Science.gov

Sample records for 2c table 2a

  1. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range (degrees F) Criteria Reactivityfactor 21 280-290...

  2. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range(degrees F) Criteria Reactivityfactor (g O3/g VOC) 21...

  3. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range (degrees F) Criteria Reactivityfactor 21 280-290...

  4. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range(degrees F) Criteria Reactivityfactor (g O3/g VOC) 21...

  5. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range(degrees F) Criteria Reactivityfactor (g O3/g VOC) 21...

  6. 50 CFR Table 2c to Part 660... - Sablefish North of 36° N. lat. Allocations, 2014 and Beyond

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Sablefish North of 36° N. lat. Allocations, 2014 and Beyond 2c Table 2c to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE...

  7. Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases.

    PubMed

    Luo, J; Pato, M D; Riordan, J R; Hanrahan, J W

    1998-05-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity declines rapidly when excised from transfected Chinese hamster ovary (CHO) or human airway cells because of membrane-associated phosphatase activity. In the present study, we found that CFTR channels usually remained active in patches excised from baby hamster kidney (BHK) cells overexpressing CFTR. Those patches with stable channel activity were used to investigate the regulation of CFTR by exogenous protein phosphatases (PP). Adding PP2A, PP2C, or alkaline phosphatase to excised patches reduced CFTR channel activity by > 90% but did not abolish it completely. PP2B caused weak deactivation, whereas PP1 had no detectable effect on open probability (Po). Interestingly, the time course of deactivation by PP2C was identical to that of the spontaneous rundown observed in some patches after excision. PP2C and PP2A had distinct effects on channel gating Po declined during exposure to exogenous PP2C (and during spontaneous rundown, when it was observed) without any change in mean burst duration. By contrast, deactivation by exogenous PP2A was associated with a dramatic shortening of burst duration similar to that reported previously in patches from cardiac cells during deactivation of CFTR by endogenous phosphatases. Rundown of CFTR-mediated current across intact T84 epithelial cell monolayers was insensitive to toxic levels of the PP2A inhibitor calyculin A. These results demonstrate that exogenous PP2C is a potent regulator of CFTR activity, that its effects on single-channel gating are distinct from those of PP2A but similar to those of endogenous phosphatases in CHO, BHK, and T84 epithelial cells, and that multiple protein phosphatases may be required for complete deactivation of CFTR channels.

  8. 40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at a Major Source of HAP...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Ignition Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE â¤500 HP Located at a Major Source of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE...

  9. 40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at a Major Source of HAP...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Ignition Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ⤠500 HP Located at a Major Source of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ≤...

  10. 40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at a Major Source of HAP...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Ignition Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE â¤500 HP Located at a Major Source of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE...

  11. 40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary RICE Located at a Major Source of HAP...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Ignition Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ⤠500 HP Located at a Major Source of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary RICE Located at a Major Source of HAP Emissions and Existing Spark Ignition Stationary RICE ≤...

  12. 40 CFR Table 2c to Subpart Zzzz of... - Requirements for Existing Compression Ignition Stationary Rice Located at Major Sources of HAP...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Ignition Stationary Rice Located at Major Sources of HAP Emissions 2c Table 2c to Subpart ZZZZ of Part 63... Stationary Rice Located at Major Sources of HAP Emissions As stated in §§ 63.6600 and 63.6640, you must comply with the following requirements for existing compression ignition stationary RICE: For...

  13. Deletion of the α2A2C-adrenoceptors accelerates cutaneous wound healing in mice

    PubMed Central

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-01-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. PMID:25186490

  14. Deletion of the α2A2C-adrenoceptors accelerates cutaneous wound healing in mice.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A2C-adrenoceptor deletion accelerates cutaneous wound healing in mice.

  15. 50 CFR Table 2a to Part 679 - Species Codes: FMP Groundfish

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Species Codes: FMP Groundfish 2a Table 2a... ALASKA Pt. 679, Table 2a Table 2a to Part 679—Species Codes: FMP Groundfish Species description Code Atka mackerel (greenling) 193 Flatfish, miscellaneous (flatfish species without separate codes) 120...

  16. Preferentially grown nanostructured MgB2C2: A new material for lightening applications

    NASA Astrophysics Data System (ADS)

    Singh, Paviter; Singh, Kulwinder; Kaur, Manpreet; Kaur, Harpreet; Singh, Bikmramjeet; Kaur, Gurpreet; Kaur, Manjot; Kumar, Manjeet; Kaur, Kamalpreet; Bala, Rajni; Kumar, Akshay

    2017-03-01

    Nanostructured MgB2C2 is a promising candidate as functional material. High Temperature synthesis conditions were the limitations for its exploitation in materials research. Present study deals with the synthesis of specifically oriented nanostructured MgB2C2 at relatively low temperature by solvothermal route. The synthesis conditions are modified to grow these nanostructures in least dense plane (002). Optical properties are explored for the first time. XRD analysis confirms the formation of MgB2C2 phase. Morphological analysis (Transmission/Scanning Electron Microscopy) indicated that the synthesized material is in nano range. Photoluminescence study shows that the synthesized material emits light in visible spectrum when excited at 380 nm. The quantum efficiency of synthesized material calculated by De Mello's method is approximately 23% which makes the material efficient enough for lightening applications.

  17. Serotonin-2C and -2A Receptor Co-expression on Cells in the Rat Medial Prefrontal Cortex

    PubMed Central

    Nocjar, Christine; Alex, Katherine D; Sonneborn, Alex; Abbas, Atheir I; Roth, Bryan L; Pehek, Elizabeth A

    2015-01-01

    Neural function within the medial prefrontal cortex (mPFC) regulates normal cognition, attention and impulse control, implicating neuroregulatory abnormalities within this region in mental dysfunction related to schizophrenia, depression and drug abuse. Both serotonin -2A (5-HT2A) and -2C (5-HT2C) receptors are known to be important in neuropsychiatric drug action and are distributed throughout the mPFC. However, their interactive role in serotonergic cortical regulation is poorly understood. While the main signal transduction mechanism for both receptors is stimulation of phosphoinositide production, they can have opposite effects downstream. 5-HT2A versus 5-HT2C receptor activation oppositely regulates behavior and can oppositely affect neurochemical release within the mPFC. These distinct receptor effects could be caused by their differential cellular distribution within the cortex and/or other areas. It is known that both receptors are located on GABAergic and pyramidal cells within the mPFC, but it is not clear whether they are expressed on the same or different cells. The present work employed immunofluorescence with confocal microscopy to examine this in layers V-VI of the prelimbic mPFC. The majority of GABA cells in the deep prelimbic mPFC expressed 5-HT2C receptor immunoreactivity. Furthermore, most cells expressing 5-HT2C receptor immunoreactivity notably co-expressed 5-HT2A receptors. However, 27% of 5-HT2C receptor immunoreactive cells were not GABAergic, indicating that a population of prelimbic pyramidal projection cells could express the 5-HT2C receptor. Indeed, some cells with 5-HT2C and 5-HT2A receptor co-labeling had a pyramidal shape and were expressed in the typical layered fashion of pyramidal cells. This indirectly demonstrates that 5-HT2C and 5-HT2A receptors may be commonly co-expressed on GABAergic cells within the deep layers of the prelimbic mPFC and perhaps co-localized on a small population of local pyramidal projection cells. Thus a

  18. Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.

    PubMed

    Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E

    1998-11-01

    Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT.

  19. Regiospecific synthesis of 3-substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2-c]pyrimidine.

    PubMed

    Katritzky, Alan R; Xu, Yong-Jiang; Tu, Hongbin

    2003-06-13

    3-Substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2-c]pyrimidine were obtained regiospecifically in yields of 35-92% in one pot by reaction of 2-aminopyridines or 2-(or 4-)aminopyrimidines, respectively, with 1,2-bis(benzotriazolyl)-1,2-(dialkylamino)ethanes.

  20. Role for NKG2-A and NKG2-C surface receptors in chronic CD4+ T-cell responses.

    PubMed

    Ortega, Consuelo; Romero, Pilar; Palma, Agustín; Orta, Teresa; Peña, José; García-Vinuesa, Amaya; Molina, Ignacio J; Santamaría, Manuel

    2004-12-01

    The participation of CD94 and NKG2 gene family members in the function of NK cells and CD8+ cytolytic cells has recently been addressed in detail. However, the role that these molecules play in the key CD4+ regulatory cells remains largely unexplored. This study has examined the expression and regulation of CD94 and NKG2 genes in purified human peripheral CD4+ cells stimulated with several agents. We found a constitutive expression of NKG2-E in CD94-depleted resting peripheral CD4+ cells, whereas inductions of NKG2-A and NKG2-C required chronic cell activation and occurred after expression of CD94. We found that CD3-mediated stimulation induces the expression of CD94 first by day 5 of culture, followed by NKG2-A by day 15 and finally NKG2-C, which is not detected until 20 days after repeated stimulation. This pattern of gene expression differs sharply from that observed in purified CD8+ T cells, where mRNA from all NKG2 gene family members are detected after 5 days of stimulation. Selective activation of TCR V beta 2-bearing cells with toxic shock syndrome toxin-1 superantigen reveals that mRNA induction of NKG2-A and NKG2-C genes is significantly influenced by the presence of cytokines (IL-10 and TGF-beta) and by the restimulation of the cells. In addition, the occupancy of the CD94/NKG2-A receptor expressed on these superantigen-stimulated CD4+ T lymphocytes abrogates TNF-alpha and IFN-gamma production, whereas NKG2-C enhances production of these cytokines. Taken together our results reveal strict gene regulatory mechanisms for CD94 and NKG2 gene expression on CD4+ cells that are different from those governing the expression of these same genes in CD8+ cells. The results suggest that these genes also participate in chronic CD4+ T-cell responses.

  1. Recent spreading of a divergent canine parvovirus type 2a (CPV-2a) strain in a CPV-2c homogenous population.

    PubMed

    Pérez, Ruben; Bianchi, Pablo; Calleros, Lucía; Francia, Lourdes; Hernández, Martín; Maya, Leticia; Panzera, Yanina; Sosa, Katia; Zoller, Stephanie

    2012-03-23

    Canine parvovirus type 2 (CPV-2), which causes acute hemorrhagic enteritis in dogs, is comprised of three antigenic variants (2a, 2b, and 2c) that are distributed worldwide with different frequencies. Variant prevalence was analyzed in 150 CPV-2-positive samples collected from the Uruguayan dog population in 2007-2010. Samples were analyzed with polymerase chain reaction, restriction fragment length polymorphism, and sequencing of the coding region for the largest and most variable loop of the VP2 capsid protein. CPV-2c was the only strain detected from 2007 to 2009. Uruguayan CPV-2c showed high homogeneity in both nucleotide and amino acid sequences, indicating a low level of genetic variability. In 2010, an unexpected epidemiological change occurred in Uruguay as a consequence of the appearance of a novel CPV-2a strain. This variant rapidly spread through the Uruguayan dog population and was detected in 20 of the 52 cases (38%) analyzed in 2010. CPV-2a sequences were identical in all field viruses analyzed, and in addition to the characteristic 426Asn residue, the sequences showed amino acid substitutions (267Tyr, 324Ile, and 440Ala) not observed in the Uruguayan CPV-2c. These data and the first detection in April 2010 suggest that the CPV-2a variant recently emerged in Uruguay and underwent clonal expansion. This observation is the first case in which a CPV-2a variant increased its frequency in a dog population where CPV-2c was prevalent. Our results emphasize the dynamic changes in CPV variants and highlight the importance of ongoing surveillance programs to provide a better understanding of virus epidemiology.

  2. Common α2A and α2C adrenergic receptor polymorphisms do not affect plasma membrane trafficking.

    PubMed

    Hurt, Carl M; Sorensen, Matt W; Angelotti, Timothy

    2014-06-01

    Various naturally occurring polymorphic forms of human G protein-coupled receptors (GPCRs) have been identified and linked to diverse pathological diseases, including receptors for vasopressin type 2 (nephrogenic diabetes insipidus) and gonadotropin releasing hormone (hypogonadotropic hypogonadism). In most cases, polymorphic amino acid mutations disrupt protein folding, altering receptor function as well as plasma membrane expression. Other pathological GPCR variants have been found that do not alter receptor function, but instead affect only plasma membrane trafficking (e.g., delta opiate and histamine type 1 receptors). Thus, altered membrane trafficking with retained receptor function may be another mechanism causing polymorphic GPCR dysfunction. Two common human α2A and α2C adrenergic receptor (AR) variants have been identified (α2A N251K and α2C Δ322-325 ARs), but pharmacological analysis of ligand binding and second messenger signaling has not consistently demonstrated altered receptor function. However, possible alterations in plasma membrane trafficking have not been investigated. We utilized a systematic approach previously developed for the study of GPCR trafficking motifs and accessory proteins to assess whether these α2 AR variants affected intracellular trafficking or plasma membrane expression. By combining immunofluorescent microscopy, glycosidic processing analysis, and quantitative fluorescent-activated cell sorting (FACS), we demonstrate that neither variant receptor had altered intracellular localization, glycosylation, nor plasma membrane expression compared to wild-type α2 ARs. Therefore, pathopharmacological properties of α2A N251K and α2C Δ322-325 ARs do not appear to be due to altered receptor pharmacology or plasma membrane trafficking, but may involve interactions with other intracellular signaling cascades or proteins.

  3. Involvement of 5-HT(2A/2B/2C) receptors on memory formation: simple agonism, antagonism, or inverse agonism?

    PubMed

    Meneses, Alfredo

    2002-12-01

    1. The 5-HT2 receptors subdivision into the 5-HT(2A/2B/2C) subtypes along with the advent of the selective antagonists has allowed a more detailed investigation on the role and therapeutic significance of these subtypes in cognitive functions. The present study further analyzed the 5-HT2 receptors role on memory consolidation. 2. The SB-200646 (a selective 5-HT(2B/2C) receptor antagonist) and LY215840 (a nonselective 5-HT(2/7) receptor antagonist) posttraining administration had no effect on an autoshaped memory consolidation. However, both drugs significantly and differentially antagonized the memory impairments induced by 1-(3-chlorophenyl)piperazine (mCPP), 1-naphtyl-piperazine (1-NP), mesulergine, or N-(3-trifluoromethylphenyl) piperazine (TFMPP). 3. In contrast, SB-200646 failed to modify the facilitatory procognitive effect produced by (+/-)-2.5-dimethoxy-4-iodoamphetamine (DOI) or ketanserin, which were sensitive to MDL100907 (a selective 5-HT2A receptor antagonist) and to a LY215840 high dose. 4. Finally, SB-200646 reversed the learning deficit induced by dizocilpine, but not that by scopolamine: while SB-200646 and MDL100907 coadministration reversed memory deficits induced by both drugs. 5. It is suggested that 5-HT(2B/2C) receptors might be involved on memory formation probably mediating a suppressive or constraining action. Whether the drug-induced memory impairments in this study are explained by simple agonism, antagonism, or inverse agonism at 5-HT2 receptors remains unclear at this time. 6. Notably, the 5-HT2 receptor subtypes blockade may provide some benefit to reverse poor memory consolidation conditions associated with decreasedcholinergic, glutamatergic, and/or serotonergic neurotransmission.

  4. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis.

    PubMed

    Loegl, J; Hiden, U; Nussbaumer, E; Schliefsteiner, C; Cvitic, S; Lang, I; Wadsack, C; Huppertz, B; Desoye, G

    2016-11-01

    The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis.

  5. M2A and M2C Macrophage Subsets Ameliorate Inflammation and Fibroproliferation in Acute Lung Injury Through Interleukin 10 Pathway.

    PubMed

    Tang, Lunxian; Zhang, Hua; Wang, Chunmei; Li, Hongqiang; Zhang, Qian; Bai, Jianwen

    2016-12-09

    The role of M2 macrophages in the resolution and fibroproliferation of acute lung injury (ALI) is poorly understood. In this study, we investigated the effects of two M2 macrophage subtypes, M2a induced by interleukin (IL)-4/IL-13 and M2c induced by IL-10/transforming growth factor (TGF)-β, on the pathogenesis of ALI. M2a and M2c were adoptively transferred into LPS-induced ALI mice model. Data showed that Vybrant-labeled macrophages appeared in the lungs of ALI mice. Subsequently, we observed that both subsets significantly reduced lung inflammation and injury including a reduction of neutrophil influx into the lung and an augmentation of apoptosis. Interestingly, M2c macrophages more effectively suppressed indices of lung injury than M2a macrophages. M2c macrophages were also more effective than M2a in reduction of lung fibrosis. In addition, we found that M2c but not M2a macrophages increased IL-10 level in lung tissues of the recipient ALI mice partially mediated by activating the JAK1/STAT3/SOCS3 signaling pathway. After blocking IL-10, these superior effects of M2c over M2a were abolished. These data imply that M2c are more potent than M2a macrophages in protecting against lung injury and subsequent fibrosis due to their ability to produce IL-10. Therefore, reprogramming macrophages to M2c subset may be a novel treatment modality with transitional potential.

  6. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease.

    PubMed

    Lu, Junyu; Cao, Qi; Zheng, Dong; Sun, Yan; Wang, Changqi; Yu, Xiao; Wang, Ya; Lee, Vincent W S; Zheng, Guoping; Tan, Thian K; Wang, Xin; Alexander, Stephen I; Harris, David C H; Wang, Yiping

    2013-10-01

    Two types of alternatively activated macrophages, M(2a) induced by IL-4/IL-13 and M(2c) by IL-10/TGF-β, exhibit anti-inflammatory functions in vitro and protect against renal injury in vivo. Since their relative therapeutic efficacy is unclear, we compared the effects of these two macrophage subsets in murine adriamycin nephrosis. Both subsets significantly reduced renal inflammation and renal injury; however, M(2c) macrophages more effectively reduced glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than M(2a) macrophages. The M(2c) macrophages were also more effective than M(2a) in reduction of macrophage and CD4(+) T-cell infiltration in kidney. Moreover, nephrotic mice treated with M(2c) had a greater reduction in renal fibrosis than those treated with M(2a). M(2c) but not M(2a) macrophages induced regulatory T cells (Tregs) from CD4(+)CD25(-) T cells in vitro, and increased Treg numbers in local draining lymph nodes of nephrotic mice. To determine whether the greater protection with M(2c) was due to their capability to induce Tregs, the Tregs were depleted by PC61 antibody in nephrotic mice treated with M(2a) or M(2c). Treg depletion diminished the superior effects of M(2c) compared to M(2a) in protection against renal injury, inflammatory infiltrates, and renal fibrosis. Thus, M(2c) are more potent than M(2a) macrophages in protecting against renal injury due to their ability to induce Tregs.

  7. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning.

    PubMed

    Meneses, A; Hong, E

    1997-08-01

    The effects of post-training (i.p.) injection of TFMPP, mCPP, DOI or 1-NP in the autoshaping learning task was explored. Furthermore, the post-training effects of these agonists after treatment with the antagonists (+/-)-pindolol, (+/-)-propranolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL-72222 or p-chloroamphetamine (5-HT depleter) were studied. Rats were individually trained with a lever-press response (conditioned response; CR) on the autoshaping task and tested 24 h later. The results showed that the injection of TFMPP (1-10 mg/kg), mCPP (1-10 mg/kg), 1-NP (0.1-1.0 mg/kg) or mesulergine (0.4 mg/kg) decreased the rate of CR, while DOI (0.01-0.1 mg/kg) and ritanserin (0.5 mg/kg) and ketanserin (0.001-0.1 mg/kg) increased it. However, the effect induced by TFMPP was reversed by (+/-)-pindolol, ketanserin, ritanserin and PCA; the mCPP-induced effect was antagonized by (+/-)-propranolol, ketanserin, ritanserin and MDL-72222; and the effect produced by 1-NP was reversed by ketanserin, ritanserin and PCA. In addition, the increment in CR provoked by DOI was enhanced by ketanserin, and reversed by ritanserin, mesulergine and PCA. These findings suggest that TFMPP, 1-NP and DOI exerted their effects via stimulation of presynaptic 5-HT receptors. The effects of mCPP most probably reflect activation of postsynaptic receptors. The present data suggest that both 5-HT1B and 5-HT2A-2C receptors play a significant role in the consolidation of learning.

  8. Discovering the mechanisms underlying serotonin (5-HT)2A and 5-HT2C receptor regulation following nicotine withdrawal in rats.

    PubMed

    Zaniewska, Magdalena; Alenina, Natalia; Wydra, Karolina; Fröhler, Sebastian; Kuśmider, Maciej; McCreary, Andrew C; Chen, Wei; Bader, Michael; Filip, Małgorzata

    2015-08-01

    We have previously demonstrated that nicotine withdrawal produces depression-like behavior and that serotonin (5-HT)2A/2C receptor ligands modulate that mood-like state. In the present study we aimed to identify the mechanisms (changes in radioligand binding, transcription or RNA-editing) related to such a behavioral outcome. Rats received vehicle or nicotine (0.4 mg/kg, s.c.) for 5 days in home cages. Brain 5-HT2A/2C receptors were analyzed on day 3 of nicotine withdrawal. Nicotine withdrawal increased [(3)H]ketanserin binding to 5-HT2A receptors in the ventral tegmental area and ventral dentate gyrus, yet decreased binding in the nucleus accumbens shell. Reduction in [(3)H]mesulergine binding to 5-HT2C receptors was seen in the ventral dentate gyrus. Profound decrease in the 5-HT2A receptor transcript level was noted in the hippocampus and ventral tegmental area. Out of five 5-HT2C receptor mRNA editing sites, deep sequencing data showed a reduction in editing at the E site and a trend toward reduction at the C site in the hippocampus. In the ventral tegmental area, a reduction for the frequency of CD 5-HT2C receptor transcript was seen. These results show that the reduction in the 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor density in the hippocampus and ventral tegmental area during nicotine withdrawal, while decreased 5-HT2C receptor mRNA editing may explain the reduction in receptor labeling in the hippocampus. Serotonin (5-HT)2A/2C receptor ligands alleviate depression-like state in nicotine-withdrawn rats. Here, we show that the reduction in 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor number in the hippocampus and ventral tegmental area during nicotine withdrawal, while attenuated 5-HT2C receptor mRNA editing in the hippocampus might explain reduced inverse agonist binding to 5-HT2C receptor and suggest a shift toward a population of more active receptors. 5

  9. Identification of high-risk Listeria monocytogenes serotypes in lineage I (serotype 1/2a, 1/2c, 3a and 3c) using multiplex PCR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: Using molecular subtyping techniques, Listeria monocytogenes is divided into three major phylogenetic lineages, and a multiplex PCR method can differentiate five L. monocytogenes subgroups: 1/2a-3a, 1/2c-3c, 1/2b-3b-7, 4b-4d-4e, and 4a-4c. In the current study, we conducted genome comparison...

  10. Association of FCGR2A p.R131H and CCL2 c.-2518 A>G gene variants with thrombocytopenia in patients with dengue virus infection.

    PubMed

    Alagarasu, Kalichamy; Bachal, Rupali V; Damle, Indraneel; Shah, Paresh S; Cecilia, Dayaraj

    2015-11-01

    FCGR2A and CCL2 gene variants are important in dengue pathogenesis and were investigated in 122 dengue patients (DENs) [89 dengue fever (DF) and 33 dengue hemorrhagic fever (DHF)] and 107 healthy controls (HCs) to find out their association with severity of dengue. Genotype frequencies of FCGR2A p.R131H and CCL2 c.-2518 A > G polymorphisms were not different between DF, DHF and HC. Significantly higher frequency of R/R genotype of FCGR2A p.R131H was observed in DEN cases with thrombocytopenia (TP) while the G/G genotype of CCL2 c.-2518 A > G was observed only in DEN cases with TP (p < 0.005). These results suggest that FCGR2A and CCL2 gene variants were associated with the risk of TP in dengue infections.

  11. Dephosphorylation of Ser-137 in DARPP-32 by protein phosphatases 2A and 2C: different roles in vitro and in striatonigral neurons.

    PubMed Central

    Desdouits, F; Siciliano, J C; Nairn, A C; Greengard, P; Girault, J A

    1998-01-01

    DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr=32000) is highly expressed in striatonigral neurons in which its phosphorylation is regulated by several neurotransmitters including dopamine and glutamate. DARPP-32 becomes a potent inhibitor of protein phosphatase 1 when it is phosphorylated on Thr-34 by cAMP- or cGMP-dependent protein kinases. DARPP-32 is also phosphorylated on Ser-137 by protein kinase CK1 (CK1), in vitro and in vivo. This phosphorylation has an important regulatory role since it inhibits the dephosphorylation of Thr-34 by calcineurin in vitro and in striatonigral neurons. Here, we show that DARPP-32 phosphorylated by CK1 is a substrate in vitro for protein phosphatases 2A and 2C, but not protein phosphatase 1 or calcineurin. However, in substantia nigra slices, dephosphorylation of Ser-137 was markedly sensitive to decreased temperature, and not detectably affected by the presence of okadaic acid under conditions in which dephosphorylation of Thr-34 by protein phosphatase 2A was inhibited. These results suggest that, in neurons, phospho-Ser-137-DARPP-32 is dephosphorylated by protein phosphatase 2C, but not 2A. Thus, DARPP-32 appears to be a component of a regulatory cascade of phosphatases in which dephosphorylation of Ser-136 by protein phosphatase 2C facilitates dephosphorylation of Thr-34 by calcineurin, removing the cyclic nucleotide-induced inhibition of protein phosphatase 1. PMID:9461512

  12. Dephosphorylation of Ser-137 in DARPP-32 by protein phosphatases 2A and 2C: different roles in vitro and in striatonigral neurons.

    PubMed

    Desdouits, F; Siciliano, J C; Nairn, A C; Greengard, P; Girault, J A

    1998-02-15

    DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr=32000) is highly expressed in striatonigral neurons in which its phosphorylation is regulated by several neurotransmitters including dopamine and glutamate. DARPP-32 becomes a potent inhibitor of protein phosphatase 1 when it is phosphorylated on Thr-34 by cAMP- or cGMP-dependent protein kinases. DARPP-32 is also phosphorylated on Ser-137 by protein kinase CK1 (CK1), in vitro and in vivo. This phosphorylation has an important regulatory role since it inhibits the dephosphorylation of Thr-34 by calcineurin in vitro and in striatonigral neurons. Here, we show that DARPP-32 phosphorylated by CK1 is a substrate in vitro for protein phosphatases 2A and 2C, but not protein phosphatase 1 or calcineurin. However, in substantia nigra slices, dephosphorylation of Ser-137 was markedly sensitive to decreased temperature, and not detectably affected by the presence of okadaic acid under conditions in which dephosphorylation of Thr-34 by protein phosphatase 2A was inhibited. These results suggest that, in neurons, phospho-Ser-137-DARPP-32 is dephosphorylated by protein phosphatase 2C, but not 2A. Thus, DARPP-32 appears to be a component of a regulatory cascade of phosphatases in which dephosphorylation of Ser-136 by protein phosphatase 2C facilitates dephosphorylation of Thr-34 by calcineurin, removing the cyclic nucleotide-induced inhibition of protein phosphatase 1.

  13. Double disruption of α2A- and α2C-adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype.

    PubMed

    Fonseca, Tatiana L; Jorgetti, Vanda; Costa, Cristiane C; Capelo, Luciane P; Covarrubias, Ambart E; Moulatlet, Ana C; Teixeira, Marilia B; Hesse, Eric; Morethson, Priscilla; Beber, Eduardo H; Freitas, Fatima R; Wang, Charles C; Nonaka, Keico O; Oliveira, Ricardo; Casarini, Dulce E; Zorn, Telma M; Brum, Patricia C; Gouveia, Cecilia H

    2011-03-01

    Evidence demonstrates that sympathetic nervous system (SNS) activation causes osteopenia via β(2)-adrenoceptor (β2-AR) signaling. Here we show that female mice with chronic sympathetic hyperactivity owing to double knockout of adrenoceptors that negatively regulate norepinephrine release, α(2A)-AR and α(2C)-AR (α(2A) /α(2C)-ARKO), present an unexpected and generalized phenotype of high bone mass with decreased bone resorption and increased formation. In α(2A) /α(2C)-ARKO versus wild-type (WT) mice, micro-computed tomographic (µCT) analysis showed increased, better connected, and more plate-shaped trabeculae in the femur and vertebra and increased cortical thickness in the vertebra, whereas biomechanical analysis showed increased tibial and femoral strength. Tibial mRNA expression of tartrate-resistant acid phosphatase (TRACP) and receptor activator of NF-κB (RANK), which are osteoclast-related factors, was lower in knockout (KO) mice. Plasma leptin and brain mRNA levels of cocaine amphetamine-regulated transcript (CART), which are factors that centrally affect bone turnover, and serum levels of estradiol were similar between mice strains. Tibial β(2)-AR mRNA expression also was similar in KO and WT littermates, whereas α(2A)-, α(2B)- and α(2C)-AR mRNAs were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By immunohistochemistry, we detected α(2A)-, α(2B)-, α(2C)- and β(2)-ARs in osteoblasts, osteoclasts, and chondrocytes of 18.5-day-old mouse fetuses and 35-day-old mice. Finally, we showed that isolated osteoclasts in culture are responsive to the selective α(2)-AR agonist clonidine and to the nonspecific α-AR antagonist phentolamine. These findings suggest that β(2)-AR is not the single adrenoceptor involved in bone turnover regulation and show that α(2)-AR signaling also may mediate the SNS actions in the skeleton.

  14. Repeated adolescent MDMA ("Ecstasy") exposure in rats increases behavioral and neuroendocrine responses to a 5-HT2A/2C agonist.

    PubMed

    Biezonski, Dominik K; Courtemanche, Andrea B; Hong, Sang B; Piper, Brian J; Meyer, Jerrold S

    2009-02-03

    MDMA (3,4-methylenedioxymethamphetamine) is a popular recreational drug among adolescents. The present study aimed to determine the effects of repeated intermittent administration of 10 mg/kg MDMA during adolescence on behavioral (Experiment 1) and neuroendocrine (Experiment 2) responses of rats to the 5-HT(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and on [(3)H]ketanserin binding to 5-HT(2A) receptors. In the first experiment, MDMA pretreatment increased the frequency of head twitches and back muscle contractions, but not wet-dog shakes, to a high-dose DOI challenge. In the second experiment, both the prolactin and corticosterone responses to DOI were potentiated in MDMA-pretreated animals. No changes were found in 5-HT(2A) receptor binding in the hypothalamus or other forebrain areas that were examined. These results indicate that intermittent adolescent MDMA exposure enhances sensitivity of 5-HT(2A/2C) receptors in the CNS, possibly through changes in downstream signaling mechanisms.

  15. A 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, mitigates developmental neurotoxicity of ethanol to serotonergic neurons.

