB65. 4. It was concluded that cannabinoid-induced feeding behaviour is probably modulated by dopamine receptors in neonatal layer-type chickens. It seems that their interaction may be mediated by the D2-dopamine receptor.

Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration

Directory of Open Access Journals (Sweden)

Juan Mendizabal-Zubiaga

2016-10-01

Full Text Available The cannabinoid type 1 (CB1 receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1, where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles. Immunoelectron microscopy for CB1 was used in skeletal muscles (gastrocnemius and rectus abdominis and myocardium from wild-type and CB1-KO mice. Functional assessments were performed in mitochondria purified from the heart of the mice and the mitochondrial oxygen consumption upon application of different acute delta-9-tetrahidrocannabinol (Δ9-THC concentrations (100 nM or 200 nM was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in the rectus abdominis and 17% in the myocardium expressed CB1. Furthermore, the proportion of mtCB1 versus total CB1 immunoparticles was about 60% in the gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium. Importantly, the CB1 immunolabeling pattern disappeared in muscles of CB1-KO mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased mitochondria coupled respiration between 12% and 15% in wild-type isolated mitochondria of myocardial muscles but no significant difference was noticed between THC treated and vehicle in mitochondria isolated from CB1-KO heart. Furthermore, gene expression of key enzymes involved in pyruvate synthesis, tricarboxylic acid (TCA cycle and mitochondrial respiratory chain was evaluated in the striated muscle of CB1-WT and CB1-KO. CB1-KO showed an increase in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased production of pyruvate. In contrast, no significant

CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

Science.gov (United States)

Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

2006-10-01

Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

Sensitivity study applied to the CB4 VVER-440 benchmark on burnup credit

International Nuclear Information System (INIS)

Markova, Ludmila

2003-01-01

A brief overview of four completed portions (CB1, CB2, CB3, CB3+, CB4) of the international VVER-440 benchmark focused on burnup credit and a sensitivity study as one of the final views of the benchmark results are presented in the paper. Finally, the influence of real and conservative VVER-440 fuel assembly models taken for the isotopics calculation by SCALE sas2 on the system k eff is shown in the paper. (author)

50 CFR 600.752 - Use of conveners and facilitators.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Use of conveners and facilitators. 600.752..., by consensus. The facilitator may be the same person as the convener used under paragraph (a) of this... facilitator, the FNP shall select, by consensus, a person to serve as facilitator. A person designated to...

LEP measurements of $V_{cb}$ and $V_{ub}$

CERN Document Server

Hawkings, R

2001-01-01

The measurements of the magnitudes of the CKM matrix elements V/sub cb/ and V/sub ub/ from LEP are reviewed. V/sub cb/ is measured using the decay B/sup 0/ to D*/sup +/l/sup -/ nu , whilst V/sub ub/ is measured using inclusive charmless semileptonic b decays. Particular attention is paid to the limiting systematic errors in each case. (20 refs).

Stimulation of cannabinoid receptor 2 (CB2 suppresses microglial activation

Directory of Open Access Journals (Sweden)

Fernandez Francisco

2005-12-01

Full Text Available Abstract Background Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD, multiple sclerosis (MS, and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO, cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2. Methods In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB2 small interfering RNA (siRNA analyses. Furthermore, we examined if the stimulation of CB2 could modulate the capacity of microglial cells to phagocytise Aβ1–42 peptide using a phagocytosis assay. Results We found that the selective stimulation of cannabinoid receptor CB2 by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB2 agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB2 activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ1–42 peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.

Orbital frustration induced unusual ordering in semiconductor alloys

Science.gov (United States)

Liu, Kai; Yin, Wanjian; Chen, Shiyou; Gong, Xingao; Wei, Suhuai; Xiang, Hongjun

It is well known that ternary zinc-blende semiconductors are always more stable in the chalcopyrite (CH) structure than the Cu-Au (CA) structure because CH structure has large Coulomb interaction and reduced strain energy. Surprisingly, an experimental study showed that ZnFeSe2 alloy takes the CA order as the ground state structure, which is consistent with our density function theory (DFT) calculations showing that the CA order has lower energy than the CH order for ZnFeSe2. We reveal that the orbital degree of freedom of high-spin Fe2+ ion (d6) in the tetrahedral crystal field plays a key role in stabilizing the CA order. First, the spin-minority d electron of the Fe2+ ion tends to occupy the dx2-y 2 -like orbital instead of the d3z2 -r2 -like orbital because of its large negative Coulomb energy. Second, for a nearest-neighboring Fe2+ pair, two spin-minority d electrons with occupied dx2-y 2 -like orbitals in the plane containing the Fe-Fe bond has lower electronic kinetic energy. Both conditions can be satisfied in the CA ordered ZnFeSe2 alloy, while there is an orbital frustration in the CH structure. Our results suggest that orbital degree of freedom provides a new way to manipulate the structure and properties of alloys. Work at Fudan was supported by NSFC (11374056), the Special Funds for Major State Basic Research (2012CB921400, 2015CB921700), Program for Professor of Special Appointment (Eastern Scholar), and Fok Ying Tung Education Foundation.

Sonographic demonstration of Cruveilhier-Baumgarten (CB) syndrome

Energy Technology Data Exchange (ETDEWEB)

Schulze, P J; Vogel, H M

1982-02-01

The term 'CB syndrome' comprises the presence of umbilical vein collateral circulation due to portal hypertension associated with cirrhosis or other recognizable structural anomalies of the liver. Usually the dilated remnant of the umbilical vein is the main collateral pathway. Demonstration of this structure not only indicates the presence of portal hypertension but also that the underlying obstruction is intra- or posthepatic rather than prehepatic. This paper reports sonographic visualization of CB syndrome in 23 patients with cirrhosis of the liver. Questions of differential diagnosis and nomenclature are discussed with respect to developmental and anatomical preconditions.

Sonographic demonstration of Cruveilhier-Baumgarten (CB) syndrome

International Nuclear Information System (INIS)

Schulze, P.J.; Vogel, H.M.

1982-01-01

The term 'CB syndrome' comprises the presence of umbilical vein collateral circulation due to portal hypertension associated with cirrhosis or other recognizable structural anomalies of the liver. Usually the dilated remnant of the umbilical vein is the main collateral pathway. Demonstration of this structure not only indicates the presence of portal hypertension but also that the underlying obstruction is intra- or posthepatic rather than prehepatic. This paper reports sonographic visualization of CB syndrome in 23 patients with cirrhosis of the liver. Questions of differential diagnosis and nomenclature are discussed with respect to developmental and anatomical preconditions. (orig.)

Müller cells express the cannabinoid CB2 receptor in the vervet monkey retina

DEFF Research Database (Denmark)

Bouskila, Joseph; Javadi, Pasha; Casanova, Christian

2013-01-01

The presence of the cannabinoid receptor type 1 (CB1R) has been largely documented in the rodent and primate retinae in recent years. There is, however, some controversy concerning the presence of the CB2 receptor (CB2R) within the central nervous system. Only recently, CB2R has been found in the...

Carbon Incorporation and Anion Dynamics as Synergistic Drivers for Ultrafast Diffusion in Superionic LiCB11H12 and NaCB11H12

Energy Technology Data Exchange (ETDEWEB)

Dimitrievska, Mirjana [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Shea, Patrick [Lawrence Livermore National Laboratory; Kweon, Kyoung E. [Lawrence Livermore National Laboratory; Bercx, Marnik [University of Antwerp; Varley, Joel B. [Lawrence Livermore National Laboratory; Tang, Wan Si [National Institute of Standards and Technology; University of Maryland; Skripov, Alexander V. [Ural Division of the Russian Academy of Sciences; Stavila, Vitalie [Sandia National Laboratories; Udovic, Terrence J. [National Institute of Standards and Technology; Wood, Brandon C. [Lawrence Livermore National Laboratory

2018-02-02

The disordered phases of LiCB11H12 and NaCB11H12 possess superb superionic conductivities that make them suitable as solid electrolytes. In these materials, cation diffusion correlates with high orientational mobilities of the CB11H12- anions; however, the precise relationship has yet to be demonstrated. In this work, ab initio molecular dynamics and quasielastic neutron scattering are combined to probe anion reorientations and their mechanistic connection to cation mobility over a range of timescales and temperatures. It is found that anions do not rotate freely, but rather transition rapidly between orientations defined by the cation sublattice symmetry. The symmetry-breaking carbon atom in CB11H12- also plays a critical role by perturbing the energy landscape along the instantaneous orientation of the anion dipole, which couples fluctuations in the cation probability density directly to the anion motion. Anion reorientation rates exceed 3 x 1010 s-1, suggesting the underlying energy landscape fluctuates dynamically on diffusion-relevant timescales. Furthermore, carbon is found to modify the orientational preferences of the anions and aid rotational mobility, creating additional symmetry incompatibilities that inhibit ordering. The results suggest that synergy between the anion reorientational dynamics and the carbon-modified cation-anion interaction accounts for the higher ionic conductivity in CB11H12- salts compared with B12H122-.

CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

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Balázs Csóka

2009-07-01

Full Text Available Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2 receptors on immune cells. Here we examined the role of CB(2 receptors in regulating the host's response to sepsis.The role of CB(2 receptors was studied by subjecting CB(2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+ and CD19(+ cells during CLP.Taken together, our results establish for the first time that CB(2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.

CB1 cannabinoid receptor expression in the striatum: Association with corticostriatal circuits and developmental regulation

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Vincent eVan Waes

2012-03-01

Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader–Willi syndrome

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Ibrahim Knani

2016-12-01

Full Text Available Objective: Extreme obesity is a core phenotypic feature of Prader–Willi syndrome (PWS. Among numerous metabolic regulators, the endocannabinoid (eCB system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects. Methods: We studied eCB ‘tone’ in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice. Results: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB ‘tone’, manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype. Conclusions: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS. Author Video: Author Video Watch what authors say about their articles Keywords: Endocannabinoids, PWS, Magel2, Peripheral CB1 blockade, Metabolic syndrome

Acute Pharmacological Effects of 2C-B in Humans: An Observational Study

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Esther Papaseit

2018-03-01

Full Text Available 2,5-dimethoxy-4-bromophenethylamine (2C-B is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine-2A (5-HT2A, 5-hydroxytryptamine-2B (5-HT2B, and 5-hydroxytryptamine-2C (5-HT2C receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg. Vital signs (blood pressure and heart rate were measured at baseline 1, 2, 3, 4, and 6 hours (h. Each participant completed subjective effects using three rating scales: the visual analog scale (VAS, the Addiction Research Centre Inventory (ARCI, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h, and the Hallucinogenic Rating Scale (maximum effects along 6 h. Oral fluid (saliva was collected to assess 2C-B and cortisol concentrations during 24 h. Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated, and changes in perceptions (distances, colors, shapes, and lights and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.

The Caulobacter crescentus phage phiCbK: genomics of a canonical phage

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Gill Jason J

2012-10-01

Full Text Available Abstract Background The bacterium Caulobacter crescentus is a popular model for the study of cell cycle regulation and senescence. The large prolate siphophage phiCbK has been an important tool in C. crescentus biology, and has been studied in its own right as a model for viral morphogenesis. Although a system of some interest, to date little genomic information is available on phiCbK or its relatives. Results Five novel phiCbK-like C. crescentus bacteriophages, CcrMagneto, CcrSwift, CcrKarma, CcrRogue and CcrColossus, were isolated from the environment. The genomes of phage phiCbK and these five environmental phage isolates were obtained by 454 pyrosequencing. The phiCbK-like phage genomes range in size from 205 kb encoding 318 proteins (phiCbK to 280 kb encoding 448 proteins (CcrColossus, and were found to contain nonpermuted terminal redundancies of 10 to 17 kb. A novel method of terminal ligation was developed to map genomic termini, which confirmed termini predicted by coverage analysis. This suggests that sequence coverage discontinuities may be useable as predictors of genomic termini in phage genomes. Genomic modules encoding virion morphogenesis, lysis and DNA replication proteins were identified. The phiCbK-like phages were also found to encode a number of intriguing proteins; all contain a clearly T7-like DNA polymerase, and five of the six encode a possible homolog of the C. crescentus cell cycle regulator GcrA, which may allow the phage to alter the host cell’s replicative state. The structural proteome of phage phiCbK was determined, identifying the portal, major and minor capsid proteins, the tail tape measure and possible tail fiber proteins. All six phage genomes are clearly related; phiCbK, CcrMagneto, CcrSwift, CcrKarma and CcrRogue form a group related at the DNA level, while CcrColossus is more diverged but retains significant similarity at the protein level. Conclusions Due to their lack of any apparent relationship to

Developmental and visual input-dependent regulation of the CB1 cannabinoid receptor in the mouse visual cortex.

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Taisuke Yoneda

Full Text Available The mammalian visual system exhibits significant experience-induced plasticity in the early postnatal period. While physiological studies have revealed the contribution of the CB1 cannabinoid receptor (CB1 to developmental plasticity in the primary visual cortex (V1, it remains unknown whether the expression and localization of CB1 is regulated during development or by visual experience. To explore a possible role of the endocannabinoid system in visual cortical plasticity, we examined the expression of CB1 in the visual cortex of mice. We found intense CB1 immunoreactivity in layers II/III and VI. CB1 mainly localized at vesicular GABA transporter-positive inhibitory nerve terminals. The amount of CB1 protein increased throughout development, and the specific laminar pattern of CB1 appeared at P20 and remained until adulthood. Dark rearing from birth to P30 decreased the amount of CB1 protein in V1 and altered the synaptic localization of CB1 in the deep layer. Dark rearing until P50, however, did not influence the expression of CB1. Brief monocular deprivation for 2 days upregulated the localization of CB1 at inhibitory nerve terminals in the deep layer. Taken together, the expression and the localization of CB1 are developmentally regulated, and both parameters are influenced by visual experience.

Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

DEFF Research Database (Denmark)

Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

2002-01-01

-induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA...... a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo....

Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.

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Shim, Joong-Youn; Ahn, Kwang H; Kendall, Debra A

2013-11-08

The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein-coupled receptor superfamily. The human CB1 receptor, which is among the most expressed receptors in the brain, has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. Different classes of CB1 agonists evoke signaling pathways through the activation of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling to its cognate G protein is unknown. As a first step toward understanding CB1 receptor-mediated G protein signaling, we have constructed a ternary complex structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the x-ray structure of β2-adrenergic receptor (β2AR) in complex with Gs (β2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We identified a group of residues at the juxtamembrane regions of the intracellular loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr-224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as potential key contacts with the extreme C-terminal helix α5 of Gαi. Ala mutations of these residues at the receptor-Gi interface resulted in little G protein coupling activity, consistent with the present model of the CB1-Gi complex, which suggests tight interactions between CB1 and the extreme C-terminal helix α5 of Gαi. The model also suggests that unique conformational changes in the extreme C-terminal helix α5 of Gα play a crucial role in the receptor-mediated G protein activation.

The Effect of Nonnormality on CB-SEM and PLS-SEM Path Estimates

OpenAIRE

Z. Jannoo; B. W. Yap; N. Auchoybur; M. A. Lazim

2014-01-01

The two common approaches to Structural Equation Modeling (SEM) are the Covariance-Based SEM (CB-SEM) and Partial Least Squares SEM (PLS-SEM). There is much debate on the performance of CB-SEM and PLS-SEM for small sample size and when distributions are nonnormal. This study evaluates the performance of CB-SEM and PLS-SEM under normality and nonnormality conditions via a simulation. Monte Carlo Simulation in R programming language was employed to generate data based on the theoretical model w...

Association of cannabis use during adolescence, prefrontal CB1 receptor signaling and schizophrenia

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Adriana eCaballero

2012-05-01

Full Text Available The cannabinoid receptor 1 (CB1R is the G-protein coupled receptor responsible for the majority of the endocannabinoid signaling in the human brain. It is widely distributed in the limbic system, basal ganglia, and cerebellum, which are areas responsible for cognition, memory, and motor control. Because of this widespread distribution, it is not surprising that drugs that co-opt CB1R have expected behavioral outcomes consistent with dysregulated signaling from these areas (e.g. memory loss, cognitive deficits, etc. In the context of this review, we present evidence for the role of CB1R signaling in the prefrontal cortex (PFC, an area involved in executive functions, with emphasis on the developmental regulation of CB1R signaling in the acquisition of mature PFC function. We further hypothesize how alterations of CB1R signaling specifically during adolescent maturation might confer liability to psychiatric disorders.

Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

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Emmanuel S Onaivi

Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

Cannabinoid CB1 /CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

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Scherma, Maria; Satta, Valentina; Collu, Roberto; Boi, Maria Francesca; Usai, Paolo; Fratta, Walter; Fadda, Paola

2017-08-01

Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 -tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance. © 2017 The British Pharmacological Society.

Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer.

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Pérez-Gómez, Eduardo; Andradas, Clara; Blasco-Benito, Sandra; Caffarel, María M; García-Taboada, Elena; Villa-Morales, María; Moreno, Estefanía; Hamann, Sigrid; Martín-Villar, Ester; Flores, Juana M; Wenners, Antonia; Alkatout, Ibrahim; Klapper, Wolfram; Röcken, Christoph; Bronsert, Peter; Stickeler, Elmar; Staebler, Annette; Bauer, Maret; Arnold, Norbert; Soriano, Joaquim; Pérez-Martínez, Manuel; Megías, Diego; Moreno-Bueno, Gema; Ortega-Gutiérrez, Silvia; Artola, Marta; Vázquez-Villa, Henar; Quintanilla, Miguel; Fernández-Piqueras, José; Canela, Enric I; McCormick, Peter J; Guzmán, Manuel; Sánchez, Cristina

2015-06-01

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen, and Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical tests were two-sided. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis (decreased overall survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71, P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI = 0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI = 0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade and that an increased CB2 expression activates the HER2 pro-oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with

Review of $V_{cb}$ and $V_{td}/V_{ts}$

OpenAIRE

Forty, Roger W

1997-01-01

The current experimental status of the CKM matrix element V_cb and the ratio V_td/V_ts is reviewed. Knowledge of these elements has a strong impact on the unitarity triangle, of interest for studies of CP violation in the B system. The measurements of V_cb from both inclusive semileptonic b decays and the exclusive channel B -> D* l nu are reaching high precision. For V_td/V_ts the strongest upper limit is derived from studies of B-Bbar mixing.

Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis.

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Vanessa Deveaux

Full Text Available BACKGROUND: Obesity-associated inflammation is of critical importance in the development of insulin resistance and non-alcoholic fatty liver disease. Since the cannabinoid receptor CB2 regulates innate immunity, the aim of the present study was to investigate its role in obesity-induced inflammation, insulin resistance and fatty liver. METHODOLOGY: Murine obesity models included genetically leptin-deficient ob/ob mice and wild type (WT mice fed a high fat diet (HFD, that were compared to their lean counterparts. Animals were treated with pharmacological modulators of CB2 receptors. Experiments were also performed in mice knock-out for CB2 receptors (Cnr2 -/-. PRINCIPAL FINDINGS: In both HFD-fed WT mice and ob/ob mice, Cnr2 expression underwent a marked induction in the stromal vascular fraction of epididymal adipose tissue that correlated with increased fat inflammation. Treatment with the CB2 agonist JWH-133 potentiated adipose tissue inflammation in HFD-fed WT mice. Moreover, cultured fat pads isolated from ob/ob mice displayed increased Tnf and Ccl2 expression upon exposure to JWH-133. In keeping, genetic or pharmacological inactivation of CB2 receptors decreased adipose tissue macrophage infiltration associated with obesity, and reduced inductions of Tnf and Ccl2 expressions. In the liver of obese mice, Cnr2 mRNA was only weakly induced, and CB2 receptors moderately contributed to liver inflammation. HFD-induced insulin resistance increased in response to JWH-133 and reduced in Cnr2 -/- mice. Finally, HFD-induced hepatic steatosis was enhanced in WT mice treated with JWH-133 and blunted in Cnr2 -/- mice. CONCLUSION/SIGNIFICANCE: These data unravel a previously unrecognized contribution of CB2 receptors to obesity-associated inflammation, insulin resistance and non-alcoholic fatty liver disease, and suggest that CB2 receptor antagonists may open a new therapeutic approach for the management of obesity-associated metabolic disorders.

GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

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Leire Reguero

Full Text Available BACKGROUND: Type-1 cannabinoid receptors (CB(1R are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH that participates in homeostatic and behavioral functions including food intake. Although CB(1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB(1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB(1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. METHODOLOGY/PRINCIPAL FINDINGS: Light and electron microscopy techniques were used to analyze CB(1R distribution in the VMH of CB(1R-WT, CB(1R-KO and conditional mutant mice bearing a selective deletion of CB(1R in cortical glutamatergic (Glu-CB(1R-KO or GABAergic neurons (GABA-CB(1R-KO. At light microscopy, CB(1R immunolabeling was observed in the VMH of CB(1R-WT and Glu-CB(1R-KO animals, being remarkably reduced in GABA-CB(1R-KO mice. In the electron microscope, CB(1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB(1R immunopositive profiles and CB(1R density in terminals making asymmetric or symmetric synapses in CB(1R-WT mice. Furthermore, the proportion of CB(1R immunopositive terminals/preterminals in CB(1R-WT and Glu-CB(1R-KO mice was reduced in GABA-CB(1R-KO mutants. CB(1R density was similar in all animal conditions. Finally, the percentage of CB(1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB(1R-KO mutants relative to CB(1R-WT mice, indicating that CB(1R was distributed in cortical and subcortical excitatory synaptic terminals. CONCLUSIONS/SIGNIFICANCE: Our anatomical results support the idea that the VMH is a relevant hub candidate in

Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

Science.gov (United States)

Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

2014-01-01

The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731

What Determines Lean Manufacturing Implementation? A CB-SEM Model

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Tan Ching Ng

2018-02-01

Full Text Available This research aims to ascertain the determinants of effective Lean Manufacturing (LM. In this research, Covariance-based Structural Equation Modeling (CB-SEM analysis will be used in order to analyze the determinants. Through CB-SEM analysis, the significant key determinants can be determined and the direct relationships among determinants can be analyzed. Thus, the findings of this research can act as guidelines for achievement of LM effectiveness, not only providing necessary steps for successful implementation of lean, but also helping lean companies to achieve higher level of lean cost and time savings.

METHODS FOR RECOMBINANT EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF HUMAN CANNABINOID RECEPTOR CB2

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Alexei A. Yeliseev

2013-03-01

Full Text Available Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane protein that belongs to a large superfamily of G protein-coupled receptors (GPCR. CB2 is a part of the endocannabinoid system that plays vital role in regulation of immune response, inflammation, pain sensitivity, obesity and other physiological responses. Information about the structure and mechanisms of functioning of this receptor in cell membranes is essential for the rational development of specific pharmaceuticals. Here we review the methodology for recombinant expression, purification, stabilization and biochemical characterization of CB2 suitable for preparation of multi-milligram quantities of functionally active receptor. The biotechnological protocols include expression of the recombinant CB2 in E. coli cells as a fusion with the maltose binding protein, stabilization with a high affinity ligand and a derivative of cholesterol in detergent micelles, efficient purification by tandem affinity chromatography, and reconstitution of the receptor into lipid bilayers. The purified recombinant CB2 receptor is amenable to functional and structural studies including nuclear magnetic resonance spectroscopy and a wide range of biochemical and biophysical techniques.

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

Science.gov (United States)

Sagredo, Onintza; González, Sara; Aroyo, Ilia; Pazos, María Ruth; Benito, Cristina; Lastres-Becker, Isabel; Romero, Juan P.; Tolón, Rosa M.; Mechoulam, Raphael; Brouillet, Emmanuel; Romero, Julián; Fernández-Ruiz, Javier

2009-01-01

Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington’s disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions but they are markedly up-regulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labelled with the marker of reactive microglia OX-42, and also in cells labelled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-α (TNF-α) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be up-regulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-α. Altogether our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. PMID:19115380

Methanol Electro-Oxidation on Pt-Ru Alloy Nanoparticles Supported on Carbon Nanotubes

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Yangchuan Xing

2009-09-01

Full Text Available Carbon nanotubes (CNTs have been investigated in recent years as a catalyst support for proton exchange membrane fuel cells. Improved catalyst activities were observed and attributed to metal-support interactions. We report a study on the kinetics of methanol electro-oxidation on CNT supported Pt-Ru alloy nanoparticles. Alloy catalysts with different compositions, Pt53Ru47/CNT, Pt69Ru31/CNT and Pt77Ru23/CNT, were prepared and investigated in detail. Experiments were conducted at various temperatures, electrode potentials, and methanol concentrations. It was found that the reaction order of methanol electro-oxidation on the PtRu/CNT catalysts was consistent with what has been reported for PtRu alloys with a value of 0.5 in methanol concentrations. However, the electro-oxidation reaction on the PtRu/CNT catalysts displayed much lower activation energies than that on the Pt-Ru alloy catalysts unsupported or supported on carbon black (PtRu/CB. This study provides an overall kinetic evaluation of the PtRu/CNT catalysts and further demonstrates the beneficial role of CNTs.

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

Science.gov (United States)

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

1998-02-01

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

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

Science.gov (United States)

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

SUBMILLIMETER ARRAY AND SPITZER OBSERVATIONS OF BOK GLOBULE CB 17: A CANDIDATE FIRST HYDROSTATIC CORE?

Energy Technology Data Exchange (ETDEWEB)

Chen Xuepeng; Arce, Hector G.; Dunham, Michael M. [Department of Astronomy, Yale University, Box 208101, New Haven, CT 06520-8101 (United States); Zhang Qizhou; Bourke, Tyler L. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Launhardt, Ralf; Schmalzl, Markus; Henning, Thomas, E-mail: xuepeng.chen@yale.edu [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany)

2012-06-01

We present high angular resolution Submillimeter Array (SMA) and Spitzer observations toward the Bok globule CB 17. SMA 1.3 mm dust continuum images reveal within CB 17 two sources with an angular separation of {approx}21'' ({approx}5250 AU at a distance of {approx}250 pc). The northwestern continuum source, referred to as CB 17 IRS, dominates the infrared emission in the Spitzer images, drives a bipolar outflow extending in the northwest-southeast direction, and is classified as a low-luminosity Class 0/I transition object (L{sub bol} {approx} 0.5 L{sub Sun }). The southeastern continuum source, referred to as CB 17 MMS, has faint dust continuum emission in the SMA 1.3 mm observations ({approx}6{sigma} detection; {approx}3.8 mJy), but is not detected in the deep Spitzer infrared images at wavelengths from 3.6 to 70 {mu}m. Its bolometric luminosity and temperature, estimated from its spectral energy distribution, are {<=}0.04 L{sub Sun} and {<=}16 K, respectively. The SMA CO (2-1) observations suggest that CB 17 MMS may drive a low-velocity molecular outflow ({approx}2.5 km s{sup -1}), extending in the east-west direction. Comparisons with prestellar cores and Class 0 protostars suggest that CB 17 MMS is more evolved than prestellar cores but less evolved than Class 0 protostars. The observed characteristics of CB 17 MMS are consistent with the theoretical predictions from radiative/magnetohydrodynamical simulations of a first hydrostatic core, but there is also the possibility that CB 17 MMS is an extremely low luminosity protostar deeply embedded in an edge-on circumstellar disk. Further observations are needed to study the properties of CB 17 MMS and to address more precisely its evolutionary stage.

A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens.

Science.gov (United States)

Wright, William J; Schlüter, Oliver M; Dong, Yan

2017-04-01

The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1 + FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1 + FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1 + FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1 + FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1 + FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc.

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Science.gov (United States)

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Site layout, site-specific erection plan and construction... Steel Erection § 1926.752 Site layout, site-specific erection plan and construction sequence. (a... strength or sufficient strength to support the loads imposed during steel erection. (c) Site layout. The...

Risperidone treatment increases CB1 receptor binding in rat brain

DEFF Research Database (Denmark)

Secher, Anna; Husum, Henriette; Holst, Birgitte

2010-01-01

, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

Comparison of Corner-Butt 45 (Cb-45 and Corner-Lap (Cl joints in friction stir welding

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Setiawan Widia

2018-01-01

Full Text Available The 10 mm thick Aluminum 6061 plates have been corner joined using varied design and those were 45° Corner Butt and Corner Lap Joints (CB-45 & CL. Friction tool was hardened EMS 45. True experimental method was used with independent parameters is feed rate which varied at 10 mm/min, 15 mm/min and 30 mm/min respectively. Other parameter such as rotating speed was kept constant. Experiment results show that, CB-45 yields better properties than CL. The tensile strength of CB-45 reaches 163.7 MPa for 10 mm/min feed rate. Whilst CL produces joint with tensile strength equal 120 MPa for equal parameters. Microstructure observation showed that CB-45 produces fine and homogenous appearance of MgO compared to CL. This phenomenon is caused by the pin of CB-45 joint which fully penetrates the nugget zone which is not found in CL design. This microstructure in turn promotes higher tensile strength of CB-45.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors.

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Martínez-Pinilla, Eva; Varani, Katia; Reyes-Resina, Irene; Angelats, Edgar; Vincenzi, Fabrizio; Ferreiro-Vera, Carlos; Oyarzabal, Julen; Canela, Enric I; Lanciego, José L; Nadal, Xavier; Navarro, Gemma; Borea, Pier Andrea; Franco, Rafael

2017-01-01

The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB 2 receptors (CB 2 Rs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB 2 R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB 2 R. Using membrane preparations from CB 2 R-expressing HEK-293T (human embryonic kidney 293T) cells, we confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB 2 R where the synthetic cannabinoid, [ 3 H]-WIN 55,212-2, binds. CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugated CB 2 R-selective compound, CM-157. The effect on binding to CB 2 R-expressing living cells was different to that exerted by the orthosteric antagonist, SR144528, which decreased the maximum binding without changing the K D . CBD at nanomolar concentrations was also able to significantly reduce the effect of the selective CB 2 R agonist, JWH133, on forskolin-induced intracellular cAMP levels and on activation of the MAP kinase pathway. These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors

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Eva Martínez-Pinilla

2017-10-01

Full Text Available The mechanism of action of cannabidiol (CBD, the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB2 receptors (CB2Rs it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs; however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB2R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB2R. Using membrane preparations from CB2R-expressing HEK-293T (human embryonic kidney 293T cells, we confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB2R where the synthetic cannabinoid, [3H]-WIN 55,212-2, binds. CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugated CB2R-selective compound, CM-157. The effect on binding to CB2R-expressing living cells was different to that exerted by the orthosteric antagonist, SR144528, which decreased the maximum binding without changing the KD. CBD at nanomolar concentrations was also able to significantly reduce the effect of the selective CB2R agonist, JWH133, on forskolin-induced intracellular cAMP levels and on activation of the MAP kinase pathway. These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.

Simultaneous biodegradation of bifenthrin and chlorpyrifos by Pseudomonas sp. CB2.

Science.gov (United States)

Zhang, Qun; Li, Shuhuai; Ma, Chen; Wu, Nancun; Li, Chunli; Yang, Xinfeng

2018-05-04

The degradation of bifenthrin (BF) and chlorpyrifos (CP), either together or individually, by a bacterial strain (CB2) isolated from activated sludge was investigated. Strain CB2 was identified as belonging to genus Pseudomonas based on the morphological, physiological, and biochemical characteristics and a homological analysis of the 16S rDNA sequence. Strain CB2 has the potential to degrade BF and CP, either individually or in a mixture. The optimum conditions for mixture degradation were as follows: OD 600nm = 0.5; incubation temperature = 30°C; pH = 7.0; BF-CP mixture (10 mg L -1 of each). Under these optimal conditions, the degradation rate constants (and half-lives) were 0.4308 d -1 (1.61 d) and 0.3377 d -1 (2.05 d) for individual BF and CP samples, respectively, and 0.3463 d -1 (2.00 d) and 0.2931 d -1 (2.36 d) for the BF-CP mixture. Major metabolites of BF and CP were 2-methyl-3-biphenylyl methanol and 3,5,6-trichloro-2-pyridinol, respectively. No metabolite bioaccumulation was observed. The ability of CB2 to efficiently degrade BF and CP, particularly in a mixture, may be useful in bioremediation efforts.

Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

Science.gov (United States)

Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

2016-08-30

Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.

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Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

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David J Marcus

Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

Science.gov (United States)

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Studies on the effects of EPDM, SR on PTC- of HDPE/CB before and after γ-radiation

International Nuclear Information System (INIS)

Jia Shaojin; Jiang Pingkai; Xiu Qihui; Wang Zongguang; Zhang Zhicheng

2004-01-01

High-density-polyethylene (HDPE), Si rubber (SR) and ethylene-density-polyethylene (EPDM) were used as the polymer matrices. A kinds of carbon blacks was used as the conductive filler. The positive temperature coefficient (PTC) intensity of the HDPE/CB, HDPE/EPDM/CB composites flow during extrusion to produced was tested before and after irradiation. Compared to that of HDPE/CB composites, the electrical reproducibility of the irradiated HDPE/EPDM/CB composites of is better. The effects of γ-rays irradiation were also estimated. The results showed that the reproductive of the PTC effect was related to the adhesion between the interface of the polymer matrices and CB particles. These PTC phenomena and their distinctive aspects were described. The explanations were given from the structural characteristics of the blends, CB particles distribution and motion of polymer segments. (authors)

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Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

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Yuting Tang

Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

Science.gov (United States)

Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

2017-08-01

Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

Modulación del tono vascular por la sobre-expresión de receptores a canabinoides CB1 y CB2 en arterioesclerosis inducida en ratas

OpenAIRE

Espinoza P., María Rosa

2013-01-01

La arteriosclerosis, es un proceso degenerativo responsable de la mayor parte de las enfermedades cardiovasculares, es una enfermedad compleja que se produce a partir de múltiples factores de riesgo. Se ha observado que los compuestos derivados de la planta cannabis sativa provocan efectos vasorelajantes por medio de receptores específicos CB1 y CB2. ACPA y JWH 133 son potentes agonistas a estos receptores, se desconoce el papel que desempeñan en la arteriosclerosis provocando una relajación ...

The central cannabinoid CB1 receptor is required for diet-induced obesity and rimonabant's antiobesity effects in mice.

Science.gov (United States)

Pang, Zhen; Wu, Nancy N; Zhao, Weiguang; Chain, David C; Schaffer, Erica; Zhang, Xin; Yamdagni, Preeti; Palejwala, Vaseem A; Fan, Chunpeng; Favara, Sarah G; Dressler, Holly M; Economides, Kyriakos D; Weinstock, Daniel; Cavallo, Jean S; Naimi, Souad; Galzin, Anne-Marie; Guillot, Etienne; Pruniaux, Marie-Pierre; Tocci, Michael J; Polites, H Greg

2011-10-01

Cannabinoid receptor CB1 is expressed abundantly in the brain and presumably in the peripheral tissues responsible for energy metabolism. It is unclear if the antiobesity effects of rimonabant, a CB1 antagonist, are mediated through the central or the peripheral CB1 receptors. To address this question, we generated transgenic mice with central nervous system (CNS)-specific knockdown (KD) of CB1, by expressing an artificial microRNA (AMIR) under the control of the neuronal Thy1.2 promoter. In the mutant mice, CB1 expression was reduced in the brain and spinal cord, whereas no change was observed in the superior cervical ganglia (SCG), sympathetic trunk, enteric nervous system, and pancreatic ganglia. In contrast to the neuronal tissues, CB1 was undetectable in the brown adipose tissue (BAT) or the liver. Consistent with the selective loss of central CB1, agonist-induced hypothermia was attenuated in the mutant mice, but the agonist-induced delay of gastrointestinal transit (GIT), a primarily peripheral nervous system-mediated effect, was not. Compared to wild-type (WT) littermates, the mutant mice displayed reduced body weight (BW), adiposity, and feeding efficiency, and when fed a high-fat diet (HFD), showed decreased plasma insulin, leptin, cholesterol, and triglyceride levels, and elevated adiponectin levels. Furthermore, the therapeutic effects of rimonabant on food intake (FI), BW, and serum parameters were markedly reduced and correlated with the degree of CB1 KD. Thus, KD of CB1 in the CNS recapitulates the metabolic phenotype of CB1 knockout (KO) mice and diminishes rimonabant's efficacy, indicating that blockade of central CB1 is required for rimonabant's antiobesity actions.

Electrodeposited ultrafine TaOx/CB catalysts for PEFC cathode application: Their oxygen reduction reaction kinetics

KAUST Repository

Seo, Jeongsuk

2014-12-01

Ultrafine TaOx nanoparticles were electrodeposited on carbon black (CB) powder in a nonaqueous Ta complex solution at room temperature, and the resultant TaOx/CB catalysts were assessed as oxygen reduction reaction (ORR) electrocatalysts for polymer electrolyte fuel cell (PEFC) cathodes. The Ta electrodeposition process was scaled up using a newly designed working electrode containing a CB dense layer, without introducing any binder such as the ionomer Nafion in the electrode for electrodeposition. The electrodeposited TaOx/CB powders were removed from the deposition electrode and subsequent H2 treatment at varying temperatures between 523 and 1073 K was attempted to increase the ORR performance. The TaOx/CB samples were characterized by SEM, STEM, XPS, and EELS measurements. XPS and EELS results indicated the reduced nature of the Ta species caused by the high-temperature treatment in H2, while STEM images clearly revealed that the TaOx particles aggregated as the treatment temperature increased. When the TaOx/CB catalyst, which was treated at 873 K for 2 h, was deposited on a glassy carbon substrate with Nafion ionomer, it resulted in the highest activity among the samples investigated, giving an onset potential of 0.95 VRHE at -2 μA cm-2 in a 0.1 M H2SO4 solution. Moreover, the long-term stability test with 10,000 cycles of the voltammetry only led to a 6% loss in the ORR currents, demonstrating the high stability of the TaOx/CB catalysts. Kinetic analysis by R(R)DE indicated that the four-electron transfer pathway in the ORR process was dominant for this TaOx/CB catalyst, and Tafel plots showed a slope corresponding to a one-electron reaction for the rate-determining step.

Electrodeposited ultrafine TaOx/CB catalysts for PEFC cathode application: Their oxygen reduction reaction kinetics

KAUST Repository

Seo, Jeongsuk; Anjum, Dalaver H.; Takanabe, Kazuhiro; Kubota, Jun; Domen, Kazunari

2014-01-01

Ultrafine TaOx nanoparticles were electrodeposited on carbon black (CB) powder in a nonaqueous Ta complex solution at room temperature, and the resultant TaOx/CB catalysts were assessed as oxygen reduction reaction (ORR) electrocatalysts for polymer electrolyte fuel cell (PEFC) cathodes. The Ta electrodeposition process was scaled up using a newly designed working electrode containing a CB dense layer, without introducing any binder such as the ionomer Nafion in the electrode for electrodeposition. The electrodeposited TaOx/CB powders were removed from the deposition electrode and subsequent H2 treatment at varying temperatures between 523 and 1073 K was attempted to increase the ORR performance. The TaOx/CB samples were characterized by SEM, STEM, XPS, and EELS measurements. XPS and EELS results indicated the reduced nature of the Ta species caused by the high-temperature treatment in H2, while STEM images clearly revealed that the TaOx particles aggregated as the treatment temperature increased. When the TaOx/CB catalyst, which was treated at 873 K for 2 h, was deposited on a glassy carbon substrate with Nafion ionomer, it resulted in the highest activity among the samples investigated, giving an onset potential of 0.95 VRHE at -2 μA cm-2 in a 0.1 M H2SO4 solution. Moreover, the long-term stability test with 10,000 cycles of the voltammetry only led to a 6% loss in the ORR currents, demonstrating the high stability of the TaOx/CB catalysts. Kinetic analysis by R(R)DE indicated that the four-electron transfer pathway in the ORR process was dominant for this TaOx/CB catalyst, and Tafel plots showed a slope corresponding to a one-electron reaction for the rate-determining step.

Data of evolutionary structure change: 1A5CB-2QUTA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 4> 2QUT A 2QUTA ...yChain> 2QUT A 2QUTA ...hain>A 2QUTA ence>LKIGE--HTPSAence> ...1A5CB-2QUTA 1A5C 2QUT B A ------LPADVAEELATTAQKLVQAGKGILAADESTQTI...entryIDChain>1A5CB ence>LFGTK-GLGKFence> HHH -

Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

Science.gov (United States)

Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

2017-01-01

We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. PMID:28426670

Magnesium isotope evidence for single stage formation of CB chondrules by colliding planetesimals

DEFF Research Database (Denmark)

Olsen, Mia Bjørg Stolberg; Schiller, Martin; Krot, Alexander N.

2013-01-01

Chondrules are igneous spherical objects preserved in chondritic meteorites and believed to have formed during transient heating events in the solar protoplanetary disk. Chondrules present in the metal-rich CB chondrites show unusual chemical and petrologic features not observed in other chondrit...... planetesimals. The inferred μMg* value of -3.87 ± 0.93 ppm for the CB parent body is significantly lower than the bulk solar system value of 4.5 ± 1.1 ppm inferred from CI chondrites, suggesting that CB chondrites accreted material comprising an early formed Al-free component.......Chondrules are igneous spherical objects preserved in chondritic meteorites and believed to have formed during transient heating events in the solar protoplanetary disk. Chondrules present in the metal-rich CB chondrites show unusual chemical and petrologic features not observed in other chondrite......, indicating substantial suppression of isotopic fractionation during evaporative loss of Mg, possibly due to evaporation at high Mg partial pressure. Thus, the Mg-isotope data of skeletal chondrules from HH237 are consistent with their origin as melts produced in the impact-generated plume of colliding...

Localization and function of the cannabinoid CB1 receptor in the anterolateral bed nucleus of the stria terminalis.

Directory of Open Access Journals (Sweden)

Nagore Puente

Full Text Available BACKGROUND: The bed nucleus of the stria terminalis (BNST is involved in behaviors related to natural reward, drug addiction and stress. In spite of the emerging role of the endogenous cannabinoid (eCB system in these behaviors, little is known about the anatomy and function of this system in the anterolateral BNST (alBNST. The aim of this study was to provide a detailed morphological characterization of the localization of the cannabinoid 1 (CB1 receptor a necessary step toward a better understanding of the physiological roles of the eCB system in this region of the brain. METHODOLOGY/PRINCIPAL FINDINGS: We have combined anatomical approaches at the confocal and electron microscopy level to ex-vivo electrophysiological techniques. Here, we report that CB1 is localized on presynaptic membranes of about 55% of immunopositive synaptic terminals for the vesicular glutamate transporter 1 (vGluT1, which contain abundant spherical, clear synaptic vesicles and make asymmetrical synapses with alBNST neurons. About 64% of vGluT1 immunonegative synaptic terminals show CB1 immunolabeling. Furthermore, 30% and 35% of presynaptic boutons localize CB1 in alBNST of conditional mutant mice lacking CB1 mainly from GABAergic neurons (GABA-CB1-KO mice and mainly from cortical glutamatergic neurons (Glu-CB1-KO mice, respectively. Extracellular field recordings and whole cell patch clamp in the alBNST rat brain slice preparation revealed that activation of CB1 strongly inhibits excitatory and inhibitory synaptic transmission. CONCLUSIONS/SIGNIFICANCE: This study supports the anterolateral BNST as a potential neuronal substrate of the effects of cannabinoids on stress-related behaviors.

KTA 625 alloy tube with excellent corrosion resistance and heat resistance

International Nuclear Information System (INIS)

Fujiwara, Kazuo; Kadonaga, Toshiki; Kikuma, Seiji.