    PubMed

    Ishiguro, Tsukasa; Sakata-Haga, Hiromi; Fukui, Yoshihiro

    2016-07-01

    Prenatal ethanol exposure causes the reduction of serotonergic (5-HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5-HT2A and 5-HT2C receptors during the fetal period is able to prevent the reduction of 5-HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague-Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair-fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist for 5-HT2A/2C receptors, during GDs 13 to 19 (Et-DOI or Pf-DOI), and another was injected with saline vehicle only (Et-Sal or Pf-Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5-HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5-HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et-Sal fetuses compared to that of the Pf-Sal and Pf-DOI fetuses, whereas there were no significant differences between Et-DOI and each Pf control. Thus, we concluded that the reduction of 5-HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5-HT2A/2C receptors during the fetal period.

  16. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    PubMed

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2.

  17. Avionic Sensor Systems and Aerospace Photographic Systems Repair Career Ladders AFSCs 322X2A, 322X2C, and 404X1.

    DTIC Science & Technology

    1984-07-01

    3ABR322X2C is 98 days; and course 3ABR404X1 is 73 days in duration. The A- and C-shred attend a 226-hour G3AQR32020-005 Electronics Principles Course...The 404X1 receive electronics principles incorporated into their regular curriculum for a total of 183 hours. Successful completion of the tech school... Electronics Principles Inventory (EPI) was recently completed which included the 322X2A AFSC. The goal of an EPI is to obtain information on percent

  18. Pharmacological evidence that spinal α(2C)- and, to a lesser extent, α(2A)-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation.

    PubMed

    Villalón, Carlos M; Galicia-Carreón, Jorge; González-Hernández, Abimael; Marichal-Cancino, Bruno A; Manrique-Maldonado, Guadalupe; Centurión, David

    2012-05-15

    During a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), producing cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the role of spinal α₂-adrenoceptors and their subtypes (i.e. α(2A), α(2B) and/or α(2C)-adrenoceptors) in the inhibition of the canine external carotid vasodilator responses to capsaicin. Anaesthetized vagosympathectomized dogs were prepared to measure arterial blood pressure, heart rate and external carotid conductance. The thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine. A cannula was inserted intrathecally for spinal (C₁-C₃) administration of 2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin-dihydrochloride (B-HT 933; a selective α₂-adrenoceptor agonist) and/or the α₂-adrenoceptor antagonists rauwolscine (α(2A/2B/2C)), 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL44408; α(2A)), imiloxan (α(2B)) or acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine (JP-1302; α(2C)). Infusions of capsaicin, α-CGRP and acetylcholine dose-dependently increased the external carotid conductance. Intrathecal B-HT 933 (1000 and 3100 μg) inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. This inhibition, abolished by rauwolscine (310 μg), was: (i) unaffected by 3,100 μg imiloxan; (ii) partially blocked by 310 μg of BRL44408 or 100 μg of JP-1302; and (iii) abolished by 1,000 μg of BRL44408 or 310 μg of JP-1302. Thus, intrathecal B-HT 933 inhibited the external carotid vasodilator responses to capsaicin. This response, mediated by spinal α₂-adrenoceptors unrelated to the α(2B)-adrenoceptor subtype, resembles the pharmacological profile of α(2C)-adrenoceptors and, to a lesser extent, α(2A)-adrenoceptors.

  19. 40 CFR Table A-4 to Subpart A of... - Source Category List for § 98.2(a)(2)

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Source Category List for § 98.2(a)(2) A Table A-4 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  20. 40 CFR Table A-4 to Subpart A of... - Source Category List for § 98.2(a)(2)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Source Category List for § 98.2(a)(2) A Table A-4 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  1. 40 CFR Table A-4 to Subpart A of... - Source Category List for § 98.2(a)(2)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Source Category List for § 98.2(a)(2) A Table A-4 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  2. 40 CFR Table A-4 to Subpart A of... - Source Category List for § 98.2(a)(2)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Source Category List for § 98.2(a)(2) A Table A-4 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  3. PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line

    PubMed Central

    Di Lascio, Simona; Saba, Elena; Belperio, Debora; Raimondi, Andrea; Lucchetti, Helen; Fornasari, Diego; Benfante, Roberta

    2016-01-01

    PHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making. PMID:26902400

  4. Pharmacological profile of the clonidine-induced inhibition of vasodepressor sensory outflow in pithed rats: correlation with α2A/2C-adrenoceptors

    PubMed Central

    Villalón, C M; Albarrán-Juárez, J A; Lozano-Cuenca, J; Pertz, H H; Görnemann, T; Centurión, D

    2008-01-01

    Background and purpose: Resistance blood vessels are innervated by sympathetic and primary sensory nerves, which modulate vascular tone through the release of noradrenaline and calcitonin gene-related peptide (CGRP), respectively. Moreover, electrical stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses which are mainly mediated by CGRP release. The present study has investigated the role of α2-adrenoceptors in the inhibition of these vasodepressor responses. Experimental approach: 144 pithed male Wistar rats were pretreated with hexamethonium (2 mg kg−1 min−1) followed by i.v. continuous infusions of either methoxamine (15 and 30 μg kg−1 min−1) or clonidine (3, 10 and 30 μg kg−1 min−1). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the spinal cord (T9–T12) resulted in frequency-dependent decreases in diastolic blood pressure. Key results: The infusion of clonidine (10 μg kg−1 min−1), as compared to those of methoxamine (15 or 30 μg kg−1 min−1), inhibited the vasodepressor responses to electrical stimulation without affecting those to i.v. bolus injections of α-CGRP (0.1–1 μg kg−1). This inhibition by clonidine was: (i) antagonized by 300 μg kg−1 rauwolscine (α2A/2B/2C), 300 and 1000 μg kg−1 BRL44408 (α2A), or 10 and 30 μg kg−1 MK912 (α2C); and (ii) unaffected by 1 ml kg−1 saline, 100 μg kg−1 BRL44408, 3000 and 10000 μg kg−1 imiloxan (α2B) or 3 μg kg−1 MK912. Conclusions and implications: The inhibition produced by 10 μg kg−1 min−1 clonidine on the vasodepressor (perivascular) sensory outflow in rats may be mainly mediated by prejunctional α2A2C-adrenoceptors. PMID:18297098

  5. Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats.

    PubMed

    Zaniewska, Magdalena; McCreary, Andrew C; Przegaliński, Edmund; Filip, Malgorzata

    2007-10-01

    The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands (<32% nicotine-lever responding), conversely 5-IA induced a full substitution (100% nicotine-lever responding). In combination studies, fixed doses of M100,907 (0.5-1 mg/kg) or SB 242,084 (0.25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0.3 mg/kg), Ro 60-0175 (1 mg/kg) and WAY 163,909 (1 and 1.5 mg/kg) attenuated the discriminative stimulus effects of nicotine. The decrease in the expression of the discriminative stimulus effects of nicotine produced by DOI was blocked by M100,907 (1 mg/kg), but not by SB 242,084 (1 mg/kg), while that evoked by Ro 60-0175 or WAY 163,909 was blocked by SB 242,084 (1 mg/kg), but not by M100,907 (1 mg/kg). Further studies showed that

  6. 40 CFR Table A-5 to Subpart A of... - Supplier Category List for § 98.2(a)(4)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Supplier Category List for § 98.2(a)(4) A Table A-5 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  7. 40 CFR Table A-3 to Subpart A of... - Source Category List for § 98.2(a)(1)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Source Category List for § 98.2(a)(1) A Table A-3 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  8. 40 CFR Table A-3 to Subpart A of... - Source Category List for § 98.2(a)(1)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Source Category List for § 98.2(a)(1) A Table A-3 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  9. 40 CFR Table A-5 to Subpart A of... - Supplier Category List for § 98.2(a)(4)

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Supplier Category List for § 98.2(a)(4) A Table A-5 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  10. 40 CFR Table A-3 to Subpart A of... - Source Category List for § 98.2(a)(1)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Source Category List for § 98.2(a)(1) A Table A-3 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  11. 40 CFR Table A-5 to Subpart A of... - Supplier Category List for § 98.2(a)(4)

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Supplier Category List for § 98.2(a)(4) A Table A-5 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  12. 40 CFR Table A-5 to Subpart A of... - Supplier Category List for § 98.2(a)(4)

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Supplier Category List for § 98.2(a)(4) A Table A-5 to Subpart A of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Provision Pt. 98, Subpt....

  13. Telecom 2-B and 2-C (TC2B and TC2C)

    NASA Technical Reports Server (NTRS)

    Dulac, J.; Alvarez, H.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  14. Effect of GABAergic ligands on the anxiolytic-like activity of DOI (a 5-HT(2A/2C) agonist) in the four-plate test in mice.

    PubMed

    Massé, Fabienne; Hascoët, Martine; Bourin, Michel

    2007-01-01

    5-HTergic and GABAergic systems are involved in neurobiology of anxiety. Precedent studies have demonstrated that SSRIs possessed an anxiolytic-like effect in the four-plate test (FPT) at doses that did not modify spontaneous locomotor activity. This effect seems to be mediated through the activation of 5-HT(2A) postsynaptic receptors. The purpose of the present study was to examine the implication of GABA system in the anxiolytic-like activity of DOI in the FPT. To achieve this, the co-administration of DOI (5-HT(2A/2C) receptor agonists) with GABA(A) and GABA(B) receptor ligands was evaluated in the FPT. Alprazolam, diazepam and muscimol (for higher dose) potentiated the anxiolytic-like effect of DOI. Bicuculline, picrotoxin and baclofen inhibited the anxiolytic-like effect of DOI. Flumazenil and CGP 35348 had no effect on the anxiolytic-like activity of DOI. These results suggest that the GABA system seems to be strongly implicated in the anxiolytic-like activity of DOI in the FPT.

  15. Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys.

    PubMed

    Perez Diaz, Maylen; Andersen, Monica L; Rice, Kenner C; Howell, Leonard L

    2017-01-18

    Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT2C receptor agonist, WAY163909, and a 5-HT2A receptor antagonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT2C receptor and antagonists at the 5-HT2A receptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY.Neuropsychopharmacology advance online publication, 18 January 2017; doi:10.1038/npp.2016.280.

  16. 40 CFR Table 2a to Subpart Ce of... - Emissions Limits for Small HMIWI Which Meet the Criteria Under § 60.33e(b)(1)

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 7 2012-07-01 2012-07-01 false Emissions Limits for Small HMIWI Which... SOURCES Emission Guidelines and Compliance Times for Hospital/Medical/Infectious Waste Incinerators Pt. 60, Subpt. Ce, Table 2A Table 2A to Subpart Ce of Part 60—Emissions Limits for Small HMIWI Which Meet...

  17. Characterization of Human Disease Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1

    PubMed Central

    Crow, Yanick J.; Chase, Diana S.; Schmidt, Johanna Lowenstein; Szynkiewicz, Marcin; Forte, Gabriella M.A.; Gornall, Hannah L.; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S.; Abdel-Salam, Ghada M.; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M.; Bahi-Buisson, Nadia; Bailey, Kathryn M.; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W.; Bernard, Geneviève; Bianchi, Marika; de Villemeur, Thierry Billette; Blair, Edward M.; Bloom, Miriam; Burlina, Alberto B.; Carpanelli, Maria Luisa; Carvalho, Daniel R.; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E.; Chitayat, David A.; Collins, Abigail E.; Corcoles, Concepcion Sierra; Cordeiro, Nuno J.V.; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C.; D’Arrigo, Stefano; De Goede, Christian G.E.L.; De Laet, Corinne; De Waele, Liesbeth M.H.; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C.; Fazzi, Elisa; Ferrie, Colin D.; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R.; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D.; Kirk, Edwin P.; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J.; Lin, Jean-Pierre S.-M.; Linnankivi, Tarja; Mackay, Mark T.; Marom, Daphna R.; Lourenço, Charles Marques; McKee, Shane A.; Moroni, Isabella; Morton, Jenny E.V.; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J.; Olivieri, Ivana; Ostergaard, John R.; Pérez-Dueñas, Belén; Prendiville, Julie S.; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A.; Sinha, Gyanranjan P.; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I.; Straussberg, Rachel; Swoboda, Kathryn J.; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y.; Naude, Johann te Water; Teik, Keng Wee; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S.; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B.; Wassmer, Evangeline; Webb, Hannah J.; Whitehouse, William P.; Whitney, Robyn N.; Zaki, Maha S.; Zuberi, Sameer M.; Livingston, John H.; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I.

    2015-01-01

    Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome

  18. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

    PubMed

    Crow, Yanick J; Chase, Diana S; Lowenstein Schmidt, Johanna; Szynkiewicz, Marcin; Forte, Gabriella M A; Gornall, Hannah L; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S; Abdel-Salam, Ghada M; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M; Bahi-Buisson, Nadia; Bailey, Kathryn M; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W; Bernard, Geneviève; Bianchi, Marika; Billette de Villemeur, Thierry; Blair, Edward M; Bloom, Miriam; Burlina, Alberto B; Carpanelli, Maria Luisa; Carvalho, Daniel R; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E; Chitayat, David A; Collins, Abigail E; Sierra Corcoles, Concepcion; Cordeiro, Nuno J V; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C; D'Arrigo, Stefano; De Goede, Christian G E L; De Laet, Corinne; De Waele, Liesbeth M H; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C; Fazzi, Elisa; Ferrie, Colin D; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D; Kirk, Edwin P; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J; Lin, Jean-Pierre S-M; Linnankivi, Tarja; Mackay, Mark T; Marom, Daphna R; Marques Lourenço, Charles; McKee, Shane A; Moroni, Isabella; Morton, Jenny E V; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J; Olivieri, Ivana; Ostergaard, John R; Pérez-Dueñas, Belén; Prendiville, Julie S; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A; Sinha, Gyanranjan P; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I; Straussberg, Rachel; Swoboda, Kathryn J; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y; te Water Naude, Johann; Wee Teik, Keng; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B; Wassmer, Evangeline; Webb, Hannah J; Whitehouse, William P; Whitney, Robyn N; Zaki, Maha S; Zuberi, Sameer M; Livingston, John H; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I

    2015-02-01

    Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes

  19. Chronic betahistine co-treatment reverses olanzapine's effects on dopamine D₂ but not 5-HT2A/2C bindings in rat brains.

    PubMed

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2015-01-02

    Olanzapine is widely prescribed for treating schizophrenia and other mental disorders, although it leads to severe body weight gain/obesity. Chronic co-treatment with betahistine has been found to significantly decrease olanzapine-induced weight gain; however, it is not clear whether this co-treatment affects the therapeutic effects of olanzapine. This study investigated the effects of chronic treatment of olanzapine and/or betahistine on the binding density of the serotonergic 5-HT2A (5-HT2AR) and 5-HT2C (5-HT2CR) receptors, 5-HT transporter (5-HTT), and dopaminergic D₂ receptors (D₂R) in the brain regions involved in antipsychotic efficacy, including the prefrontal cortex (PFC), cingulate cortex (Cg), nucleus accumbens (NAc), and caudate putamen (CPu). Rats were treated with olanzapine (1 mg/kg, t.i.d.) or vehicle for 3.5 weeks, and then olanzapine treatment was withdrawn for 19 days. From week 6, the two groups were divided into 4 groups (n=6) for 5 weeks' treatment: (1) olanzapine-only (1 mg/kg, t.i.d.), (2) betahistine-only (9.6 mg/kg, t.i.d.), (3) olanzapine and betahistine co-treatment (O+B), and (4) vehicle. Compared to the control, the olanzapine-only treatment significantly decreased the bindings of 5-HT2AR, 5-HT2CR, and 5-HTT in the PFC, Cg, and NAc. Similar changes were observed in the rats receiving the O+B co-treatment. The olanzapine-only treatment significantly increased the D₂R binding in the Cg, NAc, and CPu, while the betahistine-only treatment reduced D₂R binding. The co-treatment of betahistine reversed the D₂R bindings in the NAc and CPu that were increased by olanzapine. Therefore, chronic O+B co-treatment has similar effects on serotonin transmission as the olanzapine-only treatment, but reverses the D₂R that is up-regulated by chronic olanzapine treatment. The co-treatment maintains the therapeutic effects of olanzapine but decreases/prevents the excess weight gain.

  20. Hp-41CV flight performance advisory system (FPAS) for the E-2c, E-2B, and C-2A aircraft. Final technical report Apr-Jun 82

    SciTech Connect

    Ferrell, D.R.

    1982-06-01

    This report describes follow-on work performed under the auspices of AE 4900, Directed Studies in Aeronautical Engineering at the Naval Postgraduate School, to complement the original design of a Flight Performance Advisory System (FPAS) for the E-2C aircraft. The original design fulfilled the requirements of AE 3001, Aircraft Energy Conservation. AE 3001, offered in the Fall Quarter 1981, and conducted by Professor Allen E. Fuhs, was sponsored in part by the Naval Air Development Center (NADC). NADC desired to obtain the input of several fleet experienced aviators in order to design program code for the HP-41CV handheld, programmable calculator that would benefit pilots by providing them with fuel efficiency parameters in flight. Calculators were made available to the participants with the proviso that a completed and operable code for each aircraft be submitted by the end of the academic quarter, September 1981. Upon completion of the E-2C program, attempts were made to use the calculator in flight. One test was conducted informally in an E-2C at RVAW-110, NAS Miramar. Unfortunately, the voltage field induced in the cockpit by the main lobe of the radar passing over the cockpit caused the calculator to cease functioning. The need to devise shielding for the calculator, plus the desire to simplify and improve the existing code lead to this effort.

  1. The relative cellular levels of CP2a and CP2b potentiates erythroid cell-specific expression of the {alpha}-globin gene by regulating the nuclear localization of CP2c

    SciTech Connect

    Chae, Ji Hyung; Kang, Ho Chul; Kim, Chul Geun

    2009-03-20

    CP2b activates {alpha}-globin expression in an erythroid cell-specific manner, through interaction with CP2c and PIAS1. Although CP2a is identical to CP2b except for lacking an exon encoding additional 36 amino acids and has the intrinsic DNA binding and transactivation properties, it does not exert any role in {alpha}-globin expression. Investigation of subcellular localization of exogenous CP2 proteins revealed that CP2a and CP2b were exclusively localized in the cytosol and nucleus, respectively. The CP2b-specific exon was in charge of the nuclear localization of CP2b. Interestingly, subcellular localization of CP2c was either in the nucleus or cytosol depending on the relative level of CP2a and CP2b although CP2c intrinsically localized in the cytosol in the absence of CP2a/CP2b. Finally, dramatic increment of hemoglobin expression was correlated with nuclear translocation of CP2c during MEL cell differentiation. Our data suggest that CP2b potentiate erythroid cell-specific {alpha}-globin expression by recruiting CP2c into the nucleus.

  2. Crucial role of the 5-HT2C receptor, but not of the 5-HT2A receptor, in the down regulation of stimulated dopamine release produced by pressure exposure in freely moving rats.

    PubMed

    Kriem, B; Rostain, J C; Abraini, J H

    1998-06-15

    Helium pressure of more than 2 MPa is a well known factor underlying pressure-dependent central neuroexcitatory disorders, referred to as the high-pressure neurological syndrome. This includes an increase in both serotonin (5-HT) and dopamine (DA) release. The relationship between the increase in 5-HT transmission produced by helium pressure and its effect on DA release has been clarified in a recent study, which have first demonstrated that the helium pressure-induced increase in DA release was dependent on some 5-HT receptor activation. In the present study, we examined in freely moving rats the role of 5-HT2A and 5-HT2C receptors in the increase in DA release induced by 8 MPa helium pressure. We used the 5-HT2A receptor antagonist ketanserin and the 5-HT2C receptor agonist m-CPP which have been demonstrated to reduce DA function. Because neither ketanserin is an ideal 5-HT2A receptor antagonist nor m-CPP an ideal 5-HT2C receptor agonist, additional experiments were made at normal pressure to check up on the selectivity of ketanserin and m-CPP for 5-HT2A and 5-HT2C receptors, respectively. Administration of m-CPP reduced both DA basal level and the helium pressure-induced increase in DA release, whereas administration of ketanserin only showed a little effect on the increase in DA release produced by high helium pressure. These results suggest that the 5-HT2C receptor, but not the 5-HT2A receptor, would play a crucial role in the helium pressure-induced increase in DA release. This further suggests that helium pressure may simultaneously induce an increase in 5-HT transmission at the level of 5-HT2A receptors and a decrease in 5-HT transmission at the level of 5-HT2C receptors.

  3. CT Scans of NASA BSTRA Balls 5f5, f2, f3, sr2c, nb2a, hb2b

    SciTech Connect

    Gross, J; Thompson, R; Perry, R; Schneberk, D

    2004-01-29

    At the request of Jose Hernandez we performed some feasibility DR/CT scanning of BSTRA Balls of different sizes. To this point we have scanned all the specimens on a single system, HECAT. This particular system employs a 9 meV LINAC as the x-ray source and a THALES 12 x 16 inch 14-bit Amorphous Silicon panel as the detector. In this report we describe the system, detail some of its properties, describe the scans performed and present the data. Figure 1 contains a couple of images of the system as fielded in the 9 MeV bay. The LINAC is in the right portion of the picture. The black panels in the blue frame constitute the High Energy collimator developed specifically for High Energy DR/CT scanning (known here as Stonehenge II). The holes in the collimator panels are beveled to match the distribution of the x-rays from the LINAC, and are sized to just subtend the active area of the THALES Amorphous Silicon panel. Consequently the source to detector distance is restricted to a few positions. Nominally our source to detector distance is 6 meters. The part manipulator, part holder fixturing consists of a translate-rotate assembly on a NEWPORT air bearing table. The stages are NEWPORT RV160PP for rotation and NEWPORT IMS400CC for translation. Both are interfaced through an ESP7000 controller, which is connected to our data acquisition computer over USB. The detector holder also resides on this table and includes pitch, roll and yaw adjustments for aligning the panel to the plane of the rotational table and the x-ray beam. The relatively large source to detector distance and LINAC properties (1 mm spot size) conspire to recommend rotation-only scanning. We use a VARIAN LINATRON 3000 with the small spot retrofit implemented. We have measured the source spot size at about 1 mm. Pixel size on the THALES panel is 0.127 um. Consequently we are in a low-cone angle scanning regime which enables rotation-only 3D CT scanning of objects and assemblies with little ''cone

  4. Identification of high-risk Listeria monocytogenes serotypes in lineage I(serotype 1/2a, 1/2c,3a, and 3c) using multiplex PCR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using molecular subtyping techniques, Listeria monocytogenes is divided into three major phylogenetic lineages, and a multiplex PCR method can differentiate five L. monocytogenes subgroups: 1/2a-3a, 1/2c-3c, 1/2b-3b-7, 4b-4d-4e, and 4a-4c. In the current study, we conducted genome comparisons and e...

  5. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family.

    PubMed

    Koh, Cheng-Gee; Tan, E-Jean; Manser, Edward; Lim, Louis

    2002-02-19

    The Rho GTPases are involved in many signaling pathways and cellular functions, including the organization of the actin cytoskeleton, regulation of transcription, cell motility, and cell division. The p21 (Cdc42/Rac)-activated kinase PAK mediates a number of biological effects downstream of these Rho GTPases (reviewed by [1]). The phosphorylation state of mammalian PAK is highly regulated: upon binding of GTPases, PAK is potently activated by autophosphorylation at multiple sites, although the mechanisms of PAK downregulation are not known. We now report two PP2C-like serine/threonine phosphatases (POPX1 and POPX2) that efficiently inactivate PAK. POPX1 was isolated as a binding partner for the PAK interacting guanine nucleotide exchange factor PIX. The dephosphorylating activity of POPX correlates with an ability to block the in vivo effects of active PAK. Consonant with these effects on PAK, POPX can also inhibit actin stress fiber breakdown and morphological changes driven by active Cdc42(V12). The association of the POPX phosphatases with PAK complexes may allow PAK to cycle rapidly between active and inactive states; it represents a unique regulatory component of the signaling pathways of the PAK kinase family.

  6. Contribution of a helix 5 locus to selectivity of hallucinogenic and nonhallucinogenic ligands for the human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors: direct and indirect effects on ligand affinity mediated by the same locus.

    PubMed

    Almaula, N; Ebersole, B J; Ballesteros, J A; Weinstein, H; Sealfon, S C

    1996-07-01

    An important determinant of the neurobehavioral responses induced by a drug is its relative receptor selectivity. The molecular basis of ligand selectivity of hallucinogenic and nonhallucinogenic compounds of varying structural classes for the human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors was investigated with the use of reciprocal site-directed mutagenesis. Because these two closely related receptor subtypes differ in the amino acid present at position 5.46 (residues 242 and 222 in the sequences, respectively), the effects of corresponding substitutions in the 5-HT2A[S5.46(242)-->A] and 5-HT2C[A5.46(222)-->S] receptors were studied in tandem. By studying both receptors, the direct and indirect effects of mutations on affinity and selectivity can be distinguished. The ergolines studied, mesulergine (selective for the 5-HT2C receptor) and d-lysergic acid diethylamide (selective for the 5-HT2A receptor), reversed their relative affinity with mutations in each receptor, supporting a direct role of this locus in the selectivity of these ligands. However, interchange mutations in either receptor led to decreased or unchanged affinity for (+/-)-1-)(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and ketanserin, which have higher affinity for the 5-HT2A receptor, consistent with little contribution of this locus to the selectivity of these ligands. The indoleamines studied were affected differently by mutations in each receptor, suggesting that they bind differently to the two receptor subtypes. Mutation of this locus in the 5-HT2A receptor decreased the affinity of all indoleamines, whereas the interchange mutation of the 5-HT2C receptor did not affect indoleamine affinity. These results are consistent with a direct interaction between this side chain and indoleamines for the 5-HT2A receptor but not for the 5-HT2C receptor. Furthermore, this analysis shows that the higher affinity of 5-HT and tryptamine for the 5-HT2C receptor than for the 5-HT2A receptors is not

  7. EPR Spectroscopy of MolB2C2-A Reveals Mechanism of Transport for a Bacterial Type II Molybdate Importer*♦

    PubMed Central

    Rice, Austin J.; Alvarez, Frances J. D.; Schultz, Kathryn M.; Klug, Candice S.; Davidson, Amy L.; Pinkett, Heather W.

    2013-01-01

    In bacteria, ATP-binding cassette (ABC) transporters are vital for the uptake of nutrients and cofactors. Based on differences in structure and activity, ABC importers are divided into two types. Type I transporters have been well studied and employ a tightly regulated alternating access mechanism. Less is known about Type II importers, but much of what we do know has been observed in studies of the vitamin B12 importer BtuC2D2. MolB2C2 (formally known as HI1470/71) is also a Type II importer, but its substrate, molybdate, is ∼10-fold smaller than vitamin B12. To understand mechanistic differences among Type II importers, we focused our studies on MolBC, for which alternative conformations may be required to transport its relatively small substrate. To investigate the mechanism of MolBC, we employed disulfide cross-linking and EPR spectroscopy. From these studies, we found that nucleotide binding is coupled to a conformational shift at the periplasmic gate. Unlike the larger conformational changes in BtuCD-F, this shift in MolBC-A is akin to unlocking a swinging door: allowing just enough space for molybdate to slip into the cell. The lower cytoplasmic gate, identified in BtuCD-F as “gate I,” remains open throughout the MolBC-A mechanism, and cytoplasmic gate II closes in the presence of nucleotide. Combining our results, we propose a peristaltic mechanism for MolBC-A, which gives new insight in the transport of small substrates by a Type II importer. PMID:23709218

  8. Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China

    PubMed Central

    Geng, Yufei; Guo, Donghua; Li, Chunqiu; Wang, Enyu; Wei, Shan; Wang, Zhihui; Yao, Shuang; Zhao, Xiwen; Su, Mingjun; Wang, Xinyu; Wang, Jianfa; Wu, Rui; Feng, Li; Sun, Dongbo

    2015-01-01

    To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains. PMID:26348721

  9. 40 CFR Table 2a to Subpart Zzzz of... - Emission Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE >500...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions 2a Table 2a to Subpart ZZZZ of Part 63... 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary...

  10. 40 CFR Table 2a to Subpart Zzzz of... - Emission Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE >500...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions 2a Table 2a to Subpart ZZZZ of Part 63... 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary...

  11. 40 CFR Table 2a to Subpart Zzzz of... - Emission Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE >500...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions 2a Table 2a to Subpart ZZZZ of Part 63... 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary...

  12. 40 CFR Table 2a to Subpart Zzzz of... - Emission Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE >500...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions 2a Table 2a to Subpart ZZZZ of Part 63... 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary...

  13. 40 CFR Table 2a to Subpart Zzzz of... - Emission Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE >500...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions 2a Table 2a to Subpart ZZZZ of Part 63... 2SLB and Compression Ignition Stationary RICE >500 HP and New and Reconstructed 4SLB Stationary...

  14. 50 CFR Table 2a to Part 660... - 2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons)

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons) 2a Table 2a to Part 660, Subpart C Wildlife and Fisheries..., Subpart C—2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons)...

  15. 50 CFR Table 2a to Part 660... - 2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons)

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons) 2a Table 2a to Part 660, Subpart G Wildlife and Fisheries..., Subpart G—2010, Specifications of ABCs, OYs, and HGs, by Management Area (weights in metric tons) Link...

  16. 50 CFR Table 2a to Part 660... - 2014, and Beyond, Specifications of OFL, ABC, ACL, ACT and Fishery Harvest guidelines (weights in...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false 2014, and Beyond, Specifications of OFL, ABC, ACL, ACT and Fishery Harvest guidelines (weights in metric tons) 2a Table 2a to Part 660, Subpart C Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND...

  17. Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor knock out mice brain.

    PubMed

    Höcker, Jan; Weber, Bernd; Tonner, Peter H; Scholz, Jens; Brand, Philipp-Alexander; Ohnesorge, Henning; Bein, Berthold

    2008-03-17

    alpha(2)-adrenoceptor agonists like clonidine or dexmedetomidine increase the sedative and analgesic actions of opioids. Furthermore opioids like meperidine show potent anti-shivering effects like alpha(2)-adrenoceptor agonists. The underlying molecular mechanisms of these effects are still poorly defined. The authors therefore studied the ability of four different opioids (meperidine, remifentanil, sufentanil and tramadol) to interact with different alpha(2)-adrenoceptor subtypes in mice lacking individual alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptors (alpha(2)-adrenoceptor knock out (alpha(2)-AR KO) mice)). The interaction of opioids with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]-paraiodoclonidine ([(125)I]-PIC) from alpha(2)-adrenoceptors in different brain regions by increasing opioid concentrations was measured, and binding affinity of the analysed opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified. Meperidine, remifentanil and tramadol but not sufentanil provoked dose dependent displacement of specifically bound [(125)I]-PIC from all alpha(2)-adrenoceptor subtypes in cortex, cerebellum, medulla oblongata, thalamus, hippocampus and pons. Required concentrations of meperidine and remifentanil for [(125)I]-PIC displacement from alpha(2B)- and alpha(2C)-adrenoceptors were lower than from alpha(2A)-adrenoceptors, indicating higher binding affinity for alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, [(125)I]-PIC displacement by tramadol indicated higher binding affinity to alpha(2A)-adrenoceptors than to alpha(2B)- and alpha(2C)-adrenoceptors. Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C

  18. Effects of anthocyanidins and anthocyanins on the expression and catalytic activities of CYP2A6, CYP2B6, CYP2C9, and CYP3A4 in primary human hepatocytes and human liver microsomes.