1982-01-01

The problems when seamless tubes are produced by using nickel base 625 alloy (61Ni-22Cr-9Mo-Cb) which is known as a corrosion resistant and heat resistant alloyF were examined, and the confirmation experiment was carried out on its corrosion resistance and heat resistance. Various difficulties have been experienced in the tube making owing to the characteristics due to the chemical composition, but they were able to be solved by the repeated experiments. As for the characteristics of the product, the corrosion resistance was excellent particularly in the environment containing high temperature, high concentration chloride, and also the heat resistance was excellent in the wide temperature range from normal temperature to 1000 deg C. From these facts, the wide fields of application are expected for these alloy tubes, including the evaporation and concentration equipment for radioactive wastes in atomic energy field. Expecting the increase of demand hereafter, Kobe Steel Ltd. examined the problems when seamless tubes are produced from the 625 alloy by Ugine Sejournet process. The aptitude for tube production such as the chemical composition, production process and the product characteristics, the corrosion resistance against chloride, hydrogen sulfide, polythionic and other acids,F the high temperature strength and oxidation resistance are reported. (Kako, I.)

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

Science.gov (United States)

Albayram, Onder; Alferink, Judith; Pitsch, Julika; Piyanova, Anastasia; Neitzert, Kim; Poppensieker, Karola; Mauer, Daniela; Michel, Kerstin; Legler, Anne; Becker, Albert; Monory, Krisztina; Lutz, Beat; Zimmer, Andreas; Bilkei-Gorzo, Andras

2011-07-05

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure

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Sally Miller

2018-05-01

Full Text Available Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Δ9-THC lowers intraocular pressure (IOP. Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Δ9-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors. However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy. We have recently shown that blocking monoacylglycerol lipase (MAGL, an enzyme that breaks the endocannabinoid 2-arachidonoyl glycerol (2-AG, substantially lowers IOP. Another strategy is to develop cannabinoid CB1 receptor agonists that are optimized for topical application to the eye. Recently we have reported on a controlled-deactivation approach where the “soft” drug concept of enzymatic deactivation was combined with a “depot effect” that is commonly observed with Δ9-THC and other lipophilic cannabinoids. This approach allowed us to develop novel cannabinoids with a predictable duration of action and is particularly attractive for the design of CB1 activators for ophthalmic use with limited or no psychoactive effects. We have tested a novel class of compounds using a combination of electrophysiology in autaptic hippocampal neurons, a well-characterized model of endogenous cannabinoid signaling, and measurements of IOP in a mouse model. We now report that AM7410 is a reasonably potent and efficacious agonist at CB1 in neurons and that it substantially (30% lowers IOP for as long as 5 h after a single topical treatment. This effect is absent in CB1 knockout mice. Our results indicate that the direct targeting of CB1 receptors with controlled-deactivation ligands is a viable approach to lower IOP in a murine model and merits further study in other model systems.

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

Energy Technology Data Exchange (ETDEWEB)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

International Nuclear Information System (INIS)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

2011-01-01

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (−/−) mice. Mice of both genotypes (n = 5–6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82–95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 μM) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20–23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: ► C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. ► Wild type and cannabinoid CB1 receptor knockout littermates

Beta decomposition processes in Hf-rich Hf--Nb alloys

International Nuclear Information System (INIS)

Jones, W.B.; Taggart, R.; Polonis, D.H.

1978-01-01

The decomposition of the bcc β-phase by both athermal and isothermal processes has been investigated in Hf-rich Hf--Nb alloys. An all β-phase structure is retained in chill-cast alloys containing 30 to 50 at.% Nb (Cb), although electron diffraction streaking effects and the behavior of the temperature coefficient of electrical resistivity indicate the presence of a bcc lattice instability similar to that reported in solute lean Ti and Zr alloys. Aging a Hf 0 . 65 Nb 0 . 35 alloy at 400 and 600 0 C resulted in the direct precipitation of a fine dispersion of α-phase needles; this morphology differs from the discs of transition α (α/sub t/) which Carpenter et al observed in Nb-rich Nb 0 . 68 Hf 0 . 32 . During continued aging, the needles grow selectively to form colonies or groups of needles in which both the individual needles and the groups of needles have major axes aligned along (110)/sub β/ type directions. The initial α-phase particles exhibit the Burgers orientation relationship with the parent matrix; continued aging changes the electron diffraction patterns in a way that is similar to that observed in aged Ti--Mo and Ti--Mo--Al alloys where they were attributed to the α-phase having a different crystallographic relationship to the β-phase (Type 2 α-phase). The observed changes in the electron diffraction patterns of aged Hf 0 . 65 Nb 0 . 35 cannot be described as resulting from strained Burgers α-phase

Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

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Jessica Freundt-Revilla

Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

Extraterrestrial Amino Acids Identified in Metal-Rich CH and CB Carbonaceous Chondrites from Antarctica

Science.gov (United States)

Burton, Aaron S.; Elsila, Jamie E.; Hein, Jason E.; Glavin, Daniel P.; Dworkin, Jason P.

2013-01-01

Carbonaceous chondrites contain numerous indigenous organic compounds and could have been an important source of prebiotic compounds required for the origin of life on Earth or elsewhere. Extraterrestrial amino acids have been reported in five of the eight groups of carbonaceous chondrites and are most abundant in CI, CM, and CR chondritesbut are also present in the more thermally altered CV and CO chondrites. We report the abundance, distribution, and enantiomeric and isotopic compositions of simple primary amino acids in six metal-rich CH and CB carbonaceous chondrites that have not previously been investigated for amino acids: Allan Hills (ALH) 85085 (CH3), Pecora Escarpment(PCA) 91467 (CH3), Patuxent Range (PAT) 91546 (CH3), MacAlpine Hills (MAC) 02675(CBb), Miller Range (MIL) 05082 (CB), and Miller Range (MIL) 07411 (CB). Amino acid abundances and carbon isotopic values were obtained by using both liquid chromatography time-of-flight mass spectrometry and fluorescence, and gas chromatography isotope ratiomass spectrometry. The (delta D, delta C-13, delta N-15) ratios of multiple amino acids fall outside of the terrestrial range and support their extraterrestrial origin. Extracts of CH chondrites were found to be particularly rich in amino acids (1316 parts per million, ppm) while CB chondrite extracts had much lower abundances (0.22 ppm). The amino acid distributions of the CH and CB chondrites were distinct from the distributions observed in type 2 and 3 CM and CR chondrites and contained elevated levels of beta-, gamma-, and delta-amino acids compared to the corresponding alpha-amino acids, providing evidence that multiple amino acid formation mechanisms were important in CH and CB chondrites.

Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex.

Science.gov (United States)

Dalton, Victoria S; Long, Leonora E; Weickert, Cyndi Shannon; Zavitsanou, Katerina

2011-07-01

A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB(1) receptor (CB(1)R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB(1)R ligand [(3)H] CP 55,940 and CB(1)R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB(1)R expression. There was a main effect of diagnosis on [(3)H] CP 55,940 binding quantified across all layers of the DLPFC (F(2,71) = 3.740, p = 0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB(1)R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67) = 6.048, p = 0.004) with paranoid SCZ patients differing significantly from the control (p = 0.004) and from the non-paranoid group (p = 0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB(1)R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.

Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments

Science.gov (United States)

Stornaiuolo, Mariano; Bruno, Agostino; Botta, Lorenzo; Regina, Giuseppe La; Cosconati, Sandro; Silvestri, Romano; Marinelli, Luciana; Novellino, Ettore

2015-10-01

A Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.

Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

Directory of Open Access Journals (Sweden)

Rodríguez-Muñoz María

2009-03-01

Full Text Available Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than

Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus

DEFF Research Database (Denmark)

Soni, Neeraj; Satpathy, Shankha; Kohlmeier, Kristi Anne

2014-01-01

Marijuana, which acts within the endocannabinoid (eCB) system as an agonist of the cannabinoid type 1 receptor (CB1R), exhibits addictive properties and has powerful actions on the state of arousal of an organism. The laterodorsal tegmental nucleus (LDT), as a component of the reticular activating...... the firing frequency and synaptic activity of neurons in this nucleus. Therefore, endogenous eCB transmission could play a role in processes involving the LDT, such as cortical activation and motivated behaviours and, further, behavioural actions of marijuana are probably mediated, in part, via cellular...

Spitzer Observations of a 24 μm Shadow: Bok Globule CB 190

Science.gov (United States)

Stutz, Amelia M.; Bieging, John H.; Rieke, George H.; Shirley, Yancy L.; Balog, Zoltan; Gordon, Karl D.; Green, Elizabeth M.; Keene, Jocelyn; Kelly, Brandon C.; Rubin, Mark; Werner, Michael W.

2007-08-01

We present Spitzer observations of the dark globule CB 190 (LDN 771). We observe a roughly circular 24 μm shadow with a 70" radius. The extinction profile of this shadow matches the profile derived from 2MASS photometry at the outer edges of the globule and reaches a maximum of ~32 visual magnitudes at the center. The corresponding mass of CB 190 is ~10 Msolar. Our 12CO and 13CO J=2-1 data over a 10'×10' region centered on the shadow show a temperature ~10 K. The thermal continuum indicates a similar temperature for the dust. The molecular data also show evidence of freezeout onto dust grains. We estimate a distance to CB 190 of 400 pc using the spectroscopic parallax of a star associated with the globule. Bonnor-Ebert fits to the density profile, in conjunction with this distance, yield ξmax=7.2, indicating that CB 190 may be unstable. The high temperature (56 K) of the best-fit Bonnor-Ebert model is in contradiction with the CO and thermal continuum data, leading to the conclusion that the thermal pressure is not enough to prevent free-fall collapse. We also find that the turbulence in the cloud is inadequate to support it. However, the cloud may be supported by the magnetic field, if this field is at the average level for dark globules. Since the magnetic field will eventually leak out through ambipolar diffusion, it is likely that CB 190 is collapsing or in a late precollapse stage. This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under NASA contract 1407.

Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

Science.gov (United States)

Fernández-Trapero, María; Espejo-Porras, Francisco; Rodríguez-Cueto, Carmen; Coates, Joan R.; Pérez-Díaz, Carmen; de Lago, Eva; Fernández-Ruiz, Javier

2017-01-01

ABSTRACT Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells. PMID:28069688

Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

María Fernández-Trapero

2017-05-01

Full Text Available Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS. The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM, caused by mutations in the superoxide dismutase 1 gene (SOD1. We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity. Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.

Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

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Müller Anke

2010-06-01

Full Text Available Abstract Background Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC and Cannabidiol (CBD fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1 deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. Results THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX-expressing intermediate progenitor cells. Conclusion CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

The numerical benchmark CB2-S, final evaluation

International Nuclear Information System (INIS)

Chrapciak, V.

2002-01-01

In this paper are final results of numerical benchmark CB2-S compared (activity, gamma and neutron sources, concentration of important nuclides and decay heat). The participants are: Vladimir Chrapciak (SCALE), Ludmila Markova (SCALE), Svetlana Zabrodskaja (SCALA), Pavel Mikolas (WIMS). Eva Tinkova (HELIOS) and Maria Manolova (SCALE) (Authors)

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

Science.gov (United States)

Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

2014-01-01

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

LEP measurements of $V_{cb}$ using $B^{0} \\to D^{*}^{+}l^{-}\

CERN Document Server

Tarem, S

2001-01-01

CKM elements are free parameters to be measured. V/sub cb/ is the main CKM element allowing b decay. Its smallness accounts for the long b lifetime and our ability to observe higher order effects such as B oscillations. V/sub cb/ can be measured from the inclusive semileptonic decay rate of B hadrons to charm states or from the study of the decay rate of B/sup 0/ to D*/sup +/l/sup -/ nu as a function of D*+ recoil kinematics. Inclusive and exclusive channels, a four-velocity product and errors are discussed. (8 refs).CER 1121756 BASE L 13

Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

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Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

2013-01-01

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

Cannabinoid CB2 Receptors Contribute to Upregulation of β-endorphin in Inflamed Skin Tissues by Electroacupuncture

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Su Tang-feng

2011-12-01

Full Text Available Abstract Background Electroacupuncture (EA can produce analgesia by increasing the β-endorphin level and activation of peripheral μ-opioid receptors in inflamed tissues. Endogenous cannabinoids and peripheral cannabinoid CB2 receptors (CB2Rs are also involved in the antinociceptive effect of EA on inflammatory pain. However, little is known about how peripheral CB2Rs interact with the endogenous opioid system at the inflammatory site and how this interaction contributes to the antinociceptive effect of EA on inflammatory pain. In this study, we determined the role of peripheral CB2Rs in the effects of EA on the expression of β-endorphin in inflamed skin tissues and inflammatory pain. Results Inflammatory pain was induced by injection of complete Freund's adjuvant into the left hindpaw of rats. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified using von Frey filaments. The mRNA level of POMC and protein level of β-endorphin were quantified by real-time PCR and Western blotting, respectively. The β-endorphin-containing keratinocytes and immune cells in the inflamed skin tissues were detected by double-immunofluorescence labeling. The CB2R agonist AM1241 or EA significantly reduced thermal hyperalgesia and mechanical allodynia, whereas the selective μ-opioid receptor antagonist β-funaltrexamine significantly attenuated the antinociceptive effect produced by them. AM1241 or EA significantly increased the mRNA level of POMC and the protein level of β-endorphin in inflamed skin tissues, and these effects were significantly attenuated by pretreatment with the CB2R antagonist AM630. AM1241 or EA also significantly increased the percentage of β-endorphin-immunoreactive keratinocytes, macrophages, and T-lymphocytes in inflamed skin tissues, and these effects were blocked by AM630. Conclusions EA and CB2R stimulation reduce inflammatory pain through activation of μ-opioid receptors. EA increases

Prototypic implementations of the building block for component based open Hypermedia systems (BB/CB-OHSs)

DEFF Research Database (Denmark)

Mohamed, Omer I. Eldai

2005-01-01

In this paper we describe the prototypic implementations of the BuildingBlock (BB/CB-OHSs) that proposed to address some of the Component-based Open Hypermedia Systems (CB-OHSs) issues, including distribution and interoperability [4, 11, 12]. Four service implementations were described below. The...

In vitro biocorrosion of Ti-6Al-4V implant alloy by a mouse macrophage cell line.

Science.gov (United States)

Lin, Hsin-Yi; Bumgardner, Joel D

2004-03-15

Corrosion of implant alloys releasing metal ions has the potential to cause adverse tissue reactions and implant failure. We hypothesized that macrophage cells and their released reactive chemical species (RCS) affect the alloy's corrosion properties. A custom cell culture corrosion box was used to evaluate how cell culture medium, macrophage cells and RCS altered the Ti-6Al-4V corrosion behaviors in 72 h and how corrosion products affected the cells. There was no difference in the charge transfer in the presence (75.2 +/- 17.7 mC) and absence (62.3 +/- 18.8 mC) of cells. The alloy had the lowest charge transfer (28.2 +/- 4.1 mC) and metal ion release (Ti < 10 ppb, V < 2 ppb) with activated cells (releasing RCS) compared with the other two conditions. This was attributed to an enhancement of the surface oxides by RCS. Metal ion release was very low (Ti < 20 ppb, V < 10 ppb) with nonactivated cells and did not change cell morphology, viability, and NO and ATP release compared with controls. However, IL-1beta released from the activated cells and the proliferation of nonactivated cells were greater on the alloy than the controls. In summary, macrophage cells and RCS reduced the corrosion of Ti-6Al-4V alloys as hypothesized. These data are important in understanding host tissue-material interactions. Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 717-724, 2004

Interdiffusion behavior of tungsten or rhenium and group 5 and 6 elements and alloys of the periodic table, part 1. [at dissimilar metal joints

Science.gov (United States)

Arcella, F. G.

1974-01-01

Arc cast W, CVD W, CVD Re, and powder metallurgy Re materials were hot isostatically pressure welded to ten different refractory metals and alloys (Cb, Cb-1Zr, Ta, Ta-10W, T-111, ASTAR-811C, W-25Re, Mo-50Re, W-30Re-20Mo, ect.) and thermally aged at 10 to the minus 8th power torr at 1200, 1500, 1630, 1800, and 2000 C for 100 to 2000 hours. Electron beam microprobe analysis was used to characterize the interdiffusion zone width of each couple system as a function of age time and temperature. Extrapolations of interdiffusion zone thickness to 10,000 hours were made. Classic interdiffusion analysis was performed for several of the systems by Boltzmann-Matano analysis. A method of inhibiting Kirkendall voids from forming during thermal ageing of dissimilar metal junctions was devised and experimentally demonstrated. An electron beam weld study of Cb-1Zr to Re and W-25Re demonstrated the limited acceptability of these welds.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Science.gov (United States)

Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

2012-06-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Cardiovascular angiography system Infinix{sub TM} CB; Shinzoyo junkanki shindan system Infinix{sub TM} CB

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

A cardiovascular angiography system Infinix{sub TM} CB is developed, which is a dedicated system for cardiovascular catheter treatment (intervention), from PTCA (percutaneous transluminal coronary angioplasty) down, capable of two-way biplanar photography. It is designed to be thoroughly operator-friendly, and some of its features are stated below. It is capable of high-speed biplanar positioning at the maximum speed of 10 degrees/second (25% faster than in the conventional type). A side beam vertical motion mechanism is provided rendering biplanar framing faster and easier. Hyper-handling is embodied with ergonomics introduced into the system. (translated by NEDO)

Cardiovascular angiography system Infinix[sub TM] CB. Shinzoyo junkanki shindan system Infinix[sub TM] CB

Energy Technology Data Exchange (ETDEWEB)

1999-03-01

A cardiovascular angiography system Infinix[sub TM] CB is developed, which is a dedicated system for cardiovascular catheter treatment (intervention), from PTCA (percutaneous transluminal coronary angioplasty) down, capable of two-way biplanar photography. It is designed to be thoroughly operator-friendly, and some of its features are stated below. It is capable of high-speed biplanar positioning at the maximum speed of 10 degrees/second (25% faster than in the conventional type). A side beam vertical motion mechanism is provided rendering biplanar framing faster and easier. Hyper-handling is embodied with ergonomics introduced into the system. (translated by NEDO)

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

Science.gov (United States)

Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

2016-11-01

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identifying the causes of differences in ozone production from the CB05 and CBMIV chemical mechanisms

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R. D. Saylor

2012-02-01

Full Text Available An investigation was conducted to identify the mechanistic differences between two versions of the carbon bond gas-phase chemical mechanism (CB05 and CBMIV which consistently lead to larger ground-level ozone concentrations being produced in the CB05 version of the National Air Quality Forecasting Capability (NAQFC modeling system even though the two parallel forecast systems utilize the same meteorology and base emissions and similar initial and boundary conditions. Box models of each of the mechanisms as they are implemented in the NAQFC were created and a set of 12 sensitivity simulations was designed. The sensitivity simulations independently probed the conceptual mechanistic differences between CB05 and CBMIV and were exercised over a 45-scenario simulation suite designed to emulate the wide range of chemical regimes encountered in a continental-scale atmospheric chemistry model. Results of the sensitivity simulations indicate that two sets of reactions that were included in the CB05 mechanism, but which were absent from the CBMIV mechanism, are the primary causes of the greater ozone production in the CB05 version of the NAQFC. One set of reactions recycles the higher organic peroxide species of CB05 (ROOH, resulting in additional photochemically reactive products that act to produce additional ozone in some chemical regimes. The other set of reactions recycles reactive nitrogen from less reactive forms back to NO₂, increasing the effective NO_x concentration of the system. In particular, the organic nitrate species (NTR, which was a terminal product for reactive nitrogen in the CBMIV mechanism, acts as a reservoir species in CB05 to redistribute NO_x from major source areas to potentially NO_x-sensitive areas where additional ozone may be produced in areas remote from direct NO_x sources.

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

Science.gov (United States)

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-01-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

Artificial Intelligence in Prediction of Secondary Protein Structure Using CB513 Database

Science.gov (United States)

Avdagic, Zikrija; Purisevic, Elvir; Omanovic, Samir; Coralic, Zlatan

2009-01-01

In this paper we describe CB513 a non-redundant dataset, suitable for development of algorithms for prediction of secondary protein structure. A program was made in Borland Delphi for transforming data from our dataset to make it suitable for learning of neural network for prediction of secondary protein structure implemented in MATLAB Neural-Network Toolbox. Learning (training and testing) of neural network is researched with different sizes of windows, different number of neurons in the hidden layer and different number of training epochs, while using dataset CB513. PMID:21347158

Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

Science.gov (United States)

Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

2010-04-01

Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

Effect of various lanthanum sol-gel coatings on the 330Cb (Fe-35Ni-18Cr-1Nb-2Si) oxidation at 900 deg. C

Energy Technology Data Exchange (ETDEWEB)

Buscail, H., E-mail: buscail@iut.u-clermont1.fr [Clermont Universite- LVEEM, 8 rue J.B. Fabre, BP 219, 43006 Le Puy en Velay (France); Issartel, C.; Riffard, F.; Rolland, R.; Perrier, S. [Clermont Universite- LVEEM, 8 rue J.B. Fabre, BP 219, 43006 Le Puy en Velay (France); Fleurentin, A. [CETIM, 52 av Felix Louat, BP 80067, 60304 Senlis (France); Josse, C. [L' ICB UMR5209 CNRS, BP 47870, 21078 Dijon (France)

2011-11-01

The influence of a lanthanum sol-gel coating on the oxide scale adherence has been studied during the 330Cb (Fe-35Ni-18Cr-1Nb-2Si) oxidation at 900 deg. C, in air. The alloy oxidation is performed in order to generate a protective chromia scale acting as a good barrier against carburization. Argon annealing of lanthanum sol-gel coatings have been performed at various temperatures in order to find the best conditions to insure the scale adherence. Kinetic results show that lanthanum sol-gel coatings lead to a lower oxidation rate compared to blank specimens. Thermal cycling tests on lanthanum the sol-gel coated specimen show that the oxide scale formed at 900 deg. C, in air, is adherent.

Is compulsive buying related to materialism, depression or temperament? Findings from a sample of treatment-seeking patients with CB.

Science.gov (United States)

Müller, Astrid; Claes, Laurence; Georgiadou, Ekaterini; Möllenkamp, Maike; Voth, Eva M; Faber, Ron J; Mitchell, James E; de Zwaan, Martina

2014-04-30

The aim of the present work was to examine the influence of reactive and regulatory temperament on compulsive buying (CB) in a sample of 102 patients (79 women, 23 men) with clinical CB. All participants answered the Compulsive Buying Scale (CBS), the Behavioral Inhibition System and Behavioral Activation System Scales (BIS/BAS), and the Effortful Control subscale (ATQ-EC) of the Adult Temperament Questionnaire-Short Form. Based on previous studies demonstrating that depression and materialism are linked with CB, in addition, the Patient Health Questionnaire depression scale (PHQ-9) and the Materialistic Values Scale (MVS) were administered. CBS scores were significantly correlated with the MVS, PHQ-9, and BAS scores. The findings of the hierarchical regression analysis, however, indicated that in the present sample of treatment-seeking patients the only significant association was found between CB and depression. The results highlight the prominent role of depression in CB. There is a need for longitudinal studies in order to answer the question whether depression is the cause or the consequence of CB. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

International Nuclear Information System (INIS)

Sarafian, Theodore; Montes, Cindy; Harui, Airi; Beedanagari, Sudheer R.; Kiertscher, Sylvia; Stripecke, Renata; Hossepian, Derik; Kitchen, Christina; Kern, Rita; Belperio, John; Roth, Michael D.

2008-01-01

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ 9 -tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p m ) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψ m than did control cells. Since both Ψ m and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK was regulated in a CB2R- and THC

Expression analysis and functional characterization of a novel cold-responsive gene CbCOR15a from Capsella bursa-pastoris.

Science.gov (United States)

Zhou, Mingqi; Wu, Lihua; Liang, Jing; Shen, Chen; Lin, Juan

2012-05-01

The cold-responsive (COR) genes involved in C-repeat binding factor signaling pathway function essentially in cold acclimation of higher plants. A novel COR gene CbCOR15a from shepherd's purse (Capsella bursa-pastoris) was predicted to be a homolog of COR15 in Arabidopsis. The analysis of tissue specific expression pattern as well as characterization of the CbCOR15a promoter revealed that the expression of CbCOR15a was induced by coldness not only in leaves and stem but also in roots. Sequence analysis showed that a 909 bp promoter region of CbCOR15a contained two CRT/DRE elements, two ABRE elements, one auxin-responsive TGA-element and one MeJA-responsive CGTCA-motif. In young seedlings the expression of CbCOR15a could be apparently increased by SA, ABA, MeJA and IAA, and transiently increased by GA(3) accompanied by obvious feedback suppression. According to the altered physiological index values in tobacco under cold treatments, the overexpression of CbCOR15a significantly increased the cold tolerance of transgenic tobacco plants. It can be suggested that CbCOR15a was involved in cold response of Capsella bursa-pastoris associated with SA, ABA, MeJA, IAA and GA(3) regulation and confers enhanced cold acclimation in transgenic plants.

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

Science.gov (United States)

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-12-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

Growth Promotion and Disease Suppression Ability of a Streptomyces sp. CB-75 from Banana Rhizosphere Soil

Science.gov (United States)

Chen, Yufeng; Zhou, Dengbo; Qi, Dengfeng; Gao, Zhufen; Xie, Jianghui; Luo, Yanping

2018-01-01

An actinomycete strain, CB-75, was isolated from the soil of a diseased banana plantation in Hainan, China. Based on phenotypic and molecular characteristics, and 99.93% sequence similarity with Streptomyces spectabilis NBRC 13424 (AB184393), the strain was identified as Streptomyces sp. This strain exhibited broad-spectrum antifungal activity against 11 plant pathogenic fungi. Type I polyketide synthase (PKS-I) and non-ribosomal peptide synthetase (NRPS) were detected, which were indicative of the antifungal compounds that Streptomyces sp. CB-75 could produce. An ethyl acetate extract from the strain exhibited the lowest minimum inhibitory concentration (MIC) against Colletotrichum musae (ATCC 96167) (0.78 μg/ml) and yielded the highest antifungal activity against Colletotrichum gloeosporioides (ATCC 16330) (50.0 μg/ml). Also, spore germination was significantly inhibited by the crude extract. After treatment with the crude extract of Streptomyces sp. CB-75 at the concentration 2 × MIC, the pathogenic fungi showed deformation, shrinkage, collapse, and tortuosity when observed by scanning electron microscopy (SEM). By gas chromatography-mass spectrometry (GC-MS) of the crude extract, 18 chemical constituents were identified; (Z)-13-docosenamide was the major constituent. Pot experiments showed that the incidence of banana seedlings was reduced after using Streptomyces sp. CB-75 treatment. The disease index was 10.23, and the prevention and control effect was 83.12%. Furthermore, Streptomyces sp. CB-75 had a growth-promoting effect on banana plants. The chlorophyll content showed 88.24% improvement, the leaf area, root length, root diameter, plant height, and stem showed 88.24, 90.49, 136.17, 61.78, and 50.98% improvement, respectively, and the shoot fresh weight, root fresh weight, shoot dry weight, and root dry weight showed 82.38, 72.01, 195.33, and 113.33% improvement, respectively, compared with treatment of fermentation broth without Streptomyces sp. CB-75

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

Directory of Open Access Journals (Sweden)

Islam Gamaleddin

Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

DEFF Research Database (Denmark)

Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal

2016-01-01

release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1...

Genome Sequence of the 1,4-Dioxane-Degrading Pseudonocardia dioxanivoransStrain CB1190▿

Science.gov (United States)

Sales, Christopher M.; Mahendra, Shaily; Grostern, Ariel; Parales, Rebecca E.; Goodwin, Lynne A.; Woyke, Tanja; Nolan, Matt; Lapidus, Alla; Chertkov, Olga; Ovchinnikova, Galina; Sczyrba, Alexander; Alvarez-Cohen, Lisa

2011-01-01

Pseudonocardia dioxanivoransCB1190 is the first bacterium reported to be capable of growth on the environmental contaminant 1,4-dioxane and the first member of the genus Pseudonocardiafor which there is an annotated genome sequence. Preliminary analysis of the genome (chromosome and three plasmids) indicates that strain CB1190 possesses several multicomponent monooxygenases that could be involved in the aerobic degradation of 1,4-dioxane and other environmental contaminants. PMID:21725009

The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

Science.gov (United States)

Friemel, Chris M; Zimmer, Andreas; Schneider, Miriam

2014-01-01

The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex—the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing. PMID:24718372

Hot pressing effect on (Bi0⋅25Sb0⋅75)2Te3 mechanical and ...

Indian Academy of Sciences (India)

Administrator

Abstract. (Bi0⋅25Sb0⋅75)2Te3 thermoelectric material is a well known p type of compound that has higher fig- ... The crystal of this compound was prepared, pulverized in a particle .... ing fracture surfaces of the materials as shown in figures.

A Novel Selective Inverse Agonist of the CB2 Receptor as a Radiolabeled Tool Compound for Kinetic Binding Studies.

Science.gov (United States)

Martella, Andrea; Sijben, Huub; Rufer, Arne C; Grether, Uwe; Fingerle, Juergen; Ullmer, Christoph; Hartung, Thomas; IJzerman, Adriaan P; van der Stelt, Mario; Heitman, Laura H

2017-10-01

The endocannabinoid system, and in particular the cannabinoid type 2 receptor (CB2R), raised the interest of many medicinal chemistry programs for its therapeutic relevance in several (patho)physiologic processes. However, the physico-chemical properties of tool compounds for CB2R (e.g., the radioligand [ 3 H]CP55,940) are not optimal, despite the research efforts in developing effective drugs to target this system. At the same time, the importance of drug-target binding kinetics is growing since the kinetic binding profile of a ligand may provide important insights for the resulting in vivo efficacy. In this context we synthesized and characterized [ 3 H]RO6957022, a highly selective CB2R inverse agonist, as a radiolabeled tool compound. In equilibrium and kinetic binding experiments [ 3 H]RO6957022 showed high affinity for human CB2R with fast association ( k on ) and moderate dissociation ( k off ) kinetics. To demonstrate the robustness of [ 3 H]RO6957022 binding, affinity studies were carried out for a wide range of CB2R reference ligands, spanning the range of full, partial, and inverse agonists. Finally, we used [ 3 H]RO6957022 to study the kinetic binding profiles (i.e., k on and k off values) of selected synthetic and endogenous (i.e., 2-arachidonoylglycerol, anandamide, and noladin ether) CB2R ligands by competition association experiments. All tested ligands, and in particular the endocannabinoids, displayed distinct kinetic profiles, shedding more light on their mechanism of action and the importance of association rates in the determination of CB2R affinity. Altogether, this study shows that the use of a novel tool compound, i.e., [ 3 H]RO6957022, can support the development of novel ligands with a repertoire of kinetic binding profiles for CB2R. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Stabilization of functional recombinant cannabinoid receptor CB(2 in detergent micelles and lipid bilayers.

Directory of Open Access Journals (Sweden)

Krishna Vukoti

Full Text Available Elucidation of the molecular mechanisms of activation of G protein-coupled receptors (GPCRs is among the most challenging tasks for modern membrane biology. For studies by high resolution analytical methods, these integral membrane receptors have to be expressed in large quantities, solubilized from cell membranes and purified in detergent micelles, which may result in a severe destabilization and a loss of function. Here, we report insights into differential effects of detergents, lipids and cannabinoid ligands on stability of the recombinant cannabinoid receptor CB(2, and provide guidelines for preparation and handling of the fully functional receptor suitable for a wide array of downstream applications. While we previously described the expression in Escherichia coli, purification and liposome-reconstitution of multi-milligram quantities of CB(2, here we report an efficient stabilization of the recombinant receptor in micelles - crucial for functional and structural characterization. The effects of detergents, lipids and specific ligands on structural stability of CB(2 were assessed by studying activation of G proteins by the purified receptor reconstituted into liposomes. Functional structure of the ligand binding pocket of the receptor was confirmed by binding of (2H-labeled ligand measured by solid-state NMR. We demonstrate that a concerted action of an anionic cholesterol derivative, cholesteryl hemisuccinate (CHS and high affinity cannabinoid ligands CP-55,940 or SR-144,528 are required for efficient stabilization of the functional fold of CB(2 in dodecyl maltoside (DDM/CHAPS detergent solutions. Similar to CHS, the negatively charged phospholipids with the serine headgroup (PS exerted significant stabilizing effects in micelles while uncharged phospholipids were not effective. The purified CB(2 reconstituted into lipid bilayers retained functionality for up to several weeks enabling high resolution structural studies of this GPCR at

Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

Science.gov (United States)

Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

2014-07-01

In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

Polymer membranes modified by fullerene C-60 for pervaporation of organic mixtures

Czech Academy of Sciences Publication Activity Database

Polotskaya, G. A.; Penkova, A. V.; Pientka, Zbyněk; Toikka, A. M.

2010-01-01

Roč. 14, 1-3 (2010), s. 83-88 ISSN 1944-3994. [PERMEA 2009. Prague, 07.06.2009-11.06.2009] R&D Projects: GA ČR GA104/09/1165 Institutional research plan: CEZ:AV0Z40500505 Keywords : pervaporation * fullerene -containing membranes * poly(phenylene oxide) Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.752, year: 2010

Fracture toughness evaluation of select advanced replacement alloys for LWR core internals

Energy Technology Data Exchange (ETDEWEB)

Tan, Lizhen [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chen, Xiang [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-08-01

ferritic alloys showing slight decreases (Grade 92) or significant decreases (14YWT) in fracture toughness at elevated temperatures, the fracture toughness of the austenitic stainless steels and Ni-base superalloys were not strongly dependent upon the test temperatures. The fracture toughness of the alloys at the LWR-relevant temperatures was estimated by averaging the toughness values within 250– 350°C, which suggested the fracture toughness of the alloys in a descending order as 316L (752±98 MPa√m), 310 (513±66 MPa√m), 718A (313±43 MPa√m), 690 (267±48 MPa√m), 725 (218±55 MPa√m), X750 (145±16 MPa√m), Grade 92 (112±12 MPa√m), and 14YWT (63±3 MPa√m). Tearing modulus of the alloys was analyzed in the meantime, which were not strongly dependent upon the test temperatures. The high-strength alloys 718A, 725, X750, and 14YWT had the lowest tearing modulus, ranging from ~45 to ~7. Alloy 690 exhibited the highest tearing modulus on the order of 450, followed by 316L and 310 on the order of 260. Grade 92 had a noticeably lower tearing modulus on the order of 70.

Influence of S, P, C on grain boundary diffusion and creep properties of Alloy 800; Einfluss von S, P, C auf die Korngrenzendiffusion und Kriecheigenschaften von Alloy 800

Energy Technology Data Exchange (ETDEWEB)

Lindemann, J.; Hannesen, K.; Mast, R.; Viefhaus, H. [Max-Planck-Institut fuer Eisenforschung GmbH, Duesseldorf (Germany); Grabke, H.J.

1998-12-31

The paper reports examinations of Alloy 800 and specific commercially available variants known under the names of 800H, 800HT, and 800LC, differing in their concentrations of C, Al, and Ti. In addition, melts also containing phosphorus (0.09 wt-%) or sulfur (0.04 wt-%) as additional alloying materials have been prepared for the experiments. The volume diffusion and the grain boundary diffusion of {sup 59}Fe in those alloys was measured at temperatures between 800 and 1000 C by means of a radioactive tracer method combined with residual activity measurements. It was found that accompanying elements like phosphorus and sulfur increase the activation energy of the grain boundary diffusion of the iron and thus delay the grain boundary self-diffusion in Alloy 800. Creep curves were measured of the same materials after age-hardening treatment for 100 hours at 800 C, measurements performed at constant temperature but at three different, constant creep stress loads. The results showed that addition of phosphorus markedly increases the lifetime of Alloy 800, and reduces the creep rupture strain. The minimum strain rate in Alloy 800 containing 0.09 wt-% of phosphorus was found to be lower by a factor of 100, as compared to the other Alloy 800 materials used. (orig./CB) [Deutsch] Alloy 800 ist ein austenitischer Fe-Ni-Cr Stahl, der relativ geringe, aber wichtige Konzentrationen von Kohlenstoff, Aluminium und Titan enthaelt. Besondere Varianten von Alloy 800, bekannt als 800H, 800HT und 800LC, unterscheiden sich in den Konzentrationen dieser Elemente. Diese kommerziellen Legierungen wurden untersucht, und zusaetzlich wurden Schmelzen mit zulegiertem Phosphor (0,09 Gew-%) bzw. Schwefel (0,04 Gew-%) hergestellt. Mittels einer radioaktiven Tracermethode in Verbindung mit Restaktivitaetsmessungen wurde die Volumen- und Korngrenzendiffusion von {sup 59}Fe in diesen Legierungen im Temperaturbereich 800-1000 C gemessen. Es wurde gefunden, dass Begleitelemente wie Phosphor und

Status of the SPES-charge breeder (SPES-CB) and its beam line at INFN-LNL

International Nuclear Information System (INIS)

Galatá, Àlessio; Comunian, M.; Bellan, L.; Maggiore, M.; Patti, G.; Roncolato, C.; Bisoffi, G.; Russo, A.D.; Calabretta, L.; Angot, J.; Lamy, T.

2016-01-01

The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UC_x target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.

Status of the SPES-charge breeder (SPES-CB) and its beam line at INFN-LNL

Energy Technology Data Exchange (ETDEWEB)

Galatá, Àlessio; Comunian, M. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Bellan, L. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Dipartimento di Fisica e Astronomia, Universitá degli Studi di Padova e Sezione INFN, Padova (Padova) (Italy); Maggiore, M.; Patti, G.; Roncolato, C.; Bisoffi, G. [INFN-Laboratori Nazionali di Legnaro, Viale dell’Universitá 2, 35020 Legnaro, Padova (Italy); Russo, A.D.; Calabretta, L. [INFN-Laboratori Nazionali del Sud, via S. Sofia 62, 95123 Catania (Italy); Angot, J.; Lamy, T. [LPSC – Université Grenoble Alpes – CNRS/IN2P3, 53 rue des Martyrs, 38026 Grenoble Cedex (France)

2016-06-01

The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UC{sub x} target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.

The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis.

Science.gov (United States)

Sanchez, Ana-Maria; Quattrone, Federica; Pannese, Maria; Ulisse, Adele; Candiani, Massimo; Diaz-Alonso, Javier; Velasco, Guillermo; Panina-Bordignon, Paola

2017-01-01

Does signaling via the cannabinoid (CB 1 ) receptor play a role in the pathogenesis of endometriosis in a mouse model? Mice treated with a CB 1 agonist developed larger ectopic lesions, while less severe lesions developed in the absence of functional CB 1 expression. The expression of components of the endocannabinoid system has been demonstrated in both mouse and human uteri. CB 1 receptors are expressed in human epithelial and stromal cell lines derived from eutopic endometrium and deep infiltrating endometriosis nodules. This was a randomized study in a mouse model of endometriosis. In a first set of experiments, mice with endometriosis were treated with the CB 1 receptor agonist methanandamide (MET) (5 mg/kg, n = 20) on Days 1-5 and 8-12. In a second set of experiments, endometriosis development was evaluated in CB 1 -/- mice and in their wild-type (WT) littermates. Endometriosis-like lesions were induced in Balb/c and C57/Bl6 mice. Two weeks after disease induction, the lesions were counted, measured and either included for immunohistochemistry analysis or frozen for gene expression profiling by semi-quantitative real-time PCR. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. The lesion total volume was significantly higher in MET-treated compared with vehicle-treated mice (P endometriosis in a mouse model. However, the relative contribution of the CB 1 -mediated signaling pathways active in inflammatory, uterine and peritoneal cells remains to be ascertained. Since the study was performed in a mouse model, the significance of the findings in the human system warrants further investigation. Clarifying the function and regulation of CB 1 and its molecular interactions with endogenous ligands, and how endocannabinoids levels are regulated in women with endometriosis, represent critical areas of research for the potential development of a novel medical treatment of the disease. A

The low-temperature structural behavior of sodium 1-carba-closo-decaborate: NaCB{sub 9}H{sub 10}

Energy Technology Data Exchange (ETDEWEB)

Wu, Hui, E-mail: hui.wu@nist.gov [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Tang, Wan Si [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742-2115 (United States); Zhou, Wei [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Tarver, Jacob D. [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); National Renewable Energy Laboratory, Golden, CO 80401 (United States); Stavila, Vitalie [Energy Nanomaterials, Sandia National Laboratories, Livermore, CA 94551 (United States); Brown, Craig M. [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States); Udovic, Terrence J., E-mail: udovic@nist.gov [NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899-6102 (United States)

2016-11-15

Two ordered phases of the novel solid superionic conductor sodium 1-carba-closo-decaborate (NaCB{sub 9}H{sub 10}) were identified via synchrotron x-ray powder diffraction in combination with first-principles calculations and neutron vibrational spectroscopy. A monoclinic packing of the large ellipsoidal CB{sub 9}H{sub 10}{sup −} anions prevails at the lowest temperatures, but a first-order transformation to a slightly modified orthorhombic packing is largely complete by 240 K. The CB{sub 9}H{sub 10}{sup −} anion orientational alignments and Na{sup +} cation interstitial sitings in both phases are arranged so as to minimize the cation proximities to the uniquely more positive C-bonded H atoms of the anions. These results provide valuable structural information pertinent to understanding the relatively low-temperature, entropy-driven, order-disorder phase transition for this compound. - Graphical abstract: Ordered monoclinic and orthorhombic NaCB{sub 9}H{sub 10} phases were determined by XRD and DFT computations and corroborated by neutron vibrational spectroscopy. - Highlights: • Two T-dependent ordered structures of Na(1-CB{sub 9}H{sub 10}) were determined by XRD. • The lower-T monoclinic to higher-T orthorhombic transition occurs from 210 to 240 K. • The main structural differences involve changes in the canting of the CB{sub 9}H{sub 10}{sup −} anions. • DFT and neutron vibrational spectroscopy corroborate the lower-T monoclinic structure. • The results are important for understanding the nature of this superionic conductor.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

OpenAIRE

Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

2011-01-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl(CB187) with liver microsomes of rats, hamsters and guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Koga, N.; Ohta, C.; Kanamaru, T. [Nakamura Gakuen Univ., Fukuoka (Japan); Haraguchi, K. [Daiichi Coll. of Pharmaceutical Sciences, Fukuoka (Japan); Kato, Y.; Yamada, S. [Univ. of Shizuoka, Shizuoka (Japan)

2004-09-15

PCB congeners possess extremely high lipophilicity and biological stability, and as a result they are not easily eliminated from the body once ingested. In particular, not only 2,4,5-trichlorosubstituted but also 6 or more chlorine-substituted PCBs such as 2,2',3',4,4',5-hexa-chlorobiphenyl (hexaCB) (CB138), 2,2',4,4',5,5'-hexaCB (CB153), 2,2',3,4,4',5,5'-heptachloro-biphenyl (heptaCB) (CB180) and 2,2',3,4',5,5',6-heptaCB (CB187) have been detected in blood and adipose tissues of mammals and human mother's milk at higher concentration. In addition, the 4-hydroxy (OH)-metabolite of CB187 has been reported to be present in human blood at the highest concentration of that derived from other PCB congeners. Although CB187, a tri-ortho-PCB, is one of the minor component in the commercial PCB preparations such as Clophen, Aroclor and Kanechlor, the toxic equivalency factor (TEF) which is used for dioxin-like PCB congeners including coplanar-PCBs and mono-ortho-PCBs to assess the potency of the toxicity has not been set up for di- and tri-ortho-PCB congeners. These facts indicate that 4-OH-PCB187 become more persistent and more important toxicologically than the parent CB187. However, there is little report about biotransformation in vivo or in vitro of CB187 in animals. Therefore, we examined CB187 metabolism by liver microsomes of rats, hamsters and guinea pigs.

Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats.

Science.gov (United States)

Fang, Qin; Li, Fang-Qiong; Li, Yan-Qin; Xue, Yan-Xue; He, Ying-Ying; Liu, Jian-Feng; Lu, Lin; Wang, Ji-Shi

2011-10-01

Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB(1) receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB(1) receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of 3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1) receptor antagonists may be a potential target for managing nicotine addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

CB 1/2 dual agonists with 3-carbamoyl 2-pyridone derivatives as antipruritics: reduction of CNS side effects by introducing polar functional groups.

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Odan, Masahide; Ishizuka, Natsuki; Hiramatsu, Yoshiharu; Inagaki, Masanao; Hashizume, Hiroshi; Fujii, Yasuhiko; Mitsumori, Susumu; Morioka, Yasuhide; Soga, Masahiko; Deguchi, Masashi; Yasui, Kiyoshi; Arimura, Akinori

2012-04-15

Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

CbRCI35, a cold responsive peroxidase from Capsella bursa-pastoris regulates reactive oxygen species homeostasis and enhances cold tolerance in tobacco

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Juan Lin

2016-10-01

Full Text Available Low temperature affects gene regulatory networks and alters cellular metabolism to inhibit plant growth. Peroxidases are widely distributed in plants and play a large role in adjusting and controlling reactive oxygen species (ROS homeostasis in response to abiotic stresses such as low temperature. The Rare Cold-Inducible 35 gene from Capsella bursa-pastoris (CbRCI35 belongs to the type III peroxidase family and has been reported to be a cold responsive gene in plants. Here we performed an expressional characterization of CbRCI35 under cold and ionic liquid treatments. The promoter of CbRCI35 was also cloned and its activity was examined using the GUS reporter system. CbRCI35 protein was localized in the cytoplasm according to sequence prediction and GFP fusion assay. Heterologous expression tests revealed that CbRCI35 conferred enhanced resistance to low temperature and activated endogenous cold responsive signaling in tobacco. Furthermore, in the normal condition the ROS accumulation was moderately enhanced while after chilling exposure superoxide dismutase (SOD activity was increased in CbRCI53 transgenic plants. The ROS metabolism related genes expression was altered accordingly. We conclude that CbRCI35 modulates ROS homeostasis and contributes to cold tolerance in plants.

Interactions of CB1 and mGlu5 receptor antagonists in food intake, anxiety and memory models in rats.

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Varga, Balázs; Kassai, Ferenc; Gyertyán, István

2012-12-01

CB(1) receptor antagonists proved to be effective anti-obesity drugs, however, their depressive and anxiogenic effects became also evident. Finding solution to overcome these psychiatric side effects is still in focus of research. Based on the available clinical and preclinical results we hypothesized that the combination of CB(1) and mGlu(5) receptor antagonisms may result in a pharmacological intervention, where the anxiolytic mGlu(5) receptor inhibition may counteract the anxiogenic psychiatric side effects of CB(1) antagonism, while CB(1) antagonism may ameliorate the memory impairing effect of mGlu(5) receptor antagonism. Further, the two components will synergistically interact in blocking food-intake and reducing obesity. For testing the interaction of mGlu(5) and CB(1) receptor antagonism MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pridine; SIB-1757, 6-methyl-2-(phenylazo)-3-pyridinol)] (mGlu(5) antagonist) and rimonabant [(5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide)hydrochloride] (CB(1) antagonist) were used. All experiments were carried out in rats. Effects of the compounds on anxiety were tested in two foot shock induced ultrasonic vocalization paradigms, appetite suppression was assessed in the food intake test, while memory effects were tested in a context conditioned ultrasonic vocalization setup. MTEP abolished the anxiogenic effect of rimonabant, while there was an additive cooperation in suppressing appetite. However, rimonabant did not ameliorate the memory impairing effect of MTEP. By combination of CB(1) and mGluR5 antagonism, anxiety related side effects might be attenuated, appetite suppression maintained, nevertheless, the possible emergence of unwanted memory impairments can overshadow its therapeutic success. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

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Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

2012-03-02

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells

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Sung-Yun Cho

2013-01-01

Full Text Available Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPKα blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPKα in hypoxic SW620 cells, implying cross-talk between ERK and AMPKα. Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1α and Akt/mTOR and the activation of AMPKα and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPKα in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPKα and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

Combined multi-spectrum and orthogonal Laplacianfaces for fast CB-XLCT imaging with single-view data

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Zhang, Haibo; Geng, Guohua; Chen, Yanrong; Qu, Xuan; Zhao, Fengjun; Hou, Yuqing; Yi, Huangjian; He, Xiaowei

2017-12-01

Cone-beam X-ray luminescence computed tomography (CB-XLCT) is an attractive hybrid imaging modality, which has the potential of monitoring the metabolic processes of nanophosphors-based drugs in vivo. Single-view data reconstruction as a key issue of CB-XLCT imaging promotes the effective study of dynamic XLCT imaging. However, it suffers from serious ill-posedness in the inverse problem. In this paper, a multi-spectrum strategy is adopted to relieve the ill-posedness of reconstruction. The strategy is based on the third-order simplified spherical harmonic approximation model. Then, an orthogonal Laplacianfaces-based method is proposed to reduce the large computational burden without degrading the imaging quality. Both simulated data and in vivo experimental data were used to evaluate the efficiency and robustness of the proposed method. The results are satisfactory in terms of both location and quantitative recovering with computational efficiency, indicating that the proposed method is practical and promising for single-view CB-XLCT imaging.

LDRD final report on synthesis of shape-and size-controlled platinum and platinum alloy nanostructures on carbon with improved durability.

Energy Technology Data Exchange (ETDEWEB)

Shelnutt, John Allen; Garcia, Robert M.; Song, Yujiang; Moreno, Andres M.; Stanis, Ronald J.

2008-10-01

This project is aimed to gain added durability by supporting ripening-resistant dendritic platinum and/or platinum-based alloy nanostructures on carbon. We have developed a new synthetic approach suitable for directly supporting dendritic nanostructures on VXC-72 carbon black (CB), single-walled carbon nanotubes (SWCNTs), and multi-walled carbon nanotubes (MWCNTs). The key of the synthesis is to creating a unique supporting/confining reaction environment by incorporating carbon within lipid bilayer relying on a hydrophobic-hydrophobic interaction. In order to realize size uniformity control over the supported dendritic nanostructures, a fast photocatalytic seeding method based on tin(IV) porphyrins (SnP) developed at Sandia was applied to the synthesis by using SnP-containing liposomes under tungsten light irradiation. For concept approval, one created dendritic platinum nanostructure supported on CB was fabricated into membrane electrode assemblies (MEAs) for durability examination via potential cycling. It appears that carbon supporting is essentially beneficial to an enhanced durability according to our preliminary results.

Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway

Energy Technology Data Exchange (ETDEWEB)

Zheng, Xuqin [Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029 (China); Sun, Tao [Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province 210002 (China); Wang, Xiaodong, E-mail: xdwang666@hotmail.com [Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029 (China)

2013-07-05

Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

16 CFR Appendix I to Part 1402 - Recommended Outline for Instruction Booklet on “How To Safely Install Your CB Base Station Antenna”

Science.gov (United States)

2010-01-01

... on âHow To Safely Install Your CB Base Station Antennaâ I Appendix I to Part 1402 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CB BASE STATION... Outline for Instruction Booklet on “How To Safely Install Your CB Base Station Antenna” I. Required...

Mapping CB1 cannabinoid receptors with [3H]OMAR in the Flinders rodent model of depression

DEFF Research Database (Denmark)

Nahimi, A.; Gjedde, A.; Wong, D. F.

2012-01-01

not significantly different. Conclusions: Although changes in CB1 receptor expression have been demonstrated in human suicide victims with depression and in animal models of depression, the present maps of [3H]OMAR binding revealed no difference between FSL and FRL rats. We used a single concentration of [3H......Background: The endocannabinoid system regulates cognitive and emotional processes and pathology of this system is implicated in psychiatric disorders, including depression and schizophrenia. The precise role of the endocannabinoid system in psychiatric disorders remains unclear, but changes...... in expression of CB1 receptors and subsequent altered modulation of monoamines is suggested in depression (Esteban & Garcia-Sevilla, 2011). CB1 receptor agonists, such as WIN55,212-2 and CP55,940 regulate synthesis and release of monoamines and are suggested as a novel therapy in the treatment of depression...

Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice.

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Yu, Lu-lu; Wang, Xue-yi; Zhao, Mei; Liu, Yu; Li, Yan-qin; Li, Fang-qiong; Wang, Xiaoyi; Xue, Yan-xue; Lu, Lin

2009-06-01

Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory. The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP). Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration. Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation. Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

CB-SMoT+: UNA EXTENSIÓN AL ALGORITMO CB-SMoT

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FRANCISCO MORENO

2012-12-01

Full Text Available Una trayectoria es un registro de la evoluciónde la posición de un objeto móvil. Por ejemplo,un vehículo que se mueve en el espacio durante unintervalo de tiempo. Una trayectoria se representamediante una secuencia de observaciones que indicanla posición y el tiempo en el que fue tomada cadaobservación. CB-SMoT es un algoritmo que identificalas partes de una trayectoria durante las cuales elobjeto mantuvo una velocidad promedio por debajode un límite dado. En este artículo se propone unaextensión para dicho algoritmo que permite identificarlas partes de una trayectoria durante las cualesel objeto mantuvo una velocidad promedio entre observacionespor debajo de un límite dado. Esto posibilitala identificación, por ejemplo, de violacionesa un límite de velocidad que no son advertidas porel algoritmo original. Para el estudio se usó el sistemade gestión de bases de datos PostgreSQL y losalgoritmos se implementaron en su lenguaje de programación,llamado PL/pgSQL. Además, se hicieronexperimentos con 100 trayectorias de vehículos conel propósito de mostrar la utilidad y la viabilidad de lapropuesta.

A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

Science.gov (United States)

Fay, Jonathan F; Farrens, David L

2012-09-28

Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

Availability Perception And Constraints Of Final Year Students To The Use Of Computer-Based Information Communication Technologies Cb-Icts.

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Nto

2015-08-01

Full Text Available There is no doubt that ICTs are the major focus for the day to day running of every society. ICTs create a room for a quicker faster easier access and exchange of information in the world today. The study investigated the availability attitude and constraints of final year students in the use of computer-based ICTs CB-ICTs in Abia State. Data were collected with the use of a well structured questionnaire. Data collected were analysed with descriptive statistics. Results from analysis revealed that the mean age of the respondents was 23 years 7 CB-ICTs were available to the respondents at varying degrees. The respondents had a positive attitude x amp773 3.11 to the use of CB-ICTs and the major constraint to their use of CB-ICTs was poor resource centre where they can access CB-ICTs. Based on the findings we recommended that resource centres should be built in the institution and if it exists should be well equipped and running. Equally awareness to the fact that there is or there will be a resource centre in the institution should be widely spread so that students can utilize the opportunity of its existence and make maximum use of the facilities there in. On the other hand internet service provider should scale up their services in the area so as to provide a more stable internet connection in the institution as this will enable the students to use more effectively CB-ICTs in the institution and for their academic work.

Integrated cannabinoid CB1 receptor transmission within the amygdala-prefrontal cortical pathway modulates neuronal plasticity and emotional memory encoding.

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Tan, Huibing; Lauzon, Nicole M; Bishop, Stephanie F; Bechard, Melanie A; Laviolette, Steven R

2010-06-01

The cannabinoid CB1 receptor system is functionally involved in the processing and encoding of emotionally salient sensory information, learning and memory. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). In addition, synaptic plasticity in the form of long-term potentiation (LTP) within the BLA > mPFC pathway is an established correlate of exposure to emotionally salient events. We performed a series of in vivo LTP studies by applying tetanic stimulation to the BLA combined with recordings of local field potentials within prelimbic cortical (PLC) region of the rat mPFC. Systemic pretreatment with AM-251 dose dependently blocked LTP along the BLA-PLC pathway and also the behavioral acquisition of conditioned fear memories. We next performed a series of microinfusion experiments wherein CB1 receptor transmission within the BLA > PLC circuit was pharmacologically blocked. Asymmetrical, interhemispheric blockade of CB1 receptor transmission along the BLA > PLC pathway prevented the acquisition of emotionally salient associative memory. Our results indicate that coordinated CB1 receptor transmission within the BLA > PLC pathway is critically involved in the encoding of emotional fear memories and modulates neural plasticity related to the encoding of emotionally salient associative learning.

Evaluation of [11C]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

International Nuclear Information System (INIS)

Vallez Garcia, David; Vries, Erik F.J. de; Dierckx, Rudi A.J.O.; Doorduin, Janine; Toyohara, Jun; Ishiwata, Kiichi; Hatano, Kentaro

2015-01-01

Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [ 11 C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [ 11 C]CB184 was evaluated as a potentially more sensitive PET tracer. A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [ 11 C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [ 11 C]CB184 and [ 11 C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis. The biodistribution study showed significantly higher [ 11 C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r 2 = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [ 11 C]CB184 uptake in the whole brain. Both, [ 11 C]CB184 and [ 11 C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BP ND ) was not significantly different between the HSE rats and the control rats. In HSE rats BP ND for [ 11 C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [ 11 C]PK11195 was only detected in the medulla. [ 11 C]CB184 showed nonspecific binding to healthy tissue comparable to that observed for [ 11 C]PK11195, but it

Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study

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Neumeister, Alexander; Normandin, Marc D.; Pietrzak, Robert H.; Piomelli, Daniele; Zheng, Ming-Qiang; Gujarro-Anton, Ana; Potenza, Marc N.; Bailey, Christopher R.; Lin, Shu-fei; Najafzadeh, Soheila; Ropchan, Jim; Henry, Shannan; Corsi-Travali, Stefani; Carson, Richard E.; Huang, Yiyun

2013-01-01

Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder. PMID:23670490

[Energy dispersive spectrum analysis of surface compositions of selective laser melting cobalt-chromium alloy fabricated by different processing parameters].

Science.gov (United States)

Qian, Liang; Zeng, Li; Wei, Bin; Gong, Yao

2015-06-01

To fabricate selective laser melting cobalt-chromium alloy samples by different processing parameters, and to analyze the changes of energy dispersive spectrum(EDS) on their surface. Nine groups were set up by orthogonal experimental design according to different laser powers,scanning speeds and powder feeding rates(laser power:2500-3000 W, scanning speed: 5-15 mm/s, powder feeding rate: 3-6 r/min). Three cylinder specimens(10 mm in diameter and 3 mm in thickness) were fabricated in each group through Rofin DL 035Q laser cladding system using cobalt-chromium alloy powders which were developed independently by our group.Their surface compositions were then measured by EDS analysis. Results of EDS analysis of the 9 groups fabricated by different processing parameters(Co:62.98%-67.13%,Cr:25.56%-28.50%,Si:0.49%-1.23%) were obtained. They were similar to the compositions of cobalt-chromium alloy used in dental practice. According to EDS results, the surface compositions of the selective laser melting cobalt-chromium alloy samples are stable and controllable, which help us gain a preliminary sight into the range of SLM processing parameters. Supported by "973" Program (2012CB910401) and Research Fund of Science and Technology Committee of Shanghai Municipality (12441903001 and 13140902701).

Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice

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Diego C. Mascarenhas

2017-10-01

Full Text Available Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1 and Cannabinoid type 1 (CB1 receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist, capsaicin (TRPV1 agonist, WIN (CB1 agonist, AM251 (CB1 antagonist, and 6-iodonordihydrocapsaicin (6-IODO (TRPV1 selective antagonist and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1- and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.

Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation.

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Ashton, John C; Zheng, Yiwen; Liu, Ping; Darlington, Cynthia L; Smith, Paul F

2004-09-24

CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.

Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

Science.gov (United States)

Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

2017-05-01

Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum.

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Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

2018-04-01

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

47 CFR 95.413 - (CB Rule 13) What communications are prohibited?

Science.gov (United States)

2010-10-01

..., traveler assistance, brief tests (radio checks), or voice paging; (5) To advertise or solicit the sale of any goods or services; (6) To transmit music, whistling, sound effects or any material to amuse or... (155.3 miles) away; (10) To advertise a political candidate or political campaign; (you may use your CB...

Evaluation of [{sup 11}C]CB184 for imaging and quantification of TSPO overexpression in a rat model of herpes encephalitis

Energy Technology Data Exchange (ETDEWEB)

Vallez Garcia, David; Vries, Erik F.J. de; Dierckx, Rudi A.J.O.; Doorduin, Janine [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Toyohara, Jun; Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Research Team for Neuroimaging, Tokyo (Japan); Hatano, Kentaro [National Center for Geriatrics and Gerontology, Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, Obu, Aichi (Japan)

2015-03-13

Evaluation of translocator protein (TSPO) overexpression is considered an attractive research tool for monitoring neuroinflammation in several neurological and psychiatric disorders. [{sup 11}C]PK11195 PET imaging has been widely used for this purpose. However, it has a low sensitivity and a poor signal-to-noise ratio. For these reasons, [{sup 11}C]CB184 was evaluated as a potentially more sensitive PET tracer. A model of herpes simplex encephalitis (HSE) was induced in male Wistar rats. On day 6 or 7 after virus inoculation, [{sup 11}C]CB184 PET scans were acquired followed by ex vivo evaluation of biodistribution. In addition, [{sup 11}C]CB184 and [{sup 11}C]PK11195 PET scans with arterial blood sampling were acquired to generate input for pharmacokinetic modelling. Differences between the saline-treated control group and the virus-treated HSE group were explored using volumes of interest and voxel-based analysis. The biodistribution study showed significantly higher [{sup 11}C]CB184 uptake in the amygdala, olfactory bulb, medulla, pons and striatum (p < 0.05) in HSE rats than in control rats, and the voxel-based analysis showed higher bilateral uptake in the pons and medulla (p < 0.05, corrected at the cluster level). A high correlation was found between tracer uptake in the biodistribution study and on the PET scans (p < 0.001, r {sup 2} = 0.71). Pretreatment with 5 mg/kg of unlabelled PK11195 effectively reduced (p < 0.001) [{sup 11}C]CB184 uptake in the whole brain. Both, [{sup 11}C]CB184 and [{sup 11}C]PK11195, showed similar amounts of metabolites in plasma, and the binding potential (BP{sub ND}) was not significantly different between the HSE rats and the control rats. In HSE rats BP{sub ND} for [{sup 11}C]CB184 was significantly higher (p < 0.05) in the amygdala, hypothalamus, medulla, pons and septum than in control rats, whereas higher uptake of [{sup 11}C]PK11195 was only detected in the medulla. [{sup 11}C]CB184 showed nonspecific binding to healthy

Electrical Resistance Alloys and Low-Expansion Alloys

DEFF Research Database (Denmark)

Kjer, Torben

1996-01-01

The article gives an overview of electrical resistance alloys and alloys with low thermal expansion. The electrical resistance alloys comprise resistance alloys, heating alloys and thermostat alloys. The low expansion alloys comprise alloys with very low expansion coefficients, alloys with very low...... thermoelastic coefficients and age hardenable low expansion alloys....

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

Science.gov (United States)

Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

A three-dimensional-weighted cone beam filtered backprojection (CB-FBP) algorithm for image reconstruction in volumetric CT-helical scanning

International Nuclear Information System (INIS)

Tang Xiangyang; Hsieh Jiang; Nilsen, Roy A; Dutta, Sandeep; Samsonov, Dmitry; Hagiwara, Akira

2006-01-01

Based on the structure of the original helical FDK algorithm, a three-dimensional (3D)-weighted cone beam filtered backprojection (CB-FBP) algorithm is proposed for image reconstruction in volumetric CT under helical source trajectory. In addition to its dependence on view and fan angles, the 3D weighting utilizes the cone angle dependency of a ray to improve reconstruction accuracy. The 3D weighting is ray-dependent and the underlying mechanism is to give a favourable weight to the ray with the smaller cone angle out of a pair of conjugate rays but an unfavourable weight to the ray with the larger cone angle out of the conjugate ray pair. The proposed 3D-weighted helical CB-FBP reconstruction algorithm is implemented in the cone-parallel geometry that can improve noise uniformity and image generation speed significantly. Under the cone-parallel geometry, the filtering is naturally carried out along the tangential direction of the helical source trajectory. By exploring the 3D weighting's dependence on cone angle, the proposed helical 3D-weighted CB-FBP reconstruction algorithm can provide significantly improved reconstruction accuracy at moderate cone angle and high helical pitches. The 3D-weighted CB-FBP algorithm is experimentally evaluated by computer-simulated phantoms and phantoms scanned by a diagnostic volumetric CT system with a detector dimension of 64 x 0.625 mm over various helical pitches. The computer simulation study shows that the 3D weighting enables the proposed algorithm to reach reconstruction accuracy comparable to that of exact CB reconstruction algorithms, such as the Katsevich algorithm, under a moderate cone angle (4 deg.) and various helical pitches. Meanwhile, the experimental evaluation using the phantoms scanned by a volumetric CT system shows that the spatial resolution along the z-direction and noise characteristics of the proposed 3D-weighted helical CB-FBP reconstruction algorithm are maintained very well in comparison to the FDK

Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

Directory of Open Access Journals (Sweden)

Gabriela P Chaves-Kirsten

Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

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Matthias eKlugmann

2011-07-01

Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

Science.gov (United States)

Navarro, Gemma; Carriba, Paulina; Gandí, Jorge; Ciruela, Francisco; Casadó, Vicent; Cortés, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carmen; Franco, Rafael

2008-01-01

Functional interactions in signaling occur between dopamine D2 (D2R) and cannabinoid CB1 (CB1R) receptors, between CB1R and adenosine A2A (A2AR) receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells. PMID:18956124

Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

Directory of Open Access Journals (Sweden)

Gemma Navarro

2008-01-01

Full Text Available Functional interactions in signaling occur between dopamine D2 (D2R and cannabinoid CB1 (CB1R receptors, between CB1R and adenosine A2A (A2AR receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells.

Chronic alcohol exposure disrupts CB₁ regulation of GABAergic transmission in the rat basolateral amygdala

DEFF Research Database (Denmark)

Varodayan, Florence P.; Bajo, Michal; Soni, Neeraj

2017-01-01

in BLA pyramidal neurons of rats exposed to 2–3 weeks intermittent ethanol. In the naïve rat BLA, the CB1 agonist WIN 55,212-2 (WIN) decreased GABA release, and this effect was prevented by the CB1 antagonist AM251. AM251 alone increased GABA release via a mechanism requiring postsynaptic calcium-dependent......1 influence on BLA GABAergic transmission that is dysregulated by chronic ethanol exposure and, thus, may contribute to the alcohol-dependent state....

Internal nitridation of nickel-base alloys; Innere Nitrierung von Nickelbasis-Legierungen

Energy Technology Data Exchange (ETDEWEB)

Krupp, U.; Christ, H.J. [Siegen Univ. (Gesamthochschule) (Germany). Inst. fuer Werkstofftechnik

1998-12-31

The chromuim concentration is the crucial variable in nitridation processes in nickel-base alloys. Extensive nitridation experiments with various specimen alloys of the system Ni-Cr-Al-Ti have shown that the Cr itself starts to form nitrides as from elevated initial concentrations of about 10 to 20 weight%, (depending on temperature), but that lower concentrations have an earlier effect in that they induce a considerable increase in the N-solubility of the nickel-base alloys. This causes an accelerated nitridation attack on the alloying elements Ti and Al. Apart from experimental detection and analysis, the phenomenon of internal nitridation could be described as well by means of a mathematical model calculating the diffusion with the finite-differences method and determining the precipitation thermodynamics by way of integrated equilibrium calculations. (orig./CB) [Deutsch] Im Verlauf der Hochtemperaturkorrosion von Nickelbasis-Superlegierungen kann durch beanspruchungsbedingte Schaedigungen der Oxiddeckschicht ein Verlust der Schutzwirkung erfolgen und als Konsequenz Stickstoff aus der Atmosphaere in den Werkstoff eindringen. Der eindiffundierende Stickstoff bildet vor allem mit den Legierungselementen Al, Cr und Ti Nitridausscheidungen, die zu einer relativ rasch fortschreitenden Schaedigung fuehren koennen. Eine bedeutende Rolle bei diesen Nitrierungsprozessen in Nickelbasislegierungen spielt die Cr-Konzentration in der Legierung. So ergaben umfangreiche Nitrierungsexperimente an verschiedenen Modellegierungen des Systems Ni-Cr-Al-Ti, dass Cr zwar selbst erst ab Ausgangskonzentrationen von ca. 10-20 Gew.% (abhaengig von der Temperatur) Nitride bildet, allerdings bereits bei geringen Konzentrationen die N-Loeslichkeit von Nickelbasis-Legierungen entscheidend erhoeht. Dies hat zur Folge, dass es zu einem beschleunigten Nitrierungsangriff auf die Legierungselemente Ti und Al kommt. Neben den experimentellen Untersuchungen konnte das Phaenomen der inneren

CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.

Science.gov (United States)

Kossatz, Elk; Maldonado, Rafael; Robledo, Patricia

2016-12-01

The role of CB2 cannabinoid receptors (CB 2 R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB 2 R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB 2 R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days. In KO mice, more extensive brain injury was observed. Behavioural deficits in the Irwin test were observed in both genotypes; while WT mice showed progressive recovery by day 7, KO mice did not. Only KO mice showed alterations in motor learning, coordination and balance, and did not recover over time. A higher expression of microglia and astrocytes was observed in several brain areas of lesioned WT and KO mice. The possible alteration of the inflammatory-related factors HIF-1α and TIM-3 was evaluated in these animals. In both genotypes, HIF-1α and TIM-3 expression was observed in lesioned areas associated with activated microglia. However, the expression levels of these proteins were exacerbated in KO mice in several lesioned and non-lesioned brain structures. Our results indicate that CB 2 R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

Science.gov (United States)

Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

2018-01-02

Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

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Changyu Pan

2011-01-01

Full Text Available Rimonabant, a selective cannabinoid-1 (CB1 receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit and randomized to rimonabant 20 mg (n=318 or placebo (n=325 for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P<.0001. The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp. (P<.0001. Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P<.0001. This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death

International Nuclear Information System (INIS)

Tomiyama, Ken-ichi; Funada, Masahiko

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB 1 receptor antagonist AM251, but not with the selective CB 2 receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB 1 receptor, but not by the CB 2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB 1 receptor, but not by the CB 2 receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB 1 receptors

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

Directory of Open Access Journals (Sweden)

Nicola H. Morgan

2008-01-01

Full Text Available Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM, increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Silicon Alloying On Aluminium Based Alloy Surface

International Nuclear Information System (INIS)

Suryanto

2002-01-01

Silicon alloying on surface of aluminium based alloy was carried out using electron beam. This is performed in order to enhance tribological properties of the alloy. Silicon is considered most important alloying element in aluminium alloy, particularly for tribological components. Prior to silicon alloying. aluminium substrate were painted with binder and silicon powder and dried in a furnace. Silicon alloying were carried out in a vacuum chamber. The Silicon alloyed materials were assessed using some techniques. The results show that silicon alloying formed a composite metal-non metal system in which silicon particles are dispersed in the alloyed layer. Silicon content in the alloyed layer is about 40% while in other place is only 10.5 %. The hardness of layer changes significantly. The wear properties of the alloying alloys increase. Silicon surface alloying also reduced the coefficient of friction for sliding against a hardened steel counter face, which could otherwise be higher because of the strong adhesion of aluminium to steel. The hardness of the silicon surface alloyed material dropped when it underwent a heating cycle similar to the ion coating process. Hence, silicon alloying is not a suitable choice for use as an intermediate layer for duplex treatment

Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

Science.gov (United States)

Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

2015-08-01

There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

Science.gov (United States)

Scarlett, Kisha A; White, El-Shaddai Z; Coke, Christopher J; Carter, Jada R; Bryant, Latoya K; Hinton, Cimona V

2018-04-01

G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease. Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728-39. ©2018 AACR . ©2018 American Association for Cancer Research.

Dielectric relaxation studies in 5CB nematic liquid crystal at 9 GHz ...

Indian Academy of Sciences (India)

Resonance width, shift in resonance frequency, relaxation time and activation energy of 5CB nematic liquid crystal are measured using microwave cavity technique under the influence of an external magnetic field at 9 GHz and at different temperatures. The dielectric response in liquid crystal at different temperatures and ...

CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

Directory of Open Access Journals (Sweden)

Shivakumar Subbanna

2018-02-01

Full Text Available Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD. However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7 mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2 levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB activation, and activity-regulated cytoskeleton-associated protein (Arc expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP, spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD.

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

Science.gov (United States)

Basavarajappa, Balapal S; Subbanna, Shivakumar

2014-02-01

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

Candidate PET radioligands for cannabinoid CB1 receptors: [18F]AM5144 and related pyrazole compounds

International Nuclear Information System (INIS)

Li Zizhong; Gifford, Andrew; Liu Qian; Thotapally, Rajesh; Ding Yushin; Makriyannis, Alexandros; Gatley, S. John

2005-01-01

Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB 1 receptors that respond to Δ 9 -tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB 1 receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[ 18 F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[ 18 F]fluoroaniline. The labeled precursor was synthesized from 1-[ 18 F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/μmol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB 1 receptors, absolute uptake at 1 receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB 1 receptor that may require very lipophilic ligands

Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

Directory of Open Access Journals (Sweden)

M Zendehdel

Full Text Available ABSTRACT Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3 neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2µg significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5µg (P0.05. Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25µg was not affected by Picrotoxin or CGP54626 (p>0.05. Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 µg and SR141716A (CB1 receptors antagonist, 6.25µg significantly decreased Gaboxadol-induced hyperphagia (P0.05. These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB{sub 1} receptors and apoptotic cell death

Energy Technology Data Exchange (ETDEWEB)

Tomiyama, Ken-ichi; Funada, Masahiko, E-mail: mfunada@ncnp.go.jp

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB{sub 1} receptor antagonist AM251, but not with the selective CB{sub 2} receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB{sub 1} receptors.

Effects of perfusion pressure and insulin on (3H) cytochalasin B (CB) binding to control and diabetic rat hearts

International Nuclear Information System (INIS)

Pleta, M.; Chan, T.

1987-01-01

Using ( 3 H) CB, they attempted to quantitate the changes in the amount of glucose transporters in the plasma membrane (PM) and intracellular membranes (HSP) prepared from rat hearts perfused with insulin, under low and high pressure. Membranes isolated from non-perfused hearts showed a PM/HSP ratio of (0.593). Hearts perfused with low pressure showed a lower ratio of (0.474). Perfusion with insulin increased the ratio to (1.8), almost a 3-4 fold increase from low perfusion pressure. These data correlate with insulin effects in glucose transport and CB binding in the fat cells. High pressure perfusion increased the PM/HSP ratio by 1-2 fold. ( 3 H) 2-DG transport indicates a comparable increase in glucose uptake with high pressure, but with insulin only a 1.5 fold increase was observed. Initial data obtained from streptozotocin (STZ) injected diabetic rats indicate low CB binding in the PM fraction. Only insulin, but not high perfusion pressure increased PM/HSP ratio in the STZ-diabetic hearts. Their data imply that while both caused apparent translocation of glucose transporters, influences on cardiac glucose metabolism by work load are different. Furthermore, STZ induced diabetes affected only the high perfusion pressure-induced and not the insulin-stimulated change in CB binding

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Directory of Open Access Journals (Sweden)

Xavier Viñals

2015-07-01

Full Text Available Activation of cannabinoid CB1 receptors (CB1R by delta9-tetrahydrocannabinol (THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

Science.gov (United States)

Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

2015-07-01

Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

Het endocannabinoïdsysteem, overgewicht en de CB1-endocannabinoïdreceptorblokker rimonabant

NARCIS (Netherlands)

Boekholdt, S. M.; Jukema, J. W.; Peters, R. J. G.

2007-01-01

--Obesity is an important healthcare issue. --Recent research has led to insights into the role of the endocannabinoid system in the regulation of body weight. --Rimonabant is a CB1-endocannabinoid-receptor antagonist. --Four trials were published recently on the efficacy and safety of rimonabant in

Alloy Design and Development of Cast Cr-W-V Ferritic Steels for Improved High-Temperature Strength for Power Generation Applications

Energy Technology Data Exchange (ETDEWEB)

Klueh, R L; Maziasz, P J; Vitek, J M; Evans, N D; Hashimoto, N

2006-09-23

Economic and environmental concerns demand that the power-generation industry seek increased efficiency for gas turbines. Higher efficiency requires higher operating temperatures, with the objective temperature for the hottest sections of new systems {approx} 593 C, and increasing to {approx} 650 C. Because of their good thermal properties, Cr-Mo-V cast ferritic steels are currently used for components such as rotors, casings, pipes, etc., but new steels are required for the new operating conditions. The Oak Ridge National Laboratory (ORNL) has developed new wrought Cr-W-V steels with 3-9% Cr, 2-3% W, 0.25% V (compositions are in wt.%), and minor amounts of additional elements. These steels have the strength and toughness required for turbine applications. Since cast alloys are expected to behave differently from wrought material, work was pursued to develop new cast steels based on the ORNL wrought compositions. Nine casting test blocks with 3, 9, and 11% Cr were obtained. Eight were Cr-W-V-Ta-type steels based on the ORNL wrought steels; the ninth was COST CB2, a 9Cr-Mo-Co-V-Nb cast steel, which was the most promising cast steel developed in a European alloy-development program. The COST CB2 was used as a control to which the new compositions were compared, and this also provided a comparison between Cr-W-V-Ta and Cr-Mo-V-Nb compositions. Heat treatment studies were carried out on the nine castings to determine normalizing-and-tempering treatments. Microstructures were characterized by both optical and transmission electron microscopy (TEM). Tensile, impact, and creep tests were conducted. Test results on the first nine cast steel compositions indicated that properties of the 9Cr-Mo-Co-V-Nb composition of COST CB2 were better than those of the 3Cr-, 9Cr-, and 11Cr-W-V-Ta steels. Analysis of the results of this first iteration using computational thermodynamics raised the question of the effectiveness in cast steels of the Cr-W-V-Ta combination versus the Cr

The 16 CB11(CH3)(n)(CD3)(12-n)(center dot) Radicals with 5-Fold Substitution Symmetry: Spin Density Distribution in CB11Me12 center dot

Czech Academy of Sciences Publication Activity Database

Kaleta, Jiří; Tarábek, Ján; Akdag, A.; Pohl, Radek; Michl, Josef

2012-01-01

Roč. 51, č. 20 (2012), s. 10819-10824 ISSN 0020-1669 R&D Projects: GA ČR GC203/09/J058 Grant - others:AV ČR(CZ) M200550906 Institutional support: RVO:61388963 Keywords : anion * oxidation * polymerization * isobutylene * carboranes * CB11Me12 Subject RIV: CC - Organic Chemistry Impact factor: 4.593, year: 2012

An analysis of the thermodynamic efficiency for exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB)

International Nuclear Information System (INIS)

Lee, Chang-Eon; Yu, Byeonghun; Lee, Seungro

2015-01-01

This study presents fundamental research on the development of a new boiler that is expected to have a higher efficiency and lower emissions than existing boilers. The thermodynamic efficiency of exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB) was calculated using thermodynamic analysis and was compared with other boilers. The results show the possibility of obtaining a high efficiency when the temperature of the exhaust gas is controlled within 50–60 °C because water in the exhaust gas is condensed within this temperature range. In addition, the enthalpy emitted by the exhaust gas for the new boiler is smaller because the amount of condensed water is increased by the high dew-point temperature and the low exhaust gas temperature. Thus, the new boiler can obtain a higher efficiency than can older boilers. The efficiency of the EGR-CWR-WHR CB proposed in this study is 93.91%, which is 7.04% higher than that of existing CB that is currently used frequently. - Highlights: • The study presents the development of a new boiler expected to have a high efficiency. • Thermodynamic efficiency of EGR-CWR-WHR condensing boiler was calculated. • Efficiency of EGR-CWR-WHR CB is 93.91%, which is 7.04% higher than existing CB

Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

Energy Technology Data Exchange (ETDEWEB)

Zizhong, Li [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Qian, Liu [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Yushin, Ding [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)

2005-05-01

Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

Highly Branched Polyisobutylene by Radical Polymerization under Li[CB11(CH3)(12)] Catalysis

Czech Academy of Sciences Publication Activity Database

Volkis, V.; Shoemaker, R. K.; Michl, Josef

2012-01-01

Roč. 45, č. 23 (2012), s. 9250-9257 ISSN 0024-9297 Institutional research plan: CEZ:AV0Z40550506 Keywords : Dodecamethylcarba-closo-dodecaborate(-)Anion * polymerization * LiCB11(CH3)(12) Subject RIV: CC - Organic Chemistry Impact factor: 5.521, year: 2012

Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.

Science.gov (United States)

Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

2011-01-01

The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). We first tested the hypothesis that an A(1)-CB(1) interaction influences GABA and glutamate release in the hippocampus. We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory.

Laser surface alloying of aluminium-transition metal alloys

International Nuclear Information System (INIS)

Almeida, A.; Vilar, R.

1998-01-01

Laser surface alloying has been used as a tool to produce hard and corrosion resistant Al-transition metal (TM) alloys. Cr and Mo are particularly interesting alloying elements to produce stable high-strength alloys because they present low diffusion coefficients and solid solubility in Al. To produce Al-TM surface alloys a two-step laser process was developed: firstly, the material is alloyed using low scanning speed and secondly, the microstructure is modified by a refinement step. This process was used in the production of Al-Cr, Al-Mo and Al-Mo and Al-Nb surface alloys by alloying Cr, Mo or Nb powder into an Al and 7175 Al alloy substrate using a CO 2 laser . This paper presents a review of the work that has been developed at Instituto Superior Tecnico on laser alloying of Al-TM alloy, over the last years. (Author) 16 refs

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

CB5C affects the glucosinolate profile in Arabidopsis thaliana

DEFF Research Database (Denmark)

Vik, Daniel; Crocoll, Christoph; Andersen, Tonni Grube

2016-01-01

were reduced in one of the mutant lines - a phenotype that was exaggerated upon methyl-jasmonate treatment. These results support the hypothesis, that CB5C influences glucosinolate biosynthesis, however, the mode of action remains unknown. Furthermore, the mutants differed in their biomass response...

Analysis of Cumulonimbus (Cb), Thunderstorm and Fog for Izmir Adnan Menderes Airport

Science.gov (United States)

Avsar, Ercument

2016-07-01

Demand for airline transport has been increasing day by day with the development of the aviation industry in Turkey. Meteorological conditions are among the most important factors that influence aviation facilities. Meteorological events cause delays and cancellation of flights which create economic and time losses, and they even lead to accidents and breakups. The most important meteorological events that affect the takeoff and landing of airplanes can be listed as wind, runway visual range, cloud, rain, icing, turbulence, and low level windshear. Meteorological events that affect the aviation facilities most often in Adnan Menderes Airport (LTBJ), the fourth largest airport in Turkey in terms of air traffic, are fog, Cumulonimbus (Cb) clouds and thunderstorms (TS-Thunderstorm). Therefore, it is important to identify the occurrence time of these events based on the analysis of data over many years and do the flight plans based on this meteorological information in order to make the aviation facilities safer and without delays. In this study, statistical analysis on the formation of Cb clouds, thunderstorm and foggy days is conducted using observations produced for aviation (METAR) and special observers (SPECI). It is found that there are two types of fog that are observed most often at LTBJ, namely radiation and advection fogs, accordingly to the results of statistical analysis based on data from 2004 to 2014. Fog events are found to occur most often in the months of December and January, during 04:00 - 07:00 UTC time interval, between pressure values over 1015-1020 hPa, in 130-190 degree light breeze (1-5KT) and in temperature levels between 5°C and 8°C. Thunderstorm events recorded at LTBJ between the years 2004 and 2014 are most often observed in the months of January and February, in 120-210 degree gentle breeze winds (6-10KT), and in temperature levels between 8 and 18 °C. Key Words: Adnan Menderes International Airport, LTBJ, Fog, Thunderstorm (TS), Cb

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors

Science.gov (United States)

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2016-01-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ9-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of meth-amphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24709540

Electro-optically responsive composites of gold nanospheres in 5CB liquid crystal under direct current and alternating current joint action

International Nuclear Information System (INIS)

Hadjichristov, Georgi B.; Marinov, Yordan G.; Petrov, Alexander G.; Bruno, Emanuela; Marino, Lucia; Scaramuzza, Nicola

2014-01-01

Direct current (DC) electro-optical (EO) control of transmitted laser beam intensity based on EO controlled coherent light scattering and diffraction by stationary longitudinal texture pattern (LTP) is achieved in planar-oriented cells with a composite mixture of polymer-coated gold spherical nanoparticles (Au-NPs) with a mean diameter of about 12 nm and the room-temperature nematic pentylcyanobiphenyl (5CB). At relatively low DC voltage of about 5 V, the effective scattering/diffraction by Au-NPs/5CB composites leads to a spatial spreading of transmitted coherent light from a low-power continuous wave laser beam, resulting in a drastic reduction of its local intensity. The effect is polarization dependent and is strongest when the polarization of the input laser beam is along the LTP. The EO response of Au-NPs/5CB mixtures is studied under DC and alternating current (AC) joint action with the aim of the potential use of these composite materials as EO controlled diffusers. The specific V-shaped sharp dip in the DC voltage-dependent coherent light transmittance of Au-NPs/5CB planar films, as well as the possibility for erasing the scattering/diffractive LTP in the films by joint low AC voltage, can be useful for EO applications in the field of process control and for detection of weak dynamic electric fields

Electro-optically responsive composites of gold nanospheres in 5CB liquid crystal under direct current and alternating current joint action

Energy Technology Data Exchange (ETDEWEB)

Hadjichristov, Georgi B.; Marinov, Yordan G.; Petrov, Alexander G. [Institute of Solid State Physics, Bulgarian Academy of Sciences, Sofia 1784 (Bulgaria); Bruno, Emanuela [Dipartimento di Fisica, Università della Calabria, Via Pietro Bucci, Cubo 31C, 87036 Rende (CS) (Italy); Marino, Lucia, E-mail: lucia.marino@fis.unical.it [CNR-IPCF UoS di Cosenza, Licryl Laboratory, and Centro di Eccellenza CEMIF.CAL, Università della Calabria, 87036 Rende (CS) (Italy); Scaramuzza, Nicola [Dipartimento di Fisica, Università della Calabria, Via Pietro Bucci, Cubo 31C, 87036 Rende (CS) (Italy); CNR-IPCF UoS di Cosenza, Licryl Laboratory, and Centro di Eccellenza CEMIF.CAL, Università della Calabria, 87036 Rende (CS) (Italy)

2014-02-28

Direct current (DC) electro-optical (EO) control of transmitted laser beam intensity based on EO controlled coherent light scattering and diffraction by stationary longitudinal texture pattern (LTP) is achieved in planar-oriented cells with a composite mixture of polymer-coated gold spherical nanoparticles (Au-NPs) with a mean diameter of about 12 nm and the room-temperature nematic pentylcyanobiphenyl (5CB). At relatively low DC voltage of about 5 V, the effective scattering/diffraction by Au-NPs/5CB composites leads to a spatial spreading of transmitted coherent light from a low-power continuous wave laser beam, resulting in a drastic reduction of its local intensity. The effect is polarization dependent and is strongest when the polarization of the input laser beam is along the LTP. The EO response of Au-NPs/5CB mixtures is studied under DC and alternating current (AC) joint action with the aim of the potential use of these composite materials as EO controlled diffusers. The specific V-shaped sharp dip in the DC voltage-dependent coherent light transmittance of Au-NPs/5CB planar films, as well as the possibility for erasing the scattering/diffractive LTP in the films by joint low AC voltage, can be useful for EO applications in the field of process control and for detection of weak dynamic electric fields.

Photometric and spectroscopic analysis of the eclipsing binary DS Andromedae - a member of NGC 752

International Nuclear Information System (INIS)

Schiller, S.J.; Milone, E.F.