    PubMed

    Srovnalova, Alzbeta; Svecarova, Michaela; Zapletalova, Michaela Kopecna; Anzenbacher, Pavel; Bachleda, Petr; Anzenbacherova, Eva; Dvorak, Zdenek

    2014-01-22

    Anthocyanidins and anthocyanins are pharmacologically active constituents of various berry fruits, such as blueberry and cranberry. These compounds are also contained in massively used nutritional supplements based on extracts or dry matter from berry fruits. The current study evaluated the effects of anthocyanidins and anthocyanins on the expression and catalytic activity of major drug-metabolizing enzymes CYP2C9, CYP2A6, CYP2B6, and CYP3A4 in primary cultures of human hepatocytes and human liver microsomes. Expression of mRNA was quantified by qRT-PCR. Expression of proteins was evaluated by Western blotting and immunochemiluminescence. The catalytic activity of CYP enzymes was measured by HPLC using specific enzyme substrates. Tested anthocyanidins (6) and anthocyanins (21) did not induce the expression of mRNA and protein of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 genes in human hepatocytes. Catalytic activities of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 enzymes were inhibited by all anthocyanidins to different extents (e.g., delphinidin inhibits CYP3A4 by >90% at 100 μM with IC50 = 32 μM). Of 21 anthocyanins tested, only cyanidin-3-O-rhamnoside (CYP3A4 by >75% at 100 μM with IC50 = 44 μM) and two glycosides of delphinidin significantly inhibited examined cytochromes P450. It may be concluded that in the ranges of common ingestion of either food or dietary supplement an induction or significant inhibition of CYP2C9, CYP2A6, CYP2B6, and CYP3A4 activity is most probably not expected.

  19. Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

    PubMed

    Banks, Matthew L; Negus, S Stevens

    2017-04-01

    Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT2C receptor activation nor 5-HT2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT2C agonists and 5-HT2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

  20. Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement.

    PubMed

    Fletcher, Paul J; Rizos, Zoë; Noble, Kevin; Soko, Ashlie D; Silenieks, Leo B; Lê, Anh Dzung; Higgins, Guy A

    2012-06-01

    The reinforcing effects of nicotine are mediated in part by brain dopamine systems. Serotonin, acting via 5-HT(2A) and 5-HT(2C) receptors, modulates dopamine function. In these experiments we examined the effects of the 5-HT(2C) receptor agonist Ro60-0175 and the 5-HT(2A) receptor antagonist (M100907, volinanserin) on nicotine self-administration and reinstatement of nicotine-seeking. Male Long-Evans rats self-administered nicotine (0.03 mg/kg/infusion, IV) on either a FR5 or a progressive ratio schedule of reinforcement. Ro60-0175 reduced responding for nicotine on both schedules. While Ro60-0175 also reduced responding for food reinforcement, response rates under drug treatment were several-fold higher than in animals responding for nicotine. M100907 did not alter responding for nicotine, or food, on either schedule. In tests of reinstatement of nicotine-seeking, rats were first trained to lever press for IV infusions of nicotine; each infusion was also accompanied by a compound cue consisting of a light and tone. This response was then extinguished over multiple sessions. Injecting rats with a nicotine prime (0.15 mg/kg) reinstated responding; reinstatement was also observed when responses were accompanied by the nicotine associated cue. Ro60-0175 attenuated reinstatement of responding induced by nicotine and by the cue. The effects of Ro60-0175 on both forms of reinstatement were blocked by the 5-HT(2C) receptor antagonist SB242084. M100907 also reduced reinstatement induced by either the nicotine prime or by the nicotine associated cue. The results indicate that 5-HT(2C) and 5-HT(2A) receptors may be potential targets for therapies to treat some aspects of nicotine dependence.

  1. Heterologous expression of the cloned guinea pig alpha 2A, alpha 2B, and alpha 2C adrenoceptor subtypes. Radioligand binding and functional coupling to a CAMP-responsive reporter gene.

    PubMed

    Svensson, S P; Bailey, T J; Porter, A C; Richman, J G; Regan, J W

    1996-02-09

    Functional studies have shown that 6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1H-2,3,4,5-tetrahydro-3- benzazepine (SKF 104078) has very low affinity for prejunctional alpha 2-adrenoceptors (alpha 2-AR) in the guinea pig atrium. In this study, we have cloned guinea pig homologues of the human alpha 2-C10, alpha 2-C4 AR subtypes and have studied them in isolation by heterologous expression in cultured mammalian cells. Oligonucleotide primers, designed from conserved areas of the human alpha 2-ARs were used in a polymerase chain reaction (PCR) with template cDNA synthesized from guinea pig atrial mRNA. Three PCR products were obtained that shared identity with the three human alpha 2-AR subtypes. A guinea pig (gp) genomic library was screened with a cDNA clone encoding a portion of the gp-alpha 2A, and genes containing the complete coding sequences of the guinea pig alpha 2A, alpha 2B, and alpha 2C AR subtypes were obtained. These guinea pig genes were subcloned into a eukaryotic expression plasmid and were expressed transiently in COS-7 cells. The binding of the alpha 2-selective antagonist [3H]MK-912 to membranes prepared from these cells was specific and of high affinity with Kd values of 810 pM for gp-alpha 2A, 2700 pM for gp-alpha 2B and 110 pM for gp-alpha 2C. Competition for the binding of [3H]MK-912 by SKF 104078 indicated that it was of moderately high affinity (approximately 100 nM) but that it was not selective for any of the guinea pig alpha 2-AR subtypes. Co-expression of guinea pig alpha 2-AR subtypes with a cyclicAMP-responsive chloramphenicol acetyltransferase (CAT) reporter gene resulted in agonist-dependent modulation of CAT activity. For the gp-alpha 2 A, a biphasic response was obtained with low concentrations of noradrenaline (NE) decreasing forskolin-stimulated CAT activity and high concentrations causing a reversal. For the gp-alpha 2B, NE produced mostly potentiation of forskolin-stimulated activity, and for the gp-alpha 2C, NE caused

  2. Direct sequencing and comprehensive screening of genetic polymorphisms on CYP2 family genes (CYP2A6, CYP2B6, CYP2C8, and CYP2E1) in five ethnic populations.

    PubMed

    Kim, Jeong-Hyun; Cheong, Hyun Sub; Park, Byung Lae; Kim, Lyoung Hyo; Shin, Hee Jung; Na, Han Sung; Chung, Myeon Woo; Shin, Hyoung Doo

    2015-01-01

    Recently, CYP2A6, CYP2B6, CYP2C8, and CYP2E1 have been reported to play a role in the metabolic effect of pharmacological and carcinogenic compounds. Moreover, genetic variations of drug metabolism genes have been implicated in the interindividual variation in drug disposition and pharmacological response. To define the distribution of single nucleotide polymorphisms (SNPs) in these four CYP2 family genes and to discover novel SNPs across ethnic groups, 288 DNAs composed of 48 African-Americans, 48 European-Americans, 48 Japanese, 48 Han Chinese, and 96 Koreans were resequenced. A total of 143 SNPs, 26 in CYP2A6, 45 in CYP2B6, 29 in CYP2C8, and 43 in CYP2E1, were identified, including 13 novel variants. Notably, two SNPs in the regulatory regions, a promoter SNP rs2054675 and a nonsynonymous rs3745274 (p.172Q>H) in CYP2B6, showed significantly different minor allele frequencies (MAFs) among ethnic groups (minimum P = 4.30 × 10(-12)). In addition, rs2031920 in the promoter region of CYP2E1 showed a wide range of MAF between different ethnic groups, and even among other various ethnic groups based on public reports. Among 13 newly discovered SNPs in this study, 5 SNPs were estimated to have potential functions in further in silico analyses. Some differences in genetic variations and haplotypes of CYP2A6, CYP2B6, CYP2C8, and CYP2E1 were observed among populations. Our findings could be useful in further researches, such as genetic associations with drug responses.

  3. Responding for a conditioned reinforcer, and its enhancement by nicotine, is blocked by dopamine receptor antagonists and a 5-HT(2C) receptor agonist but not by a 5-HT(2A) receptor antagonist.

    PubMed

    Guy, Elizabeth Glenn; Fletcher, Paul J

    2014-10-01

    An aspect of nicotine reinforcement that may contribute to tobacco addiction is the effect of nicotine to enhance the motivational properties of reward-associated cues, or conditioned stimuli (CSs). Several studies have now shown that nicotine enhances responding for a stimulus that has been paired with a natural reinforcer. This effect of nicotine to enhance responding for a conditioned reinforcer is likely due to nicotine-induced enhancements in mesolimbic dopaminergic activity, but this has not been directly assessed. In this study, we assessed roles for dopamine (DA) D1 or D2 receptors, and two serotonin (5-HT) receptor subtypes known to modulate DA activity, the 5-HT2C or 5-HT2A subtypes, on nicotine-enhanced responding for a conditioned reinforcer. Water-restricted rats were exposed to Pavlovian conditioning sessions, where a CS was paired with water delivery. Then, in a second phase, animals were required to perform a novel, lever-pressing response for presentations of the CS as a conditioned reinforcer. Nicotine (0.4 mg/kg) enhanced responding for the conditioned reinforcer. To examine potential roles for dopamine (DA) and serotonin (5-HT) receptors in this effect, separate groups of animals were used to assess the impact of administering the D1 receptor antagonist SCH 23390, D2 receptor antagonist eticlopride, 5-HT2C receptor agonist Ro 60-0175, or 5-HT2A receptor antagonist M100907 on nicotine-enhanced responding for conditioned reinforcement. SCH 23390, eticlopride, and Ro 60-0175 all reduced responding for conditioned reinforcement, and the ability of nicotine to enhance this effect. M100907 did not alter this behavior. Together, these studies indicate that DA D1 and D2 receptors, but not 5-HT2A receptors, contribute to the effect of nicotine to enhance responding for a conditioned reinforcer. This effect can also be modulated by 5-HT2C receptor activation.

  4. Specific role of α2A - and α2B -, but not α2C -, adrenoceptor subtypes in the inhibition of the vasopressor sympathetic out-flow in diabetic pithed rats.

    PubMed

    Altamirano-Espinoza, Alain H; Manrique-Maldonado, Guadalupe; Marichal-Cancino, Bruno A; Villalón, Carlos M

    2015-07-01

    Several lines of evidence have shown an association of diabetes with a catecholamines' aberrant homeostasis involving a drastic change in the expression of adrenoceptors. This homeostatic alteration includes, among other things, atypical actions of α2 -adrenoceptor agonists within central and peripheral α2 -adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α2 -adrenoceptor subtypes that inhibit the vasopressor sympathetic out-flow in streptozotocin-pre-treated (diabetic) pithed rats. For this purpose, B-HT 933 (up to 30 μg/kg min) was used as a selective α2 -adrenoceptor agonist and rauwolscine as a non-selective α2A/2B/2C -adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP-1302 were used as subtype-selective α2A -, α2B - and α2C -adrenoceptor antagonists, respectively (all given i.v.). I.v. continuous infusions of B-HT 933 inhibited the vasopressor responses induced by electrical sympathetic stimulation without affecting those by i.v. bolus injections of noradrenaline in both normoglycaemic and diabetic rats. Interestingly, the ED50 for B-HT 933 in diabetic rats (25 μg/kg min) was almost 1-log unit greater than that in normoglycaemic rats (3 μg/kg.min). Moreover, the sympatho-inhibition induced by 10 μg/kg min B-HT 933 in diabetic rats was (i) abolished by 300 μg/kg rauwolscine or 100 and 300 μg/kg BRL 44408; (ii) partially blocked by 1000 μg/kg imiloxan; and (iii) unchanged by 1000 μg/kg JP-1302. Our findings, taken together, suggest that B-HT 933 has a less potent inhibitory effect on the sympathetic vasopressor responses in diabetic (compared to normoglycaemic) rats and that can probably be ascribed to a down-regulation of α2C -adrenoceptors.

  5. High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C.

    PubMed

    Zhou, Huilei; Wang, Lin; Huang, Juxiang; Jiang, Minghu; Zhang, Xiaoyu; Zhang, Liyuan; Wang, Yangming; Jiang, Zhenfu; Zhang, Zhongjie

    2015-01-01

    48 different Pearson mutual-positive-correlation epidermal growth factor receptor (EGFR_1)-activatory molecular feedback, up- and down-stream network was constructed from 171 overlapping of 366 GRNInfer and 223 Pearson under EGFR_1 CC ≥0.25 in high lung adenocarcinoma compared with low human normal adjacent tissues. Our identified EGFR_1 inside-out upstream activated molecular network showed SLC2A1 (solute carrier family 2 (facilitated glucose transporter) member 1), CCNB2 (cyclin B2), HMMR (hyaluronan-mediated motility receptor (RHAMM)), KIF11 (kinesin family member 11), NUSAP1 (nucleolar and spindle associated protein 1), PRC1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin-conjugating enzyme E2C) in high lung adenocarcinoma. EGFR_1 inside-out upstream activated terms network includes intracellular, membrane fraction, cytoplasm, plasma membrane, integral to membrane, basolateral plasma membrane, transmembrane transport, nucleus, cytosol, cell surface; T cell homeostasis, inflammation; microtubule cytoskeleton, embryonic development (sensu Mammalia), cell cycle, mitosis, thymus development, cell division, regulation of cell cycle, Contributed--cellular process--Hs cell cycle KEGG, cytokinesis, M phase, M phase of mitotic cell cycle, estrogen-responsive protein Efp controls cell cycle and breast tumors growth, cell motility, locomotion, locomotory behavior, neoplasm metastasis, spindle pole, spindle microtubule, microtubule motor activity, microtubule-based movement, mitotic spindle organization and biogenesis, mitotic centrosome separation, spindle pole body organization and biogenesis, microtubule-based process, microtubule, cytokinesis after mitosis, mitotic chromosome condensation, establishment of mitotic spindle localization, positive regulation of mitosis, mitotic spindle elongation, spindle organization and biogenesis, positive regulation of exit from mitosis, regulation of cell proliferation, positive regulation of cell proliferation based on

  6. Synthesis and biological evaluation of benzo[4,5]imidazo[1,2-c]pyrimidine and benzo[4,5]imidazo[1,2-a]pyrazine derivatives as anaplastic lymphoma kinase inhibitors.

    PubMed

    Tardy, Sébastien; Orsato, Alexandre; Mologni, Luca; Bisson, William H; Donadoni, Carla; Gambacorti-Passerini, Carlo; Scapozza, Leonardo; Gueyrard, David; Goekjian, Peter G

    2014-02-15

    Chromosomal translocations involving anaplastic lymphoma kinase (ALK) are the driving mutations for a range of cancers and ALK is thus considered an attractive therapeutic target. We synthesized a series of functionalized benzo[4,5]imidazo[1,2-c]pyrimidines and benzo[4,5]imidazo[1,2-a]pyrazines by an aza-Graebe-Ullman reaction, followed by palladium-catalyzed cross-coupling reactions. A sequential regioselective cross-coupling route is reported for the synthesis of unsymmetrically disubstituted benzo[4,5]imidazo[1,2-a]pyrazines. The inhibition of ALK was evaluated and compound 19 in particular showed good activity against both the wild type and crizotinib-resistant L1196M mutant in vitro and in ALK-transfected BaF3 cells.

  7. Serotonin 5-HT2A but not 5-HT2C receptor antagonism reduces hyperlocomotor activity induced in dopamine-depleted rats by striatal administration of the D1 agonist SKF 82958.

    PubMed

    Bishop, Christopher; Daut, Gregory S; Walker, Paul D

    2005-09-01

    While recent work has indicated that D1 receptor agonist-induced hyperlocomotion in DA-depleted rats is reduced by striatal 5-HT2 receptor antagonism, the 5-HT receptor(s) subtypes mediating these effects are not yet known. In the present study, we examined the influence(s) of striatal 5-HT2A and 5-HT2C receptors on locomotor behavior induced by D1 agonism in neonatal DA-depleted rats. On postnatal day 3, male Sprague-Dawley rats (n=68) were treated with either vehicle or 6-hydroxydopamine (6-OHDA; 60 microg) which produced >98% DA depletion. Sixty days later, all rats were fitted with bilateral striatal cannulae. A subset of control and 6-OHDA-lesioned rats (n=20) was tested for locomotor responses to striatal infusion of the D1 agonist SKF 82958 (0, 0.1, 1.0, 10 microg/side). The remaining rats (n=48) were tested for locomotor responses to intrastriatal SKF 82958 (2.0 microg/side) alone or in combination with the 5-HT2A- or 5-HT2C-preferring antagonists M100907 or RS102221 (0.1 or 1.0 microg/side), respectively. Intrastriatal SKF 82958 dose-dependently increased measures of motor activity within DA-depleted rats. This hyperlocomotor activity was suppressed by co-infusion of M100907, but not RS102221. These results indicate that DA depletion strengthens striatal 5-HT2A/D1 receptor interactions and suggest that 5-HT2A receptor antagonists may prove useful in reducing D1-related movements.

  8. Expression of potato RNA-binding proteins StUBA2a/b and StUBA2c induces hypersensitive-like cell death and early leaf senescence in Arabidopsis

    PubMed Central

    Na, Jong-Kuk; Kim, Jae-Kwang; Kim, Dool-Yi; Assmann, Sarah M.

    2015-01-01

    The Arabidopsis thaliana genome encodes three RNA-binding proteins (RBPs), UBP1-associated protein 2a (UBA2a), UBA2b, and UBA2c, that contain two RNA-recognition motif (RRM) domains. They play important roles in wounding response and leaf senescence, and are homologs of Vicia faba abscisic-acid-activated protein kinase-interacting protein 1 (VfAKIP1). The potato (Solanum tuberosum) genome encodes at least seven AKIP1-like RBPs. Here, two potato RBPs have been characterized, StUBA2a/b and StUBA2c, that are homologous to VfAKIP1 and Arabidopsis UBA2s. Transient expression of StUBA2s induced a hypersensitive-like cell death phenotype in tobacco leaves, and an RRM-domain deletion assay of StUBA2s revealed that the first RRM domain is crucial for the phenotype. Unlike overexpression of Arabidopsis UBA2s, constitutive expression of StUBA2a/b in Arabidopsis did not cause growth arrest and lethality at the young seedling stage, but induced early leaf senescence. This phenotype was associated with increased expression of defence- and senescence-associated genes, including pathogen-related genes (PR) and a senescence-associated gene (SAG13), and it was aggravated upon flowering and ultimately resulted in a shortened life cycle. Leaf senescence of StUBA2a/b Arabidopsis plants was enhanced under darkness and was accompanied by H2O2 accumulation and altered expression of autophagy-associated genes, which likely cause cellular damage and are proximate causes of the early leaf senescence. Expression of salicylic acid signalling and biosynthetic genes was also upregulated in StUBA2a/b plants. Consistent with the localization of UBA2s-GFPs and VfAKIP1-GFP, soluble-modified GFP-StUBA2s localized in the nucleus within nuclear speckles. StUBA2s potentially can be considered for transgenic approaches to induce potato shoot senescence, which is desirable at harvest. PMID:25944928

  9. Accounting for intracell flow in models with emphasis on water table recharge and stream-aquifer interaction. 2. A procedure

    USGS Publications Warehouse

    Jorgensen, D.G.; Signor, D.C.; Imes, J.L.

    1989-01-01

    Intercepted intracell flow, especially if cell includes water table recharge and a stream (sink), can result in significant model error if not accounted for. A procedure utilizing net flow per cell (Fn) that accounts for intercepted intracell flow can be used for both steady state and transient simulations. Germane to the procedure is the determination of the ratio of area of influence of the interior sink to the area of the cell (Ai/Ac). Ai is the area in which water table recharge has the potential to be intercepted by the sink. Determining Ai/Ac requires either a detailed water table map or observation of stream conditions within the cell. A proportioning parameter M, which is equal to 1 or slightly less and is a function of cell geometry, is used to determine how much of the water that has potential for interception is intercepted by the sink within the cell. Also germane to the procedure is the determination of the flow across the streambed (Fs) which is not directly a function of cell size, due to difference in head between the water level in the stream and the potentiometric surface of the aquifer underlying the streambed. -from Authors

  10. Effects of central activation of serotonin 5-HT2A/2C or dopamine D2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test

    PubMed Central

    Feng, Min; Gao, Jun; Sui, Nan; Li, Ming

    2014-01-01

    Rationale: Acute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect. Objective: The present study investigated the neuroanatomical basis and receptor mechanisms of acute and repeated effects of clozapine treatment in the conditioned avoidance response test in male Sprague-Dawley rats. Methods: DOI (2,5-dimethoxy-4-iodo-amphetamine, a preferential 5-HT2A/2C agonist) or quinpirole (a preferential dopamine D2/3 agonist) was microinjected into the medial prefrontal cortex (mPFC) or nucleus accumbens shell (NAs), and their effects on the acute and long-term avoidance-disruptive effect of clozapine were tested. Results: Intra-mPFC microinjection of quinpirole enhanced the acute avoidance disruptive effect of clozapine (10 mg/kg, sc), while DOI microinjections reduced it marginally. Repeated administration of clozapine (10 mg/kg, sc) daily for 5 days caused a progressive decrease in its inhibition of avoidance responding, indicating tolerance development. Intra-mPFC microinjection of DOI at 25.0 (but not 5.0) μg/side during this period completely abolished the expression of clozapine tolerance. This was indicated by the finding that clozapine-treated rats centrally infused with 25.0 μg/side DOI did not show higher levels of avoidance responses than the vehicle-treated rats in the clozapine challenge test. Microinjection of DOI into the mPFC immediately before the challenge test also decreased the expression of clozapine tolerance. Conclusions: Acute behavioral effect of clozapine can be enhanced by activation of the D2/3 receptors in the mPFC. Clozapine tolerance expression relies on the neuroplasticity initiated by its antagonist action against 5-HT2A/2C receptors in the mPFC. PMID:25288514

  11. Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory.

    PubMed

    Meneses, Alfredo

    2007-11-22

    In order to determine whether short- (STM) and long-term memory (LTM) function in serial or parallel manner, serotonin (5-hydroxtryptamine, 5-HT) receptor agonists were tested in autoshaping task. Results show that control-vehicle animals were modestly but significantly mastering the autoshaping task as illustrated by memory scores between STM and LTM. Thus, post-training administration of 8-OHDPAT (agonist for 5-HT(1A/7) receptors) only at 0.250 and 0.500 mg/kg impaired both STM and LTM. CGS12066 (agonist for 5-HT(1B)) produced biphasic affects, at 5.0 mg/kg impaired STM but at 1.0 and 10.0 mg/kg, respectively, improved or impaired LTM. DOI (agonist for 5-HT(2A/2C) receptors) dose-dependently impaired STM and, at 10.0 mg/kg only impaired LTM. Both, STM and LTM were impaired by either mCPP (mainly agonist for 5-HT(2C) receptors) or mesulergine (mainly antagonist for 5-HT(2C) receptors) lower dose. The 5-HT(3) agonist mCPBG at 1.0 impaired STM and its higher dose impaired both STM and LTM. RS67333 (partial agonist for 5-HT(4) receptors), at 5.0 and 10.0 mg/kg facilitated both STM and LTM. The higher dose of fluoxetine (a 5-HT uptake inhibitor) improved both STM and LTM. Using as head-pokes during CS as an indirect measure of food-intake showed that of 30 memory changes, 21 of these were unrelated to the former. While some STM or LTM impairments can be attributed to decrements in food-intake, but not memory changes (either increase or decreases) produced by 8-OHDPAT, CGS12066, RS67333 or fluoxetine. Except for animals treated with DOI, mCPBG or fluoxetine, other groups treated with 5-HT agonists 6 h following autoshaping training showed similar LTM and unmodified CS-head-pokes scores.

  12. The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

    PubMed Central

    Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

    2014-01-01

    Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

  13. Differential thiol oxidation of the signaling proteins Akt, PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle.

    PubMed

    Tan, Pearl Lin; Shavlakadze, Tea; Grounds, Miranda D; Arthur, Peter G

    2015-05-01

    Oxidative stress, caused by excess reactive oxygen species (ROS), has been hypothesized to cause or exacerbate skeletal muscle wasting in a number of diseases and chronic conditions. ROS, such as hydrogen peroxide, have the potential to affect signal transduction pathways such as the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt pathway that regulates protein synthesis. Previous studies have found contradictory outcomes for the effect of ROS on the PI3K/Akt signaling pathway, where oxidative stress can either enhance or inhibit Akt phosphorylation. The apparent contradictions could reflect differences in experimental cell types or types of ROS treatments. We replicate both effects in myotubes of cultured skeletal muscle C2C12 cells, and show that increased oxidative stress can either inhibit or enhance Akt phosphorylation. This differential response could be explained: thiol oxidation of Akt, but not the phosphatases PTEN or PP2A, caused a decline in Akt phosphorylation; whereas the thiol oxidation of Akt, PTEN and PP2A increased Akt phosphorylation. These observations indicate that a more complete understanding of the effects of oxidative stress on a signal transduction pathway comes not only from identifying the proteins susceptible to thiol oxidation, but also their relative sensitivity to ROS.

  14. Restricted access to standard or high fat chow alters sensitivity of rats to the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)

    PubMed Central

    Serafine, Katherine M.; France, Charles P.

    2017-01-01

    Feeding conditions can impact sensitivity to drugs acting on dopamine receptors; less is known about the impact of feeding conditions on the effects of drugs acting on serotonin (5-HT) receptors. This study examined the effects of feeding condition on sensitivity to the direct-acting 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 0.1–3.2 mg/kg) and the direct-acting dopamineD3/D2 receptor agonist quinpirole (0.0032–0.32 mg/kg). Male Sprague-Dawley rats had free access (11 weeks) followed by restricted access (6 weeks) to high (34.3%, n = 8) fat or standard (5.7% fat; n = 7) chow. Rats eating high fat chow became insulin resistant and gained more weight than rats eating standard chow. Free access to high fat chow did not alter sensitivity to DOM-induced head twitch but increased sensitivity to quinpirole-induced yawning. Restricting access to high fat or standard chow shifted the DOM-induced head twitch dose-response curve to the right and shifted the quinpirole-induced yawning dose-response curve downward in both groups of rats. Some drugs of abuse and many therapeutic drugs act on 5-HT and dopamine systems; these results demonstrate that feeding condition impacts sensitivity to drugs acting on these systems, thereby possibly impacting vulnerability to abuse as well as therapeutic effectiveness of drugs. PMID:24346289

  15. 40 CFR Table 3 of Subpart Bbbbbbb... - Test Methods

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Other Requirements and Information What definitions apply to this subpart? Pt. 63, Subpt. BBBBBBB, Table.... Determining the velocity and volumetric flow rate EPA test method 2, 2A, 2C, 2D, 2F, or 2G, as appropriate, in appendix A to part 60. 3. Determining the gas molecular weight used for flow rate determination EPA...

  16. Extending David Horrobin's membrane phospholipid theory of schizophrenia: overactivity of cytosolic phospholipase A(2) in the brain is caused by overdrive of coupled serotonergic 5HT(2A/2C) receptors in response to stress.

    PubMed

    Eggers, Arnold E

    2012-12-01

    David Horrobin's membrane phospholipid theory of schizophrenia has held up well over time because his therapeutic prediction that dietary supplementation with eicosapentaenoic acid (EPA) would have a therapeutic effect has been partially verified and undergoes continued testing. In the final version of his theory, he hypothesized that there was hyperactivity of phosphoslipase A(2) (PLA(2)) or a related enzyme but did not explain how the hyperactivity came about. It is known that serotonergic 5HT(2A/2C) receptors are coupled to PLA(2), which hydrolyzes both arachidonic acid (AA) and EPA from diacylglycerides at the sn-2 position. In this paper, Horrobin's theory is combined with a previously published theory of chronic stress in which it was hypothesized that a disinhibited dorsal raphe nucleus, the principal nucleus of the serotonergic system, can organize the neuropathology of diseases such as migraine, hypertension, and the metabolic syndrome. The new or combined theory is that schizophrenia is a disease of chronic stress in which a disinhibited DRN causes widespread serotonergic overdrive in the cerebral cortex. This in turn causes overdrive of cPLA(2) and both central and peripheral depletion of AA and EPA. Because EPA is present in smaller amounts, it falls below threshold for maintaining an intracellular balance between AA-derived and EPA-derived second messenger cascades, which leads to abnormal patterns of neuronal firing. There are two causes of neuronal dysfunction: the disinhibited DRN and EPA depletion. Schizophrenia is statistically associated with metabolic syndrome, hypertension, and migraine because they form a cluster of diseases with similar pathophysiology. The theory provides an explanation for both the central and peripheral phospholipid abnormalities in schizophrenia. It also explains the role of stress in schizophrenia, elevated serum PLA(2) activity in schizophrenia, the relationship between untreated schizophrenia and metabolic syndrome

  17. Helium tables.

    NASA Technical Reports Server (NTRS)

    Havill, Clinton H

    1928-01-01

    These tables are intended to provide a standard method and to facilitate the calculation of the quantity of "Standard Helium" in high pressure containers. The research data and the formulas used in the preparation of the tables were furnished by the Research Laboratory of Physical Chemistry, of the Massachusetts Institute of Technology.

  18. WTAQ version 2-A computer program for analysis of aquifer tests in confined and water-table aquifers with alternative representations of drainage from the unsaturated zone

    USGS Publications Warehouse

    Barlow, Paul M.; Moench, Allen F.

    2011-01-01

    The computer program WTAQ simulates axial-symmetric flow to a well pumping from a confined or unconfined (water-table) aquifer. WTAQ calculates dimensionless or dimensional drawdowns that can be used with measured drawdown data from aquifer tests to estimate aquifer hydraulic properties. Version 2 of the program, which is described in this report, provides an alternative analytical representation of drainage to water-table aquifers from the unsaturated zone than that which was available in the initial versions of the code. The revised drainage model explicitly accounts for hydraulic characteristics of the unsaturated zone, specifically, the moisture retention and relative hydraulic conductivity of the soil. The revised program also retains the original conceptualizations of drainage from the unsaturated zone that were available with version 1 of the program to provide alternative approaches to simulate the drainage process. Version 2 of the program includes all other simulation capabilities of the first versions, including partial penetration of the pumped well and of observation wells and piezometers, well-bore storage and skin effects at the pumped well, and delayed drawdown response of observation wells and piezometers.