1988-01-01

Complete BVRI light curves and radial-velocity curves of both components of the 1.01 d period eclipsing binary DS And are presented. The Wilson-Devinney synthetic light curve program is used to determine the absolute parameters of this system, and it is confirmed that the primary component is nearly filling its Roche lobe. The distance modulus and systemic velocity conclusively establish cluster membership. The age of NGC 752, determined by fitting the theoretical isochrones of VandenBerg (1985) to the C-M diagram of Cannon (1970), is assigned to DS And. This enables a showing that, although the primary component is nearly filling its Roche lobe, it has thus far evolved as a single isolated star. 54 references

Effect of sintering temperature on structure of C-B4C-SiC composites with silicon additive

International Nuclear Information System (INIS)

Wu Lijun; Academia Sinica, Shenyang; Huang Qizhong; Yang Qiaoqin; Zhao Lihu; Xu Zhongyu

1996-01-01

Carbon materials possess good electric conductivity, heat conductivity, corrosion-resistance, self-lubrication and hot-shocking resistance, and are easily machined. However, they have low mechanical strength, and are easily oxidized in air at high temperature. On the contrary, ceramic materials have high mechanical strength and hardness, and have good wear-resistance and oxidation-resistance. However, they have the shortages of poor thermal-shock resistance lubrication, and are difficult to machine. Therefore, carbon/ceramic composites with the advantages of both carbon and ceramic materials have been widely studied in the recent years. Huang prepared C-B 4 C-SiC composites with the free sintering method and the hot pressing method, and studied the effects of Si, Al, Al 2 O 3 , Ni and Ti additives on the properties of the composites. The results showed that these additives could improve the properties of the composites. Zhao et al. studies the structure of C-B 4 C-SiC composites with Si additive sintered at 2,000 C and found two c-center monoclinic phases. In this paper, the authors discussed the effect of the sintering temperature on the structure of C-B 4 C-SiC composites with Si additive by means of transmission electron microscope (TEM) and x-ray diffractometer (XRD)

Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

Directory of Open Access Journals (Sweden)

Sofia Sisay

Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

Magnesium secondary alloys: Alloy design for magnesium alloys with improved tolerance limits against impurities

Energy Technology Data Exchange (ETDEWEB)

Blawert, C., E-mail: carsten.blawert@gkss.d [GKSS Forschungszentrum Geesthacht GmbH, Max-Planck-Str. 1, 21502 Geesthacht (Germany); Fechner, D.; Hoeche, D.; Heitmann, V.; Dietzel, W.; Kainer, K.U. [GKSS Forschungszentrum Geesthacht GmbH, Max-Planck-Str. 1, 21502 Geesthacht (Germany); Zivanovic, P.; Scharf, C.; Ditze, A.; Groebner, J.; Schmid-Fetzer, R. [TU Clausthal, Institut fuer Metallurgie, Robert-Koch-Str. 42, 38678 Clausthal-Zellerfeld (Germany)

2010-07-15

The development of secondary magnesium alloys requires a completely different concept compared with standard alloys which obtain their corrosion resistance by reducing the levels of impurities below certain alloy and process depending limits. The present approach suitable for Mg-Al based cast and wrought alloys uses a new concept replacing the {beta}-phase by {tau}-phase, which is able to incorporate more impurities while being electro-chemically less detrimental to the matrix. The overall experimental effort correlating composition, microstructure and corrosion resistance was reduced by using thermodynamic calculations to optimise the alloy composition. The outcome is a new, more impurity tolerant alloy class with a composition between the standard AZ and ZC systems having sufficient ductility and corrosion properties comparable to the high purity standard alloys.

Alloying principles for magnesium base heat resisting alloys

International Nuclear Information System (INIS)

Drits, M.E.; Rokhlin, L.L.; Oreshkina, A.A.; Nikitina, N.I.

1982-01-01

Some binary systems of magnesium-base alloys in which solid solutions are formed, are considered for prospecting heat resistant alloys. It is shown that elements having essential solubility in solid magnesium strongly decreasing with temperature should be used for alloying maqnesium base alloys with high strength properties at increased temperatures. The strengthening phases in these alloys should comprise essential quantity of magnesium and be rather refractory

Alloy materials

Energy Technology Data Exchange (ETDEWEB)

Hans Thieme, Cornelis Leo (Westborough, MA); Thompson, Elliott D. (Coventry, RI); Fritzemeier, Leslie G. (Acton, MA); Cameron, Robert D. (Franklin, MA); Siegal, Edward J. (Malden, MA)

2002-01-01

An alloy that contains at least two metals and can be used as a substrate for a superconductor is disclosed. The alloy can contain an oxide former. The alloy can have a biaxial or cube texture. The substrate can be used in a multilayer superconductor, which can further include one or more buffer layers disposed between the substrate and the superconductor material. The alloys can be made a by process that involves first rolling the alloy then annealing the alloy. A relatively large volume percentage of the alloy can be formed of grains having a biaxial or cube texture.

Evidence for CB2 receptor involvement in LPS-induced reduction of cAMP intracellular levels in uterine explants from pregnant mice: pathophysiological implications.

Science.gov (United States)

Salazar, Ana Inés; Carozzo, Alejandro; Correa, Fernando; Davio, Carlos; Franchi, Ana María

2017-07-01

What is the role of the endocannabinoid system (eCS) on the lipopolysaccharide (LPS) effects on uterine explants from 7-day pregnant mice in a murine model of endotoxin-induced miscarriage? We found evidence for cannabinoid receptor type2 (CB2) involvement in LPS-induced increased prostaglandin-F2α (PGF2α) synthesis and diminished cyclic adenosine monophosphate (cAMP) intracellular content in uterine explants from early pregnant mice. Genital tract infections by Gram-negative bacteria are a common complication of human pregnancy that results in an increased risk of pregnancy loss. LPS, the main component of the Gram-negative bacterial wall, elicits a strong maternal inflammatory response that results in embryotoxicity and embryo resorption in a murine model endotoxin-induced early pregnancy loss. We have previously shown that the eCS mediates the embryotoxic effects of LPS, mainly via CB1 receptor activation. An in vitro study of mice uterine explants was performed to investigate the eCS in mediating the effects of LPS on PGF2α production and cAMP intracellular content. Eight to 12-week-old virgin female BALB/c or CD1 (wild-type [WT] or CB1-knockout [CB1-KO]) mice were paired with 8- to 12-week-old BALB/c or CD1 (WT or CB1-KO) males, respectively. On day 7 of pregnancy, BALB/c, CD1 WT or CD1 CB1-KO mice were euthanized, the uteri were excised, implantation sites were removed and the uterine tissues were separated from decidual and embryo tissues. Uterine explants were cultured and exposed for an appropriate amount of time to different pharmacological treatments. The tissues were then collected for cAMP assay and PGF2α content determination by radioimmunoassay. In vitro treatment of uteri explants from 7-day pregnant BALB/c or CD1 (WT or CB1-KO) mice with LPS induced an increased production of PGF2α (P Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Carlos Davio was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013

Identification of the C-Terminal GH5 Domain from CbCel9B/Man5A as the First Glycoside Hydrolase with Thermal Activation Property from a Multimodular Bifunctional Enzyme.

Directory of Open Access Journals (Sweden)

Rong Wang

Full Text Available Caldicellulosiruptor bescii encodes at least six unique multimodular glycoside hydrolases crucial for plant cell wall polysaccharides degradation, with each having two catalytic domains separated by two to three carbohydrate binding modules. Among the six enzymes, three have one N- or C-terminal GH5 domain with identical amino acid sequences. Despite a few reports on some of these multimodular enzymes, little is known about how the conserved GH5 domains behave, which are believed to be important due to the gene duplication. We thus cloned a representative GH5 domain from the C-terminus of a multimodular protein, i.e. the bifunctional cellulase/mannanase CbCel9B/Man5A which has been reported, and expressed it in Escherichia coli. Without any appending CBMs, the recombinant CbMan5A was still able to hydrolyze a variety of mannan substrates with different backbone linkages or side-chain decorations. While CbMan5A displayed the same pH optimum as CbCel9B/Man5A, it had an increased optimal temperature (90°C and moreover, was activated by heating at 70°C and 80°C, a property not ever reported for the full-length protein. The turnover numbers of CbMan5A on mannan substrates were, however, lower than those of CbCel9B/Man5A. These data suggested that evolution of CbMan5A and the other domains into a single polypeptide is not a simple assembly; rather, the behavior of one module may be affected by the other ones in the full-length enzyme. The differential scanning calorimetry analysis further indicated that heating CbMan5A was not a simple transition state process. To the best knowledge of the authors, CbMan5A is the first glycoside hydrolase with thermal activation property identified from a multimodular bifunctional enzyme.

Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain.

Science.gov (United States)

Schuelert, N; Zhang, C; Mogg, A J; Broad, L M; Hepburn, D L; Nisenbaum, E S; Johnson, M P; McDougall, J J

2010-11-01

The present study examined whether local administration of the cannabinoid-2 (CB(2)) receptor agonist GW405833 could modulate joint nociception in control rat knee joints and in an animal model of osteoarthritis (OA). OA was induced in male Wistar rats by intra-articular injection of sodium monoiodo-acetate with a recovery period of 14 days. Immunohistochemistry was used to evaluate the expression of CB(2) and transient receptor potential vanilloid channel-1 (TRPV1) receptors in the dorsal root ganglion (DRG) and synovial membrane of sham- and sodium mono-iodoacetate (MIA)-treated animals. Electrophysiological recordings were made from knee joint primary afferents in response to rotation of the joint both before and following close intra-arterial injection of different doses of GW405833. The effect of intra-articular GW405833 on joint pain perception was determined by hindlimb incapacitance. An in vitro neuronal release assay was used to see if GW405833 caused release of an inflammatory neuropeptide (calcitonin gene-related peptide - CGRP). CB(2) and TRPV1 receptors were co-localized in DRG neurons and synoviocytes in both sham- and MIA-treated animals. Local application of the GW405833 significantly reduced joint afferent firing rate by up to 31% in control knees. In OA knee joints, however, GW405833 had a pronounced sensitising effect on joint mechanoreceptors. Co-administration of GW405833 with the CB(2) receptor antagonist AM630 or pre-administration of the TRPV1 ion channel antagonist SB366791 attenuated the sensitising effect of GW405833. In the pain studies, intra-articular injection of GW405833 into OA knees augmented hindlimb incapacitance, but had no effect on pain behaviour in saline-injected control joints. GW405833 evoked increased CGRP release via a TRPV1 channel-dependent mechanism. These data indicate that GW405833 reduces the mechanosensitivity of afferent nerve fibres in control joints but causes nociceptive responses in OA joints. The observed

A multiple linear regression analysis of hot corrosion attack on a series of nickel base turbine alloys

Science.gov (United States)

Barrett, C. A.

1985-01-01

Multiple linear regression analysis was used to determine an equation for estimating hot corrosion attack for a series of Ni base cast turbine alloys. The U transform (i.e., 1/sin (% A/100) to the 1/2) was shown to give the best estimate of the dependent variable, y. A complete second degree equation is described for the centered" weight chemistries for the elements Cr, Al, Ti, Mo, W, Cb, Ta, and Co. In addition linear terms for the minor elements C, B, and Zr were added for a basic 47 term equation. The best reduced equation was determined by the stepwise selection method with essentially 13 terms. The Cr term was found to be the most important accounting for 60 percent of the explained variability hot corrosion attack.

Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.

Science.gov (United States)

Ferreira, Jaderson V; Chaves, Gisele A; Marino, Bianca L B; Sousa, Kessia P A; Souza, Lucilene R; Brito, Maiara F B; Teixeira, Hueldem R C; da Silva, Carlos H T P; Santos, Cleydson B R; Hage-Melim, Lorane I S

2017-08-22

Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n-pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optical transmission of nematic liquid crystal 5CB doped by single-walled and multi-walled carbon nanotubes.

Science.gov (United States)

Lisetski, L N; Fedoryako, A P; Samoilov, A N; Minenko, S S; Soskin, M S; Lebovka, N I

2014-08-01

Comparative studies of optical transmission of single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), dispersed in nematic liquid crystal matrix 5CB, were carried out. The data evidence violations of Beer-Lambert-Bouguer (BLB) law both in cell thickness and concentration dependencies. The most striking is the fact that optical transmission dependencies for SWCNTs and MWCNTs were quite different in the nematic phase, but they were practically indistinguishable in the isotropic phase. Monte Carlo simulations of the impact of aggregation on direct transmission and violation of BLB law were also done. The results were discussed accounting for the tortuous shape of CNTs, their physical properties and aggregation, as well as strong impact of perturbations of the nematic 5CB structure inside coils and in the vicinity of CNT aggregates.

Measurement of |V{sub cb}| using {bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}} Decays

Energy Technology Data Exchange (ETDEWEB)

Della Ricca, Giuseppe

2003-08-12

A preliminary measurement of |V{sub cb}| and the branching fraction {Beta}({bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}}) has been performed based on a sample of about 55,700 {bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}} decays recorded with the BABAR detector. The decays are identified in the D*{sup +} {yields} D{sup 0}{pi}{sup +} final state, with the D{sup 0} reconstructed in three different decay modes. The differential decay rate is measured as a function of the relativistic boost of the D*{sup +} in the {bar B}{sup 0} rest frame. The value of the differential decay rate at ''zero recoil'', namely the point at which the D*{sup +} is at rest in the {bar B}{sup 0} frame, is predicted in Heavy Quark Effective Theory as a kinematic factor times F(1)|V{sub cb}|, where F is the unique form factor governing the decay. We extrapolate the measured differential decay rate to the zero recoil point and obtain F(1)|V{sub cb}| = (34.03 {+-} 0.24 {+-} 1.31) x 10{sup -3}. Using a theoretical calculation for F(1) we extract |V{sub cb}| = (37.27 {+-} 0.26(stat.) {+-} 1.43(syst.){sub -1.2}{sup +1.5}(theo.)) x 10{sup -3}. From the integrated decay rate we obtain {Beta}({bar B}{sup 0} {yields} D*{sup +}{ell}{sup -}{bar {nu}}{sub {ell}}) = (4.68 {+-} 0.03 {+-} 0.29)%.

Cannabinoid CB2 receptors are involved in the protection of RAW264.7 macrophages against the oxidative stress: an in vitro study

Directory of Open Access Journals (Sweden)

Sabrina Giacoppo

2017-01-01

Full Text Available Research in the last decades has widely investigated the anti-oxidant properties of natural products as a therapeutic approach for the prevention and the treatment of oxidative-stress related disorders. In this context, several studies were aimed to evaluate the therapeutic potential of phytocannabinoids, the bioactive compounds of Cannabis sativa. Here, we examined the anti-oxidant ability of Cannabigerol (CBG, a non-psychotropic cannabinoid, still little known, into counteracting the hydrogen peroxide (H2O2-induced oxidative stress in murine RAW264.7 macrophages. In addition, we tested selective receptor antagonists for cannabinoid receptors and specifically CB1R (SR141716A and CB2R (AM630 in order to investigate through which CBG may exert its action. Taken together, our in vitro results showed that CBG is able to counteract oxidative stress by activation of CB2 receptors. CB2 antagonist pre-treatment indeed blocked the protective effects of CBG in H2O2 stimulated macrophages, while CB1R was not involved. Specifically, CBG exhibited a potent action in inhibiting oxidative stress, by down-regulation of the main oxidative markers (iNOS, nitrotyrosine and PARP-1, by preventing IκB-α phosphorylation and translocation of the nuclear factor-κB (NF-κB and also via the modulation of MAP kinases pathway. On the other hand, CBG was found to increase anti-oxidant defense of cells by modulating superoxide dismutase-1 (SOD-1 expression and thus inhibiting cell death (results focused on balance between Bax and Bcl-2. Based on its antioxidant activities, CBG may hold great promise as an anti-oxidant agent and therefore used in clinical practice as a new approach in oxidative-stress related disorders.

Investigation on mechanical alloying process for v-cr-ti alloys

International Nuclear Information System (INIS)

Stanciulescu, M.; Carlan, P.; Mihalache, M.; Bucsa, G.; Abrudeanu, M.; Galateanu, A.

2015-01-01

Mechanical alloying (MA) is an efficient approach for fabricating oxide-dispersion alloys and structural materials including vanadium alloys for fusion and fission application. Dissolution behaviour of the alloying elements is a key issue for optimizing the mechanical alloying process in fabricating vanadium alloys. This paper studies the MA process of V-4wt.%Cr-4wt.%Ti alloy. The outcomes of the MA powders in a planetary ball mill are reported in terms of powder particle size and morphology evolution and elemental composition. The impact of spark-plasma sintering process on the mechanically alloyed powder is analysed. An optimal set of sintering parameters, including the maximum temperature, the dwell time and the heating rate are determined. (authors)

Laser surface alloying of aluminium-transition metal alloys

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Almeida, A.

1998-04-01

Full Text Available Laser surface alloying has been used as a tool to produce hard and corrosion resistant Al-transition metal (TM alloys. Cr and Mo are particularly interesting alloying elements to produce stable highstrength alloys because they present low diffusion coefficients and solid solubility in Al. To produce Al-TM surface alloys a two-step laser process was developed: firstly, the material is alloyed using low scanning speed and secondly, the microstructure is modified by a refinement step. This process was used in the production of Al-Cr, Al-Mo and Al-Nb surface alloys by alloying Cr, Mo or Nb powder into an Al and 7175 Al alloy substrate using a CO₂ laser. This paper presents a review of the work that has been developed at Instituto Superior Tecnico on laser alloying of Al-TM alloys, over the last years.

En el presente trabajo se estudia la aleación superficial mediante láser de aluminio con metales de transición. El cromo y el molibdeno son particularmente interesantes porque producen aleaciones de alta resistencia y por el bajo coeficiente de difusión y solución sólida en aluminio. Para producir estas aleaciones se ha seguido un procedimiento desarrollado en dos partes. En primer lugar, el material se alea usando una baja velocidad de procesado y en segundo lugar la estructura se modifica mediante un refinamiento posterior. Este procedimiento se ha empleado en la producción de aleaciones Al-Cr, Al-Mo y Al-Nb mediante aleación con láser de CO₂ de polvos de Cr, Mo o Nb en aluminio y la aleación 7175. Este trabajo es una revisión del desarrollado en el Instituto Superior Técnico de Lisboa en los últimos años.

NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile.

Science.gov (United States)

Mastinu, Andrea; Pira, Marilena; Pani, Luca; Pinna, Gérard Aimè; Lazzari, Paolo

2012-10-01

The present work aims to study the effects induced by a chronic treatment with a novel CB1 antagonist (NESS038C6) in C57BL/6N diet-induced obesity (DIO) mice. Mice treated with NESS038C6 and fed with a fat diet (NESS038C6 FD) were compared with the following three reference experimental groups: DIO mice fed with the same fat diet used for NESS038C6 and treated with vehicle or the reference CB1 antagonist/inverse agonist rimonabant, "VH FD" and "SR141716 FD", respectively; DIO mice treated with vehicle and switched to a normal diet (VH ND). NESS038C6 chronic treatment (30 mg/kg/day for 31 days) determined a significant reduction in DIO mice weight relative to that of VH FD. The entity of the effect was comparable to that detected in both SR141716 FD and VH ND groups. Moreover, if compared to VH FD, NESS038C6 FD evidenced: (i) improvement of cardiovascular risk factors; (ii) significant decrease in adipose tissue leptin expression; (iii) increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides; (iv) expression increase of metabolic enzymes and peroxisome proliferator-activated receptor-α in the liver; (v) normalization of monoaminergic transporters and neurotrophic expression in mesolimbic area. However, in contrast to the case of rimonabant, the novel CB1 antagonist improved the disrupted expression profile of genes linked to the hunger-satiety circuit, without altering monoaminergic transmission. In conclusion, the novel CB1 antagonist compound NESS038C6 may represent a useful candidate agent for the treatment of obesity and its metabolic complications, without or with reduced side effects relative to those instead observed with rimonabant. Copyright © 2012 Elsevier B.V. All rights reserved.

Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography

International Nuclear Information System (INIS)

Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.; Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.; Halldin, Christer

2010-01-01

Cannabinoid subtype 1 (CB 1 ) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB 1 receptors with two PET radioligands: 11 C-MePPEP and 18 F-FMPEP-d 2 . Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with 11 C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with 18 F-FMPEP-d 2 . Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for 18 F-FMPEP-d 2 . The effective doses of 11 C-MePPEP and 18 F-FMPEP-d 2 are 4.6 and 19.7 μSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of 11 C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from 18 F-FMPEP-d 2 showed both hepatobiliary and urinary excretion. 11 C-MePPEP and 18 F-FMPEP-d 2 yield an effective dose similar to other PET radioligands labeled with either 11 C or 18 F. The high uptake in brain confirms the utility of these two radioligands to image CB 1 receptors in brain, and both may also be useful to image CB 1 receptors in the periphery. (orig.)

Characteristics of mechanical alloying of Zn-Al-based alloys

International Nuclear Information System (INIS)

Zhu, Y.H.; Hong Kong Polytechnic; Perez Hernandez, A.; Lee, W.B.

2001-01-01

Three pure elemental powder mixtures of Zn-22%Al-18%Cu, Zn-5%Al-11%Cu, and Zn-27%Al-3%Cu (in wt.%) were mechanically alloyed by steel-ball milling processing. The mechanical alloying characteristics were investigated using X-ray diffraction, scanning electron microscopy, and transmission electron microscopy techniques. It was explored that mechanical alloying started with the formation of phases from pure elemental powders, and this was followed by mechanical milling-induced phase transformation. During mechanical alloying, phases stable at the higher temperatures formed at the near room temperature of milling. Nano-structure Zn-Al-based alloys were produced by mechanical alloying. (orig.)

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

OpenAIRE

Zlebnik, Natalie E.; Cheer, Joseph F.

2016-01-01

The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor t...

Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 receptor-Gi protein complex.

Science.gov (United States)

Mnpotra, Jagjeet S; Qiao, Zhuanhong; Cai, Jian; Lynch, Diane L; Grossfield, Alan; Leioatts, Nicholas; Hurst, Dow P; Pitman, Michael C; Song, Zhao-Hui; Reggio, Patricia H

2014-07-18

In this study, we applied a comprehensive G protein-coupled receptor-Gαi protein chemical cross-linking strategy to map the cannabinoid receptor subtype 2 (CB2)-Gαi interface and then used molecular dynamics simulations to explore the dynamics of complex formation. Three cross-link sites were identified using LC-MS/MS and electrospray ionization-MS/MS as follows: 1) a sulfhydryl cross-link between C3.53(134) in TMH3 and the Gαi C-terminal i-3 residue Cys-351; 2) a lysine cross-link between K6.35(245) in TMH6 and the Gαi C-terminal i-5 residue, Lys-349; and 3) a lysine cross-link between K5.64(215) in TMH5 and the Gαi α4β6 loop residue, Lys-317. To investigate the dynamics and nature of the conformational changes involved in CB2·Gi complex formation, we carried out microsecond-time scale molecular dynamics simulations of the CB2 R*·Gαi1β1γ2 complex embedded in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer, using cross-linking information as validation. Our results show that although molecular dynamics simulations started with the G protein orientation in the β2-AR*·Gαsβ1γ2 complex crystal structure, the Gαi1β1γ2 protein reoriented itself within 300 ns. Two major changes occurred as follows. 1) The Gαi1 α5 helix tilt changed due to the outward movement of TMH5 in CB2 R*. 2) A 25° clockwise rotation of Gαi1β1γ2 underneath CB2 R* occurred, with rotation ceasing when Pro-139 (IC-2 loop) anchors in a hydrophobic pocket on Gαi1 (Val-34, Leu-194, Phe-196, Phe-336, Thr-340, Ile-343, and Ile-344). In this complex, all three experimentally identified cross-links can occur. These findings should be relevant for other class A G protein-coupled receptors that couple to Gi proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

A cell population that strongly expresses the CB1 cannabinoid receptor in the ependyma of the rat spinal cord.

Science.gov (United States)

Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Sierra-Palomares, Yolanda; Molina-Holgado, Eduardo

2013-01-01

The cells surrounding the central canal of the spinal cord are a source of stem/precursor cells that may give rise to neurons, astrocytes, or oligodendrocytes. However, they are a heterogeneous population that remains poorly understood. Here we describe a subpopulation characterized by their strong expression of the CB(1) cannabinoid receptor, oval/round soma, apical nucleus, a variable number of cilia (0, 1, or 2), and the presence of a single short and occasionally ramified basal process. These cells are mainly located in the lateral and dorsal central canal throughout the spinal cord. These CB(1)(HIGH) cells are closely related to the basal lamina labyrinths or fractones derived from subependymal microglia. In addition, CB(1)(HIGH) cells express some stem/precursor cell markers, including vimentin, nestin, Sox2, Sox9, and GLAST, but not others such as CD15 or GFAP. In addition, this cell population does not proliferate in the intact adult spinal cord, although up to 50% of these cells express the proliferation marker Ki67 in newly born rats or after a spinal cord contusion. The present findings contribute to our understanding of the spinal cord central canal structure and reveal the targets for endocannabinoids inside this neurogenic niche. Copyright © 2012 Wiley Periodicals, Inc.

The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

Directory of Open Access Journals (Sweden)

Francisco J. Bermudez-Silva

2016-01-01

Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

Suitable exposure conditions for CB Throne? New model cone beam computed tomography unit for dental use

International Nuclear Information System (INIS)

Tanabe, Kouji; Nishikawa, Keiichi; Yajima, Aya; Mizuta, Shigeru; Sano, Tsukasa; Yajima, Yasutomo; Nakagawa, Kanichi; Kousuge, Yuuji

2008-01-01

The CB Throne is a cone beam computed tomography unit for dental use, and the smaller version of the CB MercuRay developed by Hitachi Medico Co. We investigated which exposure conditions were suitable in the clinical use. Suitable exposure conditions were determined by simple subjective comparisons. The right temporomandibular joint of the head phantom was scanned at all possible combinations of tube voltage (60, 80, 100, 120 kV) and tube current (10, 15 mA). Oblique-sagittal images of the same position were obtained using multiplanar reconstruction (MPR) function. Images obtained at 120 kV and 15 mA, which are the highest exposure conditions and certain to produce images of the best quality, were used to establish the standard. Eight oral radiologists observed each image and standard image on a LCD monitor. They compared subjectively spatial resolution and noise between each image and standard image using a 10 cm scale. Evaluation points were obtained from the check positions on the scales. The Steel method was used to determine significant differences. The images at 60 kV/10 mA and 80 kV/15 mA showed significantly lower evaluation points on spatial resolution. The images at 60 kV/10 mA, 60 kV/15 mA and 80 kV/10 mA showed significantly lower evaluation points on noise. In conclusion, even if exposure conditions are reduced to 100 kV/10 mA, 100 kV/15 mA or 120 kV/10 mA, the CB Throne will produce images of the best quality. (author)

Application of mechanical alloying to synthesis of intermetallic phases based alloys

International Nuclear Information System (INIS)

Dymek, S.

2001-01-01

Mechanical alloying is the process of synthesis of powder materials during milling in high energetic mills, usually ball mills. The central event in mechanical alloying is the ball-powder-ball collision. Powder particles are trapped between the colliding balls during milling and undergo deformation and/or fracture. Fractured parts are cold welded. The continued fracture and cold welding results in a uniform size and chemical composition of powder particles. The main applications of mechanical alloying are: processing of ODS alloys, syntheses of intermetallic phases, synthesis of nonequilibrium structures (amorphous alloys, extended solid solutions, nanocrystalline, quasi crystals) and magnetic materials. The present paper deals with application of mechanical alloying to synthesis Ni A l base intermetallic phases as well as phases from the Nb-Al binary system. The alloy were processed from elemental powders. The course of milling was monitored by scanning electron microscopy and X-ray diffraction. After milling, the collected powders were sieved by 45 μm grid and hot pressed (Nb alloys and NiAl) or hot extruded (NiAl). The resulting material was fully dense and exhibited fine grain (< 1 μm) and uniform distribution of oxide dispersoid. The consolidated material was compression and creep tested. The mechanical properties of mechanically alloys were superior to properties of their cast counterparts both in the room and elevated temperatures. Higher strength of mechanically alloyed materials results from their fine grains and from the presence of dispersoid. At elevated temperatures, the Nb-Al alloys have higher compression strength than NiAl-based alloys processed at the same conditions. The minimum creep rates of mechanically alloyed Nb alloys are an order of magnitude lower than analogously processed NiAl-base alloys. (author)

Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB{sub 1} receptors using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Terry, Garth E. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B. [National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States); Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C. [Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN (United States); Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden)

2010-08-15

Cannabinoid subtype 1 (CB{sub 1}) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB{sub 1} receptors with two PET radioligands: {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2}. Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with {sup 11}C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with {sup 18}F-FMPEP-d{sub 2}. Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for {sup 18}F-FMPEP-d{sub 2}. The effective doses of {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} are 4.6 and 19.7 {mu}Sv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of {sup 11}C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from {sup 18}F-FMPEP-d{sub 2} showed both hepatobiliary and urinary excretion. {sup 11}C-MePPEP and {sup 18}F-FMPEP-d{sub 2} yield an effective dose similar to other PET radioligands labeled with either {sup 11}C or {sup 18}F. The high uptake in brain confirms the utility of these two radioligands to image CB{sub 1} receptors in brain, and both may also be useful to image CB{sub 1} receptors in the periphery. (orig.)

Localización de los Receptores Cannabinoides 1 (CB1) en Glándulas Salivales Submandibulares y Sublinguales de Ratones Durante el Desarrollo Postnatal

OpenAIRE

Hipkaeo, Wiphawi; Watanabe, Masahiko; Kondo, Hisatake

2015-01-01

In view of the fact that human marijuana users often show dry mouth symptom, the present study was attempted to examine the localization of CB1, which was originally identified in brain, in the submandibular and sublingual salivary glands of postnatal developing male mice by immunohistochemistry. In submandibular gland, CB1-immunoreactivity was positive in a majority of acinar cells in forms of granular appearance in their apical cytoplasm, while it was negative in the ducts at newborn stage....

Nido-Carborane building-block reagents. 3. Cyclic and open-chain oligomers incorporating -CB4H6C - units. Crown carboranes

International Nuclear Information System (INIS)

Boyter, H.A. Jr.; Grimes, R.N.

1988-01-01

The open-chain dialkynes EtC≡C(CH 2 ) n C≡CEt (n = 4, 6), the trialkyne HC≡C(CH 2 ) 5 C≡CH, and the cyclic dialkynes CH 2 (CH 2 ) 4 C≡C(CH 2 ) n C≡C (n = 4-6) were treated with B 5 H 9 and (C 2 H 5 ) 3 to give the corresponding nido-carborane oligomers, in which the original -C≡C- units are converted to -CB 4 H 6 C- nido-carborane cages. In each case, all available -C≡C- groups were transformed to carborane moieties. No partially converted products (having both carborane and -C≡C- groups in the chain) were found; when the B 5 H 9 /-C≡C- ratio employed was 2+ and oxidative fusion, forming products incorporating C 4 B 8 cages. The cyclic bis(carborane) CH 2 (CH 2 ) 4 CB 4 H 6 C(CH 2 ) 5 CB 4 H 6 C is an air-stable oil that can be deprotonated but does not under metal-promoted oxidative fusion. All products were characterized by 11 B and 1 H NMR, infrared, visible-uv, and mass spectroscopy, and the 13 C NMR spectra of linear bis(carboranes) are reported. 9 references, 7 figures, 4 tables

Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189.

Science.gov (United States)

Reiner, Anton; Heldt, Scott A; Presley, Chaela S; Guley, Natalie H; Elberger, Andrea J; Deng, Yunping; D'Surney, Lauren; Rogers, Joshua T; Ferrell, Jessica; Bu, Wei; Del Mar, Nobel; Honig, Marcia G; Gurley, Steven N; Moore, Bob M

2014-12-31

We have developed a focal blast model of closed-head mild traumatic brain injury (TBI) in mice. As true for individuals that have experienced mild TBI, mice subjected to 50-60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2), we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50-60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

Science.gov (United States)

De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

2016-06-01

In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surface modification of 5083 Al alloy by electrical discharge alloying processing with a 75 mass% Si-Fe alloy electrode

Energy Technology Data Exchange (ETDEWEB)

Stambekova, Kuralay [Department of Materials Science and Engineering, National Chung Hsing University, 250 Kuo-Kuang Rd., Taichung 40227, Taiwan (China); Lin, Hung-Mao [Department of Mechanical Engineering, Far East University, No. 49, Zhonghua Rd., Xinshi Dist., Tainan City 74448, Taiwan (China); Uan, Jun-Yen, E-mail: jyuan@dragon.nchu.edu.tw [Department of Materials Science and Engineering, National Chung Hsing University, 250 Kuo-Kuang Rd., Taichung 40227, Taiwan (China)

2012-03-01

This study experimentally investigates the surface modification of 5083 Al alloy by the electrical discharge alloying (EDA) process with a Si-Fe alloy as an electrode. Samples were analyzed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), micro-hardness and corrosion resistance tests. The micro-hardness of EDA alloyed layer was evidently higher than that of the base metal (5083 Al alloy). The TEM results show that the matrix of the alloyed layer has an amorphous-like structure; the matrix contains fine needle-like Si particles, block-like Si particles and nano-size Al{sub 4.5}FeSi and Al{sub 13}Fe{sub 4} particles. The TEM results support experimental results for the high hardness of the alloyed layer. Moreover, the EDA alloyed layer with composite microstructures has good corrosion resistance in NaCl aqueous solution.

Synthesis Of NiCrAlC alloys by mechanical alloying

International Nuclear Information System (INIS)

Silva, A.K.; Pereira, J.I.; Vurobi Junior, S.; Cintho, O.M.

2010-01-01

The purpose of the present paper is the synthesis of nickel alloys (NiCrAlC), which has been proposed like a economic alternative to the Stellite family Co alloys using mechanical alloying, followed by sintering heat treatment of milled material. The NiCrAlC alloys consist of a chromium carbides dispersion in a Ni 3 Al intermetallic matrix, that is easily synthesized by mechanical alloying. The use of mechanical alloying enables higher carbides sizes and distribution control in the matrix during sintering. We are also investigated the compaction of the processed materials by compressibility curves. The milling products were characterized by X-ray diffraction, and the end product was featured by conventional metallography and scanning electronic microscopy (SEM), that enabled the identification of desired phases, beyond microhardness test, which has been shown comparable to alloys manufactured by fusion after heat treating. (author)

Determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke from baryonic Λ{sub b} decays

Energy Technology Data Exchange (ETDEWEB)

Hsiao, Y.K. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Geng, C.Q. [Shanxi Normal University, School of Physics and Information Engineering, Linfen (China); National Tsing Hua University, Department of Physics, Hsinchu (China); Hunan Normal University, Synergetic Innovation Center for Quantum Effects and Applications (SICQEA), Changsha (China)

2017-10-15

We present the first attempt to extract vertical stroke V{sub cb} vertical stroke from the Λ{sub b} → Λ{sub c}{sup +}l anti ν{sub l} decay without relying on vertical stroke V{sub ub} vertical stroke inputs from the B meson decays. Meanwhile, the hadronic Λ{sub b} → Λ{sub c}M{sub (c)} decays with M = (π{sup -},K{sup -}) and M{sub c} =(D{sup -},D{sup -}{sub s}) measured with high precisions are involved in the extraction. Explicitly, we find that vertical stroke V{sub cb} vertical stroke =(44.6 ± 3.2) x 10{sup -3}, agreeing with the value of (42.11 ± 0.74) x 10{sup -3} from the inclusive B → X{sub c}l anti ν{sub l} decays. Furthermore, based on the most recent ratio of vertical stroke V{sub ub} vertical stroke / vertical stroke V{sub cb} vertical stroke from the exclusive modes, we obtain vertical stroke V{sub ub} vertical stroke = (4.3 ± 0.4) x 10{sup -3}, which is close to the value of (4.49 ± 0.24) x 10{sup -3} from the inclusive B → X{sub u}l anti ν{sub l} decays. We conclude that our determinations of vertical stroke V{sub cb} vertical stroke and vertical stroke V{sub ub} vertical stroke favor the corresponding inclusive extractions in the B decays. (orig.)

Transfer Effect Ratio of Loosely Coupled Coils for Wireless Power through CB Wall under Station Blackout(SBO)

International Nuclear Information System (INIS)

Koo, Kil Mo; Hong, Seong Wan; Song, Jin Ho; Baek, Won Pil; Cheon, Sang Hoon

2016-01-01

Instrumentations have had the bad situation like a station blackout(SBO) as the severe accident in nuclear power plants. In recent years, there has been an increasing interest in wireless power transfer technology, In particular, significant processing has been charted for inductively coupled systems. In this paper, we introduce some new method as transfer effect ratio of loosely coupled coils for wireless power through the CB(Container Building) wall as an alternative method under a station blackout of severe accident conditions in nuclear power plants. As an equivalent circuit model that can describe wireless energy transfer systems via coupled magnetic resonances for the CB thickness wall. The solution shows that the transmission efficiency can be decreased simply by adjusting the spacing between the power and the sending coils or between the receiving and the load coils. The system design can be calculated the frequency characteristics, and then an equivalent circuit model was developed from the node equation and established in an electric design automation tool

Transfer Effect Ratio of Loosely Coupled Coils for Wireless Power through CB Wall under Station Blackout(SBO)

Energy Technology Data Exchange (ETDEWEB)

Koo, Kil Mo; Hong, Seong Wan; Song, Jin Ho; Baek, Won Pil [KAERI, Daejeon (Korea, Republic of); Cheon, Sang Hoon [ETRI, Daejeon (Korea, Republic of)

2016-05-15

Instrumentations have had the bad situation like a station blackout(SBO) as the severe accident in nuclear power plants. In recent years, there has been an increasing interest in wireless power transfer technology, In particular, significant processing has been charted for inductively coupled systems. In this paper, we introduce some new method as transfer effect ratio of loosely coupled coils for wireless power through the CB(Container Building) wall as an alternative method under a station blackout of severe accident conditions in nuclear power plants. As an equivalent circuit model that can describe wireless energy transfer systems via coupled magnetic resonances for the CB thickness wall. The solution shows that the transmission efficiency can be decreased simply by adjusting the spacing between the power and the sending coils or between the receiving and the load coils. The system design can be calculated the frequency characteristics, and then an equivalent circuit model was developed from the node equation and established in an electric design automation tool.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

Science.gov (United States)

Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

2017-01-01

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

OpenAIRE

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed.

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

Science.gov (United States)

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

CESM/CAM5 improvement and application: comparison and evaluation of updated CB05_GE and MOZART-4 gas-phase mechanisms and associated impacts on global air quality and climate

Science.gov (United States)

He, J.; Zhang, Y.; Tilmes, S.; Emmons, L.; Lamarque, J.-F.; Glotfelty, T.; Hodzic, A.; Vitt, F.

2015-12-01

Atmospheric chemistry plays a key role in determining the amounts and distributions of oxidants and gaseous precursors that control the formation of secondary gaseous and aerosol pollutants; all of those species can interact with the climate system. To understand the impacts of different gas-phase mechanisms on global air quality and climate predictions, in this work, a comprehensive comparative evaluation is performed using the Community Atmosphere Model (CAM) Version 5 with comprehensive tropospheric and stratospheric chemistry (CAM5-chem) within the Community Earth System Model (CESM) with the two most commonly used gas-phase chemical mechanisms: the 2005 Carbon Bond mechanism with Global Extension (CB05_GE) and the Model of OZone and Related chemical Tracers version 4 (MOZART-4) mechanism with additional updates (MOZART-4x). MOZART-4x and CB05_GE use different approaches to represent volatile organic compounds (VOCs) and different surrogates for secondary organic aerosol (SOA) precursors. MOZART-4x includes a more detailed representation of isoprene chemistry compared to CB05_GE. CB05_GE includes additional oxidation of SO2 by O3 over the surface of dust particles, which is not included in MOZART-4x. The results show that the two CAM5-chem simulations with CB05_GE and MOZART-4x predict similar chemical profiles for major gases (e.g., O3, CO, and NOx) compared to the aircraft measurements, with generally better agreement for NOy profiles by CB05_GE than MOZART-4x. The concentrations of SOA at four sites in the continental US (CONUS) and organic carbon (OC) over the IMPROVE sites are well predicted by MOZART-4x (with normalized mean biases (NMBs) of -1.9 and 2.1 %, respectively) but moderately underpredicted by CB05_GE (with NMBs of -23.1 and -20.7 %, respectively). This is mainly due to the higher biogenic emissions and OH levels simulated with MOZART-4x than with CB05_GE. The concentrations of OC over Europe are largely underpredicted by both MOZART-4x and CB05

Correlation between diffusion barriers and alloying energy in binary alloys

DEFF Research Database (Denmark)

Vej-Hansen, Ulrik Grønbjerg; Rossmeisl, Jan; Stephens, Ifan

2016-01-01

In this paper, we explore the notion that a negative alloying energy may act as a descriptor for long term stability of Pt-alloys as cathode catalysts in low temperature fuel cells.......In this paper, we explore the notion that a negative alloying energy may act as a descriptor for long term stability of Pt-alloys as cathode catalysts in low temperature fuel cells....

Titanium alloys. Advances in alloys, processes, products and applications

International Nuclear Information System (INIS)

Blenkinsop, P.A.

1993-01-01

The last few years have been a period of consolidation of existing alloys and processes. While the aerospace industry remains the principal driving force for alloy development, the paper illustrates examples of new markets being established in 'older' alloys, by a combination of product/process development and a re-examination of engineering design parameters. Considerable attention is still being directed towards the titanium aluminide systems, but other more conventional alloy developments are underway aimed at specific engineering and process requirements, both in the aerospace and non-aerospace sectors. Both the advanced high temperature and conventional alloy developments are considered, before the paper goes on to assess the potential of new processes and products, like spray-forming, metal matrix composites and shaped-plate rolling. (orig.)

High-temperature deformation of a mechanically alloyed niobium-yttria alloy

International Nuclear Information System (INIS)

Chou, I.; Koss, D.A.; Howell, P.R.; Ramani, A.S.

1997-01-01

Mechanical alloying (MA) and hot isostatic pressing have been used to process two Nb alloys containing yttria particles, Nb-2 vol.%Y 2 O 3 and Nb-10 vol.%Y 2 O 3 . Similar to some thermomechanically processed nickel-based alloys, both alloys exhibit partially recrystallized microstructures, consisting of a 'necklace' of small recrystallized grains surrounding much larger but isolated, unrecrystallized, cold-worked grains. Hot compression tests from 1049 to 1347 C (0.5-0.6T MP ) of the 10% Y 2 O 3 alloy show that MA material possesses a much higher yield and creep strength than its powder-blended, fully recrystallized counterpart. In fact, the density-compensated specific yield strength of the MA Nb-10Y 2 O 3 exceeds that of currently available commercial Nb alloys. (orig.)

The Combined Inhibitory Effect of the Adenosine A1 and Cannabinoid CB1 Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A1 Receptor Desensitization

OpenAIRE

Serpa, Andr?; Correia, Sara; Ribeiro, Joaquim A.; Sebasti?o, Ana M.; Cascalheira, Jos? F.

2015-01-01

Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3?30??M) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6 ? 2.7??M and an E max? of 31% ? 2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10?150?nM), an EC50 of 35 ? 19?nM, an...

Iron-based amorphous alloys and methods of synthesizing iron-based amorphous alloys

Science.gov (United States)

Saw, Cheng Kiong; Bauer, William A.; Choi, Jor-Shan; Day, Dan; Farmer, Joseph C.

2016-05-03

A method according to one embodiment includes combining an amorphous iron-based alloy and at least one metal selected from a group consisting of molybdenum, chromium, tungsten, boron, gadolinium, nickel phosphorous, yttrium, and alloys thereof to form a mixture, wherein the at least one metal is present in the mixture from about 5 atomic percent (at %) to about 55 at %; and ball milling the mixture at least until an amorphous alloy of the iron-based alloy and the at least one metal is formed. Several amorphous iron-based metal alloys are also presented, including corrosion-resistant amorphous iron-based metal alloys and radiation-shielding amorphous iron-based metal alloys.

Influence of media composition on the production of alkaline α-amylase from Bacillus subtilis CB-18.

Science.gov (United States)

Ogbonnaya, Nwokoro; Odiase, Anthonia

2012-01-01

Starch, a homopolysaccharide is an important and an abundant food reserve and energy source. Starches are processed to yield different products which find many industrial applications. Alpha-amylases hydrolyze starch by cleaving α-1,4-glucosidic bonds and have been used in food, textile and pharmaceutical industries [Sun et al. 2010]. Enzymatic conversion of starch with amylase presents an economically superior alternative to the conventional method of starch gelatinization. Alkaline α-amylase has an important position in the global enzyme market as a constituent of detergent. In this paper, we screened soil bacteria and an isolate, alkalophilic Bacillus subtilis CB-18 was found to produce an alkaline α-amylase in different media. MATERIAL AND METHODS. Screening of the isolates for amylolytic activity was carried out by growing bacteria isolated from the soil in starch agar plates and subsequently staining the plates with iodine solution to reveal zones of hydrolysis of starch. The selected isolate, Bacillus subtlis CB-18 was grown in different media at alkaline pH to evaluate the influence of media composition on alkaline α-amylase production. Enzyme assay was carried out by growing the culture in a broth medium and obtaining cell - free culture supernatant after centrifugation at 2515 × g for 15 minutes Amylase activity was determined by incubating 0.5 ml of crude enzyme solution in 0.1M Tris/HCl buffer (pH 8.5) with 0.5 ml of 1% soluble starch solution. The reaction was terminated by the addition of DNS reagent and reducing sugar produced from the amylolytic reaction was determined. Bacillus subtilis CB-18 used for this work was selected because it produced 7 mm zone diameter on starch agar plate. This organism was cultured in different alkaline broth media containing 2% soluble starch as inducer carbohydrate for α-amylase production. Among the carbon sources used for enzyme production, sorbitol was the best to stimulate enzyme production with �

Role of Cannabinoid CB2 Receptor Gene (CNR2) Polymorphism in Children with Immune Thrombocytopenic Purpura in Beni-Suef Governorate in Egypt.

Science.gov (United States)

Ezzat, Dina A; Hammam, Amira A; El-Malah, Waleed M; Khattab, Rasha A; Mangoud, Eman M

2017-01-01

The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease. Forty children diagnosed as ITP were included in this study and 20 healthy children as normal control. CNR2 gene was investigated in those children by PCR RFLP technique (restriction fragment length polymorphism). CNR2 genotyping revealed that 45% of ITP patients had the QR heterotype, 50% had the RR homotype and 5% had QQ, the wild type with significantly higher frequency of homomutant genotype in comparison to controls. The relative odds ratio suggested a double risk for developing ITP in RR homotype (OR 2.152). A significant overpresentation of the RR genotype and of R allele was observed in the chronic patients (P=0.002 and 0.003, respectively). The associated risk to develop chronic ITP increased more than two folds for the RR homotype (OR=2.854). In conclusion, this study confirms the role of CNR2 Q63R polymorphism in the susceptibility to ITP in children and chronicity of the disease. Copyright© by the Egyptian Association of Immunologists.

High strength alloys

Science.gov (United States)

Maziasz, Phillip James [Oak Ridge, TN; Shingledecker, John Paul [Knoxville, TN; Santella, Michael Leonard [Knoxville, TN; Schneibel, Joachim Hugo [Knoxville, TN; Sikka, Vinod Kumar [Oak Ridge, TN; Vinegar, Harold J [Bellaire, TX; John, Randy Carl [Houston, TX; Kim, Dong Sub [Sugar Land, TX

2010-08-31

High strength metal alloys are described herein. At least one composition of a metal alloy includes chromium, nickel, copper, manganese, silicon, niobium, tungsten and iron. System, methods, and heaters that include the high strength metal alloys are described herein. At least one heater system may include a canister at least partially made from material containing at least one of the metal alloys. At least one system for heating a subterranean formation may include a tubular that is at least partially made from a material containing at least one of the metal alloys.

Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189

Directory of Open Access Journals (Sweden)

Anton Reiner

2014-12-01

Full Text Available We have developed a focal blast model of closed-head mild traumatic brain injury (TBI in mice. As true for individuals that have experienced mild TBI, mice subjected to 50–60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2, we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50–60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

Aluminum fin-stock alloys

International Nuclear Information System (INIS)

Gul, R.M.; Mutasher, F.

2007-01-01

Aluminum alloys have long been used in the production of heat exchanger fins. The comparative properties of the different alloys used for this purpose has not been an issue in the past, because of the significant thickness of the finstock material. However, in order to make fins lighter in weight, there is a growing demand for thinner finstock materials, which has emphasized the need for improved mechanical properties, thermal conductivity and corrosion resistance. The objective of this project is to determine the effect of iron, silicon and manganese percentage increment on the required mechanical properties for this application by analyzing four different aluminum alloys. The four selected aluminum alloys are 1100, 8011, 8079 and 8150, which are wrought non-heat treatable alloys with different amount of the above elements. Aluminum alloy 1100 serve as a control specimen, as it is commercially pure aluminum. The study also reports the effect of different annealing cycles on the mechanical properties of the selected alloys. Metallographic examination was also preformed to study the effect of annealing on the precipitate phases and the distribution of these phases for each alloy. The microstructure analysis of the aluminum alloys studied indicates that the precipitated phase in the case of aluminum alloys 1100 and 8079 is beta-FeAI3, while in 8011 it is a-alfa AIFeSi, and the aluminum alloy 8150 contains AI6(Mn,Fe) phase. The comparison of aluminum alloys 8011 and 8079 with aluminum alloy 1100 show that the addition of iron and silicon improves the percent elongation and reduces strength. The manganese addition increases the stability of mechanical properties along the annealing range as shown by the comparison of aluminum alloy 8150 with aluminum alloy 1100. Alloy 8150 show superior properties over the other alloys due to the reaction of iron and manganese, resulting in a preferable response to thermal treatment and improved mechanical properties. (author)

Monoclonal antibody 1.6.1 against human MPL receptor allows HSC enrichment of CB and BM CD34(+)CD38(-) populations.

Science.gov (United States)

Petit Cocault, Laurence; Fleury, Maud; Clay, Denis; Larghero, Jérôme; Vanneaux, Valérie; Souyri, Michèle

2016-04-01

Thrombopoietin (TPO) and its receptor Mpl (CD110) play a crucial role in the regulation of hematopoietic stem cells (HSCs). Functional study of Mpl-expressing HSCs has, however, been hampered by the lack of efficient monoclonal antibodies, explaining the very few data available on Mpl(+) HSCs during human embryonic development and after birth. Investigating the main monoclonal antibodies used so far to sort CD110(+) cells from cord blood (CB) and adult bone marrow (BM), we found that only the recent monoclonal antibody 1.6.1 engineered by Immunex Corporation was specific. Using in vitro functional assays, we found that this antibody can be used to sort a CD34(+)CD38(-)CD110(+) population enriched in hematopoietic progenitor stem cells, both in CB and in adult BM. In vivo injection into NSG mice further indicated that the CB CD34(+)CD38(-)CD110(+) population is highly enriched in HSCs compared with both CD34(+)CD38(-)CD110(-) and CD34(+)CD38(-) populations. Together our results validate MAb1.6.1 as an important tool, which has so far been lacking, in the HSC field. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Nickel alloys and high-alloyed special stainless steels. Properties, manufacturing, applications. 4. compl. rev. ed.

International Nuclear Information System (INIS)

Heubner, Ulrich; Kloewer, Jutta; Alves, Helena; Behrens, Rainer; Schindler, Claudius; Wahl, Volker; Wolf, Martin

2012-01-01

This book contains the following eight topics: 1. Nickel alloys and high-alloy special stainless steels - Material overview and metallurgical principles (U. Heubner); 2. Corrosion resistance of nickel alloys and high-alloy special stainless steels (U. Heubner); 3. Welding of nickel alloys and high-alloy special stainless steels (T. Hoffmann, M. Wolf); 4. High-temperature materials for industrial plant construction (J. Kloewer); 5. Nickel alloys and high-alloy special stainless steels as hot roll clad composites-a cost-effective alternative (C. Schindler); 6. Selected examples of the use of nickel alloys and high-alloy special stainless steels in chemical plants (H. Alves); 7. The use of nickel alloys and stainless steels in environmental engineering (V. Wahl); 8: Nickel alloys and high-alloy special stainless steels for the oil and gas industry (R. Behrens).

Biocompatibility of dental alloys

Energy Technology Data Exchange (ETDEWEB)

Braemer, W. [Heraeus Kulzer GmbH and Co. KG, Hanau (Germany)

2001-10-01

Modern dental alloys have been used for 50 years to produce prosthetic dental restorations. Generally, the crowns and frames of a prosthesis are prepared in dental alloys, and then veneered by feldspar ceramics or composites. In use, the alloys are exposed to the corrosive influence of saliva and bacteria. Metallic dental materials can be classified as precious and non-precious alloys. Precious alloys consist of gold, platinum, and small amounts of non-precious components such as copper, tin, or zinc. The non-precious alloys are based on either nickel or cobalt, alloyed with chrome, molybdenum, manganese, etc. Titanium is used as Grade 2 quality for dental purposes. As well as the dental casting alloys, high purity electroplated gold (99.8 wt.-%) is used in dental technology. This review discusses the corrosion behavior of metallic dental materials with saliva in ''in vitro'' tests and the influence of alloy components on bacteria (Lactobacillus casei and Streptococcus mutans). The test results show that alloys with high gold content, cobalt-based alloys, titanium, and electroplated gold are suitable for use as dental materials. (orig.)

The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy

Directory of Open Access Journals (Sweden)

Deng Liting

2012-09-01

Full Text Available Abstract Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel. A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4 signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p. suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p., but not the CB1 antagonist AM251 (3 mg/kg i.p., consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p. failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.

Interphase thermodynamic bond in heterogeneous alloys: effects on alloy properties

International Nuclear Information System (INIS)

Savchenko, A.M.; Konovalov, Yu.V.; Yuferov, O.I.

2005-01-01

Inconsistency between a conventional thermodynamic description of alloys as a mechanical mixture of phases and a real alloys state as a common thermodynamic system in which there is a complicated physical-chemical phases interaction has been considered. It is supposed that in heterogeneous alloys (eutectic ones, for instance), so called interphase thermodynamic bond can become apparent due to a partial electron levels splitting under phase interaction. Thermodynamic description of phase equilibrium in alloys is proposed taking into account a thermodynamic bond for the system with phase diagram of eutectic type, and methods of the value of this bond estimation are presented. Experimental evidence (Al-Cu-Si, Al-Si-Mg-Cu, U-Mo + Al) of the effect of interphase thermodynamic bond on temperature and enthalpy of melting of alloys are produced as well as possibility of its effects on alloys electrical conduction, strength, heat and corrosion resistance is substantiated theoretically [ru

Effect of the temperature and the chlorine pressure, over the aluminium chlorides obtained by direct chlorination of the 6061 alloy

International Nuclear Information System (INIS)

Alvarez, Fabiola J.; Bohe, Ana E.; Pasquevich, Daniel M.

2003-01-01

The aluminium chloride is synthesized by direct chlorination of aluminium, in agreement with the following reaction: Al(s) + 3/2 Cl 2 AlCl 3 (s,g).The present work focuses on the preparation of aluminium chlorides by two methods: (a) Chlorination of 6061 aluminium alloy with gaseous chlorine in sealed containers, filled with different pressures of gas, from 0.8 to 74 Kpa and in the range of temperature between 200 0 and 500 0 C.(b) Chlorination of the same alloy in chlorine flow between 150 0 and 400 0 C.In the sealed systems, the hexahydrated aluminium trichloride predominated over the anhydrous form. For pressures lower than 14 Kpa and temperatures under 250 0 C, the chloride didn't appear.The residues were rich in aluminium, chlorine and magnesium.In the other systems, the anhydrous chloride was found in the areas of the reactor of temperatures above 100 0 C, for all the thermal treatments. The waste was composed by CrCl 3 and AlCl 3 .6H 2 O.The influence of the chlorine pressures and the heating temperature over the characteristics of the product, was studied.The characterization techniques were x-ray diffraction and energy dispersive spectroscopy, and the evolution of the structure was followed by scanning electron microscopy

The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.

Science.gov (United States)

Ratano, Patrizia; Everitt, Barry J; Milton, Amy L

2014-10-01

We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.

CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana.

Science.gov (United States)

Friend, Lindsey; Weed, Jared; Sandoval, Philip; Nufer, Teresa; Ostlund, Isaac; Edwards, Jeffrey G

2017-11-08

The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied Δ 9 -tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of Δ 9 -tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictive effects of Δ 9 -tetrahydrocannabinol in juvenile-adolescents, by potentially altering reward behavioral outcomes. SIGNIFICANCE STATEMENT The present study identifies a novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently understudied cell type that is critical for the brain's reward circuit, and how Δ 9 -tetrahydrocannabinol occludes this plasticity. This study specifically addresses a potential unifying mechanism whereby marijuana could exert rewarding and addictive/withdrawal effects. Marijuana use and legalization are a pressing issue for many states in the United States. Although marijuana is the most commonly abused illicit drug, the implications of legalized, widespread, or continued usage are speculative. This study in juvenile-adolescent aged mice identifies a novel form of synaptic plasticity in VTA GABA cells, and the synaptic remodeling that can occur after Δ 9 -tetrahydrocannabinol use. Copyright © 2017 the

Transition from Spin Dewetting to continuous film in spin coating of Liquid Crystal 5CB.

Science.gov (United States)

Dhara, Palash; Bhandaru, Nandini; Das, Anuja; Mukherjee, Rabibrata

2018-05-08

Spin dewetting refers to spontaneous rupture of the dispensed solution layer during spin coating, resulting in isolated but periodic, regular sized domains of the solute and is pre-dominant when the solute concentration (C n ) is very low. In this article we report how the morphology of liquid crystal (LC) 5CB thin films coated on flat and patterned PMMA substrate transform from spin dewetted droplets to continuous films with increase in C n . We further show that within the spin dewetted regime, with gradual increase in the solute concentration, periodicity of the isotropic droplets (λ D ) as well as their mean diameter (d D ), gradually decreases, till the film becomes continuous at a critical concentration (C n *). Interestingly, the trend that λ D reduces with increase in C n is exact opposite to what is observed in thermal/solvent vapor induced dewetting of a thin film. The spin dewetted droplets exhibit transient Radial texture, in contrast to Schlieren texture observed in elongated threads and continuous films of 5CB, which remains in the Nematic phase at room temperature. Finally we show that by casting the film on a grating patterned substrate it becomes possible to align the spin dewetted droplets along the contours substrate patterns.

Irradiation-assisted stress corrosion cracking in HTH Alloy X-750 and Alloy 625

International Nuclear Information System (INIS)

Bajaj, R.; Mills, W.J.; Lebo, M.R.; Hyatt, B.Z.; Burke, M.G.

1995-01-01

In-reactor testing of bolt-loaded compact tension specimens was performed in 360 C water to determine the irradiation-assisted stress corrosion cracking (IASCC) behavior of HTH Alloy X-750 and direct-aged Alloy 625. New data confirm previous results showing that high irradiation levels reduce SCC resistance in Alloy X-750. Heat-to-heat variability correlates with boron content, with low boron heats showing improved IASCC properties. Alloy 625 is resistant to IASCC, as no cracking was observed in any Alloy 625 specimens. Microstructural, microchemical and deformation studies were performed to characterize the mechanisms responsible for IASCC in Alloy X-750 and the lack of an effect in Alloy 625. The mechanisms under investigation are: boron transmutation effects, radiation-induced changes in microstructure and deformation characteristics, and radiation-induced segregation. Irradiation of Alloy X-750 caused significant strengthening and ductility loss that was associated with the formation of cavities and dislocation loops. High irradiation levels did not cause significant segregation of alloying or trace elements in Alloy X-750. Irradiation of Alloy 625 resulted in the formation of small dislocation loops and a fine body-centered-orthorhombic phase. The strengthening due to the loops and precipitates was apparently offset by a partial dissolution of γ double-prime precipitates, as Alloy 625 showed no irradiation-induced strengthening or ductility loss. In the nonirradiated condition, an IASCC susceptible HTH heat containing 28 ppm B showed grain boundary segregation of boron, whereas a nonsusceptible HTH heat containing 2 ppm B and Alloy 625 with 20 ppm B did not show significant boron segregation. Transmutation of boron to helium at grain boundaries, coupled with matrix strengthening, is believed to be responsible for IASCC in Alloy X-750, and the absence of these two effects results in the superior IASCC resistance displayed by Alloy 625

Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

Science.gov (United States)

Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

2010-11-01

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

B S Murty

Indian Academy of Sciences (India)

This difference in the product structure can be attributed to the difference in alloying mechanisms in MA and RSP. Volume 37 Issue 4 June 2014 pp 743-752. Porous copper template from partially spark plasma-sintered Cu–Zn aggregate via dezincification · M Mandal D Singh Gouthama B S Murty S Sangal K Mondal.

Filler metal alloy for welding cast nickel aluminide alloys

Science.gov (United States)

Santella, M.L.; Sikka, V.K.

1998-03-10

A filler metal alloy used as a filler for welding cast nickel aluminide alloys contains from about 15 to about 17 wt. % chromium, from about 4 to about 5 wt. % aluminum, equal to or less than about 1.5 wt. % molybdenum, from about 1 to about 4.5 wt. % zirconium, equal to or less than about 0.01 wt. % yttrium, equal to or less than about 0.01 wt. % boron and the balance nickel. The filler metal alloy is made by melting and casting techniques such as are melting the components of the filler metal alloy and cast in copper chill molds. 3 figs.

The Evaluation of the Corrosion Resistance of the Al-Si Alloys Antimony Alloyed

Directory of Open Access Journals (Sweden)

Svobodova J.

2014-06-01

Full Text Available This paper deals with the evaluation of the corrosion resistance of the Al-Si alloys alloyed with the different amount of antimony. Specifically it goes about the alloy AlSi7Mg0,3 which is antimony alloyed in the concentrations 0; 0,001; 0,005; 0,01 a 0,05 wt. % of antimony. The introduction of the paper is dedicated to the theory of the aluminium alloys corrosion resistance, testing and evaluation of the corrosion resistance. The influence of the antimony to the Al-Si alloys properties is described further in the introduction. The experimental part describes the experimental samples which were prepared for the experiment and further they were exposed to the loading in the atmospheric conditions for a period of the 3 months. The experimental samples were evaluated macroscopically and microscopically. The results of the experiment were documented and the conclusions in terms of the antimony impact to the corrosion resistance of the Al-Si alloy were concluded. There was compared the corrosion resistance of the Al-Si alloy antimony alloyed (with the different antimony content with the results of the Al-Si alloy without the alloying after the corrosion load in the atmospheric conditions in the experiment.

VANADIUM ALLOYS

Science.gov (United States)

Smith, K.F.; Van Thyne, R.J.

1959-05-12

This patent deals with vanadium based ternary alloys useful as fuel element jackets. According to the invention the ternary vanadium alloys, prepared in an arc furnace, contain from 2.5 to 15% by weight titanium and from 0.5 to 10% by weight niobium. Characteristics of these alloys are good thermal conductivity, low neutron capture cross section, good corrosion resistance, good welding and fabricating properties, low expansion coefficient, and high strength.

Crevice corrosion propagation on alloy 625 and alloy C276 in natural seawater

International Nuclear Information System (INIS)

McCafferty, E.; Bogar, F.D.; Thomas, E.D. II; Creegan, C.A.; Lucas, K.E.; Kaznoff, A.I.

1997-01-01

Chemical composition of the aqueous solution within crevices on two different Ni-Cr-Mo-Fe alloys immersed in natural seawater was determined using a semiquantitative thin-layer chromatographic method. Active crevices were found to contain concentrated amounts of dissolved Ni 2+ , Cr 3+ , Mo 3+ , and Fe 2+ ions. Propagation of crevice corrosion for the two alloys was determined from anodic polarization curves in model crevice solutions based upon stoichiometric dissolution or selective dissolution of alloy components. Both alloys 625 (UNS N06625) and C276 (UNS N10276) underwent crevice corrosion in the model crevice electrolytes. For the model crevice solution based upon selective dissolution of alloy constituents, the anodic dissolution rate for alloy 625 was higher than that for alloy C276. This trend was reversed for the model crevice solution based upon uniform dissolution of alloy constituents

Corrosion of aluminum alloys as a function of alloy composition

International Nuclear Information System (INIS)

Johnson, A.B. Jr.

1969-10-01

A study was initiated which included nineteen aluminum alloys. Tests were conducted in high purity water at 360 0 C and flow tests (approx. 20 ft/sec) in reactor process water at 130 0 C (TF-18 loop tests). High-silicon alloys and AlSi failed completely in the 360 0 C tests. However, coupling of AlSi to 8001 aluminum suppressed the failure. The alloy compositions containing iron and nickel survived tht 360 0 C autoclave exposures. Corrosion rates varied widely as a function of alloy composition, but in directions which were predictable from previous high-temperature autoclave experience. In the TF-18 loop flow tests, corrosion penetrations were similar on all of the alloys and on high-purity aluminum after 105 days. However, certain alloys established relatively low linear corrosion rates: Al-0.9 Ni-0.5 Fe-0.1 Zr, Al-1.0 Ni-0.15 Fe-11.5 Si-0.8 Mg, Al-1.2 Ni-1.8 Fe, and Al-7.0 Ni-4.8 Fe. Electrical polarity measurements between AlSi and 8001 alloys in reactor process water at temperatures up to 150 0 C indicated that AlSi was anodic to 8001 in the static autoclave system above approx. 50 0 C

Surface treatment of new type aluminum lithium alloy and fatigue crack behaviors of this alloy plate bonded with Ti–6Al–4V alloy strap

International Nuclear Information System (INIS)

Sun, Zhen-Qi; Huang, Ming-Hui; Hu, Guo-Huai

2012-01-01

Highlights: ► A new generation aluminum lithium alloy which special made for Chinese commercial plane was investigated. ► Pattern of aluminum lithium alloy and Ti alloy were shown after anodization. ► Crack propagation of samples bonded with different wide Ti straps were studied in this paper. -- Abstract: Samples consisting of new aluminum lithium alloy (Al–Li alloy) plate developed by the Aluminum Company of America and Ti–6Al–4V alloy (Ti alloy) plate were investigated. Plate of 400 mm × 140 mm × 2 mm with single edge notch was anodized in phosphoric solution and Ti alloy plate of 200 mm × 20 (40) mm × 2 mm was anodized in alkali solution. Patterns of two alloys were studied at original/anodized condition. And then, aluminum alloy and Ti alloy plates were assembled into a sample with FM 94 film adhesive. Fatigue crack behaviors of the sample were investigated under condition of nominal stress σ = 36 MPa and 54 MPa, stress ratio of 0.1. Testing results show that anodization treatment modifies alloys surface topography. Ti alloy bonding to Al–Li alloy plate effectively retards crack growth than that of Al–Li alloy plate. Fatigue life of sample bonded with Ti alloy strap improves about 62.5% than that of non-strap plate.

The Properties of 7xxx Series Alloys Formed by Alloying Additions

Directory of Open Access Journals (Sweden)

Kwak Z.

2015-06-01

Full Text Available Currently there is a constant development in the field of aluminium alloys engineering. This results from, i.a., better understanding of the mechanisms that direct strengthening of these alloys and the role of microalloying. Now it is microalloying in aluminum alloys that is receiving a lot of attention. It affects substantially the macro- and microstructure and kinetics of phase transformation influencing the properties during production and its exploitation. 7xxx series aluminum alloys, based on the Al-Zn-Mg-Cu system, are high-strength alloys, moreover, the presence of Zr and Sr further increases their strength and improves resistance to cracking.

Pb-Pb dating of individual chondrules from the CB_a chondrite Gujba

DEFF Research Database (Denmark)

Bollard, Jean Francois André; Connelly, James; Bizzarro, Martin

2015-01-01

-stage impact origin. Here, we report high-precision internal isochrons for four individual chondrules of the Gujba chondrite to probe the formation history of CB chondrites and evaluate the concordancy of relevant short-lived radionuclide chronometers. All four chondrules define a brief formation interval......-behaved Pb-Pb systematics of all four chondrules, a precise formation age and the concordancy of the Mn-Cr, Hf-W, and I-Xe short-lived radionuclide relative chronometers, we propose that Gujba may serve as a suitable time anchor for these systems....

Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles

Directory of Open Access Journals (Sweden)

Xiaolie He

2017-08-01

Full Text Available Background/Aims: This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Methods: Curcumin and dexanabinol-loaded solid lipid nanoparticles (Cur/SLNs-HU-211 were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Results: Treatment with Cur/SLNs-HU-211 induced greater dopamine (DA/5-hydroxytryptamine (5-HT release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo Cur/SLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA/5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK1/2 protein expression levels in the hippocampus and striatum. Cur/SLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNF/NeuN expression reduction. Conclusion: Our study implies that Cur/SLNs-HU-211 may be a useful approach for treatment of major depression.

Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity

DEFF Research Database (Denmark)

Autrup, Herman; Warwick, Gerald P.

1975-01-01

-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems. The properties listed above and dependency of enzyme activity on both NADH and NADPH indicate a similarity of CB-10...

Reducing thermal conductivity of binary alloys below the alloy limit via chemical ordering

International Nuclear Information System (INIS)

Duda, John C; English, Timothy S; Jordan, Donald A; Norris, Pamela M; Soffa, William A

2011-01-01

Substitutional solid solutions that exist in both ordered and disordered states will exhibit markedly different physical properties depending on their exact crystallographic configuration. Many random substitutional solid solutions (alloys) will display a tendency to order given the appropriate kinetic and thermodynamic conditions. Such order-disorder transitions will result in major crystallographic reconfigurations, where the atomic basis, symmetry, and periodicity of the alloy change dramatically. Consequently, the dominant scattering mechanism in ordered alloys will be different than that in disordered alloys. In this study, we present a hypothesis that ordered alloys can exhibit lower thermal conductivities than their disordered counterparts at elevated temperatures. To validate this hypothesis, we investigate the phononic transport properties of disordered and ordered AB Lennard-Jones alloys via non-equilibrium molecular dynamics and harmonic lattice dynamics calculations. It is shown that the thermal conductivity of an ordered alloy is the same as the thermal conductivity of the disordered alloy at ∼0.6T melt and lower than that of the disordered alloy above 0.8T melt .

Translating VDM to Alloy

DEFF Research Database (Denmark)

Lausdahl, Kenneth

2013-01-01

specifications. However, to take advantage of the automated analysis of Alloy, the model-oriented VDM specifications must be translated into a constraint-based Alloy specifications. We describe how a sub- set of VDM can be translated into Alloy and how assertions can be expressed in VDM and checked by the Alloy...

Electron beam and laser surface alloying of Al-Si base alloys

International Nuclear Information System (INIS)

Vanhille, P.; Tosto, S.; Pelletier, J.M.; Issa, A.; Vannes, A.B.; Criqui, B.

1992-01-01

Surface alloying on aluminium-base alloys is achieved either by using an electron beam or a laser beam, in order to improve the mechanical properties of the near-surface region. A predeposit of nickel is first realized by plasma spraying. Melting of both the coating and part of the substrate produces a surface alloy with a fine, dendritic microstructure with a high hardness. Enhancement of this property requires an increase in the nickel content. Various problems occur during the formation of nickel-rich surface layers: incomplete homogenization owing to a progressive increase of the liquidus temperature, cracks owing to the brittleness of this hard suface alloy, formation of a plasma when experiments are carried out in a gaseous environment (laser surface alloying). Nevertheless, various kinds of surface layers may be achieved; for example very hard surface alloys (HV 0.2 =900), with a thickness of about 500-600 μm, or very thick surface alloys (e>2 mm), with a fairly good hardness (greater than 350 HV 0.2 ). Thus, it is possible to obtain a large variety of new materials by using high energy beams on aluminium substrates. (orig.)

CB1 Receptor-Mediated Signaling Underlies the Hippocampal Synaptic, Learning and Memory Deficits Following Treatment with JWH-081, a New Component of Spice/K2 Preparations

OpenAIRE

Basavarajappa, Balapal S.; Subbanna, Shivakumar

2014-01-01

Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as “Spice” or “K2” to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of “Spice/K2”, including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of...

The recurrent PPP1CB mutation p.Pro49Arg in an additional Noonan-like syndrome individual: Broadening the clinical phenotype.

Science.gov (United States)

Bertola, Débora; Yamamoto, Guilherme; Buscarilli, Michelle; Jorge, Alexander; Passos-Bueno, Maria Rita; Kim, Chong

2017-03-01

We report on a 12-year-old Brazilian boy with the p.Pro49Arg mutation in PPP1CB, a novel gene associated with RASopathies. This is the fifth individual described, and the fourth presenting the same variant, suggesting a mutational hotspot. Phenotypically, he also showed the same hair pattern-sparse, thin, and with slow growing-, similar to the typical ectodermal finding observed in Noonan syndrome-like disorder with loose anagen hair. Additionally, he presented craniosynostosis, a rare clinical finding in RASopathies. This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Combinatorial thin film materials science: From alloy discovery and optimization to alloy design

Energy Technology Data Exchange (ETDEWEB)

Gebhardt, Thomas, E-mail: gebhardt@mch.rwth-aachen.de; Music, Denis; Takahashi, Tetsuya; Schneider, Jochen M.

2012-06-30

This paper provides an overview of modern alloy development, from discovery and optimization towards alloy design, based on combinatorial thin film materials science. The combinatorial approach, combining combinatorial materials synthesis of thin film composition-spreads with high-throughput property characterization has proven to be a powerful tool to delineate composition-structure-property relationships, and hence to efficiently identify composition windows with enhanced properties. Furthermore, and most importantly for alloy design, theoretical models and hypotheses can be critically appraised. Examples for alloy discovery, optimization, and alloy design of functional as well as structural materials are presented. Using Fe-Mn based alloys as an example, we show that the combination of modern electronic-structure calculations with the highly efficient combinatorial thin film composition-spread method constitutes an effective tool for knowledge-based alloy design.

Combinatorial thin film materials science: From alloy discovery and optimization to alloy design

International Nuclear Information System (INIS)

Gebhardt, Thomas; Music, Denis; Takahashi, Tetsuya; Schneider, Jochen M.

2012-01-01

This paper provides an overview of modern alloy development, from discovery and optimization towards alloy design, based on combinatorial thin film materials science. The combinatorial approach, combining combinatorial materials synthesis of thin film composition-spreads with high-throughput property characterization has proven to be a powerful tool to delineate composition–structure–property relationships, and hence to efficiently identify composition windows with enhanced properties. Furthermore, and most importantly for alloy design, theoretical models and hypotheses can be critically appraised. Examples for alloy discovery, optimization, and alloy design of functional as well as structural materials are presented. Using Fe-Mn based alloys as an example, we show that the combination of modern electronic-structure calculations with the highly efficient combinatorial thin film composition-spread method constitutes an effective tool for knowledge-based alloy design.

Shape memory alloys

International Nuclear Information System (INIS)

Kaszuwara, W.

2004-01-01

Shape memory alloys (SMA), when deformed, have the ability of returning, in certain circumstances, to their initial shape. Deformations related to this phenomenon are for polycrystals 1-8% and up to 15% for monocrystals. The deformation energy is in the range of 10 6 - 10 7 J/m 3 . The deformation is caused by martensitic transformation in the material. Shape memory alloys exhibit one directional or two directional shape memory effect as well as pseudoelastic effect. Shape change is activated by temperature change, which limits working frequency of SMA to 10 2 Hz. Other group of alloys exhibit magnetic shape memory effect. In these alloys martensitic transformation is triggered by magnetic field, thus their working frequency can be higher. Composites containing shape memory alloys can also be used as shape memory materials (applied in vibration damping devices). Another group of composite materials is called heterostructures, in which SMA alloys are incorporated in a form of thin layers The heterostructures can be used as microactuators in microelectromechanical systems (MEMS). Basic SMA comprise: Ni-Ti, Cu (Cu-Zn,Cu-Al, Cu-Sn) and Fe (Fe-Mn, Fe-Cr-Ni) alloys. Shape memory alloys find applications in such areas: automatics, safety and medical devices and many domestic appliances. Currently the most important appears to be research on magnetic shape memory materials and high temperature SMA. Vital from application point of view are composite materials especially those containing several intelligent materials. (author)

The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis

Directory of Open Access Journals (Sweden)

RICARDO N FELMER

2004-01-01

Full Text Available The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1 transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss

Spinning of refractory metals

International Nuclear Information System (INIS)

Chang Wenkua; Zheng Han

1989-01-01

The effects of spinning process parameters including max. pass percentage reduction, spinning temperature, feed rate, lubricant and annealing technology on the quality of shaped components are summarized and discussed in the present paper. The above mentioned parameters are adopted in the process of spinning of barrel-shaped and specially shaped components of refractory metals and their alloys W, Mo, Nb, Zr, TZM molybdenum alloy, C-103, C-752 niobium alloy etc. The cause of leading to usual defects of spun products of refractory metals such as lamellar as 'scaling', crack, swelling, wrinkle, etc. have been analysed and the ways to eliminate the defects have been put forward. 8 figs., 5 tabs. (Author)

Grindability of dental magnetic alloys.

Science.gov (United States)

Hayashi, Eisei; Kikuchi, Masafumi; Okuno, Osamu; Kimura, Kohei

2005-06-01

In this study, the grindability of cast magnetic alloys (Fe-Pt-Nb magnetic alloy and magnetic stainless steel) was evaluated and compared with that of conventional dental casting alloys (Ag-Pd-Au alloy, Type 4 gold alloy, and cobalt-chromium alloy). Grindability was evaluated in terms of grinding rate (i.e., volume of metal removed per minute) and grinding ratio (i.e., volume ratio of metal removed compared to wheel material lost). Solution treated Fe-Pt-Nb magnetic alloy had a significantly higher grinding rate than the aged one at a grinding speed of 750-1500 m x min(-1). At 500 m x min(-1), there were no significant differences in grinding rate between solution treated and aged Fe-Pt-Nb magnetic alloys. At a lower speed of 500 m x min(-1) or 750 m x min(-1), it was found that the grinding rates of aged Fe-Pt-Nb magnetic alloy and stainless steel were higher than those of conventional casting alloys.

Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling.

Science.gov (United States)

Rivas, Priscila M S; Vechiato, Fernanda M V; Borges, Beatriz C; Rorato, Rodrigo; Antunes-Rodrigues, Jose; Elias, Lucila L K

2017-07-01

Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. Copyright © 2017 Elsevier Inc. All rights reserved.

Mice Expressing a "Hyper-Sensitive" Form of the Cannabinoid Receptor 1 (CB1 Are Neither Obese Nor Diabetic.

Directory of Open Access Journals (Sweden)

David J Marcus

Full Text Available Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor. These mice display exaggerated and prolonged responses to acute administration of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. As a consequence these mice represent a novel model for determining the effect of enhanced endocannabinoid signaling on metabolic disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45% and low fat (10% chow control diet compared to wild-type littermate controls. S426A/S430A mutants and wild-type mice fed either high or low fat control diet displayed similar fasting blood glucose levels and normal glucose clearance following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild-type mice consumed similar amounts of chow following an overnight fast. While both THC and JZL195 significantly increased food intake two hours after injection, this increase was similar between the S426A/S430A mutant and wildtype control mice Our results indicate that S426A/S430A mutant mice expressing the desensitization-resistant form of CB1 do not exhibit differences in body weight, food intake, glucose homeostasis, or re-feeding following a fast.

Alloying Solid Solution Strengthening of Fe-Ga Alloys: A First-Principle Study

National Research Council Canada - National Science Library

Chen, Kuiying; Cheng, Leon M

2006-01-01

... and Co in cubic solid solution of Fe-Ga alloys. Mayer bond order "BO" values were used to evaluate the atomic bond strengths in the alloys, and were then used to assess the alloying strengthening characteristics...

Studies on neutron irradiation effects of iron alloys and nickel-base heat resistant alloys

International Nuclear Information System (INIS)

Watanabe, Katsutoshi

1987-09-01

The present paper describes the results of neutron irradiation effects on iron alloys and nickel-base heat resistant alloys. As for the iron alloys, irradiation hardening and embrittlement were investigated using internal friction measurement, electron microscopy and tensile testings. The role of alloying elements was also investigated to understand the irradiation behavior of iron alloys. The essential factors affecting irradiation hardening and embrittlement were thus clarified. On the other hand, postirradiation tensile and creep properties were measured of Hastelloy X alloy. Irradiation behavior at elevated temperatures is discussed. (author)

Positron emission tomography based analysis of long-circulating cross-linked triblock polymeric micelles in a U87MG mouse xenograft model and comparison of DOTA and CB-TE2A as chelators of copper-64.

Science.gov (United States)

Jensen, Andreas I; Binderup, Tina; Kumar EK, Pramod; Kjær, Andreas; Rasmussen, Palle H; Andresen, Thomas L

2014-05-12

Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of (64)Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm(2) for 30 min. The cross-linked micelles were labeled with (64)Cu at room temperature for 2 h (DOTA) or 80 °C for 3 h (CB-TE2A), giving labeling efficiencies of 60-76% (DOTA) and 40-47% (CB-TE2A). (64)Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T1/2: 20-26 h) and tumor uptake that was comparable with other nanoparticle systems. The DOTA micelles showed a biodistribution similar to the CB-TE2A micelles and the tumor uptake was comparable for both micelle types at 1 h (1.9% ID/g) and 22 h (3.9% ID/g) but diverged at 46 h with 3.6% ID/g (DOTA) and 4.9% ID/g (CB-TE2A). On the basis of our data, we conclude that cross-linked PEG-PHEMA-PCMA micelles have long circulating properties resulting in tumor accumulation and that DOTA and CB-TE2A (64)Cu-chelates show similar in vivo stability for the studied micelle system.

Neutron-absorbing alloys

International Nuclear Information System (INIS)

Portnoi, K.I.; Arabei, L.B.; Gryaznov, G.M.; Levi, L.I.; Lunin, G.L.; Kozhukhov, V.M.; Markov, J.M.; Fedotov, M.E.

1975-01-01

A process is described for the production of an alloy consiting of 1 to 20% In, 0.5 to 15% Sm, and from 3 to 18% Hf, the balance being Ni. Such alloys show a good absorption capacity for thermal and intermediate neutrons, good neutron capture efficiency, and good corrosion resistance, and find application in nuclear reactor automatic control and safety systems. The Hf provides for the maintenance of a reasonably high order of neutron capture efficiency throughout the lifetime of a reactor. The alloys are formed in a vacuum furnace operating with an inert gas atmosphere at 280 to 300 mm.Hg. They have a corrosion resistance from 3 to 3.5 times that of the Ag-based alloys commonly employed, and a neutron capture efficiency about twice that of the Ag alloys. Castability and structural strength are good. (U.K.)

Effect of mechanical alloying on FeCrC reinforced Ni alloys

Energy Technology Data Exchange (ETDEWEB)

Yilmaz, S. Osman [Univ. of Namik Kemal, Tekirdag (Turkey); Teker, Tanju [Adiyaman Univ. (Turkey). Dept. of Metallurgical and Materials Engineering; Demir, Fatih [Batman Univ. (Turkey)

2016-05-01

Mechanical alloying (MA) is a powder metallurgy processing technique involving cold welding, fracturing and rewelding of powder particles in a high-energy ball mill. In the present study, the intermetallic matrix composites (IMCs) of Ni-Al reinforced by M{sub 7}C{sub 3} were produced by powder metallurgical routes via solid state reaction of Ni, Al and M{sub 7}C{sub 3} particulates by mechanical alloying processes. Ni, Al and M{sub 7}C{sub 3} powders having 100 μm were mixed, mechanical alloyed and the compacts were combusted in a furnace. The mechanically alloyed (MAed) powders were investigated by X-ray diffraction (XRD), microhardness measurement, optic microscopy (OM), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The presence of the carbides depressed the formation of unwanted NiAl intermetallic phases. The mechanical alloyed M{sub 7}C{sub 3} particles were unstable and decomposed partially within the matrix during alloying and sintering, and the morphology of the composites changed with the dissolution ratio of M{sub 7}C{sub 3} and sintering temperature.

Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-Tetrahydrocannabinol on Spatial Memory

OpenAIRE

Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

2010-01-01

Abstract The cannabinoid CB1 receptor-mediated modulation of ?-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A1 receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A1 receptors localized in GABAergic cells do not directly influence GABA release. CB1 and A1 receptors are the main targets for the effects of two of the most heavily consumed ps...

Advances in titanium alloys

International Nuclear Information System (INIS)

Seagle, S.R.; Wood, J.R.

1993-01-01

As described above, new developments in the aerospace market are focusing on higher temperature alloys for jet engine components and higher strength/toughness alloys for airframe applications. Conventional alloys for engines have reached their maximum useful temperature of about 1000 F (540 C) because of oxidation resistance requirements. IMI 834 and Ti-1100 advanced alloys show some improvement, however, the major improvement appears to be in gamma titanium aluminides which could extend the maximum usage temperature to about 1500 F (815 C). This puts titanium alloys in a competitive position to replace nickel-base superalloys. Advanced airframe alloys such as Ti-6-22-22S, Beta C TM , Ti-15-333 and Ti-10-2-3 with higher strength than conventional Ti-6-4 are being utilized in significantly greater quantities, both in military and commercial applications. These alloys offer improved strength with little or no sacrifice in toughness and improved formability, in some cases. Advanced industrial alloys are being developed for improved corrosion resistance in more reducing and higher temperature environments such as those encountered in sour gas wells. Efforts are focused on small precious metal additions to optimize corrosion performance for specific applications at a modest increase in cost. As these applications develop, the usage of titanium alloys for industrial markets should steadily increase to approach that for aerospace applications. (orig.)

Progressive degradation of alloy 690 and the development of a significant improvement in alloy 800CR

International Nuclear Information System (INIS)

Staehle, Roger W.; Arioka, Koji; Tapping, Robert

2015-01-01

The present most widely used alloys for tubing in steam generators and structural materials in water cooled reactors are Alloy 690 and Alloy 800. However, both alloys, while improved over Alloy 600 may not meet the needs of longer range applications in the range of 80-100 years. Alloy 690 sustains damage resulting from the formation of cavities at grain boundaries which eventually cover about 50% of the area of the grain boundaries with the remainder covering being covered with carbides. The cavities seem to nucleate on the carbides leaving the grain boundaries a structure of cavities and carbides. Such a structure will lead the Alloy 690 to fail completely. Normal Alloy 800 does not produce such cavities and probably retains a large amount of its corrosion resistance but does sustain progressive SCC at low rate. A new alloy, 800CR, has been developed in a collaboration among Arioka, Tapping, and Staehle. This alloy is based on a Cr composition of 23.5-27% with the remainder retaining the previous Alloy 800 composition. 800CR sustains a crack velocity about 100 times less than Alloy 690 and a negligible rate of initiation. The 800CR, alloy is now seeking a patent. (authors)

Nonswelling alloy

Science.gov (United States)

Harkness, S.D.

1975-12-23

An aluminum alloy containing one weight percent copper has been found to be resistant to void formation and thus is useful in all nuclear applications which currently use aluminum or other aluminum alloys in reactor positions which are subjected to high neutron doses.

Nonswelling alloy

International Nuclear Information System (INIS)

Harkness, S.D.

1975-01-01

An aluminum alloy containing one weight percent copper has been found to be resistant to void formation and thus is useful in all nuclear applications which currently use aluminum or other aluminum alloys in reactor positions which are subjected to high neutron doses

PLUTONIUM-ZIRCONIUM ALLOYS

Science.gov (United States)

Schonfeld, F.W.; Waber, J.T.

1960-08-30

A series of nuclear reactor fuel alloys consisting of from about 5 to about 50 at.% zirconium (or higher zirconium alloys such as Zircaloy), balance plutonium, and having the structural composition of a plutonium are described. Zirconium is a satisfactory diluent because it alloys readily with plutonium and has desirable nuclear properties. Additional advantages are corrosion resistance, excellent fabrication propenties, an isotropie structure, and initial softness.