  19. A Table! (At the Table).

    ERIC Educational Resources Information Center

    Terry, Robert M.

    A review of French dining habits and table manners outlines: elements of the place setting, courtesies used at the table, serving conventions, restaurant tipping, the size and content of the different meals of the day, subtle differences in common foods, restaurant types, menu types, general wine and cheese choices, waiter-client communication,…

  20. First detection of canine parvovirus type 2c in Brazil

    PubMed Central

    Streck, André Felipe; de Souza, Carine Kunzler; Gonçalves, Karla Rathje; Zang, Luciana; Pinto, Luciane Dubina; Canal, Cláudio Wageck

    2009-01-01

    The presence of canine parvovirus type 2 (CPV-2), 2a and 2b has been described in Brazil, however, the type 2c had not been reported until now. In the current study, seven out of nine samples from dogs with diarrhea were characterized as CPV-2c, indicating that this virus is already circulating in the Brazilian canine population. PMID:24031389

  1. Protein phosphatase 2C (PP2C) function in higher plants.

    PubMed

    Rodriguez, P L

    1998-12-01

    In the past few years, molecular cloning studies have revealed the primary structure of plant protein serine/threonine phosphatases. Two structurally distinct families, the PP1/PP2A family and the PP2C family, are present in plants as well as in animals. This review will focus on the plant PP2C family of protein phosphatases. Biochemical and molecular genetic studies in Arabidopsis have identified PP2C enzymes as key players in plant signal transduction processes. For instance, the ABI1/ABI2 PP2Cs are central components in abscisic acid (ABA) signal transduction. Arabidopsis mutants containing a single amino acid exchange in ABI1 or ABI2 show a reduced response to ABA. Another member of the PP2C family, kinase-associated protein phosphatase (KAPP), appears to be an important element in some receptor-like kinase (RLK) signalling pathways. Finally, an alfalfa PP2C acts as a negative regulator of a plant mitogen-activated protein kinase (MAPK) pathway. Thus, the plant PP2Cs function as regulators of various signal transduction pathways.

  2. Gene expression studies of mRNAs encoding the NMDA receptor subunits NMDAR1, NMDAR2A, NMDAR2B, NMDAR2C, and NMDAR2D following long-term treatment with cis-and trans-flupenthixol as a model for understanding the mode of action of schizophrenia drug treatment.

    PubMed

    Chen, A C; McDonald, B; Moss, S J; Gurling, H M

    1998-02-01

    It has been hypothesized that glutamate receptor function is important in both the aetiology and treatment of schizophrenia. In order to understand how specific glutamate receptor genes are involved in the treatment of schizophrenia we have used a multiprobe oligonucleotide solution hybridization (MOSH) technique to examine the regulation of gene express of the NMDAR1, 2A, 2B, 2C, 2D receptor subunits in the left rat brain following treatment with the optical isomers of flupenthixol. cis- and trans-flupenthixol are both present in the commonly used oral and depot treatments for schizophrenia and a controlled trial showed that cis-flupenthixol had a significantly superior ability to ameliorate the positive symptoms of schizophrenia compared to its trans-isomer. At a dose of 0.2 mg/kg/day over a period of 1, 2, 4, 8, 12 and 24 weeks, we found that both isomers down regulated the expression of NMDAR1 mRNA in most regions of the brain. NMDAR2A, 2B and 2C receptor subunits showed a significantly decreased expression from 12 to 24 weeks but after 2 weeks NMDAR2B, 2C, 2D expression was increased in several brain regions. The NMDAR1 receptor subunit immunoreactivity in the right brain following 4 and 24 weeks of drug treatment was also examined by Western blotting. Both trans- and cis-flupenthixol significantly decreased the NR1 immunoreactivity in the right cerebellum after 24 weeks of treatment. These results suggest that NMDA receptor subunits may have a role in the action of antipsychotic drugs. If we assume that the NMDA receptor expression changes reflect a beneficial and significant mechanism in the treatment of schizophrenia, it could be argued that NMDA receptor changes are more related to the negative or non-specific symptoms of schizophrenia.

  3. Drosophila DPP2C1, a novel member of the protein phosphatase 2C (PP2C) family.

    PubMed

    Dick, T; Bahri, S M; Chia, W

    1997-10-15

    We report the molecular cloning, chromosome mapping and developmental transcription pattern of a putative serine/threonine protein phosphatase 2C (PP2C), DPP2C1, from Drosophila melanogaster. The 6-kb transcript of this first Drosophila PP2C gene encodes a 1428-aa deduced protein. The DPP2C1 protein contains a approximately 330-aa PP2C-like catalytic domain flanked by extensive N- and C-terminal sequences showing no similarities to other PP2Cs. The dpp2c1 gene maps to 4E1-2 on the X chromosome, 1.5 kb upstream of the ddlc1 gene. Northern blot analyses showed that dpp2c1 transcription is developmentally regulated, accumulating maximally during early (0-6 h) and late (12-24 h) embryogensis. The presented molecular characterisation provides the basis for a genetic dissection of DPP2C1 function.

  4. Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

    PubMed

    Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

    2016-11-10

    On the basis of the structural similarity of our previous 5-HT2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT2A, 5-HT2B, and 5-HT2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

  5. Enrollment Tables.

    ERIC Educational Resources Information Center

    University System of Georgia, Atlanta.

    A set of tables is provided summarizing fall enrollment from 1979 through 1988 in the university system of Georgia. The following types of data are provided: headcount enrollment; joint enrollment; developmental studies, freshmen, sophomores, juniors, seniors, graduate students, professional enrollment, transients, others, EFT enrollment, entering…

  6. 5-Hydroxytryptamine2A/2C receptors of nucleus raphe magnus and gigantocellularis/paragigantocellularis pars α reticular nuclei modulate the unconditioned fear-induced antinociception evoked by electrical stimulation of deep layers of the superior colliculus and dorsal periaqueductal grey matter.

    PubMed

    de Oliveira, Ricardo; de Oliveira, Rithiele Cristina; Falconi-Sobrinho, Luiz Luciano; da Silva Soares, Raimundo; Coimbra, Norberto Cysne

    2017-01-01

    The electrical stimulation of the dorsolateral columns of the periaquedutal grey matter (dlPAG) or deep layers of the superior colliculus (dlSC) evokes defensive behaviours followed by an antinociceptive response. Monoaminergic brainstem reticular nuclei are suggested to comprise the endogenous pain modulatory system. The aim of the present work was to investigate the role played by 5-HT2 subfamily of serotonergic receptors of the nucleus raphe magnus (NRM) and the gigantocellularis/paragigantocellularis pars α reticular nuclei (Gi/PGiα) in the elaboration of instinctive fear-induced antinociception elicited by electrical stimulation of dlPAG or of dlSC. The nociceptive thresholds were measured by the tail-flick test in Wistar rats. The 5-HT2A/2C-serotonergic receptors antagonist ritanserin was microinjected at different concentrations (0.05, 0.5 and 5.0μg/0.2μL) either in Gi/PGiα or in NRM. The blockade of 5-HT2 receptors in both Gi/PGiα and NRM decreased the innate fear-induced antinociception elicited by electrical stimulation of the dlSC or the dlPAG. These findings indicate that serotonin is involved in the hypo-algesia induced by unconditioned fear-induced behavioural responses and the 5-HT2A/2C-serotonergic receptor subfamily in neurons situated in the Gi/PGiα complex and NRM are critically recruited in pain modulation during the panic-like emotional behaviour.

  7. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease.

    PubMed

    Dunn, Amy R; Stout, Kristen A; Ozawa, Minagi; Lohr, Kelly M; Hoffman, Carlie A; Bernstein, Alison I; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W Michael; Miller, Gary W

    2017-03-14

    Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction.

  8. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease

    PubMed Central

    Stout, Kristen A.; Ozawa, Minagi; Lohr, Kelly M.; Hoffman, Carlie A.; Bernstein, Alison I.; Li, Yingjie; Wang, Minzheng; Sgobio, Carmelo; Sastry, Namratha; Cai, Huaibin; Caudle, W. Michael

    2017-01-01

    Members of the synaptic vesicle glycoprotein 2 (SV2) family of proteins are involved in synaptic function throughout the brain. The ubiquitously expressed SV2A has been widely implicated in epilepsy, although SV2C with its restricted basal ganglia distribution is poorly characterized. SV2C is emerging as a potentially relevant protein in Parkinson disease (PD), because it is a genetic modifier of sensitivity to l-DOPA and of nicotine neuroprotection in PD. Here we identify SV2C as a mediator of dopamine homeostasis and report that disrupted expression of SV2C within the basal ganglia is a pathological feature of PD. Genetic deletion of SV2C leads to reduced dopamine release in the dorsal striatum as measured by fast-scan cyclic voltammetry, reduced striatal dopamine content, disrupted α-synuclein expression, deficits in motor function, and alterations in neurochemical effects of nicotine. Furthermore, SV2C expression is dramatically altered in postmortem brain tissue from PD cases but not in Alzheimer disease, progressive supranuclear palsy, or multiple system atrophy. This disruption was paralleled in mice overexpressing mutated α-synuclein. These data establish SV2C as a mediator of dopamine neuron function and suggest that SV2C disruption is a unique feature of PD that likely contributes to dopaminergic dysfunction. PMID:28246328

  9. Mesa = Table

    NASA Technical Reports Server (NTRS)

    2006-01-01

    10 August 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows two mesas on the northern plains of Mars. 'Mesa' is the Spanish word for 'table,' and that is a very good description of the two elliptical features captured in this MOC image. In both cases, the mesa tops and the material beneath them, down to the level of the surrounding, rugged plain, are remnants of a once more extensive layer (or layers) of material that has been largely eroded away. The circular feature near the center of the larger mesa is the site of a filled and buried impact crater.

    Location near: 53.5oN, 153.5oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Spring

  10. Global variation in CYP2C8–CYP2C9 functional haplotypes

    PubMed Central

    Speed, William C; Kang, Soonmo Peter; Tuck, David P; Harris, Lyndsay N; Kidd, Kenneth K

    2009-01-01

    We have studied the global frequency distributions of 10 single nucleotide polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in ∼2500 individuals representing 45 populations. Five of the SNPs were in noncoding sequences; the other five involved the more common missense variants (four in CYP2C8, one in CYP2C9) that change amino acids in the gene products. One haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant reaches an average frequency of 10% in Europe; a set of haplotypes with a different CYP2C8 coding variant reaches 17% in Africa. In both cases these haplotypes are found in other regions of the world at <1%. This considerable geographic variation in haplotype frequencies impacts the interpretation of CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug interactions. PMID:19381162

  11. Ultraviolet photoelectron spectra of Ce2@C80 and La2@C80

    NASA Astrophysics Data System (ADS)

    Miyazaki, Takafumi; Okita, Sosuke; Ohta, Tomona; Yagi, Hajime; Sumii, Ryohei; Okimoto, Haruya; Ito, Yasuhiro; Shinohara, Hisanori; Hino, Shojun

    2015-02-01

    Ultraviolet photoelectron spectra (UPS) of C80-Ih cage endohedral fullerenes, La2@C80 and Ce2@C80 were measured using a synchrotron radiation light source. The spectral onset energy of La2@C80 and Ce2@C80 is around 0.8-0.9 eV, which is smaller than that of empty C80-Ih. The UPS of these endohedral fullerenes are almost identical and are discussed with an aid of density functional theory (DFT) calculation. Simulation spectra calculated with using the results of the DFT calculations on an optimized structure starting from D3d geometry reproduces the UPS of La2@C80 and Ce2@C80 very well, which supports the theoretically proposed structure.

  12. Powder neutron diffraction of α-UB 2C (α-UB 2C-type)

    NASA Astrophysics Data System (ADS)

    Rogl, Peter; Fischer, Peter

    1991-02-01

    The crystal structure of α-UB 2C (low temperature modification below T = 1675(25)°C) was determined from powder X-ray data (RT) and powder neutron diffraction data (at 29 K) employing the Rietveld-Young-Wiles profile analysis method. α-UB 2C crystallizes in the orthorhombic space group Pmma with a = 0.60338(3), b = 0.35177(2), c = 0.41067(2) nm, V = 0.0872 nm 3, Z = 2. The residuals of the neutron refinement were R1 = 0.032 and RF = 0.043. The crystal structure of α-UB 2C is a new structure type where planar nonregular 6 3-U-metal layers alternate with planar nonmetal layers of the type (B 6C 2) 3. Boron atoms are in a typical triangular prismatic metal surrounding with a tetrakaidekahedral coordination B[U 6B 2C 1], whereas carbon atoms occupy the center points of rectangular bipyramids C[U 4B 2]. The crystal structure of α-UB 2C derives from the high temperature modification β-UB 2C (ThB 2C-type, R overline3m ), which reveals a similar stacking of slightly puckered metal layers 6 3, alternating with planar layers B 6 · (B 6C 3) 2. The phase transition from β-UB 2C to α-UB 2C is thus essentially generated by carbon diffusion within the limit∞2 B 6 · (B 6C 3) 2 layers to form limit∞2 (B 6C 2) 3 layers.

  13. Telecom 2-A (TC2A)

    NASA Technical Reports Server (NTRS)

    Dulac, J.; Latour, J.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for Telecom 2-A (TC2A) are summarized. The Telecom 2-A will provide high-speed data link applications, telephone, and television service between France and overseas territories. The mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  14. Tabled Execution in Scheme

    SciTech Connect

    Willcock, J J; Lumsdaine, A; Quinlan, D J

    2008-08-19

    Tabled execution is a generalization of memorization developed by the logic programming community. It not only saves results from tabled predicates, but also stores the set of currently active calls to them; tabled execution can thus provide meaningful semantics for programs that seemingly contain infinite recursions with the same arguments. In logic programming, tabled execution is used for many purposes, both for improving the efficiency of programs, and making tasks simpler and more direct to express than with normal logic programs. However, tabled execution is only infrequently applied in mainstream functional languages such as Scheme. We demonstrate an elegant implementation of tabled execution in Scheme, using a mix of continuation-passing style and mutable data. We also show the use of tabled execution in Scheme for a problem in formal language and automata theory, demonstrating that tabled execution can be a valuable tool for Scheme users.

  15. Expression of paired-like homeodomain transcription factor 2c (PITX2c) in epidermal keratinocytes

    SciTech Connect

    Shi, Ge; Sohn, Kyung-Cheol; Choi, Tae-Young; Choi, Dae-Kyoung; Lee, Sang-Sin; Ou, Bai-sheng; Kim, Sooil; Lee, Young Ho; Yoon, Tae-Jin; Kim, Seong-Jin; Lee, Young; Seo, Young-Joon; Lee, Jeung-Hoon; Kim, Chang Deok

    2010-11-15

    Paired-like homeodomain transcription factor 2 (PITX2) has been implicated as one of the genes responsible for Rieger syndrome. It has been also shown to play a central role during development. In this study, we investigated the functional role of PITX2 in keratinocyte differentiation. RT-PCR analysis showed that PITX2c isoform was predominantly expressed in a differentiation-dependent manner. Consistent with, immunohistochemical staining showed that PITX2 expression was increased in the upper layer of epidermis. When PITX2c was overexpressed in cultured keratinocytes by a recombinant adenovirus, the differentiation markers such as involucrin and loricrin were significantly increased at both mRNA and protein levels. In addition, PITX2c overexpression led to the decrease of cell growth, concomitantly with the upregulation of cell cycle-related genes p21. To investigate the effect of PITX2c in vivo, we microinjected PITX2c expression vector into zebrafish embryo. Interestingly, overexpression of PITX2c in zebrafish embryo led to the formation of horn-like structure and thickening of epidermis, together with the increase of keratin 8 (K8) expression. These results suggest that PITX2c has a role in proliferation and differentiation of epidermal keratinocytes.

  16. The protein phosphatase 2C (PP2C) superfamily: detection of bacterial homologues.

    PubMed

    Bork, P; Brown, N P; Hegyi, H; Schultz, J

    1996-07-01

    A thorough sequence analysis of the various members of the eukaryotic protein serine/threonine phosphatase 2C (PP2C) family revealed the conservation of 11 motifs. These motifs could be identified in numerous other sequences, including fungal adenylate cyclases that are predicted to contain a functionally active PP2C domain, and a family of prokaryotic serine/threonine phosphatases including SpoIIE. Phylogenetic analysis of all the proteins indicates a widespread sequence family for which a considerable number of isoenzymes can be inferred.

  17. Periodic Table of Students.

    ERIC Educational Resources Information Center

    Johnson, Mike

    1998-01-01

    Presents an exercise in which an eighth-grade science teacher decorated the classroom with a periodic table of students. Student photographs were arranged according to similarities into vertical columns. Students were each assigned an atomic number according to their placement in the table. The table is then used to teach students about…

  18. Protein phosphatase 2C (PP2C) is responsible for VP-induced dephosphorylation of AQP2 serine 261.

    PubMed

    Cheung, Pui W; Ueberdiek, Lars; Day, Jack; Bouley, Richard; Brown, Dennis

    2017-04-05

    AQP2 trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 c-terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in the phosphorylation of serine 256 (S256), S264 and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Only sanguinarine, a specific protein phosphatase 2C (PP2C) inhibitor, abolished VP-induced S261 dephosphorylation, but not inhibitors of PP1, PP2A (okadaic acid) or PP2B (cyclosporine). However, both sanguinarine and VP significantly increased phosphorylation of ERK, a kinase that can phosphorylate S261; inhibition of ERK by PD98059 partially decreased baseline S261 phosphorylation. These data support a role of ERK in S261 phosphorylation, but suggest that upon VP treatment, increased phosphatase activity overcomes the increase in ERK activity, resulting in overall dephosphorylation of S261. We also found that sanguinarine abolished VP-induced S261 dephosphorylation in cells expressing mutated AQP2 S256A, suggesting that the phosphorylation state of S261 is independent of S256. Sanguinarine alone did not induce AQP2 membrane trafficking, nor did it inhibit VP-induced AQP2 membrane accumulation in cells and kidney tissues, suggesting that S261 does not play an observable role in acute AQP2 membrane accumulation. In conclusion, PP2C activity is required for S261 AQP2 dephosphorylation upon VP stimulation, and this occurs independent of S256 phosphorylation. Understanding the pathways involved in modulating PP2C will help obtain a deeper understanding of the role of S261 in cellular events involving AQP2.

  19. Hot cell examination table

    DOEpatents

    Gaal, Peter S.; Ebejer, Lino P.; Kareis, James H.; Schlegel, Gary L.

    1991-01-01

    A table for use in a hot cell or similar controlled environment for use in examining specimens. The table has a movable table top that can be moved relative to a table frame. A shaft is fixedly mounted to the frame for axial rotation. A shaft traveler having a plurality of tilted rollers biased against the shaft is connected to the table top such that rotation of the shaft causes the shaft traveler to roll along the shaft. An electromagnetic drive is connected to the shaft and the frame for controllably rotating the shaft.

  20. Mortality table construction

    NASA Astrophysics Data System (ADS)

    Sutawanir

    2015-12-01

    Mortality tables play important role in actuarial studies such as life annuities, premium determination, premium reserve, valuation pension plan, pension funding. Some known mortality tables are CSO mortality table, Indonesian Mortality Table, Bowers mortality table, Japan Mortality table. For actuary applications some tables are constructed with different environment such as single decrement, double decrement, and multiple decrement. There exist two approaches in mortality table construction : mathematics approach and statistical approach. Distribution model and estimation theory are the statistical concepts that are used in mortality table construction. This article aims to discuss the statistical approach in mortality table construction. The distributional assumptions are uniform death distribution (UDD) and constant force (exponential). Moment estimation and maximum likelihood are used to estimate the mortality parameter. Moment estimation methods are easier to manipulate compared to maximum likelihood estimation (mle). However, the complete mortality data are not used in moment estimation method. Maximum likelihood exploited all available information in mortality estimation. Some mle equations are complicated and solved using numerical methods. The article focus on single decrement estimation using moment and maximum likelihood estimation. Some extension to double decrement will introduced. Simple dataset will be used to illustrated the mortality estimation, and mortality table.

  1. Table of radioactive elements

    SciTech Connect

    Holden, N.E.

    1985-01-01

    As has been the custom in the past, the Commission publishes a table of relative atomic masses and halflives of selected radionuclides. The information contained in this table will enable the user to calculate the atomic weight for radioactive materials with a variety of isotopic compositions. The atomic masses have been taken from the 1984 Atomic Mass Table. Some of the halflives have already been documented.

  2. Human cyclooxygenase-2 cDNA.

    PubMed Central

    Hla, T; Neilson, K

    1992-01-01

    Cyclooxygenase (Cox), also known as prostaglandin (PG) H synthase (EC 1.14.99.1), catalyzes the rate-limiting step in the formation of inflammatory PGs. A major regulatory step in PG biosynthesis is at the level of Cox: growth factors, cytokines, and tumor promoters induce Cox activity. We have cloned the second form of the Cox gene (Cox-2) from human umbilical vein endothelial cells (HUVEC). The cDNA encodes a polypeptide of 604 amino acids that is 61% identical to the previously isolated human Cox-1 polypeptide. In vitro translation of the human (h)Cox-2 transcript in rabbit reticulocyte lysates resulted in the synthesis of a 70-kDa protein that is immunoprecipitated by antiserum to ovine Cox. Expression of the hCox-2 open reading frame in Cos-7 monkey kidney cells results in the elaboration of cyclooxygenase activity. hCox-2 cDNA hybridizes to a 4.5-kilobase mRNA species in HUVEC, whereas the hCox-1 cDNA hybridizes to 3- and 5.3-kilobase species. Both Cox-1 and Cox-2 mRNAs are expressed in HUVEC, vascular smooth muscle cells, monocytes, and fibroblasts. Cox-2 mRNA was preferentially induced by phorbol 12-myristate 13-acetate and lipopolysaccharide in human endothelial cells and monocytes. Together, these data demonstrate that the Cox enzyme is encoded by at least two genes that are expressed and differentially regulated in a variety of cell types. High-level induction of the hCox-2 transcript in mesenchymal-derived inflammatory cells suggests a role in inflammatory conditions. Images PMID:1380156

  3. The Living Periodic Table

    ERIC Educational Resources Information Center

    Nahlik, Mary Schrodt

    2005-01-01

    To help make the abstract world of chemistry more concrete eighth-grade students, the author has them create a living periodic table that can be displayed in the classroom or hallway. This display includes information about the elements arranged in the traditional periodic table format, but also includes visual real-world representations of the…

  4. 1992 tubing tables

    SciTech Connect

    Not Available

    1992-01-01

    This paper is helpful to those designing oil well completions or purchasing tubing with proprietary or premium connections. Tables contain specifications and application data for over 100 different tubing joints, including those used with fiberglass pipe. The tables this year contain dimensional and performance data for coiled tubing.

  5. Transcriptome analysis of IL-10-stimulated (M2c) macrophages by next-generation sequencing.

    PubMed

    Lurier, Emily B; Dalton, Donald; Dampier, Will; Raman, Pichai; Nassiri, Sina; Ferraro, Nicole M; Rajagopalan, Ramakrishan; Sarmady, Mahdi; Spiller, Kara L

    2017-02-20

    Alternatively activated "M2" macrophages are believed to function during late stages of wound healing, behaving in an anti-inflammatory manner to mediate the resolution of the pro-inflammatory response caused by "M1" macrophages. However, the differences between two main subtypes of M2 macrophages, namely interleukin-4 (IL-4)-stimulated "M2a" macrophages and IL-10-stimulated "M2c" macrophages, are not well understood. M2a macrophages are characterized by their ability to inhibit inflammation and contribute to the stabilization of angiogenesis. However, the role and temporal profile of M2c macrophages in wound healing are not known. Therefore, we performed next generation sequencing (RNA-seq) to identify biological functions and gene expression signatures of macrophages polarized in vitro with IL-10 to the M2c phenotype in comparison to M1 and M2a macrophages and an unactivated control (M0). We then explored the expression of these gene signatures in a publicly available data set of human wound healing. RNA-seq analysis showed that hundreds of genes were upregulated in M2c macrophages compared to the M0 control, with thousands of alternative splicing events. Following validation by Nanostring, 39 genes were found to be upregulated by M2c macrophages compared to the M0 control, and 17 genes were significantly upregulated relative to the M0, M1, and M2a phenotypes (using an adjusted p-value cutoff of 0.05 and fold change cutoff of 1.5). Many of the identified M2c-specific genes are associated with angiogenesis, matrix remodeling, and phagocytosis, including CD163, MMP8, TIMP1, VCAN, SERPINA1, MARCO, PLOD2, PCOCLE2 and F5. Analysis of the macrophage-conditioned media for secretion of matrix-remodeling proteins showed that M2c macrophages secreted higher levels of MMP7, MMP8, and TIMP1 compared to the other phenotypes. Interestingly, temporal gene expression analysis of a publicly available microarray data set of human wound healing showed that M2c-related genes were

  6. Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms.

    PubMed

    Cheng, A; Kaldis, P; Solomon, M J

    2000-11-03

    We previously reported that the activating phosphorylation on cyclin-dependent kinases in yeast (Cdc28p) and in humans (Cdk2) is removed by type 2C protein phosphatases. In this study, we characterize this PP2C-like activity in HeLa cell extract and determine that it is due to PP2C beta 2, a novel PP2C beta isoform, and to PP2C alpha. PP2C alpha and PP2C beta 2 co-purified with Mg(2+)-dependent Cdk2/Cdk6 phosphatase activity in DEAE-Sepharose, Superdex-200, and Mono Q chromatographies. Moreover, purified recombinant PP2C alpha and PP2C beta 2 proteins efficiently dephosphorylated monomeric Cdk2/Cdk6 in vitro. The dephosphorylation of Cdk2 and Cdk6 by PP2C isoforms was inhibited by the binding of cyclins. We found that the PP2C-like activity in HeLa cell extract, partially purified HeLa PP2C alpha and PP2C beta 2 isoforms, and the recombinant PP2Cs exhibited a comparable substrate preference for a phosphothreonine containing substrate, consistent with the conservation of threonine residues at the site of activating phosphorylation in CDKs.

  7. Is Clinical Stage T2C Prostate Cancer Intermediate or High-Risk Disease?

    PubMed Central

    Klaassen, Zachary; Singh, Abhay A.; Howard, Lauren E.; Feng, Zhaoyong; Trock, Bruce; Terris, Martha K.; Aronson, William J.; Cooperberg, Matthew R.; Amling, Christopher L.; Kane, Christopher J.; Partin, Alan; Han, Misop; Freedland, Stephen J.

    2014-01-01

    Background Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. In D’Amico grouping and AUA guidelines, cT2c is high-risk, whereas NCCN and EAU classify cT2c as intermediate-risk. We assessed whether cT2c tumors, without other high-risk factors (cT2c not otherwise specified (cT2c-nos)), behave as intermediate or high-risk by analyzing biochemical recurrence (BCR) after radical prostatectomy. Methods We analyzed 2,759 men from SEARCH and 12,900 men from Johns Hopkins Hospital (JHH) from 1988–2011 and 1982–2012, respectively. Patients were grouped into low (PSA<10ng/mL, Gleason sum≤6, and cT1-T2a), intermediate (PSA 10–20ng/mL, Gleason sum 7, or cT2b) and high-risk PC (PSA>20ng/mL, Gleason sum 8–10, or cT3). Men with cT2c who were not otherwise high-risk (i.e. PSA<20 ng/mL and Gleason sum<8) were placed into a separate category termed cT2c -nos. Associations between cT2c-nos and intermediate-risk, and high-risk patients and BCR were tested using log-rank test and Cox proportional analyses models. Results 99 men (4%) from SEARCH and 202 (2%) from JHH were cT2c-nos. cT2c-nos patients had similar BCR risk as intermediate-risk (SEARCH p=0.27; JHH p=0.23), but significantly lower BCR vs. high-risk (SEARCH p<0.001; JHH p<0.001). When specifically compared to intermediate and high-risk patients, and after adjusting for year and center, cT2c-nos patients had outcomes comparable to intermediate-risk (SEARCH p=0.53; JHH p=0.54), but significantly better than high-risk patients (SEARCH p=0.003; JHH p<0.001). Conclusions Patients with cT2c without other high-risk features had similar outcomes as intermediate-risk and significantly better than high-risk PC. These findings suggest men with cT2c should be considered intermediate-risk. PMID:25492369

  8. Setting the Periodic Table.

    ERIC Educational Resources Information Center

    Saturnelli, Annette

    1985-01-01

    Examines problems resulting from different forms of the periodic table, indicating that New York State schools use a form reflecting the International Union of Pure and Applied Chemistry's 1984 recommendations. Other formats used and reasons for standardization are discussed. (DH)

  9. The Periodic Table CD.

    ERIC Educational Resources Information Center

    Banks, Alton J.; Holmes, Jon L.

    1995-01-01

    Describes the characteristics of the digitized version of The Periodic Table Videodisc. Provides details about the organization of information and access to the data via Macintosh and Windows computers. (DDR)

  10. Tilt Table Test

    MedlinePlus

    ... and you're monitored closely. Most people regain consciousness almost immediately. In some cases, if blood pressure ... horizontal position, and you may not actually lose consciousness. When your tilt table test is complete, you ...

  11. Building Materials Property Table

    SciTech Connect

    2010-04-16

    This information sheet describes a table of some of the key technical properties of many of the most common building materials taken from ASHRAE Fundamentals - 2001, Moisture Control in Buildings, CMHC, NRC/IRC, IEA Annex 24, and manufacturer data.

  12. We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders.

    PubMed

    Cheng, Jianjun; Kozikowski, Alan P

    2015-12-01

    The serotonin 2C (5-HT2C ) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies.

  13. We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders

    PubMed Central

    Cheng, Jianjun; Kozikowski, Alan P.

    2016-01-01

    The serotonin 2C (5-HT2C) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies. PMID:26507582

  14. In Vitro Functional Characterisation of Cytochrome P450 (CYP) 2C19 Allelic Variants CYP2C19*23 and CYP2C19*24.

    PubMed

    Lau, Pui Shen; Leong, Kenny Voon Gah; Ong, Chin Eng; Dong, Amelia Nathania Hui Min; Pan, Yan

    2017-02-01

    Cytochrome P450 (CYP) 2C19 is essential for the metabolism of clinically used drugs including omeprazole, proguanil, and S-mephenytoin. This hepatic enzyme exhibits genetic polymorphism with inter-individual variability in catalytic activity. This study aimed to characterise the functional consequences of CYP2C19*23 (271 G>C, 991 A>G) and CYP2C19*24 (991 A>G, 1004 G>A) in vitro. Mutations in CYP2C19 cDNA were introduced by site-directed mutagenesis, and the CYP2C19 wild type (WT) as well as variants proteins were subsequently expressed using Escherichia coli cells. Catalytic activities of CYP2C19 WT and those of variants were determined by high performance liquid chromatography-based essay employing S-mephenytoin and omeprazole as probe substrates. Results showed that the level of S-mephenytoin 4'-hydroxylation activity of CYP2C19*23 (V max 111.5 ± 16.0 pmol/min/mg, K m 158.3 ± 88.0 μM) protein relative to CYP2C19 WT (V max 101.6 + 12.4 pmol/min/mg, K m 123.0 ± 19.2 μM) protein had no significant difference. In contrast, the K m of CYP2C19*24 (270.1 ± 57.2 μM) increased significantly as compared to CYP2C19 WT (123.0 ± 19.2 μM) and V max of CYP2C19*24 (23.6 ± 2.6 pmol/min/mg) protein was significantly lower than that of the WT protein (101.6 ± 12.4 pmol/min/mg). In vitro intrinsic clearance (CLint = V max/K m) for CYP2C19*23 protein was 85.4 % of that of CYP2C19 WT protein. The corresponding CLint value for CYP2C19*24 protein reduced to 11.0 % of that of WT protein. These findings suggested that catalytic activity of CYP2C19 was not affected by the corresponding amino acid substitutions in CYP2C19*23 protein; and the reverse was true for CYP2C19*24 protein. When omeprazole was employed as the substrate, K m of CYP2C19*23 (1911 ± 244.73 μM) was at least 100 times higher than that of CYP2C19 WT (18.37 ± 1.64 μM) and V max of CYP2C19*23 (3.87 ± 0.74 pmol/min/mg) dropped to 13.4 % of the CYP2C19 WT (28.84 ± 0.61

  15. Evolution of the metazoan protein phosphatase 2C superfamily.

    PubMed

    Stern, Adi; Privman, Eyal; Rasis, Michal; Lavi, Sara; Pupko, Tal

    2007-01-01

    Members of the protein phosphatase 2C (PP2C) superfamily are Mg(2+)/Mn(2+)-dependent serine/threonine phosphatases, which are essential for regulation of cell cycle and stress signaling pathways in cells. In this study, a comprehensive genomic analysis of all available metazoan PP2C sequences was conducted. The phylogeny of PP2C was reconstructed, revealing the existence of 15 vertebrate families which arose following a series of gene duplication events. Relative dating of these duplications showed that they occurred in two active periods: before the divergence of bilaterians and before vertebrate diversification. PP2C families which duplicated during the first period take part in different signaling pathways, whereas PP2C families which diverged in the second period display tissue expression differences yet participate in similar signaling pathways. These differences were found to involve variation of expression in tissues which show higher complexity in vertebrates, such as skeletal muscle and the nervous system. Further analysis was performed with the aim of identifying the functional domains of PP2C. The conservation pattern across the entire PP2C superfamily revealed an extensive domain of more than 50 amino acids which is highly conserved throughout all PP2C members. Several insertion or deletion events were found which may have led to the specialization of each PP2C family.

  16. Photoelectron spectroscopy of the hydroxymethoxide anion, H2C(OH)O-

    NASA Astrophysics Data System (ADS)

    Oliveira, Allan M.; Lehman, Julia H.; McCoy, Anne B.; Lineberger, W. Carl

    2016-09-01

    We report the negative ion photoelectron spectroscopy of the hydroxymethoxide anion, H2C(OH)O-. The photoelectron spectra show that 3.49 eV photodetachment produces two distinct electronic states of the neutral hydroxymethoxy radical (H2C(OH)Oṡ). The H2C(OH)Oṡ ground state (X ˜ 2A) photoelectron spectrum exhibits a vibrational progression consisting primarily of the OCO symmetric and asymmetric stretches, the OCO bend, as well as combination bands involving these modes with other, lower frequency modes. A high-resolution photoelectron spectrum aids in the assignment of several vibrational frequencies of the neutral H2C(OH)Oṡ radical, including an experimental determination of the H2C(OH)Oṡ 2ν12 overtone of the H-OCO torsional vibration as 220(10) cm-1. The electron affinity of H2C(OH)Oṡ is determined to be 2.220(2) eV. The low-lying A ˜ 2A excited state is also observed, with a spectrum that peaks ˜0.8 eV above the X ˜ 2A state origin. The A ˜ 2A state photoelectron spectrum is a broad, partially resolved band. Quantum chemical calculations and photoelectron simulations aid in the interpretation of the photoelectron spectra. In addition, the gas phase acidity of methanediol is calculated to be 366(2) kcal mol-1, which results in an OH bond dissociation energy, D0(H2C(OH)O-H), of 104(2) kcal mol-1, using the experimentally determined electron affinity of the hydroxymethoxy radical.

  17. The transcriptional regulation of the human CYP2C genes

    PubMed Central

    Chen, Yuping; Goldstein, Joyce A.

    2010-01-01

    In humans, four members of the CYP2C subfamily (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) metabolize more than 20% of all therapeutic drugs as well as a number of endogenous compounds. The CYP2C enzymes are found predominantly in the liver, where they comprise ∼20% of the total cytochrome P450. A variety of xenobiotics such as phenobarbital, rifampicin, and hyperforin have been shown to induce the transcriptional expression of CYP2C genes in primary human hepatocytes and to increase the metabolism of CYP2C substrates in vivo in man. This induction can result in drug-drug interactions, drug tolerance, and therapeutic failure. Several drug-activated nuclear receptors including CAR, PXR, VDR, and GR recognize drug responsive elements within the 5′ flanking promoter region of CYP2C genes to mediate the transcriptional upregulation of these genes in response to xenobiotics and steroids. Other nuclear receptors and transcriptional factors including HNF4α, HNF3γ, C/EBPα and more recently RORs, have been reported to regulate the constitutive expression of CYP2C genes in liver. The maximum transcriptional induction of CYP2C genes appears to be achieved through a coordinative cross-talk between drug responsive nuclear receptors, hepatic factors, and coactivators. The transcriptional regulatory mechanisms of the expression of CYP2C genes in extrahepatic tissues has received less study, but these may be altered by perturbations from pathological conditions such as ischemia as well as some of the receptors mentioned above. PMID:19702536

  18. Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 in vitro: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism

    PubMed Central

    Shon, Ji-Hong; Yoon, Young-Ran; Kim, Min-Jung; Kim, Kyoung-Ah; Lim, Young-Chae; Liu, Kwang-Hyeon; Shin, Dong-Hoon; Lee, Chung Han; Cha, In-June; Shin, Jae-Gook

    2005-01-01

    Aims We evaluated the involvement of cytochrome P450 (CYP) isoforms 2C9 and 2C19 in chlorpropamide 2-hydroxylation in vitro and in chlorpropamide disposition in vivo. Methods To identify CYP isoforms(s) that catalyse 2-hydroxylation of chlorpropamide, the incubation studies were conducted using human liver microsomes and recombinant CYP isoforms. To evaluate whether genetic polymorphisms of CYP2C9 and/or CYP2C19 influence the disposition of chlorpropamide, a single oral dose of 250 mg chlorpropamide was administered to 21 healthy subjects pregenotyped for CYP2C9 and CYP2C19. Results In human liver microsomal incubation studies, the formation of 2-hydroxychlorpropamide (2-OH-chlorpropamide), a major chlorpropamide metabolite in human, has been best described by a one-enzyme model with estimated Km and Vmax of 121.7 ± 19.9 µm and 16.1 ± 5.0 pmol min−1 mg−1 protein, respectively. In incubation studies using human recombinant CYP isoforms, however, 2-OH-chlorpropamide was formed by both CYP2C9 and CYP2C19 with similar intrinsic clearances (CYP2C9 vs. CYP2C19: 0.26 vs. 0.22 µl min−1 nmol−1 protein). Formation of 2-OH-chlorpropamide in human liver microsomes was significantly inhibited by sulfaphenazole, but not by S-mephenytoin, ketoconazole, quinidine, or furafylline. In in vivo clinical trials, eight subjects with the CYP2C9*1/*3 genotype exhibited significantly lower nonrenal clearance [*1/*3 vs.*1/*1: 1.8 ± 0.2 vs. 2.4 ± 0.1 ml h−1 kg−1, P < 0.05; 95% confidence interval (CI) on the difference 0.2, 1.0] and higher metabolic ratios (of chlorpropamide/2-OH-chlorpropamide in urine: *1/*3 vs. *1/*1: 1.01 ± 0.19 vs. 0.56 ± 0.08, P < 0.05; 95% CI on the difference −0.9, −0.1) than did 13 subjects with CYP2C9*1/*1 genotype. In contrast, no differences in chlorpropamide pharmacokinetics were observed for subjects with the CYP2C19 extensive metabolizer vs. poor metabolizer genotypes. Conclusions These results suggest that chlorpropamide disposition is

  19. CYP2C19 polymorphism influences Helicobacter pylori eradication

    PubMed Central

    Kuo, Chao-Hung; Lu, Chien-Yu; Shih, Hsiang-Yao; Liu, Chung-Jung; Wu, Meng-Chieh; Hu, Huang-Ming; Hsu, Wen-Hung; Yu, Fang-Jung; Wu, Deng-Chyang; Kuo, Fu-Chen

    2014-01-01

    The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration. PMID:25473155

  20. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    PubMed

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  1. Space station wardroom table

    NASA Technical Reports Server (NTRS)

    Cohen, Marc M. (Inventor); Kaplicky, Jan (Inventor); Nixon, David A. (Inventor)

    1989-01-01

    A table top for use in constricted areas has a plurality of support arms abutting at one end to form a hub. The support arms are arranged in equidistant, spaced-apart relation to each other at the ends distal to the hub. A plurality of work surface leaf sections mounted between the support arms are individually pivotable through 360 degrees about their longitudinal axes. The table top additionally has a plurality of distal leaves, each distal leaf being attached to the distal end of one of the arms. The distal leaves are pivotable between an upright position level with the support arms and a stored position below the support arms.

  2. Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model.

    PubMed

    Canal, Clinton E; Booth, Raymond G; Morgan, Drake

    2013-07-01

    There are seemingly conflicting data in the literature regarding the role of serotonin (5-HT) 5-HT2C receptors in the mouse head-twitch response (HTR) elicited by the hallucinogenic 5-HT2A/2B/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Namely, both 5-HT2C receptor agonists and antagonists, regarding 5-HT2C receptor-mediated Gq-phospholipase C (PLC) signaling, reportedly attenuate the HTR response. The present experiments tested the hypothesis that both classes of 5-HT2C receptor compounds could attenuate the DOI-elicited-HTR in a single strain of mice, C57Bl/6J. The expected results were considered in accordance with ligand functional selectivity. Commercially-available 5-HT2C agonists (CP 809101, Ro 60-0175, WAY 161503, mCPP, and 1-methylpsilocin), novel 4-phenyl-2-N,N-dimethyl-aminotetralin (PAT)-type 5-HT2C agonists (with 5-HT2A/2B antagonist activity), and antagonists selective for 5-HT2A (M100907), 5-HT2C (SB-242084), and 5-HT2B/2C (SB-206553) receptors attenuated the DOI-elicited-HTR. In contrast, there were differential effects on locomotion across classes of compounds. The 5-HT2C agonists and M100907 decreased locomotion, SB-242084 increased locomotion, SB-206553 resulted in dose-dependent biphasic effects on locomotion, and the PATs did not alter locomotion. In vitro molecular pharmacology studies showed that 5-HT2C agonists potent for attenuating the DOI-elicited-HTR also reduced the efficacy of DOI to activate mouse 5-HT2C receptor-mediated PLC signaling in HEK cells. Although there were differences in affinities of a few compounds at mouse compared to human 5-HT2A or 5-HT2C receptors, all compounds tested retained their selectivity for either receptor, regardless of receptor species. Results indicate that 5-HT2C receptor agonists and antagonists attenuate the DOI-elicited-HTR in C57Bl/6J mice, and suggest that structurally diverse 5-HT2C ligands result in different 5-HT2C receptor signaling outcomes compared to DOI.

  3. Structural, electronic and bonding properties of antifluorite crystals of Be2C, BeMgC and Mg2C

    NASA Astrophysics Data System (ADS)

    Joshi, K. B.; Trivedi, D. K.; Paliwal, U.; Galav, K. L.

    2016-05-01

    Structure prediction methods are coupled with the first-principles linear combination of atomic orbitals method to propose the crystal parameters and bulk modulus of antifluorite BeMgC. The binary antifluorite methanides Be2C, Mg2C are also studied. Electronic structure calculations and Mulliken population analyses (MPA) are performed to unravel bands dispersion and bonding properties. The values of the indirect band gap Γ → X for Be2C, Mg2C and BeMgC, in order, are 2.90, 2.05 and 1.86 eV. The calculated energies of a few occupied bands in Be2C are in very good agreement with the available experimental data. The application of pressure causes change in the band gap of three carbides. The Γ-Γ, Γ-X and Γ-K band gaps exhibit different trends with pressure. Effective charges on the basis of MPA in the three compounds are {(B{e}+1.095)}2{C}-2.19, {(M{g}+1.615)}2{C}-3.23 and B{e}+1.12M{g}+1.682{C}-2.802. It signifies covalent bonding in Be2C, ionic in Mg2C, and intermediate in the BeMgC.

  4. 27 CFR 21.34 - Formula No. 2-C.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Formula No. 2-C. 21.34... OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.34 Formula No. 2-C. (a) Formula. To every 100 gallons of alcohol add:...

  5. 27 CFR 21.34 - Formula No. 2-C.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Formula No. 2-C. 21.34... OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.34 Formula No. 2-C. (a) Formula. To every 100 gallons of alcohol add:...

  6. 27 CFR 21.34 - Formula No. 2-C.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Formula No. 2-C. 21.34... OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.34 Formula No. 2-C. (a) Formula. To every 100 gallons of alcohol add:...

  7. 27 CFR 21.34 - Formula No. 2-C.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Formula No. 2-C. 21.34... OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.34 Formula No. 2-C. (a) Formula. To every 100 gallons of alcohol add:...

  8. A Modern Periodic Table.

    ERIC Educational Resources Information Center

    Herrenden-Harker, B. D.

    1997-01-01

    Presents a modern Periodic Table based on the electron distribution in the outermost shell and the order of filling of the sublevels within the shells. Enables a student to read off directly the electronic configuration of the element and the order in which filling occurs. (JRH)

  9. Guide to the Table

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2010

    2010-01-01

    This article presents a table that provides a snapshot of how employment is expected to change in 289 occupations. For each occupation, it shows estimated employment in 2008, the projected numeric change in employment (that is, how many jobs are expected to be gained or lost) over the 2008-18 decade, and the projected percent change in employment…

  10. The Aerodynamic Plane Table

    NASA Technical Reports Server (NTRS)

    Zahm, A F

    1924-01-01

    This report gives the description and the use of a specially designed aerodynamic plane table. For the accurate and expeditious geometrical measurement of models in an aerodynamic laboratory, and for miscellaneous truing operations, there is frequent need for a specially equipped plan table. For example, one may have to measure truly to 0.001 inch the offsets of an airfoil at many parts of its surface. Or the offsets of a strut, airship hull, or other carefully formed figure may require exact calipering. Again, a complete airplane model may have to be adjusted for correct incidence at all parts of its surfaces or verified in those parts for conformance to specifications. Such work, if but occasional, may be done on a planing or milling machine; but if frequent, justifies the provision of a special table. For this reason it was found desirable in 1918 to make the table described in this report and to equip it with such gauges and measures as the work should require.

  11. NEW APPROACHES: Pool table

    NASA Astrophysics Data System (ADS)

    Parry, Malcolm

    1998-05-01

    This article explains a novel way of demonstrating the principle of conservation of energy. This can be difficult to demonstrate in the laboratory, but if students have been convinced of the conservation of momentum, two-dimensional collisions on a pool table may be used.

  12. The Dynamic Force Table

    ERIC Educational Resources Information Center

    Geddes, John B.; Black, Kelly

    2008-01-01

    We examine an experimental apparatus that is used to motivate the connections between the basic properties of vectors, potential functions, systems of nonlinear equations, and Newton's method for nonlinear systems of equations. The apparatus is an adaptation of a force table where we remove the center-pin and allow the center-ring to move freely.…

  13. Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.

    PubMed

    Shirasaka, Y; Chaudhry, A S; McDonald, M; Prasad, B; Wong, T; Calamia, J C; Fohner, A; Thornton, T A; Isoherranen, N; Unadkat, J D; Rettie, A E; Schuetz, E G; Thummel, K E

    2016-08-01

    Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.58.

  14. Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content

    PubMed Central

    Shirasaka, Y; Chaudhry, A S; McDonald, M; Prasad, B; Wong, T; Calamia, J C; Fohner, A; Thornton, T A; Isoherranen, N; Unadkat, J D; Rettie, A E; Schuetz, E G; Thummel, K E

    2016-01-01

    Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration. PMID:26323597

  15. TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling.

    PubMed

    Woodfield, George W; Horan, Annamarie D; Chen, Yizhen; Weigel, Ronald J

    2007-09-15

    Breast cancers expressing estrogen receptor-alpha (ERalpha) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERalpha, other pathways of estrogen response have been identified including ERbeta and GPR30, a membrane receptor for estrogen, and the key mechanisms regulating expression of ERs and hormone response remain controversial. Herein, we show that TFAP2C is the key regulator of hormone responsiveness in breast carcinoma cells through the control of multiple pathways of estrogen signaling. TFAP2C regulates the expression of ERalpha directly by binding to the ERalpha promoter and indirectly via regulation of FoxM1. In so doing, TFAP2C controls the expression of ERalpha target genes, including pS2, MYB, and RERG. Furthermore, TFAP2C controlled the expression of GPR30. In distinct contrast, TFAP2A, a related factor expressed in breast cancer, was not involved in estrogen-mediated pathways but regulated expression of genes controlling cell cycle arrest and apoptosis including p21(CIP1) and IGFBP-3. Knockdown of TFAP2C abrogated the mitogenic response to estrogen exposure and decreased hormone-responsive tumor growth of breast cancer xenografts. We conclude that TFAP2C is a central control gene of hormone response and is a novel therapeutic target in the design of new drug treatments for breast cancer.

  16. Protein phosphatase AP2C1 negatively regulates basal resistance and defense responses to Pseudomonas syringae.

    PubMed

    Shubchynskyy, Volodymyr; Boniecka, Justyna; Schweighofer, Alois; Simulis, Justinas; Kvederaviciute, Kotryna; Stumpe, Michael; Mauch, Felix; Balazadeh, Salma; Mueller-Roeber, Bernd; Boutrot, Freddy; Zipfel, Cyril; Meskiene, Irute

    2017-01-06

    Mitogen-activated protein kinases (MAPKs) mediate plant immune responses to pathogenic bacteria. However, less is known about the cell autonomous negative regulatory mechanism controlling basal plant immunity. We report the biological role of Arabidopsis thaliana MAPK phosphatase AP2C1 as a negative regulator of plant basal resistance and defense responses to Pseudomonas syringae AP2C2, a closely related MAPK phosphatase, also negatively controls plant resistance. Loss of AP2C1 leads to enhanced pathogen-induced MAPK activities, increased callose deposition in response to pathogen-associated molecular patterns or to P. syringae pv. tomato (Pto) DC3000, and enhanced resistance to bacterial infection with Pto. We also reveal the impact of AP2C1 on the global transcriptional reprogramming of transcription factors during Pto infection. Importantly, ap2c1 plants show salicylic acid-independent transcriptional reprogramming of several defense genes and enhanced ethylene production in response to Pto This study pinpoints the specificity of MAPK regulation by the different MAPK phosphatases AP2C1 and MKP1, which control the same MAPK substrates, nevertheless leading to different downstream events. We suggest that precise and specific control of defined MAPKs by MAPK phosphatases during plant challenge with pathogenic bacteria can strongly influence plant resistance.

  17. Type 2C Protein Phosphatases in Fungi ▿ †

    PubMed Central

    Ariño, Joaquín; Casamayor, Antonio; González, Asier

    2011-01-01

    Type 2C Ser/Thr phosphatases are a remarkable class of protein phosphatases, which are conserved in eukaryotes and involved in a large variety of functional processes. Unlike in other Ser/Thr phosphatases, the catalytic polypeptide is not usually associated with regulatory subunits, and functional specificity is achieved by encoding multiple isoforms. For fungi, most information comes from the study of type 2C protein phosphatase (PP2C) enzymes in Saccharomyces cerevisiae, where seven PP2C-encoding genes (PTC1 to -7) with diverse functions can be found. More recently, data on several Candida albicans PP2C proteins became available, suggesting that some of them can be involved in virulence. In this work we review the available literature on fungal PP2Cs and explore sequence databases to provide a comprehensive overview of these enzymes in fungi. PMID:21076010

  18. Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization.

    PubMed

    Ohlsson, Susanne M; Linge, Carl Petrus; Gullstrand, Birgitta; Lood, Christian; Johansson, Asa; Ohlsson, Sophie; Lundqvist, Andrea; Bengtsson, Anders A; Carlsson, Fredric; Hellmark, Thomas

    2014-01-01

    Anti-neutrophil cytoplasmic antibody associated vasculitides (AAV) are conditions defined by an autoimmune small vessel inflammation. Dying neutrophils are found around the inflamed vessels and the balance between infiltrating neutrophils and macrophages is important to prevent autoimmunity. Here we investigate how sera from AAV patients may regulate macrophage polarization and function. Macrophages from healthy individuals were differentiated into M0, M1, M2a, M2b or M2c macrophages using a standardized protocol, and phenotyped according to their expression surface markers and cytokine production. These phenotypes were compared with those of macrophages stimulated with serum from AAV patients or healthy controls. While the healthy control sera induced a M0 macrophage, AAV serum promoted polarization towards the M2c subtype. No sera induced M1, M2a or M2b macrophages. The M2c subtype showed increased phagocytosis capacity compared with the other subtypes. The M2c polarization found in AAV is consistent with previous reports of increased levels of M2c-associated cytokines.

  19. Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon*).

    PubMed

    Jin, Feng; Ji, Chaoneng; Liu, Lingfeng; Dai, Jianfeng; Gu, Shaohua; Sun, Xianfei; Xie, Yi; Mao, Yumin

    2004-09-01

    We have isolated a novel cDNA from the human fetal brain cDNA library with homology to the Mg2+ -dependent serine/threonine protein phosphatase 2C (PP2C) family. The cDNA is 3055 bp in length, and the predicted coding region encodes a 360-amino-acid protein, which shows 99% identity to the PP2C epsilon from rat and mouse. Then we term it human PP2C epsilon gene. The gene is mapped to chromosome 3q26.1 and contains 4 exons. RT-PCR analysis shows that the PP2C epsilon is widely expressed in human tissues and the expression levels in heart, placenta, lung, liver, kidney, and pancreas are relatively high.

  20. League tables for orthodontists

    PubMed Central

    Richmond, Stephen; Phillips, Ceri; Durning, Peter

    2008-01-01

    The aim of this study was to explore the complexities in constructing league tables purporting to measure orthodontic clinical outcomes. Eighteen orthodontists were invited to participate in a cost-effectiveness study. Each orthodontist was asked to provide information on 100 consecutively treated patients. The Index of Complexity, Outcome, and Need (ICON) was used to assess treatment need, complexity, and outcome prior to, and on completion of, orthodontic treatment. The 18 orthodontists were ranked based on achieving a successful orthodontic outcome (ICON score less than or equal to 30) and the uncertainty in both the success rates and rankings was also quantified using confidence intervals. Successful outcomes were achieved in 62 per cent of the sample (range 19–94 per cent); four of the 18 orthodontists failed to achieve more than a 50 per cent success rate. In developing league tables, it is imperative that factors such as case mix are identified and accounted for in producing rankings. Bayesian hierarchical modelling was used to achieve this and to quantify uncertainty in the rankings produced. When case mix was taken into account, the four with low success rates were clearly not as good as the top four performing orthodontists. League tables can be valuable for the individual orthodontist, groups of orthodontists, payment/insurance agencies, and the public to enable informed choice for orthodontic provision but must be correctly constructed so that users can have confidence in them. PMID:18687990

  1. Pyrolysis of table sugar.

    PubMed

    Bulut, Adnan; Karagöz, Selhan

    2013-01-01

    Table sugars were pyrolyzed at different temperatures (300, 400, and 500°C) in a fixed-bed reactor. The effect of pyrolysis temperature on yields of liquid, solid, and gaseous products was investigated. As expected the yield of liquid products gradually increased and the yield of solid products gradually decreased when the pyrolysis temperature was raised. The yield of liquid products was greatest (52 wt%) at 500°C. The composition of bio-oils extracted with diethyl ether was identified by means of gas chromatography mass spectrometry (GC-MS), nuclear magnetic resonance ((1)H-NMR), and Fourier transform infrared spectroscopy (FTIR). The following compounds were observed in bio-oils produced from the pyrolysis of table sugar at 500°C: 1,4:3,6-dianhydro- α -d-glucopyranose, 5-(hydroxymethyl) furfural, 5-acetoxymethyl-2-furaldehyde, and cyclotetradecane liquid product. The relative concentration of 5-(hydroxymethyl) furfural was the highest in bio-oils obtained from pyrolysis of table sugars at 500°C.

  2. The interstellar chemistry of H2C3O isomers.

    PubMed

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-03-11

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects.

  3. The interstellar chemistry of H2C3O isomers

    PubMed Central

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M.; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-01-01

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects. PMID:27013768

  4. Serotonin2C receptors and drug addiction: focus on cocaine.

    PubMed

    Devroye, Céline; Filip, Malgorzata; Przegaliński, Edmund; McCreary, Andrew C; Spampinato, Umberto

    2013-10-01

    This review provides an overview of the role of central serotonin2C (5-HT2C) receptors in drug addiction, specifically focusing on their impact on the neurochemical and behavioral effects of cocaine, one of the most worldwide abused drug. First, we described the neurochemical and electrophysiological mechanisms underlying the interaction between 5-HT2C receptors and the mesocorticolimbic dopaminergic network, in keeping with the key role of this system in drug abuse and dependence. Thereafter, we focused on the role of 5-HT2C receptors in the effects of cocaine in various preclinical behavioral models used in drug addiction research, such as locomotor hyperactivity, locomotor sensitization, drug discrimination, and self-administration, to end with an overview of the neurochemical mechanisms underlying the interactions between 5-HT2C receptors, mesocorticolimbic dopamine system, and cocaine. On their whole, the presented data provide compelling preclinical evidence that 5-HT2C receptor agonists may have efficacy in the treatment of cocaine abuse and dependence, thereby underlying the need for additional clinical studies to ascertain whether preclinical data translate to the human.

  5. 50 CFR Table 2c to Part 679 - Species Codes: FMP Forage Fish Species (all species of the following families)

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., lightfishes, and anglemouths (family Gonostomatidae) 209 Capelin smelt (family Osmeridae) 516 Deep-sea smelts (family Bathylagidae) 773 Eulachon smelt (family Osmeridae) 511 Gunnels (family Pholidae) 207 Krill (order... (family Stichaeidae) 208 Surf smelt (family Osmeridae) 515...

  6. 50 CFR Table 2c to Part 679 - Species Codes: FMP Forage Fish Species (all species of the following families)

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., lightfishes, and anglemouths (family Gonostomatidae) 209 Capelin smelt (family Osmeridae) 516 Deep-sea smelts (family Bathylagidae) 773 Eulachon smelt (family Osmeridae) 511 Gunnels (family Pholidae) 207 Krill (order... (family Stichaeidae) 208 Surf smelt (family Osmeridae) 515...

  7. 50 CFR Table 2c to Part 679 - Species Codes: FMP Forage Fish Species (all species of the following families)

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., lightfishes, and anglemouths (family Gonostomatidae) 209 Capelin smelt (family Osmeridae) 516 Deep-sea smelts (family Bathylagidae) 773 Eulachon smelt (family Osmeridae) 511 Gunnels (family Pholidae) 207 Krill (order... (family Stichaeidae) 208 Surf smelt (family Osmeridae) 515...

  8. 50 CFR Table 2c to Part 679 - Species Codes: FMP Forage Fish Species (all species of the following families)

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., lightfishes, and anglemouths (family Gonostomatidae) 209 Capelin smelt (family Osmeridae) 516 Deep-sea smelts (family Bathylagidae) 773 Eulachon smelt (family Osmeridae) 511 Gunnels (family Pholidae) 207 Krill (order... (family Stichaeidae) 208 Surf smelt (family Osmeridae) 515...

  9. 50 CFR Table 2c to Part 679 - Species Codes: FMP Forage Fish Species (all species of the following families)

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., lightfishes, and anglemouths (family Gonostomatidae) 209 Capelin smelt (family Osmeridae) 516 Deep-sea smelts (family Bathylagidae) 773 Eulachon smelt (family Osmeridae) 511 Gunnels (family Pholidae) 207 Krill (order... (family Stichaeidae) 208 Surf smelt (family Osmeridae) 515...

  10. The 23 K superconducting phase YPd 2B 2C

    NASA Astrophysics Data System (ADS)

    Sun, Y. Y.; Rusakova, I.; Meng, R. L.; Cao, Y.; Gautier-Picard, P.; Chu, C. W.

    1994-09-01

    We have carried out a systematic structural, electric, and magnetic study on YPdBC samples with different compositions with emphasis on the as-cast and annealed YPd 5B 3C 0.3 which was first reported to superconduct at ∼ 23 K by Cava et al. We found that the tetragonal body-centered YPd 2B 2C with lattice parameters a=3.71 Å and c=10.81 Å is the phase responsible for the 23 K superconductivity and that YPd 2B 2C is metastable, which is consistent with the suggestion made by Cava et al. [1]: it is not stable at high temperatures nor stabilizable by Ni doping, although its isostructural compound, YNi 2B 2C, exists. Two new phases with Y:Pd ratios of 1:7 and 2:3, respectively, have also bee detected.

  11. Deployable video conference table

    NASA Technical Reports Server (NTRS)

    Cohen, Marc M. (Inventor); Lissol, Peter (Inventor)

    1993-01-01

    A deployable table is presented. The table is stowed in and deployed from a storage compartment based upon a non-self rigidizing, 4-hinge, arch support structure that folds upon itself to stow and that expands to deploy. The work surfaces bypass each other above and below to allow the deployment mechanism to operate. This assembly includes the following: first and second primary pivot hinges placed at the opposite ends of the storage compartment; first and second lateral frame members with proximal ends connected to the first and second pivot hinges; a medial frame member offset from and pivotally connected to distal ends of the first and second members through third and fourth medial pivot hinges; and left-side, right-side, and middle trays connected respectively to the first, second, and third frame members and being foldable into and out of the storage compartment by articulation of the first, second, third, and fourth joints. At least one of the third and fourth joints are locked to set the first, second, and third frame members in a desired angular orientation with respect to each other.