Ultrahigh temperature intermetallic alloys

Energy Technology Data Exchange (ETDEWEB)

Brady, M.P.; Zhu, J.H.; Liu, C.T.; Tortorelli, P.F.; Wright, J.L.; Carmichael, C.A.; Walker, L.R. [Oak Ridge National Lab., TN (United States). Metals and Ceramics Div.

1997-12-01

A new family of Cr-Cr{sub 2}X based alloys with fabricability, mechanical properties, and oxidation resistance superior to previously developed Cr-Cr{sub 2}Nb and Cr-Cr{sub 2}Zr based alloys has been identified. The new alloys can be arc-melted/cast without cracking, and exhibit excellent room temperature and high-temperature tensile strengths. Preliminary evaluation of oxidation behavior at 1100 C in air indicates that the new Cr-Cr{sub 2}X based alloys form an adherent chromia-based scale. Under similar conditions, Cr-Cr{sub 2}Nb and Cr-Cr{sub 2}Zr based alloys suffer from extensive scale spallation.

Electronic structure of alloys

International Nuclear Information System (INIS)

Ehrenreich, H.; Schwartz, L.M.

1976-01-01

The description of electronic properties of binary substitutional alloys within the single particle approximation is reviewed. Emphasis is placed on a didactic exposition of the equilibrium properties of the transport and magnetic properties of such alloys. Topics covered include: multiple scattering theory; the single band alloy; formal extensions of the theory; the alloy potential; realistic model state densities; the s-d model; and the muffin tin model. 43 figures, 3 tables, 151 references

Monitoring alloy formation during mechanical alloying process by x-ray diffraction techniques

International Nuclear Information System (INIS)

Abdul Kadir Masrom; Noraizam Md Diah; Mazli Mustapha

2002-01-01

Monitoring alloying (MA) is a novel processing technique that use high energy impact ball mill to produce alloys with enhanced properties and microscopically homogeneous materials starting from various powder mixtures. Mechanical alloying process was originally developed to produce oxide dispersion strengthened nickel superalloys. In principal, in high-energy ball milling process, alloy is formed by the result of repeated welding, fracturing and rewelding of powder particles in a high energy ball mill. In this process a powder mixture in a ball mill is subjected to high-energy collisions among balls. MA has been shown to be capable of synthesizing a variety of materials. It is known to be capable to prepare equilibrium and non-equilibrium phases starting from blended elemental or prealloyed powders. The process ability to produce highly metastable materials such as amorphous alloys and nanostructured materials has made this process attractive and it has been considered as a promising material processing technique that could be used to produce many advanced materials at low cost. The present study explores the conditions under which aluminum alloys formation occurs by ball milling of blended aluminum and its alloying elements powders. In this work, attempt was made in producing aluminum 2024 alloys by milling of blended elemental aluminum powder of 2024 composition in a stainless steel container under argon atmosphere for up to 210 minutes. X-ray diffraction together with thermal analysis techniques has been used to monitor phase changes in the milled powder. Results indicate that, using our predetermined milling parameters, alloys were formed after 120 minutes milling. The thermal analysis data was also presented in this report. (Author)

Effect of ternary alloying elements on the shape memory behavior of Ti-Ta alloys

International Nuclear Information System (INIS)

Buenconsejo, Pio John S.; Kim, Hee Young; Miyazaki, Shuichi

2009-01-01

The effect of ternary alloying elements (X = V, Cr, Fe, Zr, Hf, Mo, Sn, Al) on the shape memory behavior of Ti-30Ta-X alloys was investigated. All the alloying elements decreased the martensitic transformation temperatures. The decrease in the martensitic transformation start (M s ) temperature due to alloying was affected by the atomic size and number of valence electrons of the alloying element. A larger number of valence electrons and a smaller atomic radius of an alloying element decreased the M s more strongly. The effect of the alloying elements on suppressing the aging effect on the shape memory behavior was also investigated. It was found that the additions of Sn and Al to Ti-Ta were effective in suppressing the effect of aging on the shape memory behavior, since they strongly suppress the formation of ω phase during aging treatment. For this reason the Ti-30Ta-1Al and Ti-30Ta-1Sn alloys exhibited a stable high-temperature shape memory effect during thermal cycling.

The CNO Bi-cycle in the Open Cluster NGC 752

Science.gov (United States)

Hawkins, Keith; Schuler, S.; King, J.; The, L.

2011-01-01

The CNO bi-cycle is the primary energy source for main sequence stars more massive than the sun. To test our understanding of stellar evolution models using the CNO bi-cycle, we have undertaken light-element (CNO) abundance analysis of three main sequence dwarf stars and three red giant stars in the open cluster NGC 752 utilizing high resolution (R 50,000) spectroscopy from the Keck Observatory. Preliminary results indicate, as expected, there is a depletion of carbon in the giants relative to the dwarfs. Additional analysis is needed to determine if the amount of depletion is in line with model predictions, as seen in the Hyades open cluster. Oxygen abundances are derived from the high-excitation O I triplet, and there is a 0.19 dex offset in the [O/H] abundances between the giants and dwarfs which may be explained by non-local thermodynamic equilibrium (NLTE), although further analysis is needed to verify this. The standard procedure for spectroscopically determining stellar parameters used here allows for a measurement of the cluster metallicity, [Fe/H] = 0.04 ± 0.02. In addition to the Fe abundances we have determined Na, Mg, and Al abundances to determine the status of other nucleosynthesis processes. The Na, Mg and Al abundances of the giants are enhanced relative to the dwarfs, which is consistent with similar findings in giants of other open clusters. Support for K. Hawkins was provided by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program and the Department of Defense ASSURE program through Scientific Program Order No. 13 (AST-0754223) of the Cooperative Agreement No. AST-0132798 between the Association of Universities for Research in Astronomy (AURA) and the NSF.

Effect of medium components and culture conditions in Bacillus subtilis EA-CB0575 spore production.

Science.gov (United States)

Posada-Uribe, Luisa F; Romero-Tabarez, Magally; Villegas-Escobar, Valeska

2015-10-01

Bacillus subtilis spores have important biotechnological applications; however, achieving both, high spore cell densities and sporulation efficiencies in fermentation, is poorly reported. In this study, medium components and culture conditions were optimized with different statistical methods to increase spore production of the plant growth promoting rhizobacteria B. subtilis EA-CB0575. Key medium components were determined with Plackett-Burman (PB) design, and the optimum concentration levels of two components (glucose, MgSO4·7H2O) were optimized with a full factorial and central composite design, achieving 1.37 × 10(9) CFU/mL of spore cell density and 93.5 % of sporulation efficiency in shake flask. The optimized medium was used to determine the effect of culture conditions on spore production at bioreactor level, finding that maintaining pH control did not affect significantly spore production, while the interaction of agitation and aeration rates had a significant effect on spore cell density. The overall optimization generated a 17.2-fold increase in spore cell density (8.78 × 10(9) CFU/mL) and 1.9-fold increase in sporulation efficiency (94.2 %) compared to that of PB design. These results indicate the potential of B. subtilis EA-CB0575 to produce both, high spore cell densities and sporulation efficiencies, with very low nutrient requirements and short incubation period which can represent savings of process production.

Anodic behavior of alloy 22 in bicarbonate containing media: Effect of alloying

International Nuclear Information System (INIS)

Zadorozne, N S; Giordano, C M; Rebak, R B; Ares, A E; Carranza, R M

2012-01-01

Alloy 22 is one of the candidates for the manufacture of high level nuclear waste containers. These containers provide services in natural environments characterized by multi-ionic solutions.It is estimated they could suffer three types of deterioration: general corrosion, localized corrosion (specifically crevice corrosion) and stress corrosion cracking (SCC). It has been confirmed that the presence of bicarbonate and chloride ions is necessary to produce cracking, . It has also been determined that the susceptibility to SCC could be related to the occurrence of an anodic peak in the polarization curves in these media at potentials below transpassivity. The aim of this work is to study the effect of alloying elements on the anodic behavior of Alloy 22 in media containing bicarbonate and chloride ions at different concentrations and temperatures. Polarization curves were made on alloy 22 (Ni-22% Cr-13% Mo), Ni-Mo (Ni-28, 5% Mo) and Ni-Cr (Ni-20% Cr) in the following solutions: 1 mol/L NaCl at 90 o C, and 1.148 mol/L NaHCO 3 ; 1.148 mol/L NaHCO 3 + 1 mol/L NaCl; 1.148 mol/L NaHCO 3 + 0.1 mol/L NaCl, at 90 o C, 75 o C, 60 o C and 25 o C. It was found that alloy 22 has a anodic current density peak at potentials below transpassivity, only in the presence of bicarbonate ions. Curves performed in 1 mol/L NaCl did not show any anodic peak, in any of the tested alloys. The curves made on alloys Ni-Mo and Ni-Cr in the presence of bicarbonate ions, allowed to determine that Cr, is responsible for the appearance of the anodic peak in alloy 22. The curves of alloy Ni-Mo showed no anodic peak in the studied conditions. The potential at which the anodic peak appears in alloy 22 and Ni-Cr alloy, increases with decreasing temperature. The anodic peak was also affected by solution composition. When chloride ion is added to bicarbonate solutions, the anodic peak is shifted to higher potential and current densities, depending on the concentration of added chloride ions (author)

Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression*

Science.gov (United States)

Coke, Christopher J.; Scarlett, Kisha A.; Chetram, Mahandranauth A.; Jones, Kia J.; Sandifer, Brittney J.; Davis, Ahriea S.; Marcus, Adam I.

2016-01-01

The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. PMID:26841863

INVESTIGATION OF MAGNESIUM ALLOYS MACHINABILITY

Directory of Open Access Journals (Sweden)

Berat Barıs BULDUM

2013-01-01

Full Text Available Magnesium is the lightest structural metal. Magnesium alloys have a hexagonal lattice structure, which affects the fundamental properties of these alloys. Plastic deformation of the hexagonal lattice is more complicated than in cubic latticed metals like aluminum, copper and steel. Magnesium alloy developments have traditionally been driven by industry requirements for lightweight materials to operate under increasingly demanding conditions. Magnesium alloys have always been attractive to designers due to their low density, only two thirds that of aluminium and its alloys [1]. The element and its alloys take a big part of modern industry needs. Especially nowadays magnesium alloys are used in automotive and mechanical (trains and wagons manufacture, because of its lightness and other features. Magnesium and magnesium alloys are the easiest of all metals to machine, allowing machining operations at extremely high speed. All standard machining operations such as turning, drilling, milling, are commonly performed on magnesium parts.

Characteristics of Film Formed on Alloy 600 and Alloy 690 in Water Containing lead

International Nuclear Information System (INIS)

Hwang Seong Sik; Lee, Deok Hyun; Kim, Hong Pyo; Kim, Joung Soo; Kim, Ju Yup

1999-01-01

Anodic polarization behaviors of Alloy 600 and Alloy 690 have been studied as a function of lead content in the solution of pH 4 and 10 at 90 .deg. C. As the amount of lead in the solution increased, critical current densities and passive current densities of Alloy 600 and Alloy 690 increased, while the breakdown potential of the alloys decreased. The high critical current density in the high lead solution was thought to come from the combination of an enhanced dissolution of constituents on the surface of the alloys by the lead and an anodic dissolution of metallic lead deposited on the surface of the specimens. The morphology of lead precipitated on the specimen after the anodic scan changed with the pH of solution: small irregular particles were precipitated on the surface of the specimen in the solution of pH 4, while the high density of regular sized particles was formed on it in the solution of pH 10.Pb was observed to enhance Cr depletion from the outer surface of Alloy 600 and Alloy 690 and also to increase the ratio of O 2- /OH - in the surface film formed in the high lead solution. The SCC resistance of Alloy 600 and Alloy 690 may have decreased due to the poor quality of the passive film formed and the enhanced oxygen evolution in the solution containing lead

Grain refining mechanism of Al-containing Mg alloys with the addition of Mn-Al alloys

International Nuclear Information System (INIS)

Qin, Gaowu W.; Ren Yuping; Huang Wei; Li Song; Pei Wenli

2010-01-01

Graphical abstract: Display Omitted Research highlights: The ε-AlMn phase acts as the heterogeneous nucleus of α-Mg phase during the solidification of the AZ31 Mg alloy, not the γ-Al 8 Mn 5 phase. The grain refinement effect is very clear with the addition of only 0.5 wt% Mn-28Al alloy (pure ε-AlMn). The grain refinement does not deteriorate up to the holding time of 60 min at 740 o C. - Abstract: The effect of manganese on grain refinement of Al-containing AZ31 Mg alloy has been investigated by designing a series of Mn-Al alloys composed of either pure ε-AlMn, γ 2 -Al 8 Mn 5 or both of them using optical microscopy and X-ray diffraction. It is experimentally clarified that the grain refinement of the AZ31 Mg alloy is due to the existence of the ε-AlMn phase in the Mn-Al alloys, not the γ 2 -Al 8 Mn 5 phase. The grain size of AZ31 Mg alloy is about 91 μm without any addition of Mn-Al alloys, but remarkably decreases to ∼55 μm with the addition of either Mn-34 wt% Al or Mn-28 wt% Al. With a minor addition of 0.5 wt% Mn-28Al alloy, the grain size of AZ31 alloy decreases to ∼53 μm, and the Mn-28Al alloy can be active as grain refiner for holding time up to 60 min for the melt AZ31 alloy at 750 o C.

Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

Science.gov (United States)

Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

2012-11-01

The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

Synthesis of Amorphous Powders of Ni-Si and Co-Si Alloys by Mechanical Alloying

Science.gov (United States)

Omuro, Keisuke; Miura, Harumatsu

1991-05-01

Amorphous powders of the Ni-Si and Co-Si alloys are synthesized by mechanical alloying (MA) from crystalline elemental powders using a high energy ball mill. The alloying and amorphization process is examined by X-ray diffraction, differential scanning calorimetry (DSC), and scanning electron microscopy. For the Ni-Si alloy, it is confirmed that the crystallization temperature of the MA powder, measured by DSC, is in good agreement with that of the powder sample prepared by mechanical grinding from the cast alloy ingot products of the same composition.

Cannabinoid Receptor 2 (CB2 Plays a Role in the Generation of Germinal Center and Memory B Cells, but Not in the Production of Antigen-Specific IgG and IgM, in Response to T-dependent Antigens.

Directory of Open Access Journals (Sweden)

Sreemanti Basu

Full Text Available The cannabinoid receptor 2 (CB2 has been reported to modulate B cell functions including migration, proliferation and isotype class switching. Since these processes are required for the generation of the germinal center (GC and antigen-specific plasma and memory cells following immunization with a T-dependent antigen, CB2 has the capacity to alter the quality and magnitude of T-dependent immune responses. To address this question, we immunized WT and CB2(-/- mice with the T-dependent antigen 4-hydroxy-3-nitrophenylacetyl (NP-chicken-gamma-globulin (CGG and measured GC B cell formation and the generation of antigen-specific B cells and serum immunoglobulin (Ig. While there was a significant reduction in the number of splenic GC B cells in CB2(-/- mice early in the response there was no detectable difference in the number of NP-specific IgM and IgG1 plasma cells. There was also no difference in NP-specific IgM and class switched IgG1 in the serum. In addition, we found no defect in the homing of plasma cells to the bone marrow (BM and affinity maturation, although memory B cell cells in the spleen were reduced in CB2(-/- mice. CB2-deficient mice also generated similar levels of antigen-specific IgM and IgG in the serum as WT following immunization with sheep red blood cells (sRBC. This study demonstrates that although CB2 plays a role in promoting GC and memory B cell formation/maintenance in the spleen, it is dispensable on all immune cell types required for the generation of antigen-specific IgM and IgG in T-dependent immune responses.

Formation and characterization of Al–Ti–Nb alloys by electron-beam surface alloying

Energy Technology Data Exchange (ETDEWEB)

Valkov, S., E-mail: stsvalkov@gmail.com [Institute of Electronics, Bulgarian Academy of Science, 72 Tzarigradsko Chaussee blvd., 1784 Sofia (Bulgaria); Petrov, P. [Institute of Electronics, Bulgarian Academy of Science, 72 Tzarigradsko Chaussee blvd., 1784 Sofia (Bulgaria); Lazarova, R. [Institute of Metal Science, Equipment and Technologies with Hydro and Aerodynamics Center, Bulgarian Academy of Science, 67 Shipchenski Prohod blvd., 1574 Sofia (Bulgaria); Bezdushnyi, R. [Department of Solid State Physics and Microelectronics, Faculty of Physics, Sofia University “St. Kliment Ohridsky”, 1164 Sofia (Bulgaria); Dechev, D. [Institute of Electronics, Bulgarian Academy of Science, 72 Tzarigradsko Chaussee blvd., 1784 Sofia (Bulgaria)

2016-12-15

Highlights: • Al–Ti–Nb surface alloys have been successfully obtained by electron-beam surface alloying technology. • The alloys consist of (Ti,Nb)Al{sub 3} fractions, distributed in the biphasic structure of (Ti,Nb)Al{sub 3} particles dispersed in α-Al. • The alloying speed does not affect the lattice parameters of (Ti,Nb)Al{sub 3} and, does not form additional stresses, strains etc. • It was found that lower velocity of the specimen motion during the alloying process develops more homogeneous structures. • The measured hardness of (Ti,Nb)Al{sub 3} compound reaches 775 HV[kg/cm{sup 2}] which is much greater than the values of NbAl{sub 3}. - Abstract: The combination of attractive mechanical properties, light weight and resistance to corrosion makes Ti-Al based alloys applicable in many industrial branches, like aircraft and automotive industries etc. It is known that the incorporation of Nb improves the high temperature performance and mechanical properties. In the present study on Al substrate Ti and Nb layers were deposited by DC (Direct Current) magnetron sputtering, followed by electron-beam alloying with scanning electron beam. It was chosen two speeds of the specimen motion during the alloying process: V{sub 1} = 0.5 cm/s and V{sub 2} = 1 cm/s. The alloying process was realized in circular sweep mode in order to maintain the melt pool further. The obtained results demonstrate a formation of (Ti,Nb)Al{sub 3} fractions randomly distributed in biphasic structure of intermetallic (Ti,Nb)Al{sub 3} particles, dispersed in α-Al solid solution. The evaluated (Ti,Nb)Al{sub 3} lattice parameters are independent of the speed of the specimen motion and therefore the alloying speed does not affect the lattice parameters and thus, does not form additional residual stresses, strains etc. It was found that lower velocity of the specimen motion during the alloying process develops more homogeneous structures. The metallographic analyses demonstrate a

Microbial Culturomics Application for Global Health: Noncontiguous Finished Genome Sequence and Description of Pseudomonas massiliensis Strain CB-1T sp. nov. in Brazil.

Science.gov (United States)

Bardet, Lucie; Cimmino, Teresa; Buffet, Clémence; Michelle, Caroline; Rathored, Jaishriram; Tandina, Fatalmoudou; Lagier, Jean-Christophe; Khelaifia, Saber; Abrahão, Jônatas; Raoult, Didier; Rolain, Jean-Marc

2018-02-01

Culturomics is a new postgenomics field that explores the microbial diversity of the human gut coupled with taxono-genomic strategy. Culturomics, and the microbiome science more generally, are anticipated to transform global health diagnostics and inform the ways in which gut microbial diversity contributes to human health and disease, and by extension, to personalized medicine. Using culturomics, we report in this study the description of strain CB1 T ( = CSUR P1334 = DSM 29075), a new species isolated from a stool specimen from a 37-year-old Brazilian woman. This description includes phenotypic characteristics and complete genome sequence and annotation. Strain CB1 T is a gram-negative aerobic and motile bacillus, exhibits neither catalase nor oxidase activities, and presents a 98.3% 16S rRNA sequence similarity with Pseudomonas putida. The 4,723,534 bp long genome contains 4239 protein-coding genes and 74 RNA genes, including 15 rRNA genes (5 16S rRNA, 4 23S rRNA, and 6 5S rRNA) and 59 tRNA genes. Strain CB1 T was named Pseudomonas massiliensis sp. nov. and classified into the family Pseudomonadaceae. This study demonstrates the usefulness of microbial culturomics in exploration of human microbiota in diverse geographies and offers new promise for incorporating new omics technologies for innovation in diagnostic medicine and global health.

Effects of alloying elements on thermal desorption of helium in Ni alloys

International Nuclear Information System (INIS)

Xu, Q.; Cao, X.Z.; Sato, K.; Yoshiie, T.

2012-01-01

It is well known that the minor elements Si and Sn can suppress the formation of voids in Ni alloys. In the present study, to investigate the effects of Si and Sn on the retention of helium in Ni alloys, Ni, Ni–Si, and Ni–Sn alloys were irradiated by 5 keV He ions at 723 K. Thermal desorption spectroscopy (TDS) was performed at up to 1520 K, and microstructural observations were carried out to identify the helium trapping sites during the TDS analysis. Two peaks, at 1350 and 1457 K, appeared in the TDS spectrum of Ni. On the basis of the microstructural observations, the former peak was attributed to the release of trapped helium from small cavities and the latter to its release from large cavities. Small-cavity helium trapping sites were also found in the Ni–Si and Ni–Sn alloys, but no large cavities were observed in these alloys. In addition, it was found that the oversized element Sn could trap He atoms in the Ni–Sn alloy.

Effects of alloying elements on thermal desorption of helium in Ni alloys

Energy Technology Data Exchange (ETDEWEB)

Xu, Q., E-mail: xu@rri.kyoto-u.ac.jp [Research Reactor Institute, Kyoto University, Osaka 590-0494 (Japan); Cao, X.Z.; Sato, K.; Yoshiie, T. [Research Reactor Institute, Kyoto University, Osaka 590-0494 (Japan)

2012-12-15

It is well known that the minor elements Si and Sn can suppress the formation of voids in Ni alloys. In the present study, to investigate the effects of Si and Sn on the retention of helium in Ni alloys, Ni, Ni-Si, and Ni-Sn alloys were irradiated by 5 keV He ions at 723 K. Thermal desorption spectroscopy (TDS) was performed at up to 1520 K, and microstructural observations were carried out to identify the helium trapping sites during the TDS analysis. Two peaks, at 1350 and 1457 K, appeared in the TDS spectrum of Ni. On the basis of the microstructural observations, the former peak was attributed to the release of trapped helium from small cavities and the latter to its release from large cavities. Small-cavity helium trapping sites were also found in the Ni-Si and Ni-Sn alloys, but no large cavities were observed in these alloys. In addition, it was found that the oversized element Sn could trap He atoms in the Ni-Sn alloy.

Effects of alloying elements on thermal desorption of helium in Ni alloys

Science.gov (United States)

Xu, Q.; Cao, X. Z.; Sato, K.; Yoshiie, T.

2012-12-01

It is well known that the minor elements Si and Sn can suppress the formation of voids in Ni alloys. In the present study, to investigate the effects of Si and Sn on the retention of helium in Ni alloys, Ni, Ni-Si, and Ni-Sn alloys were irradiated by 5 keV He ions at 723 K. Thermal desorption spectroscopy (TDS) was performed at up to 1520 K, and microstructural observations were carried out to identify the helium trapping sites during the TDS analysis. Two peaks, at 1350 and 1457 K, appeared in the TDS spectrum of Ni. On the basis of the microstructural observations, the former peak was attributed to the release of trapped helium from small cavities and the latter to its release from large cavities. Small-cavity helium trapping sites were also found in the Ni-Si and Ni-Sn alloys, but no large cavities were observed in these alloys. In addition, it was found that the oversized element Sn could trap He atoms in the Ni-Sn alloy.

High-Strength Low-Alloy (HSLA) Mg-Zn-Ca Alloys with Excellent Biodegradation Performance

Science.gov (United States)

Hofstetter, J.; Becker, M.; Martinelli, E.; Weinberg, A. M.; Mingler, B.; Kilian, H.; Pogatscher, S.; Uggowitzer, P. J.; Löffler, J. F.

2014-04-01

This article deals with the development of fine-grained high-strength low-alloy (HSLA) magnesium alloys intended for use as biodegradable implant material. The alloys contain solely low amounts of Zn and Ca as alloying elements. We illustrate the development path starting from the high-Zn-containing ZX50 (MgZn5Ca0.25) alloy with conventional purity, to an ultrahigh-purity ZX50 modification, and further to the ultrahigh-purity Zn-lean alloy ZX10 (MgZn1Ca0.3). It is shown that alloys with high Zn-content are prone to biocorrosion in various environments, most probably because of the presence of the intermetallic phase Mg6Zn3Ca2. A reduction of the Zn content results in (Mg,Zn)2Ca phase formation. This phase is less noble than the Mg-matrix and therefore, in contrast to Mg6Zn3Ca2, does not act as cathodic site. A fine-grained microstructure is achieved by the controlled formation of fine and homogeneously distributed (Mg,Zn)2Ca precipitates, which influence dynamic recrystallization and grain growth during hot forming. Such design scheme is comparable to that of HSLA steels, where low amounts of alloying elements are intended to produce a very fine dispersion of particles to increase the material's strength by refining the grain size. Consequently our new, ultrapure ZX10 alloy exhibits high strength (yield strength R p = 240 MPa, ultimate tensile strength R m = 255 MPa) and simultaneously high ductility (elongation to fracture A = 27%), as well as low mechanical anisotropy. Because of the anodic nature of the (Mg,Zn)2Ca particles used in the HSLA concept, the in vivo degradation in a rat femur implantation study is very slow and homogeneous without clinically observable hydrogen evolution, making the ZX10 alloy a promising material for biodegradable implants.

The influence of alloy composition on residual stresses in heat treated aluminium alloys

Energy Technology Data Exchange (ETDEWEB)

Robinson, J.S., E-mail: jeremy.robinson@ul.ie [Department of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); Redington, W. [Materials and Surface Science Institute, University of Limerick (Ireland)

2015-07-15

The as quenched properties of eight different heat treatable aluminium alloys are related to residual stress magnitudes with the objective being to establish if there is a relationship between the residual stress and the as quenched alloy hardness and strength. Near surface residual stresses were assessed with X-ray diffraction using both the established sin{sup 2}ψ method and the more recent cos α technique. Through thickness residual stresses were also characterised using neutron diffraction. The alloys were chosen to encompass a wide range of strengths. The low to medium strength alloys were 6060 and 6082, medium to high strength 2618A, 2014A, 7075, 7010 and two variants of 7449, while the very high strength alloy was the powder metallurgy alloy N707. To assess the as quenched strength, dynamic hardness and tensile properties were determined from samples tested immediately after quenching to minimise the influence of precipitation hardening by natural aging. In addition, hot hardness measurements were made in situ on samples cooled to simulate quench paths. Within the experimental constraints of the investigation, the distribution of residual stress through the thickness was found to follow the same pattern for all the alloys investigated, varying from tensile in the interior to surface compression. The influence of alloy strength was manifested as a change in the observed residual stress magnitudes, and surface residual stresses were found to vary linearly with as quenched hardness and strength. - Highlights: • As quenched aluminium alloys contain high magnitude residual stresses. • Surface is compressive balance by a tensile core. • As quenched surface residual stress is linear function of alloy strength. • In situ hot hardness demonstrates rapid change in intrinsic hardness during rapid cooling.

WC-3015 alloy (high-temperature alloy)

International Nuclear Information System (INIS)

Anon.

1974-01-01

WC-3015 Nb alloy containing 28 to 30 Hf, 1 to 2 Zr, 13 to 16 W, 0 to 4 Ta, 0 to 5 Ti, 0.07 to 0.33 C, less than or equal to 0.02 N, less than or equal to 0.03 O, less than or equal to 0.001 H was developed for use at high temperature in oxidizing environments. Its composition can be tailored to meet specific requirements. When WC-3015 is exposed to O at elevated temperature, Hf and Nb oxidized preferentially and HfO 2 dissolves in Nb 2 O 5 to form 6HfO-Nb 2 O 5 . This complex oxide has a tight cubic lattice which resists the diffusion of O into the substrate. During 24-h exposure to air at 2400 0 F, the alloy oxidizes to a depth of approximately 0.035 in. with a surface recession of 0 to 0.004 in. Oxidation resistance of WC-3015 welds and base material can be further enhanced greatly by applying silicide coatings. WC-3015 alloy can be machined by conventional and electrical-discharge methods. It can be hot worked readily by extrusion, forging or rolling. Cold working can be used at room or elevated temperature. It can be welded by the electron-beam or Tig processes. Physical constants, typical mechanical properties at 75 to 2400 0 F, and effects of composition and heat treatment on tensile and stress-rupture properties of the alloy are tabulated

Advanced ordered intermetallic alloy deployment

Energy Technology Data Exchange (ETDEWEB)

Liu, C.T.; Maziasz, P.J.; Easton, D.S. [Oak Ridge National Lab., TN (United States)

1997-04-01

The need for high-strength, high-temperature, and light-weight materials for structural applications has generated a great deal of interest in ordered intermetallic alloys, particularly in {gamma}-based titanium aluminides {gamma}-based TiAl alloys offer an attractive mix of low density ({approximately}4g/cm{sup 3}), good creep resistance, and high-temperature strength and oxidation resistance. For rotating or high-speed components. TiAl also has a high damping coefficient which minimizes vibrations and noise. These alloys generally contain two phases. {alpha}{sub 2} (DO{sub 19} structure) and {gamma} (L 1{sub 0}), at temperatures below 1120{degrees}C, the euticoid temperature. The mechanical properties of TiAl-based alloys are sensitive to both alloy compositions and microstructure. Depending on heat-treatment and thermomechanical processing, microstructures with near equiaxed {gamma}, a duplex structure (a mix of the {gamma} and {alpha}{sub 2} phases) can be developed in TiAl alloys containing 45 to 50 at. % Al. The major concern for structural use of TiAl alloys is their low ductility and poor fracture resistance at ambient temperatures. The purpose of this project is to improve the fracture toughness of TiAl-based alloys by controlling alloy composition, microstructure and thermomechanical treatment. This work is expected to lead to the development of TiAl alloys with significantly improved fracture toughness and tensile ductility for structural use.

Impact toughness of laser alloyed aluminium AA1200 alloys

CSIR Research Space (South Africa)

Mabhali, Luyolo AB

2013-08-01

Full Text Available ),. 559-563. [2] T. Tomida, K. Nakata, S. Saji, T. Kubo, T, Formation of metal matrix composite layer on aluminium alloy with TiC-Cu powder by laser surface alloying process; Surface and Coatings Technology; vol. 142-144, 2001, 585-589. [3] L. A. B...

A sulfidation-resistant nickel-base alloy

International Nuclear Information System (INIS)

Lai, G.Y.

1989-01-01

For applications in mildly to moderately sulfidizing environments, stainless steels, Fe-Ni-Cr alloys (e.g., alloys 800 and 330), and more recently Fe-Ni-Cr-Co alloys (e.g., alloy 556) are frequently used for construction of process equipment. However, for many highly sulfidizing environments, few existing commercial alloys have adequate performance. Thus, a new nickel-based alloy containing 27 wt.% Co, 28 wt.% Cr, 4 wt.% Fe, 2.75 wt.% Si, 0.5 wt.% Mn and 0.05 wt.% C (Haynes alloy HR-160) was developed

Irradiation assisted stress corrosion cracking of HTH Alloy X-750 and Alloy 625

International Nuclear Information System (INIS)

Mills, W.J.; Lebo, M.R.; Bajaj, R.; Kearns, J.J.; Hoffman, R.C.; Korinko, J.J.

1994-01-01

In-reactor testing of bolt-loaded precracked compact tension specimens was performed in 360 degree C water to determine effect of irradiation on the SCC behavior of HTH Alloy X-750 and direct aged Alloy 625. Out-of-flux and autoclave control specimens provided baseline data. Primary test variables were stress intensity factor, fluence, chemistry, processing history, prestrain. Results for the first series of experiments were presented at a previous conference. Data from two more recent experiments are compared with previous results; they confirm that high irradiation levels significantly reduce SCC resistance in HTH Alloy X-750. Heat-to-heat differences in IASCC were related to differences in boron content, with low boron heats showing improved SCC resistance. The in-reactor SCC performance of Alloy 625 was superior to that for Alloy X-750, as no cracking was observed in any Alloy 625 specimens even though they were tested at very high K 1 and fluence levels. A preliminary SCC usage model developed for Alloy X-750 indicates that in-reactor creep processes, which relax stresses but also increase crack tip strain rates, and radiolysis effects accelerate SCC. Hence, in-reactor SCC damage under high flux conditions may be more severe than that associated with postirradiation tests. In addition, preliminary mechanism studies were performed to determine the cause of IASCC In Alloy X-750

Improvement of magnetocaloric properties of Gd-Ge-Si alloys by alloying with iron

Directory of Open Access Journals (Sweden)

Erenc-Sędziak T.

2013-01-01

Full Text Available The influence of annealing of Gd5Ge2Si2Fex alloys at 1200°C and of alloying with various amount of iron on structure as well as thermal and magnetocaloric properties is investigated. It was found that annealing for 1 to 10 hours improves the entropy change, but reduces the temperature of maximum magnetocaloric effect by up to 50 K. Prolonged annealing of the Gd5Ge2Si2 alloy results in the decrease of entropy change due to the reduction of Gd5Ge2Si2 phase content. Addition of iron to the ternary alloy enhances the magnetocaloric effect, if x = 0.4 – 0.6, especially if alloying is combined with annealing at 1200°C: the peak value of the isothermal entropy change from 0 to 2 T increases from 3.5 to 11 J/kgK. Simultaneously, the temperature of maximum magnetocaloric effect drops to 250 K. The changes in magnetocaloric properties are related to the change in phase transformation from the second order for arc molten ternary alloy to first order in the case of annealed and/or alloyed with iron. The results of this study indicate that the minor addition of iron and heat treatment to Gd-Ge-Si alloys may be useful in improving the materials’ magnetocaloric properties..

Validation of models using Chernobyl fallout data from the Central Bohemia region of the Czech Republic. Scenario CB. First report of the VAMP Multiple Pathways Assessment Working Group. Part of the IAEA/CEC Co-ordinated Research Programme on the Validation of Environmental Model Predictions (VAMP)

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-04-01

The VAMP Multiple Pathways Assessment Working Group is an international forum for the testing and comparison of model predictions. The emphasis is on evaluating transfer from the environment to human via all pathways which are relevant in the environment being considered. This document is the first report of the Group and contains the results of the first test exercise on the validation of multiple pathways assessment models using Chernobyl fallout data obtained from the Central Bohemia (CB) region of the Czech Republic (Scenario CB). The report includes the following three appendixes: Documentation and evaluation of model validation data used in scenario CB (3 papers), Description of models used in scenario CB (1 paper), Individual evaluations of model predictions for scenario CB (13 papers). A separate abstract was prepared for each paper. Refs, figs and tabs.

Validation of models using Chernobyl fallout data from the Central Bohemia region of the Czech Republic. Scenario CB. First report of the VAMP Multiple Pathways Assessment Working Group. Part of the IAEA/CEC Co-ordinated Research Programme on the Validation of Environmental Model Predictions (VAMP)

International Nuclear Information System (INIS)

1995-04-01

The VAMP Multiple Pathways Assessment Working Group is an international forum for the testing and comparison of model predictions. The emphasis is on evaluating transfer from the environment to human via all pathways which are relevant in the environment being considered. This document is the first report of the Group and contains the results of the first test exercise on the validation of multiple pathways assessment models using Chernobyl fallout data obtained from the Central Bohemia (CB) region of the Czech Republic (Scenario CB). The report includes the following three appendixes: Documentation and evaluation of model validation data used in scenario CB (3 papers), Description of models used in scenario CB (1 paper), Individual evaluations of model predictions for scenario CB (13 papers). A separate abstract was prepared for each paper. Refs, figs and tabs

Non-equiatomic high entropy alloys: Approach towards rapid alloy screening and property-oriented design

Energy Technology Data Exchange (ETDEWEB)

Pradeep, K.G. [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany); Materials Chemistry, RWTH Aachen University, Kopernikusstr.10, 52074 Aachen (Germany); Tasan, C.C., E-mail: c.tasan@mpie.de [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany); Yao, M.J. [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany); Deng, Y. [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany); Department of Engineering Design and Materials, Norwegian University of Science and Technology, No-7491 Trondheim (Norway); Springer, H. [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany); Raabe, D., E-mail: d.raabe@mpie.de [Max-Planck-Institut für Eisenforschung GmbH, Max-Planck-str.1, 40237 Düsseldorf (Germany)

2015-11-11

The high entropy alloy (HEA) concept has triggered a renewed interest in alloy design, even though some aspects of the underlying thermodynamic concepts are still under debate. This study addresses the short-comings of this alloy design strategy with the aim to open up new directions of HEA research targeting specifically non-equiatomic yet massively alloyed compositions. We propose that a wide range of massive single phase solid solutions could be designed by including non-equiatomic variants. It is demonstrated by introducing a set of novel non-equiatomic multi-component CoCrFeMnNi alloys produced by metallurgical rapid alloy prototyping. Despite the reduced configurational entropy, detailed characterization of these materials reveals a strong resemblance to the well-studied equiatomic single phase HEA: The microstructure of these novel alloys exhibits a random distribution of alloying elements (confirmed by Energy-Dispersive Spectroscopy and Atom Probe Tomography) in a single face-centered-cubic phase (confirmed by X-ray Diffraction and Electron Backscatter Diffraction), which deforms through planar slip (confirmed by Electron-Channeling Contrast Imaging) and leads to excellent ductility (confirmed by uniaxial tensile tests). This approach widens the field of HEAs to non-equiatomic multi-component alloys since the concept enables to tailor the stacking fault energy and associated transformation phenomena which act as main mechanisms to design useful strain hardening behavior.

Non-equiatomic high entropy alloys: Approach towards rapid alloy screening and property-oriented design

International Nuclear Information System (INIS)

Pradeep, K.G.; Tasan, C.C.; Yao, M.J.; Deng, Y.; Springer, H.; Raabe, D.

2015-01-01

The high entropy alloy (HEA) concept has triggered a renewed interest in alloy design, even though some aspects of the underlying thermodynamic concepts are still under debate. This study addresses the short-comings of this alloy design strategy with the aim to open up new directions of HEA research targeting specifically non-equiatomic yet massively alloyed compositions. We propose that a wide range of massive single phase solid solutions could be designed by including non-equiatomic variants. It is demonstrated by introducing a set of novel non-equiatomic multi-component CoCrFeMnNi alloys produced by metallurgical rapid alloy prototyping. Despite the reduced configurational entropy, detailed characterization of these materials reveals a strong resemblance to the well-studied equiatomic single phase HEA: The microstructure of these novel alloys exhibits a random distribution of alloying elements (confirmed by Energy-Dispersive Spectroscopy and Atom Probe Tomography) in a single face-centered-cubic phase (confirmed by X-ray Diffraction and Electron Backscatter Diffraction), which deforms through planar slip (confirmed by Electron-Channeling Contrast Imaging) and leads to excellent ductility (confirmed by uniaxial tensile tests). This approach widens the field of HEAs to non-equiatomic multi-component alloys since the concept enables to tailor the stacking fault energy and associated transformation phenomena which act as main mechanisms to design useful strain hardening behavior.

Alloy Fabrication Laboratory

Data.gov (United States)

Federal Laboratory Consortium — At NETL’s Alloy Fabrication Facility in Albany, OR, researchers conduct DOE research projects to produce new alloys suited to a variety of applications, from gas...

Grain refining mechanism of Al-containing Mg alloys with the addition of Mn-Al alloys

Energy Technology Data Exchange (ETDEWEB)

Qin, Gaowu W., E-mail: qingw@smm.neu.edu.c [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Wenhu Road 3-11, Heping District, Shenyang 110004, Liaoning Province (China); Ren Yuping; Huang Wei; Li Song; Pei Wenli [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Wenhu Road 3-11, Heping District, Shenyang 110004, Liaoning Province (China)

2010-10-08

Graphical abstract: Display Omitted Research highlights: The {epsilon}-AlMn phase acts as the heterogeneous nucleus of {alpha}-Mg phase during the solidification of the AZ31 Mg alloy, not the {gamma}-Al{sub 8}Mn{sub 5} phase. The grain refinement effect is very clear with the addition of only 0.5 wt% Mn-28Al alloy (pure {epsilon}-AlMn). The grain refinement does not deteriorate up to the holding time of 60 min at 740 {sup o}C. - Abstract: The effect of manganese on grain refinement of Al-containing AZ31 Mg alloy has been investigated by designing a series of Mn-Al alloys composed of either pure {epsilon}-AlMn, {gamma}{sub 2}-Al{sub 8}Mn{sub 5} or both of them using optical microscopy and X-ray diffraction. It is experimentally clarified that the grain refinement of the AZ31 Mg alloy is due to the existence of the {epsilon}-AlMn phase in the Mn-Al alloys, not the {gamma}{sub 2}-Al{sub 8}Mn{sub 5} phase. The grain size of AZ31 Mg alloy is about 91 {mu}m without any addition of Mn-Al alloys, but remarkably decreases to {approx}55 {mu}m with the addition of either Mn-34 wt% Al or Mn-28 wt% Al. With a minor addition of 0.5 wt% Mn-28Al alloy, the grain size of AZ31 alloy decreases to {approx}53 {mu}m, and the Mn-28Al alloy can be active as grain refiner for holding time up to 60 min for the melt AZ31 alloy at 750 {sup o}C.

Kinetics and thermodynamics of hydrogen absorption and release in {beta}-titanium alloys; Kinetik und Thermodynamik der Wasserstoffaufnahme und -abgabe von {beta}-Titanlegierungen

Energy Technology Data Exchange (ETDEWEB)

Decker, M.; Christ, H.J. [Siegen Univ. (Gesamthochschule) (Germany). Inst. fuer Werkstofftechnik

1998-12-31

The work reported was intended to yield results allowing to describe as completely as possible the processes of interaction of {beta}-titanium and hydrogen. Three alloys have been selected for the experiments which suitably differ in stability of the {beta} phase. The characterisation of the hydrogen/metal interactions is primarily based on gravimetric measurements. A method was found to determine the diffusion coefficient of hydrogen, which is a significant variable for quantitative characterisation of the hydrogen absorption rate. (orig./CB) [Deutsch] In der Arbeit wird eine moeglichst vollstaendige Beschreibung der Wechselwirkung von {beta}-Titanlegierungen mit Wasserstoff angestrebt. Hierfuer wird mit drei Legierungen gearbeitet, die sich hinsichtlich der Stabilitaet der {beta}-Phase in sinnvoll abgestufter Weise unterscheiden. Fuer die Charakterisierung der Wasserstoff/Metall-Wechselwirkung wurden insbesondere gravimetrische Messungen eingesetzt. Weiterhin wurde die fuer eine quantitative Beschreibung der Wasserstoffaufnahmegeschwindigkeit wichtige Groesse des Diffusionskoeffizienten von Wasserstoff mit einem Verfahren bestimmt. (orig./MM)

Corrosion-electrochemical and mechanical properties of aluminium-berylium alloys alloyed by rare-earth metals

International Nuclear Information System (INIS)

Safarov, A.M.; Odinaev, Kh.E.; Shukroev, M.Sh.; Saidov, R.Kh.

1997-01-01

In order to study influence of rare earth metals on corrosion-electrochemical and mechanical properties of aluminium-berylium alloys the alloys contain 1 mass % beryllium and different amount of rare earth metals were obtained.-electrochemical and mechanical properties of aluminium-berylium alloys. The electrochemical characteristics of obtained alloys, including stationary potential, potentials of passivation beginning and full passivation, potentials of pitting formation and re passivation were defined.