  12. Deriving Extensional Spatial Composition Tables

    NASA Astrophysics Data System (ADS)

    El-Geresy, Baher; Abdelmoty, Alia I.; Ware, Andrew J.

    Spatial composition tables are fundamental tools for the realisation of qualitative spatial reasoning techniques. Studying the properties of these tables in relation to the spatial calculi they are based on is essential for understanding the applicability of these calculi and how they can be extended and generalised. An extensional interpretation of a spatial composition table is an important property that has been studied in the literature and is used to determine the validity of the table for the models it is proposed for. It provides means for consistency checking of ground sets of relations and for addressing spatial constraint satisfaction problems. Furthermore, two general conditions that can be used to test for extensionality of spatial composition tables are proposed and applied to the RCC8 composition table to verify the allowable models in this calculus.

  13. The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen

    PubMed Central

    Canal, Clinton E.; Olaghere da Silva, Uade B.; Gresch, Paul J.; Watt, Erin E.; Sanders-Bush, Elaine

    2010-01-01

    Rationale Hallucinogenic serotonin 2A (5-HT2A) receptor partial agonists, such as (±)-1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane hydrochloride (DOI), induce a frontal cortex-dependent head-twitch response (HTR) in rodents, a behavioral proxy of a hallucinogenic response that is blocked by 5-HT2A receptor antagonists. In addition to 5-HT2A receptors, DOI and most other serotonin-like hallucinogens have high affinity and potency as partial agonists at 5-HT2C receptors. Objectives We tested for involvement of 5-HT2C receptors in the HTR induced by DOI. Results Comparison of 5-HT2C receptor knockout and wild-type littermates revealed an approximately 50% reduction in DOI-induced HTR in knockout mice. Also, pretreatment with either the 5-HT2C receptor antagonist SB206553 or SB242084 eradicated a twofold difference in DOI-induced HTR between the standard inbred mouse strains C57BL/6J and DBA/2J, and decreased the DOI-induced HTR by at least 50% in both strains. None of several measures of 5-HT2A receptors in frontal cortex explained the strain difference, including 5-HT2A receptor density, Gαq or Gαi/o protein levels, phospholipase C activity, or DOI-induced expression of Egr1 and Egr2. 5-HT2C receptor density in the brains of C57BL/6J and DBA/2J was also equivalent, suggesting that 5-HT2C receptor-mediated intracellular signaling or other physiological modulators of the HTR may explain the strain difference in response to DOI. Conclusions We conclude that the HTR to DOI in mice is strongly modulated by 5-HT2C receptor activity. This novel finding invites reassessment of hallucinogenic mechanisms involving 5-HT2 receptors. PMID:20165943

  14. Symbol Tables and Branch Tables: Linking Applications Together

    NASA Technical Reports Server (NTRS)

    Handler, Louis M.

    2011-01-01

    This document explores the computer techniques used to execute software whose parts are compiled and linked separately. The computer techniques include using a branch table or indirect address table to connect the parts. Methods of storing the information in data structures are discussed as well as differences between C and C++.

  15. TableSeer: Automatic Table Extraction, Search, and Understanding

    ERIC Educational Resources Information Center

    Liu, Ying

    2009-01-01

    Tables are ubiquitous with a history that pre-dates that of sentential text. Authors often report a summary of their most important findings using tabular structure in documents. For example, scientists widely use tables to present the latest experimental results or statistical data in a condensed fashion. Along with the explosive development of…

  16. Robotic Range Clearance Competition (R2C2)

    DTIC Science & Technology

    2011-10-01

    was only done for the “subsurface real ” test range. After mapping the surface contour, the Rover was used to mark the locations of notable...8 Figure 6. Map of Wyoming Showing General Location of R2C2 Ranges...Figure 48. Team Sky Research Geophysical Coverage Map ........................................................49 Figure 49. Anomaly Location Accuracy

  17. 27 CFR 21.34 - Formula No. 2-C.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....Drugs and medicinal chemicals. 579.Other chemicals. (3) Miscellaneous uses: 812.Product development and... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 2-C. 21.34 Section 21.34 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU,...

  18. 40 CFR Table I-4 to Subpart I - Table I-4 to Subpart I of Part 98-Default Emission Factors (1-Uij) for Gas Utilization Rates (Uij...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Semiconductor Manufacturing for 300 mm Wafer Size I Table I-4 to Subpart I Protection of Environment... Semiconductor Manufacturing for 300 mm Wafer Size Process type/sub-type Process gas i CF4 C2F6 CHF3 CH2F2 C3F8...

  19. Trifluoromethylation of perfluorinated diacylfluorides: synthesis of the diketone CF3C(O)CF2C(O)CF3 and of new perfluorinated diol (CF3)2C(OH)CF2C(OH)(CF3)2.

    PubMed

    Corti, Sandra; Pennington, William T; DesMarteau, Darryl D

    2013-01-01

    Perfluoromalonyl difluoride reacts with TMS-CF3 (1:1) in the presence of KF to give the new diketone CF2(C(O)CF3)2. A large excess (5:1) of TMS-CF3 results in the presumed potassium dialkoxide [(CF3)2COK]2CF2 which yields the 1,3-ditertiarydiol [(CF3)2C(OH)]2CF2 on reaction with H2SO4.

  20. Phagocytosis and solubilization of fixed cells by metastatic hamster embryo fibroblasts, Nil2C2

    SciTech Connect

    Sakiyama, H.; Nishino, Y.; Nishimura, K.; Noda, Y.; Otsu, H.

    1984-05-01

    When Nil2C2, a metastatic clone derived from hamster embryo fibroblasts (Nil), was inoculated over (/sup 3/H)leucine-labeled fixed cells, Nil2C2 cells solubilized and phagocytosed fixed cells, and the radioactivity was released into the culture medium as trichloroacetic acid-soluble fragments. The solubilization of fixed cells was dependent on both the time of incubation of living cells with fixed cells and the number of living cells inoculated. Nil2C2 cells were shown by autoradiographic and electron microscopic studies to peel off fixed cells and ingest them as large fragments. The solubilization of fixed cells was significantly decreased when plasminogen was depleted from the culture medium. Protease inhibitors such as leupeptin, epsilon-aminocaproic acid, and soybean trypsin inhibitor partially inhibited the proteolysis and phagocytosis of Nil2C2 cells. Mouse peritoneal macrophages activated by Salmonella typhimurium solubilized fixed cells after the addition of 12-O-tetradecanoylphorbol-13-acetate. However, they did not phagocytose fixed cells as large fragments.

  1. LAMP-2C Inhibits MHC Class II Presentation of Cytoplasmic Antigens by Disrupting Chaperone-Mediated Autophagy.

    PubMed

    Pérez, Liliana; McLetchie, Shawna; Gardiner, Gail J; Deffit, Sarah N; Zhou, Delu; Blum, Janice S

    2016-03-15

    Cells use multiple autophagy pathways to sequester macromolecules, senescent organelles, and pathogens. Several conserved isoforms of the lysosome-associated membrane protein-2 (LAMP-2) regulate these pathways influencing immune recognition and responses. LAMP-2A is required for chaperone-mediated autophagy (CMA), which promotes Ag capture and MHC class II (MHCII) presentation in B cells and signaling in T cells. LAMP-2B regulates lysosome maturation to impact macroautophagy and phagocytosis. Yet, far less is known about LAMP-2C function. Whereas LAMP2A and LAMP2B mRNA were broadly detected in human tissues, LAMP2C expression was more limited. Transcripts for the three LAMP2 isoforms increased with B cell activation, although specific gene induction varied depending on TLR versus BCR engagement. To examine LAMP-2C function in human B cells and specifically its role in Ag presentation, we used ectopic gene expression. Increased LAMP-2C expression in B cells did not alter MHCII expression or invariant chain processing, but did perturb cytoplasmic Ag presentation via CMA. MHCII presentation of epitopes from exogenous and membrane Ags was not affected by LAMP-2C expression in B cells. Similarly, changes in B cell LAMP-2C expression did not impact macroautophagy. The gene expression of other LAMP2 isoforms and proteasome and lysosomal proteases activities were unperturbed by LAMP-2C ectopic expression. LAMP-2C levels modulated the steady-state expression of several cytoplasmic proteins that are targeted for degradation by CMA and diminished peptide translocation via this pathway. Thus, LAMP-2C serves as a natural inhibitor of CMA that can selectively skew MHCII presentation of cytoplasmic Ags.

  2. Information tables with neighborhood semantics

    NASA Astrophysics Data System (ADS)

    Yao, Yiyu

    2000-04-01

    Information tables provide a convenient and useful tool for representing a set of objects using a group of attributes. This notion is enriched by introducing neighborhood systems on attribute values. The neighborhood systems represent the semantics relationships between, and knowledge about, attribute values. With added semantics, neighborhood based information tables may provide a more general framework for knowledge discovery, data mining, and information retrieval.

  3. Computational study of the rovibrational spectra of CO2-C2H2 and CO2-C2D2

    NASA Astrophysics Data System (ADS)

    Donoghue, Geoff; Wang, Xiao-Gang; Dawes, Richard; Carrington, Tucker

    2016-12-01

    An intermolecular potential energy surface and rovibrational transition frequencies are computed for CO2-C2H2. An interpolating moving least squares method is used to fit ab initio points at the explicitly correlated coupled-cluster level. The rovibrational Schrödinger equation is solved with a symmetry-adapted Lanczos algorithm. The computed disrotatory and torsion vibrational levels of both CO2-C2H2 and CO2-C2D2 differ from those obtained by experimentalists by less than 0.5 cm-1. CO2-C2H2 has two equivalent minima with the monomers perpendicular to the inter-monomer axis. In contrast to many other Van der Waals dimers there is no disrotatory path that connects the minima. The tunnelling path follows the torsional coordinate over a high barrier and the splitting is therefore tiny. Using vibrational parent analysis we are able to fit and thus obtain rotational constants and centrifugal distortion constants. Calculated rotational constants differ from their experimental counterparts by less than 0.001 cm-1.

  4. Pharmacological characterisation of a structurally novel α2C-adrenoceptor antagonist ORM-10921 and its effects in neuropsychiatric models.

    PubMed

    Sallinen, Jukka; Holappa, Johanna; Koivisto, Ari; Kuokkanen, Katja; Chapman, Hugh; Lehtimäki, Jyrki; Piepponen, Petteri; Mijatovic, Jelena; Tanila, Heikki; Virtanen, Raimo; Sirviö, Jouni; Haapalinna, Antti

    2013-10-01

    The α2-adrenoceptors (ARs) are important modulators of a wide array of physiological responses. As only a few selective compounds for the three α2-AR subtypes (α2A , α2B and α2C ) have been available, the pharmacological profile of a new α2C-selective AR antagonist ORM-10921 is reported. Standard in vitro receptor assays and antagonism of α2, and α1-AR agonist-evoked responses in vivo were used to demonstrate the α2C-AR selectivity for ORM-10921 which was tested in established behavioural models related to schizophrenia and cognitive dysfunction with an emphasis on pharmacologically induced hypoglutamatergic state by phencyclidine or MK-801. The Kb values of in vitro α2C-AR antagonism for ORM-10921 varied between 0.078-1.2 nM depending on the applied method. The selectivity ratios compared to α2A-AR subtype and other relevant receptors were 10-100 times in vitro. The in vivo experiments supported its potent α2C-antagonism combined with only a weak α2A-antagonism. In the pharmacodynamic microdialysis study, ORM-10921 was found to increase extracellular dopamine levels in prefrontal cortex in the baseline conditions. In the behavioural tests, ORM-10921 displayed potent antidepressant and antipsychotic-like effects in the forced swimming test and prepulse-inhibition models analogously with the previously reported results with structurally different α2C-selective AR antagonist JP-1302. Our new results also indicate that ORM-10921 alleviated the NMDA-antagonist-induced impairments in social behaviour and watermaze navigation. This study extends and further validates the concept that α2C -AR is a potential therapeutic target in CNS disorders such as schizophrenia or Alzheimer's disease and suggests the potential of α2C-antagonism to treat such disorders.

  5. MCNPX Model/Table Comparison

    SciTech Connect

    J.S. Hendricks

    2003-03-03

    MCNPX is a Monte Carlo N-Particle radiation transport code extending the capabilities of MCNP4C. As with MCNP, MCNPX uses nuclear data tables to transport neutrons, photons, and electrons. Unlike MCNP, MCNPX also uses (1) nuclear data tables to transport protons; (2) physics models to transport 30 additional particle types (deuterons, tritons, alphas, pions, muons, etc.); and (3) physics models to transport neutrons and protons when no tabular data are available or when the data are above the energy range (20 to 150 MeV) where the data tables end. MCNPX can mix and match data tables and physics models throughout a problem. For example, MCNPX can model neutron transport in a bismuth germinate (BGO) particle detector by using data tables for bismuth and oxygen and using physics models for germanium. Also, MCNPX can model neutron transport in UO{sub 2}, making the best use of physics models and data tables: below 20 MeV, data tables are used; above 150 MeV, physics models are used; between 20 and 150 MeV, data tables are used for oxygen and models are used for uranium. The mix-and-match capability became available with MCNPX2.5.b (November 2002). For the first time, we present here comparisons that calculate radiation transport in materials with various combinations of data charts and model physics. The physics models are poor at low energies (<150 MeV); thus, data tables should be used when available. Our comparisons demonstrate the importance of the mix-and-match capability and indicate how well physics models work in the absence of data tables.

  6. High-Resolution Infrared Spectroscopy of Ge_2C_3

    NASA Astrophysics Data System (ADS)

    Thorwirth, S.; Lutter, V.; Schlemmer, S.; Giesen, T. F.; Gauss, J.

    2013-06-01

    Carbon-rich systems are of great importance in diverse areas of research like material science as well as astro- and structural chemistry. Despite this relevance, our knowledge of smaller cluster units is still fragmentary, particularly with respect to investigations at high-spectral resolution in the gas phase. Unequivocal assignment of spectral features to their molecular carriers is critically dependent on predictions from high-level quantum-chemical calculations. In turn, high-resolution studies provide useful information to assess the predictive power of quantum-chemical methods. This is particularly interesting for cluster systems harboring heavy elements for which so far relatively little is known from experiment. With this contribution, we would like to present a recent gas-phase study of a polyatomic germanium-carbon cluster, linear Ge_2C_3 (Ge=C=C=C=Ge), which was previously studied in an Ar matrix. The cluster was produced through laser ablation of germanium-graphite sample rods and observed in a free jet at wavelengths around 5μm. Additionally, quantum-chemical calculations of Ge_2C_3 were performed at the CCSD(T) level of theory. The production and observation of Ge_2C_3 suggests that many more binary clusters should be amenable to high-resolution spectroscopic techniques not only in the infrared but also in the microwave region. D. L. Robbins, C. M. L. Rittby, and W. R. M. Graham, J. Chem. Phys. 114, 3570 (2001).

  7. Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor.

    PubMed

    von Meyenburg, Claudia; Langhans, Wolfgang; Hrupka, Brian J

    2003-01-01

    Rats consistently reduce their food intake following injections of bacterial lipopolysaccharides (LPS). Because inhibition of serotonergic (5-HT) activity by 8-OH-DPAT (5-HT(1A) activation) attenuates LPS-induced anorexia, we conducted a series of studies to examine whether other 5-HT-receptors are involved in the mediation of peripheral LPS-induced anorexia. In all experiments, rats were injected with LPS (100 microg/kg body weight [BW] ip) at lights out (hour 0). Antagonists were administered peripherally at hour 4, shortly after the onset of anorexia, which presumably follows the enhanced cytokine production after LPS. Food intake was then recorded during the subsequent 2 h or longer. 5-HT receptor antagonists cyanopindolol and SB 224289 (5-HT(1B)), ketanserin (5-HT(2A)), RS-102221 (5-HT(2C)), and metoclopramide (5-HT(3)) failed to attenuate LPS-induced anorexia. In contrast, both ritanserin (5-HT(2A/C)-receptor antagonist) (0.5 mg/kg BW) and SB 242084 (5-HT(2C)) (0.3 mg/kg BW) attenuated LPS-induced anorexia at doses that did not alter food intake in non-LPS-treated rats (all P<.01). Our results suggest that at least part of the anorexia following peripheral LPS administration is mediated through an enhanced 5-HT-ergic activity and the 5-HT(2C) receptor.

  8. Let Us Make the Table Periodic.

    ERIC Educational Resources Information Center

    Campbell, J. Arthur

    1989-01-01

    An approach to teaching the properties of the elements and their arrangement in the periodic table is suggested. Discussed are symbols for the elements, format of the table, and coding the properties of the elements on the table. (CW)

  9. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    PubMed

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality.

  10. Nqrs Data for C10H12Br4N2Zn [Br4Zn·2(C5H6N)] (Subst. No. 1253)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H12Br4N2Zn [Br4Zn·2(C5H6N)] (Subst. No. 1253)

  11. Nqrs Data for C10H12Cl4N2Pd [Cl4H2Pd·2(C5H5N)] (Subst. No. 1261)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H12Cl4N2Pd [Cl4H2Pd·2(C5H5N)] (Subst. No. 1261)

  12. Nqrs Data for C10H10Cl4Ga2N2 [Cl4Ga2·2(C5H5N)] (Subst. No. 1236)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H10Cl4Ga2N2 [Cl4Ga2·2(C5H5N)] (Subst. No. 1236)

  13. Nqrs Data for C10H10Br4Ga2N2 [Br4Ga2·2(C5H5N)] (Subst. No. 1230)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H10Br4Ga2N2 [Br4Ga2·2(C5H5N)] (Subst. No. 1230)

  14. Nqrs Data for C10H10CdI2N2 [CdI2·2(C5H5N)] (Subst. No. 1231)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H10CdI2N2 [CdI2·2(C5H5N)] (Subst. No. 1231)

  15. Nqrs Data for C10H10I2N2Pb [I2Pb·2(C5H5N)] (Subst. No. 1238)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H10I2N2Pb [I2Pb·2(C5H5N)] (Subst. No. 1238)

  16. Nqrs Data for C10H12Cl4N2Pt [Cl4H2Pt·2(C5H5N)] (Subst. No. 1262)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H12Cl4N2Pt [Cl4H2Pt·2(C5H5N)] (Subst. No. 1262)

  17. Table of tables: A database design tool for SYBASE

    SciTech Connect

    Brown, B.C.; Coulter, K.; Glass, H.D.; Glosson, R.; Hanft, R.W.; Harding, D.J.; Trombly-Freytag, K.; Walbridge, D.G.C.; Wallis, D.B. ); Allen, M.E. )

    1991-01-04

    The Table of Tables' application system captures in a set of SYBASE tables the basic design specification for a database schema. Specification of tables, columns (including the related defaults and rules for the stored values) and keys is provided. The feature which makes this application specifically useful for SYBASE is the ability to automatically generate SYBASE triggers. A description field is provided for each database object. Based on the data stored, SQL scripts for creating complete schema including the tables, their defaults and rules, their indexes, and their SYBASE triggers, are written by TOT. Insert, update and delete triggers are generated from TOT to guarantee integrity of data relations when tables are connected by single column foreign keys. The application is written in SYBASE's APT-SQL and includes a forms based data entry system. Using the features of TOT we can create a complete database schema for which the data integrity specified by our design is guaranteed by the SYBASE triggers generated by TOT. 3 refs.

  18. Global structure search and physical properties of Os2C

    NASA Astrophysics Data System (ADS)

    Hong, Feng; Lu, Jian; Gao, Heng; Ren, Wei; Xu, Run; Xu, Fei; Ma, Zhongquan; Yan, Yanfa

    2016-09-01

    The crystal structures of Os2C were extensively investigated using the structure search method from the first-principles calculations. In contrast to the P6 3 /mmc phase previously proposed as the ground state at ambient pressure, an energetically favorable structure with space group P-6m2 was found more stable at ambient condition. The structural stabilities of the new phase are confirmed by the phonon dispersion and elastic constants. Further calculations indicate that the newly predicted P-6m2 phase is ultra-incompressible with a high bulk modulus of 387 GPa and has a larger ideal shear strength than the P6 3 /mmc phase.

  19. The redoubtable ecological periodic table

    EPA Science Inventory

    Ecological periodic tables are repositories of reliable information on quantitative, predictably recurring (periodic) habitat–community patterns and their uncertainty, scaling and transferability. Their reliability derives from their grounding in sound ecological principle...

  20. Some economic tables for airships

    NASA Technical Reports Server (NTRS)

    Neumann, R. D.

    1975-01-01

    During the course of the Southern California Aviation Council study on lighter than air it was determined that some form of economic base must be developed for estimation of costs of the airship. The tables are presented.

  1. STIL - Starlink Tables Infrastructure Library

    NASA Astrophysics Data System (ADS)

    Taylor, Mark

    STIL is a set of Java class libraries which allow input, manipulation and output of tabular data and metadata. Among its key features are support for many tabular formats (including VOTable, FITS, CDF, text-based formats and SQL databases) and support for dealing with very large tables in limited memory. As well as an abstract and format-independent definition of what constitutes a table, and an extensible framework for "pull-model" table processing, it provides a number of format-specific handlers which know how to serialize/deserialize tables. The framework for interaction between the core table manipulation facilities and the format-specific handlers is open and pluggable, so that handlers for new formats can easily be added, programmatically or at run-time. The VOTable handling in particular is provided by classes which perform efficient XML parsing and can read and write VOTables in any of the defined formats (TABLEDATA, BINARY or FITS). It supports table-aware SAX- or DOM-mode processing and may be used on its own for VOTable I/O without much reference to the format-independent parts of the library.

  2. Targeting of PP2C in budding yeast.

    PubMed

    Ota, Irene M; Mapes, James

    2007-01-01

    Type 2C Ser/Thr phosphatases or PP2Cs are monomeric metal-requiring protein phosphatases that are present in prokaryotes and eukaryotes. In the yeast Saccharomyces cerevisiae, there are seven PP2Cs called PTCs (phosphatase 2C). Molecular genetic studies have implicated PTCs in many different functions, including RNA splicing, the unfolded protein response, mitogen-activated protein kinase (MAPK) pathway, and cell-cycle regulation. We have shown that three PTCs (Ptc1, Ptc2, and Ptc3), regulate the stress-activated high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway. Proteomics studies have provided additional possible functions for these phosphatases by identifying interacting proteins. These studies have also provided the possible means by which these phosphatases are targeted to their substrates. For example, Nbp2-Ptc1 was identified as an interacting pair in yeast two-hybrid studies, and Nbp2 was found together with Ptc1 and HOG pathway kinases. We have shown that Nbp2 is an adapter in this pathway, mediating interaction between Ptc1 and the Pbs2 MAP/ERK kinase in the HOG pathway.

  3. Particle classification and dynamics in GL(2,C) gravity

    SciTech Connect

    Stern, A.

    2009-05-15

    A relatively simple approach to noncommutative gravity utilizes the gauge theory formulation of general relativity and involves replacing the Lorentz gauge group by a larger group. This results in additional field degrees of freedom which either must be constrained to vanish in a nontrivial way or require physical interpretation. With the latter in mind, we examine the coupling of the additional fields to point particles. Nonstandard particle degrees of freedom should be introduced in order to write down the most general coupling. The example we study is the GL(2,C) central extension of gravity given by Chamseddine, which contains two U(1) gauge fields and a complex vierbein matrix, along with the usual spin connections. For the general coupling one should then attach two U(1) charges and a complex momentum vector to the particle, along with the spin. The momenta span orbits in a four-dimensional complex vector space and are classified by GL(2,C) invariants and by their little groups. In addition to orbits associated with standard massive and massless particles, a number of novel orbits can be identified. We write down a general action principle for particles associated with any nontrivial orbit and show that it leads to corrections to geodesic motion. We also examine the classical and quantum theory of the particle in flat space-time.

  4. Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages.

    PubMed

    Koscsó, Balázs; Csóka, Balázs; Kókai, Endre; Németh, Zoltán H; Pacher, Pál; Virág, László; Leibovich, S Joseph; Haskó, György

    2013-12-01

    The alternatively activated macrophage phenotype induced by IL-10 is called M2c. Adenosine is an endogenous purine nucleoside that accumulates in the extracellular space in response to metabolic disturbances, hypoxia, inflammation, physical damage, or apoptosis. As adenosine is known to regulate classically activated M1 and IL4- and IL-13-activated M2a macrophages, the goal of the present study was to explore its effects on M2c macrophages. We found that adenosine augmented the IL-10-induced expression of TIMP-1 and arginase-1 by the mouse macrophage cell line RAW 264.7 and by mouse BMDMs. The effects of AR stimulation on IL-10-induced TIMP-1 or arginase-1 expression were lacking in A2BAR KO macrophages. The role of A2BAR on TIMP-1 production of RAW 264.7 cells was confirmed with specific agonist BAY606583 and antagonist PSB0788. AR stimulation augmented IL-10-induced STAT3 phosphorylation in macrophages, and pharmacological inhibition or silencing of STAT3 using siRNA reduced the stimulatory effect of AR stimulation on TIMP-1 production. In contrast to its stimulatory effect on IL-10-induced STAT3 activation, adenosine inhibited IL-6-induced STAT3 phosphorylation and SAA3 expression. In conclusion, adenosine enhances IL-10-induced STAT3 signaling and M2c macrophage activation.

  5. Snow depth sensing using the GPS L2C signal with a dipole antenna

    NASA Astrophysics Data System (ADS)

    Chen, Qiang; Won, Daehee; Akos, Dennis M.

    2014-12-01

    Prior research has shown that the currently deployed geodetic global positioning system (GPS) stations can be used to measure snow depth in an area around the antenna installation via GPS interferometric reflectometry (GPS-IR). Although such a technique provides the advantages of large spatial coverage and high temporal measurement sampling, there are also drawbacks in using geodetic equipment for this application. The geodetic antenna is costly and designed to mitigate the multipath signal, while for snow depth sensing, the reflective component contains the desired information regarding the environment. In this paper, the authors reviewed the principles of snow depth sensing via GPS-IR and show that the horizontally polarized electromagnetic wave is the desired signal for this application. A customized dipole antenna, which was designed to be horizontally polarized by properly adjusting its orientation, was built and evaluated in an experiment carried out at Table Mountain, Boulder, Colorado, during early February 2012. In this experiment, a universal software radio peripheral (USRP) is used to collect the raw data and a software-defined receiver (SDR) for L2C signal is used for data processing. Data and results from this dipole antenna/SDR implementation are compared with those from the geodetic GPS station and show an improvement for snow depth estimation.

  6. Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia

    PubMed Central

    Chung, Connie; Marson, John D.; Zhang, Quan-Guang; Kim, Jimok; Wu, Wei-Hua; Brann, Darrell W.; Chen, Bo-Shiun

    2016-01-01

    Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity. PMID:27845401

  7. Novel Marmoset Cytochrome P450 2C19 in Livers Efficiently Metabolizes Human P450 2C9 and 2C19 Substrates, S-Warfarin, Tolbutamide, Flurbiprofen, and Omeprazole.

    PubMed

    Uehara, Shotaro; Uno, Yasuhiro; Inoue, Takashi; Kawano, Mirai; Shimizu, Makiko; Toda, Akiko; Utoh, Masahiro; Sasaki, Erika; Yamazaki, Hiroshi

    2015-10-01

    The common marmoset (Callithrix jacchus), a small New World monkey, has the potential for use in human drug development due to its evolutionary closeness to humans. Four novel cDNAs, encoding cytochrome P450 (P450) 2C18, 2C19, 2C58, and 2C76, were cloned from marmoset livers to characterize P450 2C molecular properties, including previously reported P450 2C8. The deduced amino acid sequence showed high sequence identities (>86%) with those of human P450 2Cs, except for marmoset P450 2C76, which has a low sequence identity (∼70%) with any human P450 2Cs. Phylogenetic analysis showed that marmoset P450 2Cs were more closely clustered with those of humans and macaques than other species investigated. Quantitative polymerase chain reaction analysis showed that all of the marmoset P450 2C mRNAs were predominantly expressed in liver as opposed to the other tissues tested. Marmoset P450 2C proteins were detected in liver by immunoblotting using antibodies against human P450 2Cs. Among marmoset P450 2Cs heterologously expressed in Escherichia coli, marmoset P450 2C19 efficiently catalyzed human P450 2C substrates, S-warfarin, diclofenac, tolbutamide, flurbiprofen, and omeprazole. Marmoset P450 2C19 had high Vmax and low Km values for S-warfarin 7-hydroxylation that were comparable to those in human liver microsomes, indicating warfarin stereoselectivity similar to findings in humans. Faster in vivo S-warfarin clearance than R-warfarin after intravenous administration of racemic warfarin (0.2 mg/kg) to marmosets was consistent with the in vitro kinetic parameters. These results indicated that marmoset P450 2C enzymes had functional characteristics similar to those of humans, and that P450 2C-dependent metabolic properties are likewise similar between marmosets and humans.

  8. 30 CFR 250.1401 - Index table.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Index table. 250.1401 Section 250.1401 Mineral... OPERATIONS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf (OCS) Civil Penalties § 250.1401 Index table. The following table is an index of the sections in this subpart: § 250.1401Table...

  9. Expression of Serotonin2C Receptors in Pyramidal and GABAergic Neurons of Rat Prefrontal Cortex: A Comparison with Striatum.

    PubMed

    Santana, Noemí; Artigas, Francesc

    2016-06-01

    The prefrontal cortex (PFC) is enriched in several serotonin receptors, including 5-HT1A-R, 5-HT2A-R, and 5-HT3-R. These receptors modulate PFC activity due to their expression in large neuronal populations (5-HT1A-R, 5-HT2A-R) or in selected GABAergic populations (5-HT3-R). They are also relevant for antidepressant and antipsychotic drug action. Less is known about the localization of 5-HT2C-R, for which atypical antipsychotics show high affinity. Here, we report on the cellular distribution of 5-HT2C-R in rat PFC and striatum, using double in situ hybridization histochemistry. In PFC, 5-HT2C-R are expressed in pyramidal (VGLUT1-positive) and GABAergic (GAD-positive) neurons, including parvalbumin-positive neurons. There is a marked dorso-ventral gradient in the proportion of VGLUT1-positive cells expressing 5-HT2C-R (9% in the cingulate cortex, 61% in the tenia tecta and 66% in the piriform cortex), less marked for GABAergic neurons (13-27%). There is also a laminar gradient, with more cells expressing 5-HT2C-R in deep (V-VI) than in intermediate (II-III) layers. In common with 5-HT3-R, layer I GABAergic cells express 5-HT2C-R. The proportion of 5-HT2C-R-expressing striatal neurons was 23% (dorsolateral caudate-putamen), 37% (ventromedial caudate-putamen), 53% (nucleus accumbens-core), and 49% (nucleus accumbens-shell). These results help to better understand the serotonergic modulation of PFC-based networks, including basal ganglia circuits, and atypical antipsychotic drug action.

  10. Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents.

    PubMed

    Cheng, Jianjun; Giguère, Patrick M; Onajole, Oluseye K; Lv, Wei; Gaisin, Arsen; Gunosewoyo, Hendra; Schmerberg, Claire M; Pogorelov, Vladimir M; Rodriguiz, Ramona M; Vistoli, Giulio; Wetsel, William C; Roth, Bryan L; Kozikowski, Alan P

    2015-02-26

    The discovery of a new series of compounds that are potent, selective 5-HT2C receptor agonists is described herein as we continue our efforts to optimize the 2-phenylcyclopropylmethylamine scaffold. Modifications focused on the alkoxyl substituent present on the aromatic ring led to the identification of improved ligands with better potency at the 5-HT2C receptor and excellent selectivity against the 5-HT2A and 5-HT2B receptors. ADMET studies coupled with a behavioral test using the amphetamine-induced hyperactivity model identified four compounds possessing drug-like profiles and having antipsychotic properties. Compound (+)-16b, which displayed an EC50 of 4.2 nM at 5-HT2C, no activity at 5-HT2B, and an 89-fold selectivity against 5-HT2A, is one of the most potent and selective 5-HT2C agonists reported to date. The likely binding mode of this series of compounds to the 5-HT2C receptor was also investigated in a modeling study, using optimized models incorporating the structures of β2-adrenergic receptor and 5-HT2B receptor.

  11. Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes.

    PubMed

    Wang, Zhe; Sun, Wei; Huang, Cheng-Ke; Wang, Li; Xia, Meng-Ming; Cui, Xiao; Hu, Guo-Xin; Wang, Zeng-Shou

    2015-04-01

    Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4'-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug-drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L(-1) diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L(-1) and Ki = 4.473 µmol L(-1) in human liver microsomes. Curcumin's mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L(-1). The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.

  12. P2C-Type ATPases and Their Regulation.

    PubMed

    Retamales-Ortega, Rocío; Vio, Carlos P; Inestrosa, Nibaldo C

    2016-03-01

    P2C-type ATPases are a subfamily of P-type ATPases comprising Na(+)/K(+)-ATPase and H(+)/K(+)-ATPase. Na(+)/K(+)-ATPase is ubiquitously expressed and has been implicated in several neurological diseases, whereas H(+)/K(+)-ATPase is found principally in the colon, stomach, and kidney. Both ATPases have two subunits, α and β, but Na(+)/K(+)-ATPase also has a regulatory subunit called FXYD, which has an important role in cancer. The most important functions of these ATPases are homeostasis, potassium regulation, and maintaining a gradient in different cell types, like epithelial cells. Na(+)/K(+)-ATPase has become a center of attention ever since it was proposed that it might play a crucial role in neurological disorders such as bipolar disorder, mania, depression, familial hemiplegic migraine, rapid-onset dystonia parkinsonism, chronic stress, epileptogenesis, and Alzheimer's disease. On the other hand, it has been reported that lithium could have a neuroprotective effect against ouabain, which is the best known Na(+)/K(+)-ATPase inhibitor, but and high concentrations of lithium could affect negatively H(+)/K(+)-ATPase activity, that has a key role in regulating acidosis and potassium deficiencies. Finally, potassium homeostasis regulation is composed of two main mechanisms, extrarenal and renal. Extrarenal mechanism controls plasma levels, shifting potassium from the extracellular to the intracellular, whereas renal mechanism concerns with body balance and is influenced by potassium intake and its urinary excretion. In this article, we discuss the functions, isoforms, and localization of P2C-type ATPases, describe some of their modulators, and discuss their implications in some diseases.

  13. General purpose steam table library :

    SciTech Connect

    Carpenter, John H.; Belcourt, Kenneth Noel; Nourgaliev, Robert

    2013-08-01

    Completion of the CASL L3 milestone THM.CFD.P7.04 provides a general purpose tabular interpolation library for material properties to support, in particular, standardized models for steam properties. The software consists of three parts, implementations of analytic steam models, a code to generate tables from those models, and an interpolation package to interface the tables to CFD codes such as Hydra-TH. Verification of the standard model is maintained through the entire train of routines. The performance of interpolation package exceeds that of freely available analytic implementation of the steam properties by over an order of magnitude.

  14. Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI)

    PubMed Central

    Pachkoria, K; Lucena, M I; Ruiz-Cabello, F; Crespo, E; Cabello, M R; Andrade, R J

    2007-01-01

    Background and purpose: The general view on the pathogenesis of drug-induced idiosyncratic liver injury (DILI) is that parent compounds are rendered hepatotoxic by metabolism, mainly by cytochrome (CYP) 450, although other metabolic pathways can contribute. Anecdotal reports suggest a role of CYP 450 polymorphisms in DILI. We aimed to assess in a series of Spanish DILI patients the prevalence of important allelic variants of CYP2C9 and CYP2C19, known to be involved in the metabolism of several hepatotoxic drugs. Experimental approach: Genotyping of CYP2C9 (*2, *3) and CYP2C19 (*2 and *3), was carried out in a total of 28 and 32 patients with a well established diagnosis of DILI. CYP2C9 and CYP2C19 variants were analysed in genomic DNA by means of PCR-FRET and compared with previous findings in other Caucasian populations. Key results: CYP2C9 and CYP2C19 allele and genotype frequencies were in agreement with Hardy-Weinberg equilibrium. Fourteen patients (50%) were heterozygous and 1(4%) found to be compound heterozygous for the CYP2C9 allele. Seven (22%) were found to carry one and 1(3%) carried two CYP2C19 mutated alleles. No patients were homozygous for *3 allele. The distribution of both CYP2C9 and CYP2C19 allelic variants in DILI patients were similar to those in other Caucasian populations. Patients with variant and those with wild-type alleles did not differ in regard to clinical presentation of DILI, type of injury and outcome. Conclusions and Implications: We find no evidence to support CYP2C9 and CYP2C19 genetic polymorphisms as predictable potential risk factors for DILI. PMID:17279092

  15. Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines.

    PubMed

    Scheer, Nico; Kapelyukh, Yury; Chatham, Lynsey; Rode, Anja; Buechel, Sandra; Wolf, C Roland

    2012-12-01

    Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.

  16. The protein phosphatase 2C clade A protein OsPP2C51 positively regulates seed germination by directly inactivating OsbZIP10.

    PubMed

    Bhatnagar, Nikita; Min, Myung-Ki; Choi, Eun-Hye; Kim, Namhyo; Moon, Seok-Jun; Yoon, Insun; Kwon, Taekryoun; Jung, Ki-Hong; Kim, Beom-Gi

    2017-03-01

    Protein phosphatase 2C clade A members are major signaling components in the ABA-dependent signaling cascade that regulates seed germination. To elucidate the role of PP2CA genes in germination of rice seed, we selected OsPP2C51, which shows highly specific expression in the embryo compared with other protein phosphatases based on microarray data. GUS histochemical assay confirmed that OsPP2C51 is expressed in the seed embryo and that this expression pattern is unique compared with those of other OsPP2CA genes. Data obtained from germination assays and alpha-amylase assays of OsPP2C51 knockout and overexpression lines suggest that OsPP2C51 positively regulates seed germination in rice. The expression of alpha-amylase synthesizing genes was high in OsPP2C51 overexpressing plants, suggesting that elevated levels of OsPP2C51 might enhance gene expression related to higher rates of seed germination. Analysis of protein interactions between ABA signaling components showed that OsPP2C51 interacts with OsPYL/RCAR5 in an ABA-dependent manner. Furthermore, interactions were observed between OsPP2C51 and SAPK2, and between OsPP2C51 and OsbZIP10 and we found out that OsPP2C51 can dephosphorylates OsbZIP10. These findings suggest the existence of a new branch in ABA signaling pathway consisting of OsPYL/RCAR-OsPP2C-bZIP apart from the previously reported OsPYL/RCAR-OsPP2C-SAPK-bZIP. Overall, our result suggests that OsPP2C51 is a positive regulator of seed germination by directly suppressing active phosphorylated OsbZIP10.

  17. MEF2D and MEF2C pathways disruption in sporadic and familial ALS patients.

    PubMed

    Arosio, Alessandro; Sala, Gessica; Rodriguez-Menendez, Virginia; Grana, Denise; Gerardi, Francesca; Lunetta, Christian; Ferrarese, Carlo; Tremolizzo, Lucio

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuro-muscular disease characterized by motor neuron loss. MEF2D and MEF2C are members of the myocyte enhancer factor 2 family (MEF2), a group of transcription factors playing crucial roles both in muscle and in neural development and maintenance; for this reason, a possible involvement of MEF2 in ALS context has been investigated. Since the transcriptional activity of each tissue specific MEF2 isoform is conserved in different cell types, we chose to assess our parameters in an easily accessible and widely used experimental tool such as peripheral blood mononuclear cells (PBMCs) obtained from 30 sporadic ALS patients (sALS), 9 ALS patients with mutations in SOD1 gene (SOD1+) and 30 healthy controls. Gene expression analysis showed a significant up-regulation of MEF2D and MEF2C mRNA levels in both sporadic and SOD1+ ALS patients. Although protein levels were unchanged, a different pattern of distribution for MEF2D and MEF2C proteins was evidenced by immunohistochemistry in patients. A significant down-regulation of MEF2 downstream targets BDNF, KLF6 and RUFY3 was reported in both sALS and SOD1+ ALS patients, consistent with an altered MEF2 transcriptional activity. Furthermore, the potential regulatory effect of histone deacetylase 4 and 5 (HDAC4 and HDAC5) on MEF2D and MEF2C activity was also investigated. We found that MEF2D and HDAC4 colocalize in PBMC nuclei, while HDAC5 was localized in the cytoplasm. However, the unchanged HDACs localization and protein levels between sALS and controls seem to exclude their involvement in MEF2 altered function. In conclusion, our results show a systemic alteration of MEF2D and MEF2C pathways in both sporadic and SOD1+ ALS patients, underlying a possible common feature between the sporadic and the familial form of disease. Although further analyses in other neuromuscular diseases are needed to determine the specificity of changes in these pathways to ALS, measuring MEF2

  18. Design, Synthesis, and Structure–Activity Relationship of a Novel Series of GluN2C-Selective Potentiators

    PubMed Central

    2015-01-01

    NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A–D subunits that mediate a slow Ca2+-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors. PMID:24512267

  19. The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes.

    PubMed

    Mukai, Yuji; Senda, Asuna; Toda, Takaki; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo

    2016-06-01

    The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Concentrations of 6α-hydroxypaclitaxel and EXP-3174 were measured by high-performance liquid chromatography after incubations with paclitaxel, losartan or EXP-3174 in HLMs from seven donors with different CYP2C8 and CYP2C9 genotypes. The half maximal inhibitory concentration (IC50 ) values were not fully dependent on CYP2C8 genotypes. Although the degree of inhibition was small, losartan significantly inhibited the production of 6α-hydroxypaclitaxel at a concentration of 1 μmol/L in only HL20 with the CYP2C8*3/*3 genotype. HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Significant inhibition of 6α-hydroxypaclitaxel formation by EXP-3174 could only be found at levels that were 50 times higher (100 μmol/L) than the maximum concentration generated in the inhibition study using losartan. These results suggest that the metabolic interaction between losartan and paclitaxel is dependent on losartan itself rather than its metabolite and that the CYP2C8 inhibition by losartan is not affected by the CYP2C9 genotype. Further study is needed to define the effect of CYP2C8 genotypes on losartan-paclitaxel interaction.

  20. ALSED Round Table. Final Report.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    A report of a round table meeting on Anthropology and Language Science in Educational Development (ALSED) of the United Nations Educational, Scientific and Cultural Organization is presented. The purpose of the discussions was to develop national strategies to take advantage of the resources of anthropology and language science to improve the…

  1. Compressible Flow Tables for Air

    NASA Technical Reports Server (NTRS)

    Burcher, Marie A.

    1947-01-01

    This paper contains a tabulation of functions of the Mach number which are frequently used in high-speed aerodynamics. The tables extend from M = 0 to M = 10.0 in increments of 0.01 and are based on the assumption that air is a perfect gas having a specific heat ratio of 1.400.

  2. Sand and Water Table Play

    ERIC Educational Resources Information Center

    Wallace, Ann H.; White, Mary J.; Stone, Ryan

    2010-01-01

    The authors observed preschoolers engaged at the sand and water table to determine if math could be found within their play. Wanting to understand how children interact with provided materials and what kinds of math ideas they explore during these interactions, the authors offer practical examples of how such play can promote mathematical…

  3. 50 CFR Table 4 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false 4 Table 4 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT Critical habitat for the Cook Inlet beluga whale...

  4. What Price Statistical Tables Now?

    ERIC Educational Resources Information Center

    Hunt, Neville

    1997-01-01

    Describes the generation of all the tables required for school-level study of statistics using Microsoft's Excel spreadsheet package. Highlights cumulative binomial probabilities, cumulative Poisson probabilities, normal distribution, t-distribution, chi-squared distribution, F-distribution, random numbers, and accuracy. (JRH)

  5. 50 CFR Table 4 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false 4 Table 4 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT Critical habitat for the Southern Distinct Population Segment of...

  6. 50 CFR Table 4 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false 4 Table 4 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT Critical habitat for the southern Distinct Population Segment...

  7. 50 CFR Table 4 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false 4 Table 4 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS DESIGNATED CRITICAL HABITAT Critical habitat for the southern Distinct Population Segment...

  8. Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans.

    PubMed

    Bigley, A B; Rezvani, K; Shah, N; Sekine, T; Balneger, N; Pistillo, M; Agha, N; Kunz, H; O'Connor, D P; Bollard, C M; Simpson, R J

    2016-08-01

    Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A- NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was ∼threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a(+) ) and interferon (IFN)-γ production to 221.AEH cells was localized almost exclusively to the NKG2C subset, and antibody blocking of NKG2C completely eliminated the effect of CMV on NK cell cytotoxicity against 221.AEH cells. Moreover, 221.AEH feeder cells and interleukin (IL)-15 were found to expand NKG2C(+) /NKG2A(-) NK cells preferentially from CMV-seronegative donors and increase NK cell cytotoxicity against HLA-E(+) tumour cell lines. We conclude that latent CMV infection enhances NK cell cytotoxicity through accumulation of NKG2C(+) NK cells, which may be beneficial in preventing the initiation and progression of haematological malignancies characterized by high HLA-E expression.

  9. Man Made Elements Periodic Table, Astronomical Periodic Table, Geographic Periodic Table-Dimitri Mendeleev Imitation in the 21st Century

    NASA Astrophysics Data System (ADS)

    Struck, J.-T.

    2013-11-01

    A man made elements periodic table, including every single current element not just synthetic elements can be built differently than the naturally occurring element periodic table. Implications for knowing producible elements in space travel.

  10. Basic Data Report for Drillhole SNL-2 (C-2948)

    SciTech Connect

    Powers, Dennis W.

    2005-01-19

    SNL-2 was drilled in the northwest quarter of Section 12, T22S, R30E, in eastern Eddy County, New Mexico (Figure 2-1). It is located 574 ft from the north line (fnl) and 859 ft from the west line (fwl) of the section (Figure 2-2). This location places the drillhole east of the Livingston Ridge escarpment among oil wells of the Cabin Lake field. SNL-2 will be used to test hydraulic properties and to monitor ground water levels of the Culebra Dolomite Member of the Permian Rustler Formation. SNL-2 was permitted by the New Mexico State Engineer as C-2948. [Official correspondence regarding permitting and regulatory information must reference this permit number.] In the plan describing the integrated groundwater hydrology program (Sandia National Laboratories, 2003), SNL-2 is also codesignated WTS-1 because the location also satisfies needs for long-term monitoring of water quality and movement in the Culebra Dolomite for RCRA permitting; this program is under the management of Washington TRU Solutions LLC (WTS). In the event that additional wells are established on the SNL-2 drillpad to monitor other hydrological units (e.g., the Magenta Dolomite Member of the Permian Rustler Formation), the current drillhole will likely be referred to as SNL-2C because it is completed in the Culebra. Most drillholes at WIPP have been described after completion to provide an account of the geology, hydrology, or other basic data acquired during drilling and immediate completion of the drillhole. In addition, the basic data report provides an account of the drilling procedures and activities that may be helpful to later interpretations of data or for further work in the drillhole, including test activities and eventual plugging and abandoning activities. The basic data report also provides a convenient means of reporting information about administrative activities necessary to drill the hole.

  11. Molecular character of a phosphatase 2C (PP2C) gene relation to stress tolerance in Arabidopsis thaliana.

    PubMed

    Zhang, Jihong; Li, Xiushan; He, Zhimin; Zhao, Xiaoying; Wang, Qiming; Zhou, Bo; Yu, Dashi; Huang, Xinqun; Tang, Dongying; Guo, Xinhong; Liu, Xuanming

    2013-03-01

    Protein phosphatases type 2C (PP2Cs) from group A, which includes the ABI1/HAB1 and PP2CA branches, are key negative regulators of ABA signaling. HAI-1 gene had been shown to affect both seed and vegetative responses to ABA, which is one of PP2Cs clade A in Arabidopsis thaliana. Transgenic plants containing pHAI-1::GUS (β-glucuronidase) displayed GUS activity existing in the vascular system of leave veins, stems and petioles. Green fluorescent protein fused HAI-1 (HAI-1-GFP) was found in the nucleus through transient transformation assays with onion epidermal cells. The water-loss assays indicated the loss-of-function mutants did not show symptoms of wilting and they had still turgid green rosette leaves. The assays of seed germination by exogenous ABA and NaCl manifested that the loss-of-function mutants displayed higher insensitivity than wild-type plants. Taken together, the final results suggest that the HAI-1 (AT5G59220) encoded a nuclear protein and it can be highly induced by ABA and wound in Arabidposis, the stress-tolerance phenotype showed a slightly improvement when HAI-1 gene was disrupted.

  12. Inhibition of opioid release in the rat spinal cord by α2C adrenergic receptors

    PubMed Central

    Chen, Wenling; Song, Bingbing; Marvizón, Juan Carlos G.

    2008-01-01

    Neurotransmitter receptors that control the release of opioid peptides in the spinal cord may play an important role in pain modulation. Norepinephrine, released by a descending pathway originating in the brainstem, is a powerful inducer of analgesia in the spinal cord. Adrenergic α2C receptors are present in opioid-containing terminals in the dorsal horn, where they could modulate opioid release. The goal of this study was to investigate this possibility. Opioid release was evoked from rat spinal cord slices by incubating them with the sodium channel opener veratridine in the presence of peptidase inhibitors (actinonin, captopril and thiorphan), and was measured in situ through the internalization of μ-opioid receptors in dorsal horn neurons. Veratridine produced internalization in 70% of these neurons. The α2 receptor agonists clonidine, guanfacine, medetomidine and UK-14304 inhibited the evoked μ-opioid receptor internalization with IC50s of 1.7 μM, 248 nM, 0.3 nM and 22 nM, respectively. However, inhibition by medetomidine was only partial, and inhibition by UK-14304 reversed itself at concentrations higher than 50 nM. None of these agonists inhibited μ-opioid receptor internalization produced by endomorphin-2, showing that they inhibited opioid release and not the internalization itself. The inhibition produced by clonidine, guanfacine or UK-14304 was completely reversed by the selective α2C antagonist JP-1203. In contrast, inhibition by guanfacine was not prevented by the α2A antagonist BRL-44408. These results show that α2C receptors inhibit the release of opioids in the dorsal horn. This action may serve to shut down the opioid system when the adrenergic system is active. PMID:18343461

  13. Facile fabrication of transparent TiO2-C@TiO2-C free-standing film for visible-light photocatalytic application

    NASA Astrophysics Data System (ADS)

    Hu, Luyang; Zhang, Yumin; Zhang, Shanmei; Li, Benxia

    2017-02-01

    A transparent TiO2-C@TiO2-C free-standing film has been synthesized by two-step hydrothermal method and subsequent thermal annealing. The chemical composition and morphological features of the TiO2-C@TiO2-C film are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption measurement. The results indicate that the flower-like micro/nanostructure TiO2-C particle layers are intimately inhered to porous TiO2-C fibers. The fibers in film are interconnected each other to form a three-dimensional reticulate microstructure, and exhibit intense visible light absorption and high adsorptivity of dye molecules. The interaction between TiO2 and its surface carbon layer in TiO2-C particle promotes the generation of Ti-O-C bonds, which leads to effective charge transfer. Under visible-light irradiation, TiO2-C@TiO2-C film presents enhanced photocatalytic activity for degradation of methylene blue. This work may provide a new viewpoint for designing transparent photocatalytic film for promising applications in heterogeneous photocatalysis.

  14. Stream Tables and Watershed Geomorphology Education.

    ERIC Educational Resources Information Center

    Lillquist, Karl D.; Kinner, Patricia W.

    2002-01-01

    Reviews copious stream tables and provides a watershed approach to stream table exercises. Results suggest that this approach to learning the concepts of fluvial geomorphology is effective. (Contains 39 references.) (DDR)

  15. Improved water table dynamics in MODFLOW.

    PubMed

    Clemo, Tom

    2005-01-01

    The standard formulation of a block-centered finite-difference model, such as MODFLOW, uses the center of the cell as the location of a cell node. Simulations of a dynamic water table can be improved if the node of a cell containing the water table is located at the water table rather than at the center of the cell. The LPF package of MOD-FLOW-2000 was changed to position a cell's node at the water table in convertible cells with a water table. Improved accuracy in the upper regions of an unconfined aquifer is demonstrated for pumping from a partially penetrating well. The change introduces a nonlinearity into the solution of the flow equations that results in slightly slower convergence of the flow solution, 7% slower in the presented demonstration. Accuracy of simulations is improved where vertical flow is dominated by a moving water table, but not when a large water table gradient dominates over the water table movement.

  16. Solar cell efficiency tables (version 30)

    SciTech Connect

    Green, Martin A.; Emery, Keith; Hisikawa, Yoshihiro; Warta, Wilhelm

    2007-01-01

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since January 2007 are reviewed.

  17. Solar Cell Efficiency Tables (Version 34)

    SciTech Connect

    Green, M. A.; Emery, K.; Hishikawa, Y.; Warta, W.

    2009-01-01

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since January, 2009 are reviewed.

  18. 30 CFR 250.1401 - Index table.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Civil Penalties Outer Continental Shelf Lands Act Civil Penalties § 250.1401 Index table. The following table is an index of...

  19. 30 CFR 250.1401 - Index table.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Civil Penalties Outer Continental Shelf Lands Act Civil Penalties § 250.1401 Index table. The following table...

  20. 30 CFR 250.1401 - Index table.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Civil Penalties Outer Continental Shelf Lands Act Civil Penalties § 250.1401 Index table. The following table is an index of...

  1. 30 CFR 250.1401 - Index table.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Outer Continental Shelf Civil Penalties Outer Continental Shelf Lands Act Civil Penalties § 250.1401 Index table. The following table is an index of...

  2. The origins of Ptolemy's astronomical tables.

    NASA Astrophysics Data System (ADS)

    Newton, R. R.

    Following the line set by his earlier book 'The crime of Claudius Ptolemy' the author discusses here the numerous astronomical tables in Ptolemy's work that have been calculated with the aid of trigonometric tables, as well as a few that are nonlinear but that do not involve trigonometry. The purpose in this study is to determine, if possible, whether Ptolemy calculated these tables or whether he copied them from now-lost original works. The conclusion isthat Ptolemy made few if any original contributions to astronomy, either observational or computational.Contents: 1. Introduction; thetable of chords. 2. The tables of the latitude and of gnomon shadows.3. Tables of the Sun. 4. Astronomical geography. 5. The tables of theMoon. 6. Eclipse tables. 7. Tables of the planets. 8. The empirical basis for Hipparchus's mean motions of the Moon. 9. Summary and conclusions.

  3. Biosynthesis of isoprenoids: crystal structure of 4-diphosphocytidyl-2C-methyl-D-erythritol kinase.

    PubMed

    Miallau, Linda; Alphey, Magnus S; Kemp, Lauris E; Leonard, Gordon A; McSweeney, Sean M; Hecht, Stefan; Bacher, Adelbert; Eisenreich, Wolfgang; Rohdich, Felix; Hunter, William N

    2003-08-05

    4-Diphosphocytidyl-2C-methyl-d-erythritol kinase, an essential enzyme in the nonmevalonate pathway of isopentenyl diphosphate and dimethylallyl diphosphate biosynthesis, catalyzes the single ATP-dependent phosphorylation stage affording 4-diphosphocytidyl-2C-methyl-d-erythritol-2-phosphate. The 2-A resolution crystal structure of the Escherichia coli enzyme in a ternary complex with substrate and a nonhydrolyzable ATP analogue reveals the molecular determinants of specificity and catalysis. The enzyme subunit displays the alpha/beta fold characteristic of the galactose kinase/homoserine kinase/mevalonate kinase/phosphomevalonate kinase superfamily, arranged into cofactor and substrate-binding domains with the catalytic center positioned in a deep cleft between domains. Comparisons with related members of this superfamily indicate that the core regions of each domain are conserved, whereas there are significant differences in the substrate-binding pockets. The nonmevalonate pathway is essential in many microbial pathogens and distinct from the mevalonate pathway used by mammals. The high degree of sequence conservation of the enzyme across bacterial species suggests similarities in structure, specificity, and mechanism. Our model therefore provides an accurate template to facilitate the structure-based design of broad-spectrum antimicrobial agents.

  4. Ginkgolic acids induce neuronal death and activate protein phosphatase type-2C.

    PubMed

    Ahlemeyer, B; Selke, D; Schaper, C; Klumpp, S; Krieglstein, J

    2001-10-26

    The standardized extract from Ginkgo biloba (EGb 761) is used for the treatment of dementia. Because of allergenic and genotoxic effects, ginkgolic acids are restricted in EGb 761 to 5 ppm. The question arises whether ginkgolic acids also have neurotoxic effects. In the present study, ginkgolic acids caused death of cultured chick embryonic neurons in a concentration-dependent manner, in the presence and in the absence of serum. Ginkgolic acids-induced death showed features of apoptosis as we observed chromatin condensation, shrinkage of the nucleus and reduction of the damage by the protein synthesis inhibitor cycloheximide, demonstrating an active type of cell death. However, DNA fragmentation detected by the terminal-transferase-mediated ddUTP-digoxigenin nick-end labeling (TUNEL) assay and caspase-3 activation, which are also considered as hallmarks of apoptosis, were not seen after treatment with 150 microM ginkgolic acids in serum-free medium, a dose which increased the percentage of neurons with chromatin condensation and shrunken nuclei to 88% compared with 25% in serum-deprived, vehicle-treated controls. This suggests that ginkgolic acid-induced death showed signs of apoptosis as well as of necrosis. Ginkgolic acids specifically increased the activity of protein phosphatase type-2C, whereas other protein phosphatases such as protein phosphatases 1A, 2A and 2B, tyrosine phosphatase, and unspecific acid- and alkaline phosphatases were inhibited or remained unchanged, suggesting protein phosphatase 2C to play a role in the neurotoxic effect mediated by ginkgolic acids.

  5. The Different Periodic Tables of Dmitrii Mendeleev

    ERIC Educational Resources Information Center

    Laing, Michael

    2008-01-01

    Between 1869 and 1905 the Russian chemist Dmitrii Mendeleev published several tables with different arrangements of the chemical elements. Four of these are compared with periodic tables by Russian scientists from 1934 and 1969. The difficulties caused by the lanthanoid elements are clearly seen in the table of 1905, which satisfactorily includes…

  6. 40 CFR Appendix - Tables to Part 132

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT... Tables to Part 132 Table 1—Acute Water Quality Criteria for Protection of Aquatic Life in Ambient Water... is the CMC expressed as a total concentration. Table 2—Chronic Water Quality Criteria for...

  7. 40 CFR Appendix - Tables to Part 132

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT... Tables to Part 132 Table 1—Acute Water Quality Criteria for Protection of Aquatic Life in Ambient Water... is the CMC expressed as a total concentration. Table 2—Chronic Water Quality Criteria for...

  8. 40 CFR Appendix - Tables to Part 132

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY GUIDANCE FOR THE GREAT... Tables to Part 132 Table 1—Acute Water Quality Criteria for Protection of Aquatic Life in Ambient Water... is the CMC expressed as a total concentration. Table 2—Chronic Water Quality Criteria for...

  9. Air-Bearing Table for Machine Shops

    NASA Technical Reports Server (NTRS)

    Ambrisco, D.

    1986-01-01

    Frequent workpiece repositioning made easier. Air-bearing table facilitates movement of heavy workpiece during machining or between repeated operations at different positions. Table assembly consists of workpiece supporting fixture riding on air bearing. Table especially useful for inertia welding, in which ease of mobility is important.

  10. CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity

    PubMed Central

    Claywell, Ja E.

    2016-01-01

    ABSTRACT Protein phosphorylation has become increasingly recognized for its role in regulating bacterial physiology and virulence. Chlamydia spp. encode two validated Hanks'-type Ser/Thr protein kinases, which typically function with cognate protein phosphatases and appear capable of global protein phosphorylation. Consequently, we sought to identify a Ser/Thr protein phosphatase partner for the chlamydial kinases. CTL0511 from Chlamydia trachomatis L2 434/Bu, which has homologs in all sequenced Chlamydia spp., is a predicted type 2C Ser/Thr protein phosphatase (PP2C). Recombinant maltose-binding protein (MBP)-tagged CTL0511 (rCTL0511) hydrolyzed p-nitrophenyl phosphate (pNPP), a generic phosphatase substrate, in a MnCl2-dependent manner at physiological pH. Assays using phosphopeptide substrates revealed that rCTL0511 can dephosphorylate phosphorylated serine (P-Ser), P-Thr, and P-Tyr residues using either MnCl2 or MgCl2, indicating that metal usage can alter substrate preference. Phosphatase activity was unaffected by PP1, PP2A, and PP3 phosphatase inhibitors, while mutation of conserved PP2C residues significantly inhibited activity. Finally, phosphatase activity was detected in elementary body (EB) and reticulate body (RB) lysates, supporting a role for protein dephosphorylation in chlamydial development. These findings support that CTL0511 is a metal-dependent protein phosphatase with broad substrate specificity, substantiating a reversible phosphorylation network in C. trachomatis. IMPORTANCE Chlamydia spp. are obligate intracellular bacterial pathogens responsible for a variety of diseases in humans and economically important animal species. Our work demonstrates that Chlamydia spp. produce a PP2C capable of dephosphorylating P-Thr, P-Ser, and P-Tyr and that Chlamydia trachomatis EBs and RBs possess phosphatase activity. In conjunction with the chlamydial Hanks'-type kinases Pkn1 and PknD, validation of CTL0511 fulfills the enzymatic requirements for a

  11. Does the metal-metal sextuple bond exist in the bimetallic sandwich compounds Cr2(C6H6)2, Mo2(C6H6)2, and W2(C6H6)2?†

    NASA Astrophysics Data System (ADS)

    Sun, Zhi; Schaefer, Henry F., III; Xie, Yaoming; Liu, Yongdong; Zhong, Rugang

    2013-09-01

    Although evanescent at best, the bare dimers of the elements Cr, Mo, and W have been identified as possible candidates for the sextuple metal-metal bond. The corresponding dibenzene sandwich compounds Cr2(C6H6)2, Mo2(C6H6)2, and W2(C6H6)2, satisfy the '18-Electron Rule', and might achieve high-order metal-metal bonds and longer lifetimes at the same time. Twenty-two different DFT methods have been used to evaluate this possibility. Based on the present Wiberg bond index and molecular orbital analyses, however, only quadruple metal-metal bonds are predicted for the electronic ground states of Cr2(C6H6)2, Mo2(C6H6)2, and W2(C6H6)2, rather than the sextuple or even quintuple bonds, for both singlet and triplet electronic states. It is possible to force the hypothesised D 6h sextuple bond electron configuration, but the resulting energy is 39 kcal/mol above the D 2h quadruple bond structure for Cr2(C6H6)2. However, the constrained sextuple bond structure for Mo2(C6H6)2 lies 19 kcal/mol above the Mo?Mo singlet. For W2(C6H6)2 the sextuple bond structure is predicted to lie only 3 kcal/mol above the W?W structure. Thus the answer to the question raised in our title is 'almost' for the tungsten-sextuple bond.