Role of alloying additions on the properties of Cu–Al–Mn shape memory alloys

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Rupa, E-mail: rupadasgupta@ampri.res.in; Jain, Ashish Kumar; Kumar, Pravir; Hussain, Shahadat; Pandey, Abhishek

2015-01-25

Highlights: • Cu based SMAs with high transition temperature could be made using LM route. • The properties depend on alloying composition. • Property characterisation establishes feasibility of making SMAs. - Abstract: The effect of alloying seven different elements [Zn, Si, Fe, Ni, Mg, Cr and Ti] on the microstructure, hardness, phase precipitation and transformation temperature in a Cu–12.5Al–5Mn alloy with a view to possible improvements as a result of these additions is the focus of the reported study. The base alloy has been chosen keeping in mind its ability to exhibit shape memory properties and improved ductility over other Cu-based SMAs. The objective was to ascertain changes or improvements attained due to the individual tertiary additions. The samples were prepared through liquid metallurgy route using pure copper, aluminum, manganese and the respective quaternary alloying elements in right quantities to weigh 1000 g of the alloy in total and were melted together. Samples from the cast alloys were subject to homogenisation treatment at 200 °C for 2 h in a muffle furnace and furnace cooled. Samples from the homogenised alloys were heated and held for 2 h at 920 °C followed by ice quenching to obtain the desired martensitic structure for shape memory behaviour. The alloys in the cast, homogenised and quenched conditions were metallographically polished to observe the martensitic phase formation mainly in quenched samples which is a pre requisite for exhibiting shape memory properties in these alloys. X-ray Diffraction studies were carried out on the cast and quenched samples using Cu Kα target; and the phases identified indicate martensitic phase precipitation; however in some cases the precipitation is incomplete. Differential Scanning Calorimetric [DSC] studies were carried out on quenched samples from room temperature to 600 °C maintaining a constant rate of 10 °C/min. Results indicate clear transformation peaks in all the samples which

Role of alloying additions on the properties of Cu–Al–Mn shape memory alloys

International Nuclear Information System (INIS)

Dasgupta, Rupa; Jain, Ashish Kumar; Kumar, Pravir; Hussain, Shahadat; Pandey, Abhishek

2015-01-01

Highlights: • Cu based SMAs with high transition temperature could be made using LM route. • The properties depend on alloying composition. • Property characterisation establishes feasibility of making SMAs. - Abstract: The effect of alloying seven different elements [Zn, Si, Fe, Ni, Mg, Cr and Ti] on the microstructure, hardness, phase precipitation and transformation temperature in a Cu–12.5Al–5Mn alloy with a view to possible improvements as a result of these additions is the focus of the reported study. The base alloy has been chosen keeping in mind its ability to exhibit shape memory properties and improved ductility over other Cu-based SMAs. The objective was to ascertain changes or improvements attained due to the individual tertiary additions. The samples were prepared through liquid metallurgy route using pure copper, aluminum, manganese and the respective quaternary alloying elements in right quantities to weigh 1000 g of the alloy in total and were melted together. Samples from the cast alloys were subject to homogenisation treatment at 200 °C for 2 h in a muffle furnace and furnace cooled. Samples from the homogenised alloys were heated and held for 2 h at 920 °C followed by ice quenching to obtain the desired martensitic structure for shape memory behaviour. The alloys in the cast, homogenised and quenched conditions were metallographically polished to observe the martensitic phase formation mainly in quenched samples which is a pre requisite for exhibiting shape memory properties in these alloys. X-ray Diffraction studies were carried out on the cast and quenched samples using Cu Kα target; and the phases identified indicate martensitic phase precipitation; however in some cases the precipitation is incomplete. Differential Scanning Calorimetric [DSC] studies were carried out on quenched samples from room temperature to 600 °C maintaining a constant rate of 10 °C/min. Results indicate clear transformation peaks in all the samples which

Fracture of Shape Memory Alloys

OpenAIRE

Miyazaki, Shuichi; Otsuka, Kazuhiro

1981-01-01

The initiation and the propagation of cracks during both quenching and deformation in polycrystalline Cu-Al-Ni alloys have been investigated under various conditions. The fracture surfaces of Ti-Ni and Cu-Al-Ni alloys were also observed by a scanning electron microscope. From these results, it was concluded that the brittleness of Cu-Al-Ni alloy and other β phase alloys are due to large elastic anisotropy and large grain sizes, while that the large ductility in Ti-Ni alloy being due to the sm...

Alloy development for cladding and duct applications

International Nuclear Information System (INIS)

Straalsund, J.L.; Johnson, G.D.

1981-01-01

Three general classes of materials under development for cladding and ducts are listed. Solid solution strengthened, or austenitic, alloys are Type 316 stainless steel and D9. Precipitation hardened (also austenitic) alloys consist of D21, D66 and D68. These alloys are similar to such commercial alloys as M-813, Inconel 706, Inconel 718 and Nimonic PE-16. The third general class of alloys is composed of ferritic alloys, with current emphasis being placed on HT-9, a tempered martensitic alloy, and D67, a delta-ferritic steel. The program is comprised of three parallel paths. The current reference, or first generation alloy, is 20% cold worked Type 316 stainless steel. Second generation alloys for near-term applications include D9 and HT-9. Third generation materials consist of the precipitation strengthened steels and ferritic alloys, and are being considered for implementation at a later time than the first and second generation alloys. The development of second and third generation materials was initiated in 1974 with the selection of 35 alloys. This program has proceeded to today where there are six advanced alloys being evaluated. These alloys are the developmental alloys D9, D21, D57, D66 and D68, together with the commerical alloy, HT-9. The status of development of these alloys is summarized

:Examination of Sulfate production by CB05TU, RACM2 & RACM2 with SCI initiated SO2,oxidation in the Northern Hemisphere"

Science.gov (United States)

We employ the Community Multiscale Air Quality model to examine tropospheric sulfateproduction in the northern hemisphere using the Carbon Bond 2005 chemical mechanism withupdated toluene chemistry (CB05TU) and the Regional Atmospheric Chemistry Mechanism(RACM2) without and with ...

ZIRCONIUM-TITANIUM-BERYLLIUM BRAZING ALLOY

Science.gov (United States)

Gilliland, R.G.; Patriarca, P.; Slaughter, G.M.; Williams, L.C.

1962-06-12

A new and improved ternary alloy is described which is of particular utility in braze-bonding parts made of a refractory metal selected from Group IV, V, and VI of the periodic table and alloys containing said metal as a predominating alloying ingredient. The brazing alloy contains, by weight, 40 to 50 per cent zirconium, 40 to 50 per cent titanium, and the balance beryllium in amounts ranging from 1 to 20 per cent, said alloy having a melting point in the range 950 to 1400 deg C. (AEC)

Borated aluminum alloy manufacturing technology

International Nuclear Information System (INIS)

Shimojo, Jun; Taniuchi, Hiroaki; Kajihara, Katsura; Aruga, Yasuhiro

2003-01-01

Borated aluminum alloy is used as the basket material of cask because of its light weight, thermal conductivity and superior neutron absorbing abilities. Kobe Steel has developed a unique manufacturing process for borated aluminum alloy using a vacuum induction melting method. In this process, aluminum alloy is melted and agitated at higher temperatures than common aluminum alloy fabrication methods. It is then cast into a mold in a vacuum atmosphere. The result is a high quality aluminum alloy which has a uniform boron distribution and no impurities. (author)

Grain refinement of an AZ63B magnesium alloy by an Al-1C master alloy

Energy Technology Data Exchange (ETDEWEB)

Yichuan Pan; Xiangfa Liu; Hua Yang [The Key Lab. of Liquid Structure and Heredity of Materials, Shandong Univ., Jinan (China)

2005-12-01

In order to develop a refiner of Mg-Al alloys, an Al-1C (in wt.%) master alloy was synthesized using a casting method. The microstructure and grain-refining performance of the Al-1C master alloy were investigated using X-ray diffraction (XRD), electron probe microanalysis (EPMA) and a grain-refining test. The microstructure of the Al-1C master alloy is composed of {alpha}-Al solid solution, Al{sub 4}C{sub 3} particles, and graphite phases. After grain refinement of AZ63B alloy by the Al-1C master alloy, the mean grain size reached a limit when 2 wt.% Al-C master alloy was added at 800 C and held for 20 min in the melt before casting. The minimum mean grain size is approximately 48 {mu}m at the one-half radius of the ingot and is about 17% of that of the unrefined alloy. The Al-1C master alloy results in better grain refinement than C{sub 2}Cl{sub 6} and MgCO{sub 3} carbon-containing refiners. (orig.)

The physical metallurgy of mechanically-alloyed, dispersion-strengthened Al-Li-Mg and Al-Li-Cu alloys

Science.gov (United States)

Gilman, P. S.

1984-01-01

Powder processing of Al-Li-Mg and Al-Li-Cu alloys by mechanical alloying (MA) is described, with a discussion of physical and mechanical properties of early experimental alloys of these compositions. The experimental samples were mechanically alloyed in a Szegvari attritor, extruded at 343 and 427 C, and some were solution-treated at 520 and 566 C and naturally, as well as artificially, aged at 170, 190, and 210 C for times of up to 1000 hours. All alloys exhibited maximum hardness after being aged at 170 C; lower hardness corresponds to the solution treatment at 566 C than to that at 520 C. A comparison with ingot metallurgy alloys of the same composition shows the MA material to be stronger and more ductile. It is also noted that properly aged MA alloys can develop a better combination of yield strength and notched toughness at lower alloying levels.

De-alloyed platinum nanoparticles

Science.gov (United States)

Strasser, Peter [Houston, TX; Koh, Shirlaine [Houston, TX; Mani, Prasanna [Houston, TX; Ratndeep, Srivastava [Houston, TX

2011-08-09

A method of producing de-alloyed nanoparticles. In an embodiment, the method comprises admixing metal precursors, freeze-drying, annealing, and de-alloying the nanoparticles in situ. Further, in an embodiment de-alloyed nanoparticle formed by the method, wherein the nanoparticle further comprises a core-shell arrangement. The nanoparticle is suitable for electrocatalytic processes and devices.

Variations of color with alloying elements in Pd-free Au-Pt-based high noble dental alloys

International Nuclear Information System (INIS)

Shiraishi, Takanobu; Takuma, Yasuko; Miura, Eri; Fujita, Takeshi; Hisatsune, Kunihiro

2007-01-01

The effects of alloying addition of a small amount of base metals (In, Sn, Fe, Zn) on color variations in Pd-free Au-Pt-based high noble dental alloys were investigated in terms of rectilinear and polar color coordinates. The ternary Au-Pt-X (X = In, Sn, Fe, Zn) and quaternary Au-Pt-In-Y (Y = Sn, Fe, Zn) alloys were prepared from high purity component metals. The amount of alloying base metals, X and Y, were restricted up to 2 at.%. The alloying addition of a small amount of Fe, In, Sn, to a binary Au-10 at.% Pt alloy (referred to as AP10) effectively increased chroma, C *. On the other hand, the addition of Zn to the parent alloy AP10 did not change color coordinates greatly. The increase in chroma in the present Au-Pt-based high noble alloys was attributed to the increase in the slope of spectral reflectance curve at its absorption edge near 515 nm. It was found that the addition of a small amount of Fe to the parent alloy AP10 markedly increased lightness, L *, and the addition of Sn gave a very light tint of red to the parent alloy. Although red-green chromaticity index a * contributed to chroma to some extent, contribution of yellow-blue chromaticity index b * was much greater in determining chroma in this Pd-free Au-Pt-based multi-component alloys. The present results are expected to be valuable in case color is to be taken into account in designing Pd-free Au-Pt-based high noble dental alloys

Variations of color with alloying elements in Pd-free Au-Pt-based high noble dental alloys

Energy Technology Data Exchange (ETDEWEB)

Shiraishi, Takanobu [Department of Dental and Biomedical Materials Science, Unit of Basic Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588 (Japan)]. E-mail: siraisi@nagasaki-u.ac.jp; Takuma, Yasuko [Department of Dental and Biomedical Materials Science, Unit of Basic Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588 (Japan); Miura, Eri [Department of Dental and Biomedical Materials Science, Unit of Basic Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588 (Japan); Fujita, Takeshi [Department of Dental and Biomedical Materials Science, Unit of Basic Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588 (Japan); Hisatsune, Kunihiro [Department of Dental and Biomedical Materials Science, Unit of Basic Medical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588 (Japan)

2007-06-15

The effects of alloying addition of a small amount of base metals (In, Sn, Fe, Zn) on color variations in Pd-free Au-Pt-based high noble dental alloys were investigated in terms of rectilinear and polar color coordinates. The ternary Au-Pt-X (X = In, Sn, Fe, Zn) and quaternary Au-Pt-In-Y (Y = Sn, Fe, Zn) alloys were prepared from high purity component metals. The amount of alloying base metals, X and Y, were restricted up to 2 at.%. The alloying addition of a small amount of Fe, In, Sn, to a binary Au-10 at.% Pt alloy (referred to as AP10) effectively increased chroma, C *. On the other hand, the addition of Zn to the parent alloy AP10 did not change color coordinates greatly. The increase in chroma in the present Au-Pt-based high noble alloys was attributed to the increase in the slope of spectral reflectance curve at its absorption edge near 515 nm. It was found that the addition of a small amount of Fe to the parent alloy AP10 markedly increased lightness, L *, and the addition of Sn gave a very light tint of red to the parent alloy. Although red-green chromaticity index a * contributed to chroma to some extent, contribution of yellow-blue chromaticity index b * was much greater in determining chroma in this Pd-free Au-Pt-based multi-component alloys. The present results are expected to be valuable in case color is to be taken into account in designing Pd-free Au-Pt-based high noble dental alloys.

Effects of segregation of primary alloying elements on the creep response in magnesium alloys

DEFF Research Database (Denmark)

Huang, Y.D.; Dieringa, H.; Hort, N.

2008-01-01

The segregation of primary alloying elements deteriorates the high temperature creep resistance of magnesium alloys. Annealing at high temperatures alleviating their segregations can improve the creep resistance. Present investigation on the effect of segregation of primary alloying elements...... on the creep response may provide some useful information about how to improve the creep resistance of magnesium alloys in the future. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved....

Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

Science.gov (United States)

Darmani, N A

2001-01-01

We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

Effectiveness of Ti-micro alloying in relation to cooling rate on corrosion of AZ91 Mg alloy

International Nuclear Information System (INIS)

Candan, S.; Celik, M.; Candan, E.

2016-01-01

In this study, micro Ti-alloyed AZ91 Mg alloys (AZ91 + 0.5wt.%Ti) have been investigated in order to clarify effectiveness of micro alloying and/or cooling rate on their corrosion properties. Molten alloys were solidified under various cooling rates by using four stage step mold. The microstructural investigations were carried out by using scanning electron microscopy (SEM). Corrosion behaviors of the alloys were evaluated by means of immersion and electrochemical polarization tests in 3.5% NaCl solution. Results showed that the Mg 17 Al 12 (β) intermetallic phase in the microstructure of AZ91 Mg alloy formed as a net-like structure. The Ti addition has reduced the distribution and continuity of β intermetallic phase and its morphology has emerged as fully divorced eutectic. Compared to AZ91 alloy, the effect of the cooling rate in Ti-added alloy on the grain size was less pronounced. When AZ91 and its Ti-added alloys were compared under the same cooling conditions, the Ti addition showed notably high corrosion resistance. Electrochemical test results showed that while I corr values of AZ91 decrease with the increase in the cooling rate, the effect of the cooling rate on I corr values was much lower in the Ti-added alloy. The corrosion resistance of AZ91 Mg alloy was sensitive towards the cooling rates while Ti-added alloy was not affected much from the cooling conditions. - Highlights: • Effect the cooling rate on grain size was less pronounced in the Ti-added alloy. • The morphology of the β phase transformed into fully divorced eutectics. • Ti addition exhibited significantly higher corrosion resistance. • Ti micro alloying is more effective than faster cooling of the alloy on corrosion.

Mechanical and bio-corrosion properties of quaternary Mg–Ca–Mn–Zn alloys compared with binary Mg–Ca alloys

International Nuclear Information System (INIS)

Bakhsheshi-Rad, H.R.; Idris, M.H.; Abdul-Kadir, M.R.; Ourdjini, A.; Medraj, M.; Daroonparvar, M.; Hamzah, E.

2014-01-01

Highlights: • Quaternary alloy show better mechanical and corrosion properties than binary alloy. • Mg–2Ca–0.5Mn–2Zn alloy showed suitable mechanical properties for bone application. • The improved corrosion resistance with addition of Mn and Zn into the Mg–Ca alloy. • Formation of protective surface film Mn-containing magnesium on quaternary alloy. • Secondary phases have strong effect on micro-galvanic corrosion of Mg alloys. - Abstract: Binary Mg–xCa alloys and the quaternary Mg–Ca–Mn–xZn were studied to investigate their bio-corrosion and mechanical properties. The surface morphology of specimens was characterized by X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). The results of mechanical properties show that the yield strength (YS), ultimate tensile strength (UTS) and elongation of quaternary alloy increased significantly with the addition of zinc (Zn) up to 4 wt.%. However, further addition of Zn content beyond 4 wt.% did not improve yield strength and ultimate tensile strength. In contrast, increasing calcium (Ca) content has a deleterious effect on binary Mg–Ca alloys. Compression tests of the magnesium (Mg) alloys revealed that the compression strength of quaternary alloy was higher than that of binary alloy. However, binary Mg–Ca alloy showed higher reduction in compression strength after immersion in simulated body fluid. The bio-corrosion behaviour of the binary and quaternary Mg alloys were investigated using immersion tests and electrochemical tests. Electrochemical tests shows that the corrosion potential (E corr ) of binary Mg–2Ca significantly shifted toward nobeler direction from −1996.8 to −1616.6 mV SCE with the addition of 0.5 wt.% manganese (Mn) and 2 wt.% Zn content. However, further addition of Zn to 7 wt.% into quaternary alloy has the reverse effect. Immersion tests show that the quaternary

Effect of reversible hydrogen alloying and plastic deformation on microstructure development in titanium alloys

International Nuclear Information System (INIS)

Murzinova, M.A.

2011-01-01

Hydrogen leads to degradation in fracture-related mechanical properties of titanium alloys and is usually considered as a very dangerous element. Numerous studies of hydrogen interaction with titanium alloys showed that hydrogen may be considered not only as an impurity but also as temporary alloying element. This statement is based on the following. Hydrogen stabilizes high-temperature β-phase, leads to decrease in temperature of β→α transformation and extends (α + β )-phase field. The BCC β-phase exhibits lower strength and higher ductility in comparison with HCP α -phase. As a result, hydrogen improves hot workability of hard-to-deform titanium alloys. Hydrogen changes chemical composition of the phases, kinetics of phase transformations, and at low temperatures additional phase transformation (β→α + TiH 2 ) takes place, which is accompanied with noticeable change in volumes of phases. As a result, fine lamellar microstructure may be formed in hydrogenated titanium alloys after heat treatment. It was shown that controlled hydrogen alloying improves weldability and machinability of titanium alloys. After processing hydrogenated titanium preforms are subjected to vacuum annealing, and the hydrogen content decreases up to safe level. Hydrogen removal is accompanied with hydrides dissolution and β→α transformation that makes possible to control structure formation at this final step of treatment. Thus, reversible hydrogen alloying of titanium alloys allows to obtain novel microstructure with enhanced properties. The aim of the work was to study the effect of hydrogen on structure formation, namely: i) influence of hydrogen content on transformation of lamellar microstructure to globular one during deformation in (α+β)-phase field; ii) effect of dissolved hydrogen on dynamic recrystallization in single α- and β- phase regions; iii) influence of vacuum annealing temperature on microstructure development. The work was focused on the optimization of

Physical metallurgy of titanium alloys

International Nuclear Information System (INIS)

Collings, E.W.

1988-01-01

Researches in electric, magnetic, thermophysical properties of titanium alloys in the wide range of temperatures (from helium upto elevated one), as well as stability of phases in alloys of different types are generalized. Fundamental description of physical properties of binary model alloys is given. Acoustic emission, shape memory and Bauschinger effects, pseudoelasticity, aging and other aspects of physical metallurgy of titanium alloys are considered

Fe-Cr-Ni system alloys

International Nuclear Information System (INIS)

Levin, F.L.

1986-01-01

Phase diagram of Fe-Cr-Ni system, which is the basic one for production of corrosion resistant alloys, is considered. Data on corrosion resistance of such alloys are correlated depending on a number of factors: quality and composition of modifying elements, corrosion medium, temperature, alloy structure, mechanical and thermal treatment. Grades of Fe-Ni-Cr alloys are presented, and fields of their application are pointed out

Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression.

Science.gov (United States)

Coke, Christopher J; Scarlett, Kisha A; Chetram, Mahandranauth A; Jones, Kia J; Sandifer, Brittney J; Davis, Ahriea S; Marcus, Adam I; Hinton, Cimona V

2016-05-06

The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Galvanic corrosion in odontological alloys

International Nuclear Information System (INIS)

Riesgo, O.; Bianchi, G.L.; Duffo, G.S.

1993-01-01

Galvanic corrosion can occur when different alloys are placed in direct contact within the oral cavity or within tissues. Concern has been expressed associated with the coupling of selected restorative materials as well as implant material with various alloys used for restorative procedures. This could be critical if the crown or bridge had subgingival finish line with a metallic zone in contact with the tissue, and the implant was made in titanium alloy. The present work shows the results of galvanic coupling studies done on implants of titanium alloy connected to nickel-chromium and cobalt-chromium alloys. (Author)

Grain refinement of 7075Al alloy microstructures by inoculation with Al-Ti-B master alloy

Science.gov (United States)

Hotea, V.; Juhasz, J.; Cadar, F.

2017-05-01

This paper aims to bring some clarification on grain refinement and modification of high strength alloys used in aerospace technique. In this work it was taken into account 7075 Al alloy, and the melt treatment was carried out by placing in the form of master alloy wire ternary AlTiB the casting trough at 730°C. The morphology of the resulting microstructures was characterized by optical microscopy. Micrographs unfinished and finished with pre-alloy containing ternary Al5Ti1B evidence fine crystals, crystal containing no columnar structure and highlights the size of the dendrites, and intermetallic phases occurring at grain boundaries in Al-Zn-Mg-Cu alloy. It has been found that these intermetallic compounds are MgZn2 type. AlTiB master alloys finishing ensures a fine eutectic structure, which determines the properties of hardware and improving the mechanical properties of aluminum alloys used in aeronautical engineering.

Two phase titanium aluminide alloy

Science.gov (United States)

Deevi, Seetharama C.; Liu, C. T.

2001-01-01

A two-phase titanic aluminide alloy having a lamellar microstructure with little intercolony structures. The alloy can include fine particles such as boride particles at colony boundaries and/or grain boundary equiaxed structures. The alloy can include alloying additions such as .ltoreq.10 at % W, Nb and/or Mo. The alloy can be free of Cr, V, Mn, Cu and/or Ni and can include, in atomic %, 45 to 55% Ti, 40 to 50% Al, 1 to 5% Nb, 0.3 to 2% W, up to 1% Mo and 0.1 to 0.3% B. In weight %, the alloy can include 57 to 60% Ti, 30 to 32% Al, 4 to 9% Nb, up to 2% Mo, 2 to 8% W and 0.02 to 0.08% B.

Studies of the AA2519 Alloy Hot Rolling Process and Cladding with EN AW-1050A Alloy

Directory of Open Access Journals (Sweden)

Płonka B.

2016-03-01

Full Text Available The objective of the study was to determine the feasibility of plastic forming by hot rolling of the AA2519 aluminium alloy sheets and cladding these sheets with a layer of the EN AW-1050A alloy. Numerous hot-rolling tests were carried out on the slab ingots to define the parameters of the AA2519 alloy rolling process. It has been established that rolling of the AA2519 alloy should be carried out in the temperature range of 400-440°C. Depending on the required final thickness of the sheet metal, appropriate thickness of the EN AW-1050A alloy sheet, used as a cladding layer, was selected. As a next step, structure and mechanical properties of the resulting AA2519 alloy sheets clad with EN AW-1050A alloy was examined. The thickness of the coating layer was established at 0,3÷0,5mm. Studies covered alloy grain size and the core alloy-cladding material bond strength.

Investigation of a hot-pressed Nb–Ti–Al alloy: Mechanical alloying, microstructure and mechanical property

Energy Technology Data Exchange (ETDEWEB)

Shi, Zhiwu; Wei, Hua; Zhang, Hongyu; Jin, Tao; Sun, Xiaofeng; Zheng, Qi, E-mail: qzheng@imr.ac.cn

2016-01-10

The Nb–23Ti–15Al (at%) alloy was prepared by mechanical alloying (MA) and hot-pressing (HPing). The microstructure evolution of powder particles during MA and its influence on the microstructure and mechanical properties of the hot-pressed (HPed) alloy have been investigated. The powder and HPed alloy were characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicate that particle size increases in the first stage and then decreases in the second stage during MA; as milling speed increases, mechanically alloyed (MAed) powder with convoluted elemental lamellae, homogeneous Nb solid-solution and an amorphous phase could be obtained respectively in 24 h. Higher homogeneity in microstructure and composition of the MAed powder particles promotes the precipitation of the δ phase and refines the β and Ti(O,C) phases in the HPed alloy. Moreover, due to the phase equilibrium changes caused by Fe and Cr in the amorphous powder, σ phase appears in the alloy as a stable phase instead of the δ phase. Properly MAed powder contributes to higher hardness of the HPed alloy, for reasons of microstructure refinement and sufficient precipitating of strengthening phases.

Investigation of a hot-pressed Nb–Ti–Al alloy: Mechanical alloying, microstructure and mechanical property

International Nuclear Information System (INIS)

Shi, Zhiwu; Wei, Hua; Zhang, Hongyu; Jin, Tao; Sun, Xiaofeng; Zheng, Qi

2016-01-01

The Nb–23Ti–15Al (at%) alloy was prepared by mechanical alloying (MA) and hot-pressing (HPing). The microstructure evolution of powder particles during MA and its influence on the microstructure and mechanical properties of the hot-pressed (HPed) alloy have been investigated. The powder and HPed alloy were characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicate that particle size increases in the first stage and then decreases in the second stage during MA; as milling speed increases, mechanically alloyed (MAed) powder with convoluted elemental lamellae, homogeneous Nb solid-solution and an amorphous phase could be obtained respectively in 24 h. Higher homogeneity in microstructure and composition of the MAed powder particles promotes the precipitation of the δ phase and refines the β and Ti(O,C) phases in the HPed alloy. Moreover, due to the phase equilibrium changes caused by Fe and Cr in the amorphous powder, σ phase appears in the alloy as a stable phase instead of the δ phase. Properly MAed powder contributes to higher hardness of the HPed alloy, for reasons of microstructure refinement and sufficient precipitating of strengthening phases.

Positron Emission Tomography Based Analysis of Long-Circulating Cross-Linked Triblock Polymeric Micelles in a U87MG Mouse Xenograft Model and Comparison of DOTA and CB-TE2A as Chelators of Copper-64

DEFF Research Database (Denmark)

Jensen, Andreas Tue Ingemann; Binderup, Tina; Ek, Pramod Kumar

2014-01-01

Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system...... we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of 64Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm2 for 30 min. The cross-linked micelles were labeled with 64Cu at room temperature for 2 h (DOTA) or 80 °C...... for 3 h (CB-TE2A), giving labeling efficiencies of 60–76% (DOTA) and 40–47% (CB-TE2A). 64Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T1/2: 20–26 h) and tumor uptake...

A new technique to modify hypereutectic Al-24%Si alloys by a Si-P master alloy

Energy Technology Data Exchange (ETDEWEB)

Wu Yaping; Wang Shujun; Li Hui [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, 73 Jingshi Road, Jinan 250061 (China); Liu Xiangfa [Key Laboratory of Liquid Structure and Heredity of Materials, Ministry of Education, Shandong University, 73 Jingshi Road, Jinan 250061 (China)], E-mail: xfliu@sdu.edu.cn

2009-05-27

The modification effect of a Si-P master alloy on Al-24%Si alloy was investigated by using electron probe micro-analyzer (EPMA) and optical microscopy (OM). The dissolution problem of the Si-P master alloys was solved by changing the sequence of addition. When the Si-P master alloy was added into Al melt before the addition of silicon, the best modification effect could be achieved. The modification parameters of the master alloy on Al-24%Si alloy were optimized through designing and analyzing the orthogonal experiment, and their influences on the modification effect were discussed. The results show that the influence of temperature on the modification effect is the greatest, followed by the addition level, and the holding time is the least. The optimized modification parameters are the modification temperature of 810 deg. C, the addition level of 0.35 wt.%, the holding time of 30 min + 50 min whose meaning is that the Si-P master alloy is added firstly to the molten Al, and silicon is added 30 min later, then holding another 50 min. In addition, the modification mechanism of the Si-P master alloy on Al-24%Si alloy was also discussed.

Study on microstructure and properties of Mg-alloy surface alloying layer fabricated by EPC

Directory of Open Access Journals (Sweden)

Chen Dongfeng

2010-02-01

Full Text Available AZ91D surface alloying was investigated through evaporative pattern casting (EPC technology. Aluminum powder (0.074 to 0.104 mm was used as the alloying element in the experiment. An alloying coating with excellent properties was fabricated, which mainly consisted of adhesive, co-solvent, suspending agent and other ingredients according to desired proportion. Mg-alloy melt was poured under certain temperature and the degree of negative pressure. The microstructure of the surface layer was examined by means of scanning electron microscopy. It has been found that a large volume fraction of network new phases were formed on the Mg-alloy surface, the thickness of the alloying surface layer increased with the alloying coating increasing from 0.3 mm to 0.5 mm, and the microstructure became compact. Energy dispersive X-ray (EDX analysis was used to determine the chemical composition of the new phases. It showed that the new phases mainly consist of β-Mg17Al12, in addition to a small quantity of inter-metallic compounds and oxides. A micro-hardness test and a corrosion experiment to simulate the effect of sea water were performed. The result indicated that the highest micro-hardness of the surface reaches three times that of the matrix. The corrosion rate of alloying samples declines to about a fifth of that of the as-cast AZ91D specimen.

Dispersion strengthening of precipitation hardened Al-Cu-Mg alloys prepared by rapid solidification and mechanical alloying

Science.gov (United States)

Gilman, P. S.; Sankaran, K. K.

1988-01-01

Several Al-4Cu-1Mg-1.5Fe-0.75Ce alloys have been processed from either rapidly solidified or mechanically alloyed powder using various vacuum degassing parameters and consolidation techniques. Strengthening by the fine subgrains, grains, and the dispersoids individually or in combination is more effective when the alloys contain shearable precipitates; consequently, the strength of the alloys is higher in the naturally aged rather than the artificially aged condition. The strengths of the mechanically alloyed variants are greater than those produced from prealloyed powder. Properties and microstructural features of these dispersion strengthened alloys are discussed in regards to their processing histories.

Relationships between sperm DNA fragmentation, sperm apoptotic markers and serum levels of CB-153 and p,p'-DDE in European and Inuit populations

DEFF Research Database (Denmark)

Stronati, A; Manicardi, G C; Cecati, M

2006-01-01

Persistent organochlorine pollutants (POPs) are suspected to interfere with hormone activity and the normal homeostasis of spermatogenesis. We investigated the relationships between sperm DNA fragmentation, apoptotic markers identified on ejaculated spermatozoa and POP levels in the blood of 652...... adult males (200 Inuits from Greenland, 166 Swedish, 134 Polish and 152 Ukrainian). Serum levels of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), as a proxy of the total POP burden, and of 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), as a proxy of the total DDT exposure were determined...... neither sperm DNA fragmentation nor apoptotic sperm parameters and the large variations in POPs exposure was observed for the separate study groups. However, considering the European populations taken together, we showed that both %TUNEL positivity and Bcl-xL were related to CB-153 serum levels, whereas...

Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.

Science.gov (United States)

Lange, M D; Daldrup, T; Remmers, F; Szkudlarek, H J; Lesting, J; Guggenhuber, S; Ruehle, S; Jüngling, K; Seidenbecher, T; Lutz, B; Pape, H C

2017-10-01

The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.

The Development of the Low-Cost Titanium Alloy Containing Cr and Mn Alloying Elements

Science.gov (United States)

Zhu, Kailiang; Gui, Na; Jiang, Tao; Zhu, Ming; Lu, Xionggang; Zhang, Jieyu; Li, Chonghe

2014-04-01

The α + β-type Ti-4.5Al-6.9Cr-2.3Mn alloy has been theoretically designed on the basis of assessment of the Ti-Al-Cr-Mn thermodynamic system and the relationship between the molybdenum equivalent and mechanical properties of titanium alloys. The alloy is successfully prepared by the split water-cooled copper crucible, and its microstructures and mechanical properties at room temperature are investigated using the OM, SEM, and the universal testing machine. The results show that the Ti-4.5Al-6.9Cr-2.3Mn alloy is an α + β-type alloy which is consistent with the expectation, and its fracture strength, yield strength, and elongation reach 1191.3, 928.4 MPa, and 10.7 pct, respectively. Although there is no strong segregation of alloying elements under the condition of as-cast, the segregation of Cr and Mn is obvious at the grain boundary after thermomechanical treatment.

Effect of Al alloying on the martensitic temperature in Ti-Ta shape memory alloys

Energy Technology Data Exchange (ETDEWEB)

Ferrari, Alberto; Rogal, Jutta; Drautz, Ralf [Interdisciplinary Centre for Advanced Materials Simulation, Ruhr-Universitaet Bochum (Germany)

2017-07-01

Ti-Ta-based alloys are promising candidates as high temperature shape memory alloys (HTSMAs) for actuators and superelastic applications. The shape memory mechanism involves a martensitic transformation between the low-temperature α'' phase (orthorhombic) and the high-temperature β phase (body-centered cubic). In order to prevent the degradation of the shape memory effect, Ti-Ta needs to be alloyed with further elements. However, this often reduces the martensitic temperature M{sub s}, which is usually strongly composition dependent. The aim of this work is to analyze how the addition of a third element to Ti-Ta alloys affects M{sub s} by means of electronic structure calculations. In particular, it will be investigated how alloying Al to Ti-Ta alters the relative stability of the α'' and β phases. This understanding will help to identify new alloy compositions featuring both a stable shape memory effect and elevated transformation temperatures.

Density of Liquid Ni-Cr Alloy

Institute of Scientific and Technical Information of China (English)

无

2003-01-01

The density of liquid Ni-Cr alloy was measured by a modified sessile drop method. The density of liquid Ni-Cr alloywas found to decrease with increasing temperature and Cr concentration in the alloy. The molar volume of liquidNi-Cr alloy increases with increasing the Cr concentration in the alloy. The molar volume of Ni-Cr alloy determinedin the present work shows a positive deviation from the linear molar volume.

Low activation ferritic alloys

Science.gov (United States)

Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

1986-01-01

Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

Impact of the De-Alloying Kinetics and Alloy Microstructure on the Final Morphology of De-Alloyed Meso-Porous Metal Films

Directory of Open Access Journals (Sweden)

Bao Lin

2014-10-01

Full Text Available Nano-textured porous metal materials present unique surface properties due to their enhanced surface energy with potential applications in sensing, molecular separation and catalysis. In this paper, commercial alloy foils, including brass (Cu85Zn15 and Cu70Zn30 and white gold (Au50Ag50 foils have been chemically de-alloyed to form nano-porous thin films. The impact of the initial alloy micro-structure and number of phases, as well as chemical de-alloying (DA parameters, including etchant concentration, time and solution temperature on the final nano-porous thin film morphology and properties were investigated by electron microscopy (EM. Furthermore, the penetration depth of the pores across the alloys were evaluated through the preparation of cross sections by focus ion beam (FIB milling. It is demonstrated that ordered pores ranging between 100 nm and 600 nm in diameter and 2–5 μm in depth can be successfully formed for the range of materials tested. The microstructure of the foils were obtained by electron back-scattered diffraction (EBSD and linked to development of pits across the material thickness and surface during DA. The role of selective etching of both noble and sacrificial metal phases of the alloy were discussed in light of the competitive surface etching across the range of microstructures and materials tested.

Preparation of Copper and Chromium Alloyed Layers on Pure Titanium by Plasma Surface Alloying Technology

Science.gov (United States)

He, Xiaojing; Li, Meng; Wang, Huizhen; Zhang, Xiangyu; Tang, Bin

2015-05-01

Cu-Cr alloyed layers with different Cu and Cr contents on pure titanium were obtained by means of plasma surface alloying technology. The microstructure, chemical composition and phase composition of Cu-Cr alloyed layers were analyzed by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffraction (XRD), respectively. The experimental results demonstrate that the alloyed layers are bonded strongly to pure titanium substrate and consist of unbound Ti, CuTi, Cu3Ti, CuTi3 and Cr2Ti. The thickness of Cu5Cr5 and Cu7Cr3 alloyed layer are about 18 μm and 28 μm, respectively. The antibacterial properties against gram-negative Escherichia coli (E.coli, ATCC10536) and gram-positive Staphylococcus aureus (S. aureus, ATCC6538) of untreated pure titanium and Cu-Cr alloyed specimen were investigated by live/dead fluorescence staining method. The study shows that Cu-Cr alloyed layers exhibit excellent antibacterial activities against both E.coli and S.aureus within 24 h, which may be attributed to the formation of Cu-containing phases.

Preparation of a high strength Al–Cu–Mg alloy by mechanical alloying and press-forming

International Nuclear Information System (INIS)

Tang Huaguo; Cheng Zhiqiang; Liu Jianwei; Ma Xianfeng

2012-01-01

Highlights: ► A high strength aluminum alloy of Al–2 wt.%Mg–2 wt.%Cu has been prepared by mechanical alloying and press-forming. ► The alloy only consists of solid solution α-Al. ► The grains size of α-Al was about 300 nm–5 μm. ► The solid solution strengthening and the grain refinement strengthening are the main reasons for such a high strength. - Abstract: A high strength aluminum alloy, with the ratio of 96 wt.%Al–2 wt.%Mg–2 wt.%Cu, has been prepared by mechanical alloying and press-forming. The alloy exhibited a high tensile strength of 780 MPa and a high microhardness of 180 HV. X-ray diffraction characterizations confirmed that the alloy only consists of a solid solution α-Al. Microstructure characterizations revealed that the grain size of α-Al was about 300 nm–5 μm. The solid solution strengthening and the grain refinement strengthening were considered to be the reason for such a high strength.

Preparation of a high strength Al-Cu-Mg alloy by mechanical alloying and press-forming

Energy Technology Data Exchange (ETDEWEB)

Tang Huaguo [State Key Laboratory of Rare Earth Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Cheng Zhiqiang [College of Resources and Environment, Jilin Agricultural University, Changchun 130118 (China); Liu Jianwei [State Key Laboratory of Rare Earth Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Ma Xianfeng, E-mail: xfma@ciac.jl.cn [State Key Laboratory of Rare Earth Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

2012-07-30

Highlights: Black-Right-Pointing-Pointer A high strength aluminum alloy of Al-2 wt.%Mg-2 wt.%Cu has been prepared by mechanical alloying and press-forming. Black-Right-Pointing-Pointer The alloy only consists of solid solution {alpha}-Al. Black-Right-Pointing-Pointer The grains size of {alpha}-Al was about 300 nm-5 {mu}m. Black-Right-Pointing-Pointer The solid solution strengthening and the grain refinement strengthening are the main reasons for such a high strength. - Abstract: A high strength aluminum alloy, with the ratio of 96 wt.%Al-2 wt.%Mg-2 wt.%Cu, has been prepared by mechanical alloying and press-forming. The alloy exhibited a high tensile strength of 780 MPa and a high microhardness of 180 HV. X-ray diffraction characterizations confirmed that the alloy only consists of a solid solution {alpha}-Al. Microstructure characterizations revealed that the grain size of {alpha}-Al was about 300 nm-5 {mu}m. The solid solution strengthening and the grain refinement strengthening were considered to be the reason for such a high strength.

Nano-structureal and nano-chemical analysis of Ni-based alloy/low alloy steel dissimilar metal weld interfaces

International Nuclear Information System (INIS)

Choi, Kyoung Joon; Shin, Sang Hun; Kim, Jong Jin; Jung, Ju Ang; Kim, Ji Hyun

2012-01-01

The dissimilar metal joints welded between Ni-based alloy, Alloy 690 and low alloy steel, A533 Gr. B with Alloy 152 filler metal were characterized by using optical microscope, scanning electron microscope, transmission electron microscope, secondary ion mass spectrometry and 3-dimensional atom probe tomography. It was found that in the weld root region, the weld was divided into several regions including unmixed zone in Ni-base alloy, fusion boundary, and heat-affected zone in the low alloy steel. The result of nanostructural and nanochemical analyses in this study showed the non-homogeneous distribution of elements with higher Fe but lower Mn, Ni and Cr in A533 Gr. B compared with Alloy 152, and the precipitation of carbides near the fusion boundary.

Nano-structureal and nano-chemical analysis of Ni-based alloy/low alloy steel dissimilar metal weld interfaces

Energy Technology Data Exchange (ETDEWEB)

Choi, Kyoung Joon; Shin, Sang Hun; Kim, Jong Jin; Jung, Ju Ang; Kim, Ji Hyun [Interdisciplinary School of Green Energy, Ulsan National Institute of Science and Technology (UNIST), Ulsan (Korea, Republic of)

2012-06-15

The dissimilar metal joints welded between Ni-based alloy, Alloy 690 and low alloy steel, A533 Gr. B with Alloy 152 filler metal were characterized by using optical microscope, scanning electron microscope, transmission electron microscope, secondary ion mass spectrometry and 3-dimensional atom probe tomography. It was found that in the weld root region, the weld was divided into several regions including unmixed zone in Ni-base alloy, fusion boundary, and heat-affected zone in the low alloy steel. The result of nanostructural and nanochemical analyses in this study showed the non-homogeneous distribution of elements with higher Fe but lower Mn, Ni and Cr in A533 Gr. B compared with Alloy 152, and the precipitation of carbides near the fusion boundary.

Superconducting alloys

International Nuclear Information System (INIS)

Bowers, J.E.

1976-01-01

Reference is made to superconductors having high critical currents. The superconductor described comprises an alloy consisting of a matrix of a Type II superconductor which is a homogeneous mixture of 50 to 95 at.% Pb and 5 to 40 at.%Bi and/or 10 to 50 at.%In. Dispersed in the matrix is a material to provide pinning centres comprising from 0.01% to 20% by volume of the alloy; this material is a stable discontinuous phase of discrete crystalline particles of Cu, Mn, Te, Se, Ni, Ca, Cr, Ce, Ge or La, either in the form of the element or a compound with a component of the matrix. These particles should have an average diameter of not more than 2μ. A method for making this alloy is described. (U.K.)

Imparting passivity to vapor deposited magnesium alloys

Science.gov (United States)

Wolfe, Ryan C.

Magnesium has the lowest density of all structural metals. Utilization of low density materials is advantageous from a design standpoint, because lower weight translates into improved performance of engineered products (i.e., notebook computers are more portable, vehicles achieve better gas mileage, and aircraft can carry more payload). Despite their low density and high strength to weight ratio, however, the widespread implementation of magnesium alloys is currently hindered by their relatively poor corrosion resistance. The objective of this research dissertation is to develop a scientific basis for the creation of a corrosion resistant magnesium alloy. The corrosion resistance of magnesium alloys is affected by several interrelated factors. Among these are alloying, microstructure, impurities, galvanic corrosion effects, and service conditions, among others. Alloying and modification of the microstructure are primary approaches to controlling corrosion. Furthermore, nonequilibrium alloying of magnesium via physical vapor deposition allows for the formation of single-phase magnesium alloys with supersaturated concentrations of passivity-enhancing elements. The microstructure and surface morphology is also modifiable during physical vapor deposition through the variation of evaporation power, pressure, temperature, ion bombardment, and the source-to-substrate distance. Aluminum, titanium, yttrium, and zirconium were initially chosen as candidates likely to impart passivity on vapor deposited magnesium alloys. Prior to this research, alloys of this type have never before been produced, much less studied. All of these metals were observed to afford some degree of corrosion resistance to magnesium. Due to the especially promising results from nonequilibrium alloying of magnesium with yttrium and titanium, the ternary magnesium-yttrium-titanium system was investigated in depth. While all of the alloys are lustrous, surface morphology is observed under the scanning

Strength and fracture of two-phase alloys: a comparison of two alloy systems

International Nuclear Information System (INIS)

Gurland, J.

1978-01-01

The functional roles of the hard and soft constituents in the deformation and fracture of two-phase alloys are discussed on the basis of two commercially important alloy systems, namely spheroidized carbon steels and cemented carbides, WC-Co. A modified rule of mixtures provides a structural approach to the yield and flow strength. Consideration of the fracture toughness is attempted by means of a phenomenological modelling of the fracture process on the microscale. While there are large differences in properties between the two alloys, the deformation and fracture processes show broad smilarities which are associated with the features of the interaction between constituents common to both alloys

Passive Corrosion Behavior of Alloy 22

International Nuclear Information System (INIS)

R.B. Rebak; J.H. Payer

2006-01-01

Alloy 22 (NO6022) was designed to stand the most aggressive industrial applications, including both reducing and oxidizing acids. Even in the most aggressive environments, if the temperature is lower than 150 F (66 C) Alloy 22 would remain in the passive state having particularly low corrosion rates. In multi-ionic solutions that may simulate the behavior of concentrated ground water, even at near boiling temperatures, the corrosion rate of Alloy 22 is only a few nano-meters per year because the alloy is in the complete passive state. The corrosion rate of passive Alloy 22 decreases as the time increases. Immersion corrosion testing also show that the newer generation of Ni-Cr-Mo alloys may offer a better corrosion resistance than Alloy 22 only in some highly aggressive conditions such as in hot acids

Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

DEFF Research Database (Denmark)

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

2011-01-01

81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.......0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated...... for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A....

Hydrogen embrittlement and hydrogen induced stress corrosion cracking of high alloyed austenitic materials; Wasserstoffversproedung und wasserstoffinduzierte Spannungsrisskorrosion hochlegierter austenitischer Werkstoffe

Energy Technology Data Exchange (ETDEWEB)

Mummert, K; Uhlemann, M; Engelmann, H J [Institut fuer Festkoerper- und Werkstofforschung Dresden e.V. (Germany)

1998-11-01

The susceptiblity of high alloyed austenitic steels and nickel base alloys to hydrogen-induced cracking is particularly determined by 1. the distribution of hydrogen in the material, and 2. the microstructural deformation behaviour, which last process is determined by the effects of hydrogen with respect to the formation of dislocations and the stacking fault energy. The hydrogen has an influence on the process of slip localization in slip bands, which in turn affects the microstructural deformation behaviour. Slip localization increases with growing Ni contents of the alloys and clearly reduces the ductility of the Ni-base alloy. Although there is a local hydrogen source involved in stress corrosion cracking, emanating from the corrosion process at the cathode, crack growth is observed only in those cases when the hydrogen concentration in a small zone ahead of the crack tip reaches a critical value with respect to the stress conditions. Probability of onset of this process gets lower with growing Ni content of the alloy, due to increasing diffusion velocity of the hydrogen in the austenitic lattice. This is why particularly austenitic steels with low Ni contents are susceptible to transcrystalline stress corrosion cracking. In this case, the microstructural deformation process at the crack tip is also influenced by analogous processes, as could be observed in hydrogen-loaded specimens. (orig./CB) [Deutsch] Die Empfindlichkeit von hochlegierten austentischen Staehlen und Nickelbasislegierungen gegen wasserstoffinduziertes Risswachstum wird im wesentlichen bestimmt durch 1. die Verteilung von Wasserstoff im Werkstoff und 2. das mikrostrukturelle Verformungsverhalten. Das mikrostrukturelle Deformationsverhalten ist wiederum durch den Einfluss von Wasserstoff auf die Versetzungsbildung und die Stapelfehlerenergie charakterisiert. Das mikrostrukturelle Verformungsverhalten wird durch wasserstoffbeeinflusste Gleitlokalisierung in Gleitbaendern bestimmt. Diese nimmt mit

Corrosion-electrochemical behaviour and mechanical properties ofaluminium alloy-321, alloyed by barium

International Nuclear Information System (INIS)

Ganiev, I.; Mukhiddinov, G.N.; Kargapolova, T.V.; Mirsaidov, U.

1995-01-01

The purpose of present work is studying of influence of barium additionson electrochemical corrosion of casting aluminium-copper alloy Al-321,containing as base alloying components copper, chromium, manganese, titanium,zirconium, cadmium

Coupling between bulk ordering and surface segregation: from alloy surfaces to surface alloys

International Nuclear Information System (INIS)

Gallis, Coralie

1997-01-01

-The knowledge of the alloy surfaces is of prime interest to understand their catalytic properties. On the one hand, the determination of the stability of the surface alloys depends very strongly on the behaviours of the A c B 1-c alloy surfaces. On the other hand, the knowledge of the kinetics of the formation-dissolution of surface alloys can allow to understand the equilibrium segregation isotherm. We have then studied the relation between the equilibrium surface segregation in an alloy A c B 1-c and the kinetics of dissolution of a few metallic layers of A/B and the inverse deposit. We have used an energetic model derived from the electronic structure (T.I.B.M.) allowing us to study the surface segregation both in the disordered state and in the ordered one. The kinetics of dissolution were studied using the kinetic version of this model (K.T.I.B.M.) consistent with the equilibrium model. To illustrate our study, we have chosen the Cu-Pd system, a model for the formation of surface alloys and for which a great number of studies, both experimental and theoretical, are in progress. We then have shown for the (111) surface of this system that the surface alloys obtained during the dissolution are related to the alloy surfaces observed for the equilibrium segregation. The Cu-Pd system is characteristic of systems which have a weak segregation energy. Then, we have performed an equivalent study for a system with a strong segregation energy. Our choice was directly put on the Pt-Sn system. The surface behaviour, both in equilibrium and during the kinetics of dissolution, is very different from the Cu-Pd case. In particular, we have found pure 2-D surface alloys. Finally, a quenched molecular dynamics study has allowed us to determine the relative stability of various possible surface superstructures. (author) [fr

ODS Alloys for Nuclear Applications

International Nuclear Information System (INIS)

Jang, Jin Sung

2006-01-01

ODS (oxide dispersion strengthening) alloy is one of the potential candidate alloys for the cladding or in reactor components of Generation IV reactors and for the structural material even for fusion reactors. It is widely accepted as very resistant material to neutron irradiation as well as strong material at high temperature due to its finely distributed and stable oxide particles. Among Generation IV reactors SFR and SCWR are anticipated in general to run in the temperature range between 300 and 550 .deg. C, and the peak cladding temperature is supposed to reach at about 620 .deg. C during the normal operation. Therefore Zr.base alloys, which have been widely known and adopted for the cladding material due to their excellent neutron economics, are no more adequate at these operating conditions. Fe-base ODS alloys in general has a good high temperature strength at the above high temperature as well as the neutron resistance. In this study a range of commercial grade ODS alloys and their applications are reviewed, including an investigation of the stability of a commercial grade 20% Cr Fe-base ODS alloy(MA956). The alloy was evaluated in terms of the fracture toughness change along with the aging treatment. Also an attempt of the development of 9% Cr Fe-base ODS alloys is introduced

Positrons in amorphous alloys

International Nuclear Information System (INIS)

Moser, Pierre.

1981-07-01

Positron annihilation techniques give interesting informations about ''empty spaces'' in amorphous alloys. The results of an extensive research work on the properties of either pre-existing or irradiation induced ''empty spaces'' in four amorphous alloys are presented. The pre-existing empty spaces appear to be small vacancy-like defects. The irradiation induced defects are ''close pairs'' with widely distributed configurations. There is a strong interaction between vacancy like and interstitial like components. A model is proposed, which explains the radiation resistance mechanism of the amorphous alloys. An extensive joint research work to study four amorphous alloys, Fe 80 B 20 ,Fe 40 Ni 40 P 14 B 6 , Cu 50 Ti 50 , Pd 80 Si 20 , is summarized

The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-γ and CB2 pathways.

Science.gov (United States)

del Río, Carmen; Navarrete, Carmen; Collado, Juan A; Bellido, M Luz; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Cantarero, Irene; Muñoz, Eduardo

2016-02-18

Scleroderma is a group of rare diseases associated with early and transient inflammation and vascular injury, followed by fibrosis affecting the skin and multiple internal organs. Fibroblast activation is the hallmark of scleroderma, and disrupting the intracellular TGFβ signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, both PPARγ and CB2 receptors represent attractive targets for the development of cannabinoid-based therapies. We have developed a non-thiophilic and chemically stable derivative of the CBD quinol (VCE-004.8) that behaves as a dual agonist of PPARγ and CB2 receptors, VCE-004.8 inhibited TGFβ-induced Col1A2 gene transcription and collagen synthesis. Moreover, VCE-004.8 inhibited TGFβ-mediated myofibroblast differentiation and impaired wound-healing activity. The anti-fibrotic efficacy in vivo was investigated in a murine model of dermal fibrosis induced by bleomycin. VCE-004.8 reduced dermal thickness, blood vessels collagen accumulation and prevented mast cell degranulation and macrophage infiltration in the skin. These effects were impaired by the PPARγ antagonist T0070907 and the CB2 antagonist AM630. In addition, VCE-004.8 downregulated the expression of several key genes associated with fibrosis, qualifying this semi-synthetic cannabinoid as a novel compound for the management of scleroderma and, potentially, other fibrotic diseases.

Local atomic order in nanocrystalline Fe-based alloys obtained by mechanical alloying

International Nuclear Information System (INIS)

Jartych, E.

2003-01-01

Using the 57 Fe Moessbauer spectroscopy, a local atomic order in nanocrystalline alloys of iron with Al, Ni, W and Mo has been determined. Alloys were prepared by mechanical alloying method. Analysis of Moessbauer spectra was performed on the basis of the local environment model in terms of Warren-Cowley parameters. It was shown that impurity atoms are not randomly distributed in the volume of the first and the second co-ordination spheres of 57 Fe nuclei and they form clusters

Environmental fatigue in aluminum-lithium alloys

Science.gov (United States)

Piascik, Robert S.

1992-01-01

Aluminum-lithium alloys exhibit similar environmental fatigue crack growth characteristics compared to conventional 2000 series alloys and are more resistant to environmental fatigue compared to 7000 series alloys. The superior fatigue crack growth behavior of Al-Li alloys 2090, 2091, 8090, and 8091 is due to crack closure caused by tortuous crack path morphology and crack surface corrosion products. At high R and reduced closure, chemical environment effects are pronounced resulting in accelerated near threshold da/dN. The beneficial effects of crack closure are minimized for small cracks resulting in rapid growth rates. Limited data suggest that the 'chemically small crack' effect, observed in other alloy system, is not pronounced in Al-Li alloys. Modeling of environmental fatigue in Al-Li-Cu alloys related accelerated fatigue crack growth in moist air and salt water to hydrogen embrittlement.

Determination of local constitutive properties of titanium alloy matrix in boron-modified titanium alloys using spherical indentation

International Nuclear Information System (INIS)

Sreeranganathan, A.; Gokhale, A.; Tamirisakandala, S.

2008-01-01

The constitutive properties of the titanium alloy matrix in boron-modified titanium alloys are different from those of the corresponding unreinforced alloy due to the microstructural changes resulting from the addition of boron. Experimental and finite-element analyses of spherical indentation with a large penetration depth to indenter radius ratio are used to compute the local constitutive properties of the matrix alloy. The results are compared with that of the corresponding alloy without boron, processed in the same manner

The quasicrystalline phase formation in Al-Cu-Cr alloys produced by mechanical alloying

Energy Technology Data Exchange (ETDEWEB)

Sviridova, T.A.; Shevchukov, A.P.; Shelekhov, E.V. [National University of Science and Technology ' MISIS' , Moscow 119049 (Russian Federation); Diakonov, D.L. [Bardin Central Research Institute for the Iron and Steel Industry, Moscow 105005 (Russian Federation); Tcherdyntsev, V.V.; Kaloshkin, S.D. [National University of Science and Technology ' MISIS' , Moscow 119049 (Russian Federation)

2011-06-15

Research highlights: > Formation of decagonal quasicrystalline phase in Al-Cu-Cr alloys. > Obtained decagonal phase belongs to D{sub 3} family of decagonal quasicrystals. > Decagonal phase has 1.26 nm periodicity along 10-fold axis. > Alloys were produced by combination of mechanical alloying and subsequent annealing. > Phase composition of as-milled powders depending on annealing temperature. - Abstract: Almost single-phase decagonal quasicrystal with periodicity of 1.26 nm along 10-fold axis was produced in Al{sub 69}Cu{sub 21}Cr{sub 10} and Al{sub 72.5}Cu{sub 16.5}Cr{sub 11} alloys using combination of mechanical alloying (MA) and subsequent annealing. Phase transformations of as-milled powders depending on annealing temperature in the range of 200-800 deg. C are examined. Since the transformations can be explained based on kinetic and thermodynamic reasons it seems that applied technique (short preliminary MA followed by the annealing) permits to produce the equilibrium phases rather than metastable ones.

Three-dimensional single-photon emission computed tomography using cone beam collimation (CB-SPECT)

International Nuclear Information System (INIS)

Jaszczak, R.J.; Floyd, C.E. Jr.; Manglos, S.H.; Greer, K.L.; Coleman, R.E.

1986-01-01

A simple and economically practical method of improving the sensitivity of camera-based SPECT was developed using converging (cone-beam) collimation. This geometry is particularly advantageous for SPECT devices using large field-of-view cameras in imaging smaller, centrally located activity distributions. Geometric sensitivities, spatial resolutions, and fields-of-view of a cone-beam collimator having a focal length of 48 cm and a similarly designed parallel hole collimator were compared analytically. At 15 cm from the collimator surface the point-source sensitivity of the cone-beam collimator was 2.4 times the sensitivity of the parallel-hole collimator. SPECT projection data (simulated using Monte Carlo methodology) were reconstructed using a 3-D filtered backprojection algorithm. Cone-beam emission CT (CB-SPECT) seems potentially useful for animal investigations, pediatric studies, and for brain imaging

Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats

Czech Academy of Sciences Publication Activity Database

Páleníček, T.; Fujáková, M.; Brunovský, M.; Horáček, J.; Gorman, I.; Balíková, M.; Rambousek, Lukáš; Syslová, K.; Kačer, P.; Zach, P.; Bubeníková-Valešová, V.; Tylš, F.; Kubešová, A.; Puskarčíková, J.; Höschl, C.

2013-01-01

Roč. 225, č. 1 (2013), s. 75-93 ISSN 0033-3158 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) * amphetamine * serotonin * dopamine * nucleus accumbens * behavior * microdialysis * EEG power spectra * EEG coherence * rats Subject RIV: FH - Neurology Impact factor: 3.988, year: 2013

Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and reduces leukocyte transmigration in a model of blood brain barrier by activation of CB1 receptors

Directory of Open Access Journals (Sweden)

Loría Frida

2011-08-01

Full Text Available Abstract Background VCAM-1 represents one of the most important adhesion molecule involved in the transmigration of blood leukocytes across the blood-brain barrier (BBB that is an essential step in the pathogenesis of MS. Several evidences have suggested the potential therapeutic value of cannabinoids (CBs in the treatment of MS and their experimental models. However, the effects of endocannabinoids on VCAM-1 regulation are poorly understood. In the present study we investigated the effects of anandamide (AEA in the regulation of VCAM-1 expression induced by Theiler's virus (TMEV infection of brain endothelial cells using in vitro and in vivo approaches. Methods i in vitro: VCAM-1 was measured by ELISA in supernatants of brain endothelial cells infected with TMEV and subjected to AEA and/or cannabinoid receptors antagonist treatment. To evaluate the functional effect of VCAM-1 modulation we developed a blood brain barrier model based on a system of astrocytes and brain endothelial cells co-culture. ii in vivo: CB1 receptor deficient mice (Cnr1-/- infected with TMEV were treated with the AEA uptake inhibitor UCM-707 for three days. VCAM-1 expression and microglial reactivity were evaluated by immunohistochemistry. Results Anandamide-induced inhibition of VCAM-1 expression in brain endothelial cell cultures was mediated by activation of CB1 receptors. The study of leukocyte transmigration confirmed the functional relevance of VCAM-1 inhibition by AEA. In vivo approaches also showed that the inhibition of AEA uptake reduced the expression of brain VCAM-1 in response to TMEV infection. Although a decreased expression of VCAM-1 by UCM-707 was observed in both, wild type and CB1 receptor deficient mice (Cnr1-/-, the magnitude of VCAM-1 inhibition was significantly higher in the wild type mice. Interestingly, Cnr1-/- mice showed enhanced microglial reactivity and VCAM-1 expression following TMEV infection, indicating that the lack of CB1 receptor

Grain refinement of zinc-aluminium alloys

International Nuclear Information System (INIS)

Zaid, A.I.O.

2006-01-01

It is now well-established that the structure of the zinc-aluminum die casting alloys can be modified by the binary Al-Ti or the ternary Al-Ti-B master alloys. in this paper, grain refinement of zinc-aluminum alloys by rare earth materials is reviewed and discussed. The importance of grain refining of these alloys and parameters affecting it are presented and discussed. These include parameters related to the Zn-Al alloys cast, parameters related to the grain refining elements or alloys and parameters related to the process. The effect of addition of other alloying elements e.g. Zr either alone or in the presence of the main grain refiners Ti or Ti + B on the grain refining efficiency is also reviewed and discussed. Furthermore, based on the grain refinement and the parameters affecting it, a criterion for selection of the optimum grain refiner is suggested. Finally, the recent research work on the effect of grain refiners on the mechanical behaviour, impact strength, wear resistance, and fatigue life of these alloys are presented and discussed. (author)

Applications of thermodynamic calculations to Mg alloy design: Mg-Sn based alloy development

International Nuclear Information System (INIS)

Jung, In-Ho; Park, Woo-Jin; Ahn, Sang Ho; Kang, Dae Hoon; Kim, Nack J.

2007-01-01

Recently an Mg-Sn based alloy system has been investigated actively in order to develop new magnesium alloys which have a stable structure and good mechanical properties at high temperatures. Thermodynamic modeling of the Mg-Al-Mn-Sb-Si-Sn-Zn system was performed based on available thermodynamic, phase equilibria and phase diagram data. Using the optimized database, the phase relationships of the Mg-Sn-Al-Zn alloys with additions of Si and Sb were calculated and compared with their experimental microstructures. It is shown that the calculated results are in good agreement with experimental microstructures, which proves the applicability of thermodynamic calculations for new Mg alloy design. All calculations were performed using FactSage thermochemical software. (orig.)

Maternal deprivation and adolescent cannabinoid exposure impact hippocampal astrocytes, CB1 receptors and brain-derived neurotrophic factor in a sexually dimorphic fashion.

Science.gov (United States)

López-Gallardo, M; López-Rodríguez, A B; Llorente-Berzal, Á; Rotllant, D; Mackie, K; Armario, A; Nadal, R; Viveros, M-P

2012-03-01

We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9-10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28-42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug "per se" induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

MATERNAL DEPRIVATION AND ADOLESCENT CANNABINOID EXPOSURE IMPACT HIPPOCAMPAL ASTROCYTES, CB1 RECEPTORS AND BRAIN-DERIVED NEUROTROPHIC FACTOR IN A SEXUALLY DIMORPHIC FASHION

Science.gov (United States)

LÓPEZ-GALLARDO, M.; LÓPEZ-RODRÍGUEZ, A. B.; LLORENTE-BERZAL, Á.; ROTLLANT, D.; MACKIE, K.; ARMARIO, A.; NADAL, R.; VIVEROS, M.-P.

2013-01-01

We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9–10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28–42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug “per se” induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments. PMID:22001306

A highly ductile magnesium alloy system

International Nuclear Information System (INIS)

Gao, W; Liu, H

2009-01-01

Magnesium (Mg) alloys are finding increasing applications in industry mainly due to their high strength-to-weight ratio. However, they have intrinsically poor plastic deformation ability at room temperature. Therefore, the vast majority of Mg alloys are used only in cast state, severely limiting the development of their applications. We have recently discovered a new Mg alloy system that possesses exceptionally high ductility as well as good mechanical strength. The superior plasticity allows this alloy system to be mechanically deformed at room temperature, directly from an as-cast alloy plate, sheet or ingot into working parts. This type of cold mechanical forming properties has never been reported with any other Mg alloy systems.

Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

Science.gov (United States)

Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

2016-08-01

The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

HAYNES 244 alloy – a new 760 ∘C capable low thermal expansion alloy

Directory of Open Access Journals (Sweden)

Fahrmann Michael G.

2014-01-01

Full Text Available HAYNES® 244TM alloy is a new 760∘C capable, high strength low thermal expansion (CTE alloy. Its nominal chemical composition in weight percent is Ni – 8 Cr – 22.5 Mo – 6 W. Recently, a first mill-scale heat of 244 alloy was melted by Haynes International, and processed to various product forms such as re-forge billet, plate, and sheet. This paper presents key attributes of this new alloy (CTE, strength, low-cycle fatigue performance, oxidation resistance, thermal stability as they pertain to the intended use in rings and seals of advanced gas turbines.

The Peculiarities of Building Motivational Process in Bank (on the Example of PJSC CB «PrivatBank»

Directory of Open Access Journals (Sweden)

Izyumtseva Natalya V.

2017-11-01

Full Text Available The article considers the motivational process in bank. The essence of material and intangible component of encouraging employees to work has been disclosed. Attention is paid to the model of staff motivation on the example of PJSC CB «PrivatBank». The main disadvantages of motivational process have been identified and ways of improvement of the existing system of staff motivation have been suggested in favor of obtaining the best labor productivity.

Reconstruction of B{sup -} {yields} D{sup *0}e{sup -} anti {nu}{sub e} decays and determination of vertical stroke V{sub cb} vertical stroke

Energy Technology Data Exchange (ETDEWEB)

Schubert, J.

2006-12-01

In this analysis the decay B{sup -} {yields} D{sup *0}e{sup -} anti {nu}{sub e} is measured. The underlying data sample consists of about 226 million B anti B-pairs accumulated on the {upsilon}(4S) resonance by the BABAR detector at the asymmetric e{sup +}e{sup -} collider PEP-II. The reconstruction of the decay uses the channels D{sup *0} {yields} D{sup 0}{pi}{sup 0}, D{sup 0} {yields} K{sup -}{pi}{sup +} and {pi}{sup 0} {yields} {gamma}{gamma}. The neutrino is not reconstructed. Since the rest frame of the B meson is unknown, the boost w of the D{sup *0} meson in the B meson rest frame is estimated by w. The w spectrum of the data is described in terms of the partial decay width d{gamma}/dw given by theory and the detector simulation translating each spectrum d{gamma}/dw into an expectation of the measured w spectrum. d{gamma}/dw depends on a form factor F(w) parameterizing the strong interaction in the decay process. To find the best descriptive d{gamma}/dw a fit to the data determines the following two parameters of d{gamma}/dw: (i) F(1) vertical stroke V{sub cb} vertical stroke, the product between F at zero D{sup *0}-recoil and the CKM matrix element vertical stroke V{sub cb} vertical stroke; (ii) {rho}{sup 2}{sub A1}, a parameter of the form factor F(w). The former parameter scales the height of d{gamma}/dw and {rho}{sup 2}{sub A1} varies the shape of it. The determined values of F(1) vertical stroke V{sub cb} vertical stroke, {rho}{sup 2}{sub A1} and B(B{sup -} {yields} D{sup *0}e{sup -} anti {nu}{sub e}) are F(1) vertical stroke V{sub cb} vertical stroke =(35.8{+-}0.5{+-}1.5) x 10{sup -3}, {rho}{sup 2}{sub A1}=(1.08{+-}0.05{+-}0.09) and B(B{sup -} {yields} D{sup *0}e{sup -} anti {nu}{sub e})=(5.60{+-}0.08{+-}0.42)%, where the uncertainties are statistical and systematic, respectively. The values of B(B{sup -} {yields} D{sup *0}e{sup -} anti {nu}{sub e}) has been determined by an integration of d{gamma}/dw over the allowed w range using the fitted values of

Aeronautical Industry Requirements for Titanium Alloys

Science.gov (United States)

Bran, D. T.; Elefterie, C. F.; Ghiban, B.

2017-06-01

The project presents the requirements imposed for aviation components made from Titanium based alloys. A significant portion of the aircraft pylons are manufactured from Titanium alloys. Strength, weight, and reliability are the primary factors to consider in aircraft structures. These factors determine the requirements to be met by any material used to construct or repair the aircraft. Many forces and structural stresses act on an aircraft when it is flying and when it is static and this thesis describes environmental factors, conditions of external aggression, mechanical characteristics and loadings that must be satisfied simultaneously by a Ti-based alloy, compared to other classes of aviation alloys (as egg. Inconel super alloys, Aluminum alloys).For this alloy class, the requirements are regarding strength to weight ratio, reliability, corrosion resistance, thermal expansion and so on. These characteristics additionally continue to provide new opportunities for advanced manufacturing methods.

Controlled Thermal Expansion Alloys

Data.gov (United States)

National Aeronautics and Space Administration — There has always been a need for controlled thermal expansion alloys suitable for mounting optics and detectors in spacecraft applications.  These alloys help...

Electrodeposition of Al-Mn alloy on AZ31B magnesium alloy in molten salts

International Nuclear Information System (INIS)

Zhang Jifu; Yan Chuanwei; Wang Fuhui

2009-01-01

The Al-Mn alloy coatings were electrodeposited on AZ31B Mg alloy in AlCl 3 -NaCl-KCl-MnCl 2 molten salts at 170 deg. C aiming to improve the corrosion resistance. However, in order to prevent AZ31B Mg alloy from corrosion during electrodeposition in molten salts and to ensure excellent adhesion of coatings to the substrate, AZ31B Mg alloy should be pre-plated with a thin zinc layer as intermediate layer. Then the microstructure, composition and phase constituents of the coatings were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDX), and X-ray diffraction (XRD). It was indicated that, by adjusting the MnCl 2 content in the molten salts from 0.5 wt% to 2 wt%, the Mn content in the alloy coating was increased and the phase constituents were changed from f.c.c Al-Mn solid solution to amorphous phase. The corrosion resistance of the coatings was evaluated by potentiodynamic polarization measurements in 3.5% NaCl solution. It was confirmed that the Al-Mn alloy coatings exhibited good corrosion resistance with a chear passive region and significantly reduced corrosion current density at anodic potentiodynamic polarization. The corrosion resistance of the alloy coatings was also related with the microstructure and Mn content of the coatings.

Hardening of niobium alloys at precrystallization annealing

International Nuclear Information System (INIS)

Vasil'eva, E.V.; Pustovalov, V.A.

1989-01-01

Niobium base alloys were investigated. It is shown that precrystallization annealing of niobium-molybdenum, niobium-vanadium and niobium-zirconium alloys elevates much more sufficiently their resistance to microplastic strains, than to macroplastic strains. Hardening effect differs sufficiently for different alloys. The maximal hardening is observed for niobium-vanadium alloys, the minimal one - for niobium-zirconium alloys

Synthesis and preliminary biological evaluation of [{sup 123}I]Me{sub 2}Pyr, a new potential ligand for imaging of central cannabinoid CB{sub 1} receptors

Energy Technology Data Exchange (ETDEWEB)

Gielow, P. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)]. E-mail: gielow.peter@mh-hannover.de; Klinge, P. [International Neuroscience Institute, Alexis Carrel Str. 4, D-30625 Hannover (Germany); Knapp, W.H. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany); Berding, G. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)

2006-07-15

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[{sup 123}I]iodophenyl)-4-methyl-1H-pyrazole -3-carboxylic acid N',N'-dimethyl-hydrazide ([{sup 123}I]Me{sub 2}Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB{sub 1} receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [{sup 123}I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the {sup 125}I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB{sub 1} receptors.

Structural thermodynamics of alloys

CERN Document Server

Manenc, Jack

1973-01-01

Technical progress has for a very long time been directly dependent on progress in metallurgy, which is itself connected with improvements in the technology of alloys. Metals are most frequently used in the form of alloys for several reasons: the quantity of pure metal in its native state in the earth's crust is very limited; pure metals must be extracted from ores which are themselves impure. Finally, the methods of treatment used lead more easily to alloys than to pure metals. The most typical case is that of iron, where a pure ore may be found, but which is the starting point for cast iron or steel, alloys of iron and carbon. In addition, the properties of alloys are in general superior to those of pure metals and modem metallurgy consists of controlling these properties so as to make them conform to the requirements of the design office. Whilst the engineer was formerly compelled to adapt his designs and constructions to the materials available, such as wood, stone, bronze, iron, cast iron and ordinary st...

Alloying element's substitution in titanium alloy with improved oxidation resistance and enhanced magnetic properties

Energy Technology Data Exchange (ETDEWEB)

Yu, Ang-Yang, E-mail: ayyu@imr.ac.cn; Wei, Hua; Hu, Qing-Miao; Yang, Rui

2017-01-15

First-principles method is used to characterize segregation and magnetic properties of alloyed Ti/TiO{sub 2}interface. We calculate the segregation energy of the doped Ti/TiO{sub 2} interface to investigate alloying atom's distribution. The oxidation resistance of Ti/TiO{sub 2} interface is enhanced by elements Fe and Ni but reduced by element Co. Magnetism could be produced by alloying elements such as Co, Fe and Ni in the bulk of titanium and the surface of Ti at Ti/TiO{sub 2} interface. The presence of these alloying elements could transform the non-magnetic titanium alloys into magnetic systems. We have also calculated the temperature dependence of magnetic permeability for the doped and pure Ti/TiO{sub 2} interfaces. Alloying effects on the Curie temperature of the Ti/TiO{sub 2} interface have been elaborated. - Highlights: • We consider the segregation of alloying atoms on the Ti(101¯0)/TiO{sub 2}(100) interface. • Alloying the Ti//TiO{sub 2} interface with Fe and Ni has a great advantage of improving the oxidation resistance. • Fe, Co and Nican enhance the magnetic properties of the investigated system. • The variation of permeability with temperature has been presented.

Swelling in neutron-irradiated titanium alloys

International Nuclear Information System (INIS)

Peterson, D.T.

1982-04-01

Immersion density measurements have been performed on a series of titanium alloys irradiated in EBR-II to a fluence of 5 x 10 22 n/cm 2 (E > 0.1 MeV) at 450 and 550 0 C. The materials irradiated were the near-alpha alloys Ti-6242S and Ti-5621S, the alpha-beta alloy Ti-64, and the beta alloy Ti-38644. Swelling was observed in all alloys with the greater swelling being observed at 550 0 C. Microstructural examination revealed the presence of voids in all alloys. Ti-38644 was found to be the most radiation resistant. Ti-6242S and Ti-5621S also displayed good radiation resistance, whereas considerable swelling and precipitation were observed in Ti-64 at 550 0 C

Oxidation Behavior of TiAl-Based Alloy Modified by Double-Glow Plasma Surface Alloying with Cr-Mo

Science.gov (United States)

Wei, Xiangfei; Zhang, Pingze; Wang, Qiong; Wei, Dongbo; Chen, Xiaohu

2017-07-01

A Cr-Mo alloyed layer was prepared on a TiAl-based alloy using plasma surface alloying technique. The isothermal oxidation kinetics of the untreated and treated samples was examined at 850 °C. The microstructure and phase composition of the alloyed layer were analyzed by scanning electron microscope (SEM), energy dispersive spectrometer (EDS) and X-ray powder diffraction (XRD). The morphology and constituent of the oxide scales were also analyzed. The results indicated that the oxidation resistance of TiAl was improved significantly after the alloying treatment. The oxide scale eventually became a mixture of Al2O3, Cr2O3 and TiO2. The oxide scale was dense and integrated throughout the oxidation process. The improvement was mainly owing to the enhancing of scale adhesion and the preferential oxidation of aluminum brought by the alloying effect for TiAl-based alloy.

Noble metal alloys for metal-ceramic restorations.

Science.gov (United States)

Anusavice, K J

1985-10-01

A review of the comparative characteristics and properties of noble metal alloys used for metal-ceramic restorations has been presented. Selection of an alloy for one's practice should be based on long-term clinical data, physical properties, esthetic potential, and laboratory data on metal-ceramic bond strength and thermal compatibility with commercial dental porcelains. Although gold-based alloys, such as the Au-Pt-Pd, Au-Pd-Ag, and Au-Pd classes, may appear to be costly compared with the palladium-based alloys, they have clearly established their clinical integrity and acceptability over an extended period of time. Other than the relatively low sag resistance of the high gold-low silver content alloys and the potential thermal incompatibility with some commercial porcelain products, few clinical failures have been observed. The palladium-based alloys are less costly than the gold-based alloys. Palladium-silver alloys require extra precautions to minimize porcelain discoloration. Palladium-copper and palladium-cobalt alloys may also cause porcelain discoloration, as copper and cobalt are used as colorants in glasses. The palladium-cobalt alloys are least susceptible to high-temperature creep compared with all classes of noble metals. Nevertheless, insufficient clinical data exist to advocate the general use of the palladium-copper and palladium-cobalt alloys at the present time. One should base the selection and use of these alloys in part on their ability to meet the requirements of the ADA Acceptance Program. A list of acceptable or provisionally acceptable alloys is available from the American Dental Association and is published annually in the Journal of the American Dental Association. Dentists have the legal and ethical responsibility for selection of alloys used for cast restorations. This responsibility should not be delegated to the dental laboratory technician. It is advisable to discuss the criteria for selection of an alloy with the technician and the

Electroplating technologies of alloys

International Nuclear Information System (INIS)

Kim, Joung Soo; Kim, Seung Ho; Jeong, Hyun Kyu; Hwnag, Sung Sik; Seo, Yong Chil; Kim, Dong Jin; Seo, Moo Hong

2001-12-01

In localization of electrosleeving technique, there are some problems like the following articles. Firstly, Patents published by OHT have claimed Ni-P, Ni-B alloy plating and Mo, Mn Cr, W, Co as a pinning agent. Secondly, alloy platings have many restrictions. There are some method to get alloy plating in spite of the various restrictions. If current density increase above limiting current density in one of the metals, both of the metals discharge at the same time. The addition of surface active agent(sufactant) in the plating solution is one of the methods to get alloy plating. Alloy plating using pulse current easily controls chemical composition and structure of deposit. Ni-Fe alloy plating is known to exhibit anomalous type of plating behavior in which deposition of the less noble metal is favoured. Presence of hypophohphite ion can control the iron codeposition by changing the deposition mechanism. Hypophohphite suppresses the deposition of Fe and also promotes Ni. Composite plating will be considered to improve the strength at the high temperature. Addition of particle size of 10δ400μm makes residual stress compressive in plate layer and suppress the grain growth rate at the high temperature. Addition of particle makes suface roughness high and fracture stress low at high temperature. But, selection of the kinds of particle and control of additives amount overcome the problems above

Processing and properties of Nb-Ti-based alloys

International Nuclear Information System (INIS)

Sikka, V.K.; Viswanathan, S.

1992-01-01

The processing characteristics, tensile properties, and oxidation response of two Nb-Ti-Al-Cr alloys were investigated. One creep test at 650 C and 172 MPa was conducted on the base alloy which contained 40Nb-40Ti-10Al-10Cr. A second alloy was modified with 0.11 at. % carbon and 0.07 at. % yttrium. Alloys were arc melted in a chamber backfilled with argon, drop cast into a water-cooled copper mold, and cold rolled to obtain a 0.8-mm sheet. The sheet was annealed at 1,100 C for 0.5 h. Longitudinal tensile specimens and oxidation specimens were obtained for both the base alloy and the modified alloy. Tensile properties were obtained for the base alloy at room temperature, 400, 600, 700, 800, 900, and 1,000 C, and for the modified alloy at room temperature, 400, 600, 700, and 800 C. Oxidation tests on the base alloy and modified alloy, as measured by weight change, were carried out at 600, 700, 800, and 900 C. Both the base alloy and the modified alloy were extremely ductile and were cold rolled to the final sheet thickness of 0.8 mm without an intermediate anneal. The modified alloy exhibited some edge cracking during cold during cold rolling. Both alloys recrystallized at the end of a 0.5-h annealing treatment. The alloys exhibited moderate strength and oxidation resistance below 600 C, similar to the results of alloys reported in the literature

Aeronautical requirements for Inconel 718 alloy

Science.gov (United States)

Elefterie, C. F.; Guragata, C.; Bran, D.; Ghiban, B.

2017-06-01

The project goal is to present the requirements imposed by aviation components made from super alloys based on Nickel. A significant portion of fasteners, locking lugs, blade retainers and inserts are manufactured from Alloy 718. The thesis describes environmental factors (corrosion), conditions of external aggression (salt air, intense heat, heavy industrial pollution, high condensation, high pressure), mechanical characteristics (tensile strength, yield strength and fatigue resistance) and loadings (tensions, compression loads) that must be satisfied simultaneously by Ni-based super alloy, compared to other classes of aviation alloys (as egg. Titanium alloys, Aluminum alloys). For this alloy the requirements are strength durability, damage tolerance, fail safety and so on. The corrosion can be an issue, but the fatigue under high-magnitude cyclic tensile loading it’s what limits the lifetime of the airframe. Also, the excellent malleability and weldability characteristics of the 718 system make the material physical properties tolerant of manufacturing processes. These characteristics additionally continue to provide new opportunities for advanced manufacturing methods.

Recent advances in alloy design of Ni{sub 3}Al alloys for structural use

Energy Technology Data Exchange (ETDEWEB)

Liu, C.T.; George, E.P.

1996-12-31

This is a comprehensive review of recent advances in R&D of Ni{sub 3}Al-based alloys for structural use at elevated temperatures in hostile environments. Recent studies indicate that polycrystalline Ni{sub 3}Al is intrinsically quite ductile at ambient temperatures, and its poor tensile ductility and brittle grain-boundary fracture are caused mainly by moisture-induced hydrogen embrittlement when the aluminide is tested in moisture- or hydrogen-containing environments. Tensile ductility is improved by alloying with substitutional and interstitial elements. Among these additives, B is most effective in suppressing environmental embrittlement and enhancing grain-boundary cohesion, resulting in a dramatic increase of tensile ductility at room temperature. Both B-doped and B-free Ni{sub 3}Al alloys exhibit brittle intergranular fracture and low ductility at intermediate temperatures (300-850 C) because of oxygen-induced embrittlement in oxidizing environments. Cr is found to be most effective in alleviating elevated-temperature embrittlement. Parallel efforts on alloy development using physical metallurgy principles have led to development of several Ni{sub 3}Al alloys for industrial use. The unique properties of these alloys are briefly discussed. 56 refs, 15 figs, 3 tabs.

Thermal Plasma Spheroidization of High-Nitrogen Stainless Steel Powder Alloys Synthesized by Mechanical Alloying

Science.gov (United States)

Razumov, Nikolay G.; Popovich, Anatoly A.; Wang, QingSheng

2018-03-01

This paper presents the results of experimental studies on the treatment of Fe-23Cr-11Mn-1N high-nitrogen stainless steel powder alloys, synthesized by the mechanical alloying (MA) of elemental powders in the flow of a thermal plasma. Fe-23Cr-11Mn-1N high-nitrogen stainless steel powder alloys were prepared by MA in the attritor under an argon atmosphere. For spheroidization of Fe-23Cr-11Mn-1N high-nitrogen stainless steel powder alloys, the TekSphero 15 plant manufactured by Tekna Plasma Systems Inc was used. The studies have shown the possibility of obtaining Fe-23Cr-11Mn-1N high-nitrogen spherical powders steel alloys from the powder obtained by MA. According to the results of a series of experiments, it was found that the results of plasma spheroidization of powders essentially depend on the size of the fraction due to some difference in the particle shape and flowability, and on the gas regime of the plasma torch. It is established that during the plasma spheroidization process, some of the nitrogen leaves the alloy. The loss rate of nitrogen depends on the size of the initial particles.

Microstructural characterization of mechanically alloyed Al–Cu–Mn alloy with zirconium

Energy Technology Data Exchange (ETDEWEB)

Prosviryakov, A.S., E-mail: pro.alex@mail.ru; Shcherbachev, K.D.; Tabachkova, N.Yu.

2015-01-19

An evolution of Al–Cu–Mn alloy microstructure during its mechanical alloying with zirconium 20 wt% and after subsequent annealing was studied by X-ray diffraction, light microscopy and transmission electron microscopy. The effect of milling time on powder microhardness, Al lattice parameter, lattice microstrain and crystallite size was determined.

Antibacterial biodegradable Mg-Ag alloys

Directory of Open Access Journals (Sweden)

D Tie

2013-06-01

Full Text Available The use of magnesium alloys as degradable metals for biomedical applications is a topic of ongoing research and the demand for multifunctional materials is increasing. Hence, binary Mg-Ag alloys were designed as implant materials to combine the favourable properties of magnesium with the well-known antibacterial property of silver. In this study, three Mg-Ag alloys, Mg2Ag, Mg4Ag and Mg6Ag that contain 1.87 %, 3.82 % and 6.00 % silver by weight, respectively, were cast and processed with solution (T4 and aging (T6 heat treatment.The metallurgical analysis and phase identification showed that all alloys contained Mg4Ag as the dominant β phase. After heat treatment, the mechanical properties of all Mg-Ag alloys were significantly improved and the corrosion rate was also significantly reduced, due to presence of silver. Mg(OH2 and MgO present the main magnesium corrosion products, while AgCl was found as the corresponding primary silver corrosion product. Immersion tests, under cell culture conditions, demonstrated that the silver content did not significantly shift the pH and magnesium ion release. In vitro tests, with both primary osteoblasts and cell lines (MG63, RAW 264.7, revealed that Mg-Ag alloys show negligible cytotoxicity and sound cytocompatibility. Antibacterial assays, performed in a dynamic bioreactor system, proved that the alloys reduce the viability of two common pathogenic bacteria, Staphylococcus aureus (DSMZ 20231 and Staphylococcus epidermidis (DSMZ 3269, and the results showed that the killing rate of the alloys against tested bacteria exceeded 90%. In summary, biodegradable Mg-Ag alloys are cytocompatible materials with adjustable mechanical and corrosion properties and show promising antibacterial activity, which indicates their potential as antibacterial biodegradable implant materials.

Reaction kinetics of oxygen on single-phase alloys, oxidation of nickel and niobium alloys

International Nuclear Information System (INIS)

Lalauze, Rene

1973-01-01

This research thesis first addresses the reaction kinetics of oxygen on alloys. It presents some generalities on heterogeneous reactions (conventional theory, theory of jumps), discusses the core reaction (with the influence of pressure), discusses the influence of metal self-diffusion on metal oxidation kinetics (equilibrium conditions at the interface, hybrid diffusion regime), reports the application of the hybrid diffusion model to the study of selective oxidation of alloys (Wagner model, hybrid diffusion model) and the study of the oxidation kinetics of an alloy forming a solid solution of two oxides. The second part reports the investigation of the oxidation of single phase nickel and niobium alloys (phase α, β and γ)

A study of the formation of Cr-surface alloyed layer on structural alloy steel by Co2 laser

International Nuclear Information System (INIS)

Kim, T.H.; Han, W.S.

1986-01-01

In order to improve wear and erosion-resistances of a structural alloy steel (SNCM 8) during heat-cycling, chromium-alloyed layers were produced on the surface by irradiating Co 2 laser. Specimens were prepared either by electroplating of hard-chromium or coating of chromium powders on the steel followed by the laser treatment. Index values, which related the depth and the width of the alloyed layers to the scanning speed of laser, for both samples are experimentally measured. At a fixed scanning speed, while both samples resulted in a similar depth of the alloyed layers, the chromium powder coated specimen showed larger width of the alloyed layer than the chromium electroplated one. The hardness values of the alloyed layers in both samples were slightly lower than that of the martensitic region beneath the alloyed layers. But they are considerably higher than those of steel matrices. Regardless of the prior treatments before laser irradiation, distributions of chromium were fairly uniform throughout the alloyed layers. (Author)

Precipitation and Hardening in Magnesium Alloys

Science.gov (United States)