  12. Managing Restaurant Tables using Constraints

    NASA Astrophysics Data System (ADS)

    Vidotto, Alfio; Brown, Kenneth N.; Beck, J. Christopher

    Restaurant table management can have significant impact on both profitability and the customer experience. The core of the issue is a complex dynamic combinatorial problem. We show how to model the problem as constraint satisfaction, with extensions which generate flexible seating plans and which maintain stability when changes occur. We describe an implemented system which provides advice to users in real time. The system is currently being evaluated in a restaurant environment.

  13. Two Problems with Table Saws

    ERIC Educational Resources Information Center

    Vautaw, William R.

    2008-01-01

    We solve two problems that arise when constructing picture frames using only a table saw. First, to cut a cove running the length of a board (given the width of the cove and the angle the cove makes with the face of the board) we calculate the height of the blade and the angle the board should be turned as it is passed over the blade. Second, to…

  14. Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes.

    PubMed

    Huang, Shujuan; Huang, Suling; Wang, Xi; Zhang, Qingli; Liu, Jia; Leng, Ying

    2017-01-01

    Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle.

  15. Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes

    PubMed Central

    Huang, Shujuan; Huang, Suling; Wang, Xi; Zhang, Qingli; Liu, Jia; Leng, Ying

    2017-01-01

    Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle. PMID:28123341

  16. Phase stability of the nanolaminates V2Ga2C and (Mo1-xVx)2Ga2C from first-principles calculations.

    PubMed

    Thore, A; Dahlqvist, M; Alling, B; Rosen, J

    2016-05-14

    We here use first-principles calculations to investigate the phase stability of the hypothetical laminated material V2Ga2C and the related alloy (Mo1-xVx)2Ga2C, the latter for a potential parent material for synthesis of (Mo1-xVx)2C, a new two-dimensional material in the family of so called MXenes. We predict that V2Ga2C is thermodynamically stable with respect to all identified competing phases in the ternary V-Ga-C phase diagram. We further calculate the stability of ordered and disordered configurations of Mo and V in (Mo1-xVx)2Ga2C and predict that ordered (Mo1-xVx)2Ga2C for x≤ 0.25 is stable, with an order-disorder transition temperature of ∼1000 K. Furthermore, (Mo1-xVx)2Ga2C for x = 0.5 and x≥ 0.75 is suggested to be stable, but only for disordered Mo-V configurations, and only at elevated temperatures. We have also investigated the electronic and elastic properties of V2Ga2C; the calculated bulk, shear, and Young's modulus are 141, 94, and 230 GPa, respectively.

  17. A New Protein Phosphatase 2C (FsPP2C1) Induced by Abscisic Acid Is Specifically Expressed in Dormant Beechnut Seeds1

    PubMed Central

    Lorenzo, Oscar; Rodríguez, Dolores; Nicolás, Gregorio; Rodríguez, Pedro L.; Nicolás, Carlos

    2001-01-01

    An abscisic acid (ABA)-induced cDNA fragment encoding a putative protein phosphatase 2C (PP2C) was obtained by means of differential reverse transcriptase-polymerase chain reaction approach. The full-length clone was isolated from a cDNA library constructed using mRNA from ABA-treated beechnut (Fagus sylvatica) seeds. This clone presents all the features of plant type PP2C and exhibits homology to members of this family such as AthPP2CA (61%), ABI1 (48%), or ABI2 (47%), therefore it was named FsPP2C1. The expression of FsPP2C1 is detected in dormant seeds and increases after ABA treatment, when seeds are maintained dormant, but it decreases and tends to disappear when dormancy is being released by stratification or under gibberellic acid treatment. Moreover, drought stress seems to have no effect on FsPP2C1 transcript accumulation. The FsPP2C1 transcript expression is tissue specific and was found to accumulate in ABA-treated seeds rather than in other ABA-treated vegetative tissues examined. These results suggest that the corresponding protein could be related to ABA-induced seed dormancy. By expressing FsPP2C1 in Escherichia coli as a histidine tag fusion protein, we have obtained direct biochemical evidence supporting Mg2+-dependent phosphatase activity of this protein. PMID:11299374

  18. Stimulation of Medial Prefrontal Cortex Serotonin 2C (5-HT2C) Receptors Attenuates Cocaine-Seeking Behavior

    PubMed Central

    Pentkowski, Nathan S; Duke, Felicia D; Weber, Suzanne M; Pockros, Lara A; Teer, Andrew P; Hamilton, Elizabeth C; Thiel, Kenneth J; Neisewander, Janet L

    2010-01-01

    Serotonin 2C receptor (5-HT2CR) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the function of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT2CR agonist MK212 (0, 10, 30, 100 ng/side/0.2 μl) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague–Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions before tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions before tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior, but did not reliably affect cocaine self-administration. A subsequent experiment showed that the effects of MK212 (100 ng/side/0.2 μl) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT2CR antagonist SB242084 (200 ng/side/0.2 μl). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT2CRs in the mPFC attenuates the incentive motivational

  19. The Kepler False Positive Table

    NASA Astrophysics Data System (ADS)

    Bryson, Steve; Kepler False Positive Working Group

    2015-01-01

    The Kepler Space Telescope has detected thousands of candidate exoplanets by observing transit signals in a sample of more than 190,000 stars. Many of these transit signals are false positives, defined as a transit-like signal that is not due to a planet orbiting the target star (or a bound companion if the target is a multiple-star system). Astrophysical causes of false positives include background eclipsing binaries, planetary transits not associated with the target star, and non-planetary eclipses of the target star by stellar companions. The fraction of Kepler planet candidates that are false positives ranges from about 10% at high Galactic latitudes to 40% at low Galactic latitudes. Creating a high-reliability planet candidate catalog for statistical studies such as occurrence rate calculations requires removing clearly identified false positives.The Kepler Object of Interest (KOI) catalog at the NExScI NASA Exoplanet Archive flags false positives, and will soon provide a high-level classification of false positives, but lacks detailed description of why a KOI was determined to be a false positive. The Kepler False Positive Working Group (FPWG) examines each false positive in detail to certify that it is correctly identified as a false positive, and determines the primary reason(s) a KOI is classified as a false positive. The work of the FPWG will be published as the Kepler False Positive Table, hosted at the NExScI NASA Exoplanet Archive.The Kepler False Positive Table provides detailed information on the evidence for background binaries, transits caused by stellar companions, and false alarms. In addition to providing insight into the Kepler false positive population, the false positive table gives information about the background binary population and other areas of astrophysical interest. Because a planet around a star not associated with the target star is considered a false positive, the false positive table likely contains further planet candidates

  20. Cell cycle regulation and p53 activation by protein phosphatase 2C alpha.

    PubMed

    Ofek, Paula; Ben-Meir, Daniella; Kariv-Inbal, Zehavit; Oren, Moshe; Lavi, Sara

    2003-04-18

    Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates, regulating stress response and growth-related pathways in both prokaryotes and eukaryotes. We now demonstrate that PP2C alpha, a major mammalian isoform, inhibits cell growth and activates the p53 pathway. In 293 cell clones, in which PP2C alpha expression is regulated by a tetracycline-inducible promoter, PP2C alpha overexpression led to G(2)/M cell cycle arrest and apoptosis. Furthermore, PP2C alpha induced the expression of endogenous p53 and the p53-responsive gene p21. Activation of the p53 pathway by PP2C alpha took place both in cells harboring endogenous p53, as well as in p53-null cells transfected with exogenous p53. Induction of PP2C alpha resulted in an increase in the overall levels of p53 protein as well as an augmentation of p53 transcription activity. The dephosphorylation activity of PP2C alpha is essential to the described phenomena, as none of these effects was detected when an enzymatically inactive PP2C alpha mutant was overexpressed. p53 plays an important role in PP2C alpha-directed cell cycle arrest and apoptosis because perturbation of p53 expression in human 293 cells by human papillomavirus E6 led to a significant increase in cell survival. The role of PP2C alpha in p53 activation is discussed.

  1. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  2. Clustering header categories extracted from web tables

    NASA Astrophysics Data System (ADS)

    Nagy, George; Embley, David W.; Krishnamoorthy, Mukkai; Seth, Sharad

    2015-01-01

    Revealing related content among heterogeneous web tables is part of our long term objective of formulating queries over multiple sources of information. Two hundred HTML tables from institutional web sites are segmented and each table cell is classified according to the fundamental indexing property of row and column headers. The categories that correspond to the multi-dimensional data cube view of a table are extracted by factoring the (often multi-row/column) headers. To reveal commonalities between tables from diverse sources, the Jaccard distances between pairs of category headers (and also table titles) are computed. We show how about one third of our heterogeneous collection can be clustered into a dozen groups that exhibit table-title and header similarities that can be exploited for queries.

  3. TableBuster V1.0

    SciTech Connect

    2003-06-06

    Brief Description:TableBuster enables Telelogic DOORS users to export tables with split merged cells from Microsoft Word into DOORS. Practical Application: Users of Telelogic DOORS will be more easily able to track and manage requirements that are initally defined in Microsoft Word tables containing split or merged cells. Method of Solution: TableSplitter contains two procedures. The Setup subroutine unlinks all Word fields in the active Word document. It next counts all the tables in the document and then calls the SplitCells subroutine. SplitCells splits the appropriate cells for each table, so a n row by m column table actually has n by m cells that DOORS can import.

  4. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction.

    PubMed

    Zizzo, Gaetano; Hilliard, Brendan A; Monestier, Marc; Cohen, Philip L

    2012-10-01

    Mer tyrosine kinase (MerTK) is a major macrophage apoptotic cell (AC) receptor. Its functional impairment promotes autoimmunity and atherosclerosis, whereas overexpression correlates with poor prognosis in cancer. However, little is known about mechanisms regulating MerTK expression in humans. We found that MerTK expression is heterogenous among macrophage subsets, being mostly restricted to anti-inflammatory M2c (CD14(+)CD16(+)CD163(+)CD204(+)CD206(+)CD209(-)) cells, differentiated by M-CSF or glucocorticoids. Small numbers of MerTK(+) "M2c-like" cells are also detectable among circulating CD14(bright)CD16(+) monocytes. MerTK expression levels adapt to changing immunologic environment, being suppressed in M1 and M2a macrophages and in dendritic cells. Remarkably, although glucocorticoid-induced differentiation is IL-10 independent, M-CSF-driven M2c polarization and related MerTK upregulation require IL-10. However, neither IL-10 alone nor TGF-β are sufficient to fully differentiate M2c (CD16(+)CD163(+)MerTK(+)) macrophages. M-CSF and IL-10, both released by T lymphocytes, may thus be required together to promote regulatory T cell-mediated induction of anti-inflammatory monocytes-macrophages. MerTK enables M2c macrophages to clear early ACs more efficiently than other macrophage subsets, and it mediates AC clearance by CD14(bright)CD16(+) monocytes. Moreover, M2c cells release Gas6, which in turn amplifies IL-10 secretion via MerTK. IL-10-dependent induction of the Gas6/MerTK pathway may, therefore, constitute a positive loop for M2c macrophage homeostasis and a critical checkpoint for maintenance of anti-inflammatory conditions. Our findings give new insight into human macrophage polarization and favor a central role for MerTK in regulation of macrophage functions. Eliciting M2c polarization can have therapeutic utility for diseases such as lupus, in which a defective AC clearance contributes to initiate and perpetuate the pathological process.

  5. 2C-R4WM Spectroscopy of Jet Cooled NO_3

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaru; Ishiwata, Takashi; Hirota, Eizi

    2016-06-01

    We have generated NO_3 from pyrolysis of N_2O_5 following supersonic free jet expansion, and carried out two color resonant four wave mixing ( 2C-R4WM ) spectroscopy of the tilde{B} ^2E' - tilde{X} ^2A_2' electronic transition. One laser was fixed to pump NO_3 to a ro-vibronic level of the tilde{B} state, and the other laser ( probe ) was scanned across two levels of the tilde{X} ^2A_2' state lying at 1051 and 1492 cm-1, the ν_1 (a_1') and ν_3 (e') fundamentals, respectively. The 2C-R4WM spectra have unexpected back-ground signal of NO_3 ( stray signal due to experimental set-up is also detected ) similar to laser induced fluorescence ( LIF ) excitation spectrum of the 0-0 band, although the back-ground signal was not expected in considering the 2C-R4WM scheme. Despite the back-ground interference, we have observed two peaks at 1051.61 and 1055.29 cm-1 in the ν_1 region of the spectrum, and the frequencies agree with the two bands, 1051.2 and 1055.3 cm-1, of our relatively higher resolution dispersed fluorescence spectrum, the former of which has been assigned to the ν_1 fundamental. Band width of both peaks, ˜ 0.2 cm-1, is broader than twice the experimental spectral-resolution, 0.04 cm-1 ( because this experiment is double resonance spectroscopy ), and the 1051.61 cm-1 peak is attributed to a Q branch band head ( a line-like Q branch ) of the ν_1 fundamental. The other branches are suspected to be hidden in noise of the back-ground signal. The 1055.29 cm-1 peak is also attributed to a Q band head. The tilde{B} ^2E'1/2 ( J' = 3/2, K' = 1 ) - tilde{X} ^2A_2' ( N'' = 1, K'' = 0 ) ro-vibronic transition was used as the pump transition. The dump ( probe ) transition to both a_1' and e' vibronic levels are then allowed as perpendicular transition. Accordingly, it cannot be determined from present results whether the 1055.29 cm-1 band is attributed to a_1' or e' (ν_3), unfortunately. The 2C-R4WM spectrum of the 1492 cm-1 band region shows one Q head at 1499.79 cm

  6. Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies

    PubMed Central

    Daily, Elizabeth B; Aquilante, Christina L

    2009-01-01

    Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8 polymorphisms on substrate disposition in humans has been investigated in a number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical data suggest that the CYP2C8*3 allele is associated with increased metabolism of the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3 allele on the disposition of NSAIDs are conflicting and no definitive conclusions can be made at this time. The purpose of this review is to highlight these clinical studies that have investigated the association between CYP2C8 polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research. PMID:19761371

  7. 40 CFR Table 1 to Subpart Llllll... - Applicability of General Provisions to Subpart LLLLLL

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....1(a)(1), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12) (b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c)(3), (c)(4), (d) Reserved No 63.2 Definitions Yes 63.3... and Notification Requirements No 63.6(a), (b)(1)-(b)(5), (b)(7), (c)(1), (c)(2), (c)(5), (e)(1),...

  8. 40 CFR Table 1 to Subpart Llllll... - Applicability of General Provisions to Subpart LLLLLL

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....1(a)(1), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12) (b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c)(3), (c)(4), (d) Reserved No 63.2 Definitions Yes 63.3... and Notification Requirements No 63.6(a), (b)(1)-(b)(5), (b)(7), (c)(1), (c)(2), (c)(5), (e)(1),...

  9. Evolution of the PP2C family in Caenorhabditis: rapid divergence of the sex-determining protein FEM-2.

    PubMed

    Stothard, Paul; Hansen, Dave; Pilgrim, Dave

    2002-02-01

    To investigate the causes and functional significance of rapid sex-determining protein evolution we compared three Caenorhabditis elegans genes encoding members of the protein phosphatase 2C (PP2C) family with their orthologs from another Caenorhabditis species (strain CB5161). One of the genes encodes FEM-2, a sex-determining protein, while the others have no known sex-determining role. FEM-2's PP2C domain was found to be more diverged than the other PP2C domains, supporting the notion that sex-determining proteins are subjected to selective pressures that allow for or cause rapid divergence. Comparison of the positions of amino acid substitutions in FEM-2 with a solved three-dimensional structure suggests that the catalytic face of the protein is highly conserved among C. elegans, CB5161, and another closely related species C. briggsae. However, the non-conserved regions of FEM-2 cannot be said to lack functional importance, since fem-2 transgenes from the other species were unable to rescue the germ-line defect caused by a C. elegans fem-2 mutation. To test whether fem-2 functions as a sex-determining gene in the other Caenorhabditis species we used RNA-mediated interference (RNAi). fem-2 (RNAi) in C. elegans and C. briggsae caused germ-line feminization, but had no noticeable effect in CB5161. Thus the function of fem-2 in CB5161 remains uncertain.

  10. Over-expression of a Zea mays L. protein phosphatase 2C gene (ZmPP2C) in Arabidopsis thaliana decreases tolerance to salt and drought.

    PubMed

    Liu, Lixia; Hu, Xiaoli; Song, Jian; Zong, Xiaojuan; Li, Dapeng; Li, Dequan

    2009-03-15

    ZmPP2C (AY621066) is a protein phosphatase type-2c previously isolated from roots of Zea mays (LD9002). In this study, constitutive expression of ZmPP2C in Arabidopsis thaliana under the control of the Cauliflower Mosaic Virus (CaMV) 35S promoter decreased plant tolerance to salt and drought during seed germination and vegetative growth. When growing on media with NaCl or mannitol, the ZmPP2C-overexpressed plants displayed more severe damages, with weaker growth phenotypes corresponding to a series of physiological changes: lower net photosynthesis rate (Pn) and free proline content, higher malondialdehyde (MDA) level, higher relative membrane permeability (RMP), and water loss. Under these stress conditions, they also showed decreased transcription of the stress-related genes RD29A, RD29B, P5CS1, and P5CS2, and ABA-related genes ABI1 and ABI2. Further, the transgenic plants became less sensitive to abscisic acid (ABA). ZmPP2C over-expression significantly attenuated ABA inhibition on seed germination and root growth of the transgenic plants. These results demonstrate that ZmPP2C is involved in plant stress signal transduction, and ZmPP2C gene over-expression in Arabidopsis thaliana may be exploited to study its potential roles in stress-induced signaling pathway.

  11. Molecular cloning in Arabidopsis thaliana of a new protein phosphatase 2C (PP2C) with homology to ABI1 and ABI2.

    PubMed

    Rodriguez, P L; Leube, M P; Grill, E

    1998-11-01

    We report the cloning of both the cDNA and the corresponding genomic sequence of a new PP2C from Arabidopsis thaliana, named AtP2C-HA (for homology to ABI1/ABI2). The AtP2C-HA cDNA contains an open reading frame of 1536 bp and encodes a putative protein of 511 amino acids with a predicted molecular mass of 55.7 kDa. The AtP2C-HA protein is composed of two domains, a C-terminal PP2C catalytic domain and a N-terminal extension of ca. 180 amino acid residues. The deduced amino acid sequence is 55% and 54% identical to ABI1 and ABI2, respectively. Comparison of the genomic structure of the ABI1, ABI2 and AtP2C-HA genes suggests that they belong to a multigene family. The expression of the AtP2C-HA gene is up-regulated by abscisic acid (ABA) treatment.

  12. TaPP2C1, a Group F2 Protein Phosphatase 2C Gene, Confers Resistance to Salt Stress in Transgenic Tobacco

    PubMed Central

    Hu, Wei; Yan, Yan; Hou, Xiaowan; He, Yanzhen; Wei, Yunxie; Yang, Guangxiao; He, Guangyuan; Peng, Ming

    2015-01-01

    Group A protein phosphatases 2Cs (PP2Cs) are essential components of abscisic acid (ABA) signaling in Arabidopsis; however, the function of group F2 subfamily PP2Cs is currently less known. In this study, TaPP2C1 which belongs to group F2 was isolated and characterized from wheat. Expression of the TaPP2C1-GFP fusion protein suggested its ubiquitous localization within a cell. TaPP2C1 expression was downregulated by abscisic acid (ABA) and NaCl treatments, but upregulated by H2O2 treatment. Overexpression of TaPP2C1 in tobacco resulted in reduced ABA sensitivity and increased salt resistance of transgenic seedlings. Additionally, physiological analyses showed that improved resistance to salt stress conferred by TaPP2C1 is due to the reduced reactive oxygen species (ROS) accumulation, the improved antioxidant system, and the increased transcription of genes in the ABA-independent pathway. Finally, transgenic tobacco showed increased resistance to oxidative stress by maintaining a more effective antioxidant system. Taken together, these results demonstrated that TaPP2C1 negatively regulates ABA signaling, but positively regulates salt resistance. TaPP2C1 confers salt resistance through activating the antioxidant system and ABA-independent gene transcription process. PMID:26057628

  13. TaPP2C1, a Group F2 Protein Phosphatase 2C Gene, Confers Resistance to Salt Stress in Transgenic Tobacco.

    PubMed

    Hu, Wei; Yan, Yan; Hou, Xiaowan; He, Yanzhen; Wei, Yunxie; Yang, Guangxiao; He, Guangyuan; Peng, Ming

    2015-01-01

    Group A protein phosphatases 2Cs (PP2Cs) are essential components of abscisic acid (ABA) signaling in Arabidopsis; however, the function of group F2 subfamily PP2Cs is currently less known. In this study, TaPP2C1 which belongs to group F2 was isolated and characterized from wheat. Expression of the TaPP2C1-GFP fusion protein suggested its ubiquitous localization within a cell. TaPP2C1 expression was downregulated by abscisic acid (ABA) and NaCl treatments, but upregulated by H2O2 treatment. Overexpression of TaPP2C1 in tobacco resulted in reduced ABA sensitivity and increased salt resistance of transgenic seedlings. Additionally, physiological analyses showed that improved resistance to salt stress conferred by TaPP2C1 is due to the reduced reactive oxygen species (ROS) accumulation, the improved antioxidant system, and the increased transcription of genes in the ABA-independent pathway. Finally, transgenic tobacco showed increased resistance to oxidative stress by maintaining a more effective antioxidant system. Taken together, these results demonstrated that TaPP2C1 negatively regulates ABA signaling, but positively regulates salt resistance. TaPP2C1 confers salt resistance through activating the antioxidant system and ABA-independent gene transcription process.

  14. CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.

    PubMed

    Ortega-Vázquez, A; Dorado, P; Fricke-Galindo, I; Jung-Cook, H; Monroy-Jaramillo, N; Martínez-Juárez, I E; Familiar-López, I; Peñas-Lledó, E; LLerena, A; López-López, M

    2016-06-01

    We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.

  15. "PP2C7s", Genes Most Highly Elaborated in Photosynthetic Organisms, Reveal the Bacterial Origin and Stepwise Evolution of PPM/PP2C Protein Phosphatases.

    PubMed

    Kerk, David; Silver, Dylan; Uhrig, R Glen; Moorhead, Greg B G

    2015-01-01

    Mg+2/Mn+2-dependent type 2C protein phosphatases (PP2Cs) are ubiquitous in eukaryotes, mediating diverse cellular signaling processes through metal ion catalyzed dephosphorylation of target proteins. We have identified a distinct PP2C sequence class ("PP2C7s") which is nearly universally distributed in Eukaryotes, and therefore apparently ancient. PP2C7s are by far most prominent and diverse in plants and green algae. Combining phylogenetic analysis, subcellular localization predictions, and a distillation of publically available gene expression data, we have traced the evolutionary trajectory of this gene family in photosynthetic eukaryotes, demonstrating two major sequence assemblages featuring a succession of increasingly derived sub-clades. These display predominant expression moving from an ancestral pattern in photosynthetic tissues toward non-photosynthetic, specialized and reproductive structures. Gene co-expression network composition strongly suggests a shifting pattern of PP2C7 gene functions, including possible regulation of starch metabolism for one homologue set in Arabidopsis and rice. Distinct plant PP2C7 sub-clades demonstrate novel amino terminal protein sequences upon motif analysis, consistent with a shifting pattern of regulation of protein function. More broadly, neither the major events in PP2C sequence evolution, nor the origin of the diversity of metal binding characteristics currently observed in different PP2C lineages, are clearly understood. Identification of the PP2C7 sequence clade has allowed us to provide a better understanding of both of these issues. Phylogenetic analysis and sequence comparisons using Hidden Markov Models strongly suggest that PP2Cs originated in Bacteria (Group II PP2C sequences), entered Eukaryotes through the ancestral mitochondrial endosymbiosis, elaborated in Eukaryotes, then re-entered Bacteria through an inter-domain gene transfer, ultimately producing bacterial Group I PP2C sequences. A key evolutionary

  16. "PP2C7s", Genes Most Highly Elaborated in Photosynthetic Organisms, Reveal the Bacterial Origin and Stepwise Evolution of PPM/PP2C Protein Phosphatases

    PubMed Central

    Kerk, David; Silver, Dylan; Uhrig, R. Glen; Moorhead, Greg B. G.

    2015-01-01

    Mg+2/Mn+2-dependent type 2C protein phosphatases (PP2Cs) are ubiquitous in eukaryotes, mediating diverse cellular signaling processes through metal ion catalyzed dephosphorylation of target proteins. We have identified a distinct PP2C sequence class (“PP2C7s”) which is nearly universally distributed in Eukaryotes, and therefore apparently ancient. PP2C7s are by far most prominent and diverse in plants and green algae. Combining phylogenetic analysis, subcellular localization predictions, and a distillation of publically available gene expression data, we have traced the evolutionary trajectory of this gene family in photosynthetic eukaryotes, demonstrating two major sequence assemblages featuring a succession of increasingly derived sub-clades. These display predominant expression moving from an ancestral pattern in photosynthetic tissues toward non-photosynthetic, specialized and reproductive structures. Gene co-expression network composition strongly suggests a shifting pattern of PP2C7 gene functions, including possible regulation of starch metabolism for one homologue set in Arabidopsis and rice. Distinct plant PP2C7 sub-clades demonstrate novel amino terminal protein sequences upon motif analysis, consistent with a shifting pattern of regulation of protein function. More broadly, neither the major events in PP2C sequence evolution, nor the origin of the diversity of metal binding characteristics currently observed in different PP2C lineages, are clearly understood. Identification of the PP2C7 sequence clade has allowed us to provide a better understanding of both of these issues. Phylogenetic analysis and sequence comparisons using Hidden Markov Models strongly suggest that PP2Cs originated in Bacteria (Group II PP2C sequences), entered Eukaryotes through the ancestral mitochondrial endosymbiosis, elaborated in Eukaryotes, then re-entered Bacteria through an inter-domain gene transfer, ultimately producing bacterial Group I PP2C sequences. A key

  17. Variable White Dwarf Data Tables

    SciTech Connect

    Bradley, P. A.

    1997-12-31

    Below, I give a brief explanation of the information in these tables. In all cases, I list the WD {number_sign}, either from the catalog of McCook {ampersand} Sion (1987) or determined by me from the epoch 1950 coordinates. Next, I list the most commonly used name (or alias), then I list the variable star designation if it is available. If not, I list the constellation name and a V** or?? depending on what the last designated variable star for that constellation is. I present epoch 2000 coordinates for all of the stars, which I precessed from the 1950 ones in most cases. I do not include proper motion effects; this is negligible for all except the largest proper motion DAV stars, such as L 19-2, BPM 37093, B 808, and G 29-38. Even in these cases, the error is no more than 30` in declination and 2 s in right ascension. I culled effective temperatures from the latest work (listed under each table); they are now much more homogeneous than before. I pulled the magnitude estimates from the appropriate paper, and they are mean values integrated over several cycles. The amplitude given is for the height of a typical pulse in the light curve. The periods correspond the dominant ones found in the light curve. In some cases, there is a band of power in a given period range, or the light curve is very complex, and I indicate this in the table. In the references, I generally list the paper with the most comprehensive pulsation analysis for the star in question. In some cases, there is more than one good reference, and I list them as well.

  18. 49 CFR 173.425 - Table of activity limits-excepted quantities and articles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... follows: Table 4—Activity Limits for Limited Quantities, Instruments, and Articles Nature of contents... limits 1 Solids: Special form 10−2 A1 A1 10−3 A1 Normal form 10−2 A2 A2 10−3 A2 Liquids: Tritiated...

  19. Designing Readable and Persuasive Tables,

    DTIC Science & Technology

    1983-12-01

    based on no more than 100 observations. - 23 PUTTING THE PIECES TOGETHER Like a crossword puzzle , table design entails solving a number of small...marginal cost per room: $ 13 for the second room, $18 for the third room, $26 for the fourth room, $28 for the fifth, and $35 for the sixth room...increases beyond one: -6- Number of Median Monthly Marginal Rent Rooms Gross Rent () per Room() 1 76 - - 2 89 13 3 107 18 4 133 26 5 161 28 6 196 35 Note in

  20. Table-top job analysis

    SciTech Connect

    Not Available

    1994-12-01

    The purpose of this Handbook is to establish general training program guidelines for training personnel in developing training for operation, maintenance, and technical support personnel at Department of Energy (DOE) nuclear facilities. TTJA is not the only method of job analysis; however, when conducted properly TTJA can be cost effective, efficient, and self-validating, and represents an effective method of defining job requirements. The table-top job analysis is suggested in the DOE Training Accreditation Program manuals as an acceptable alternative to traditional methods of analyzing job requirements. DOE 5480-20A strongly endorses and recommends it as the preferred method for analyzing jobs for positions addressed by the Order.

  1. Object analysis of the Stilling tables.

    PubMed

    Lakowski, R

    1976-01-01

    The CIE space that is occupied by the Stilling tables was found to be similar to that occupied by the Ishihara plates [LAKOWSKI, 1965] with the notable exceptions of a single table that extends into the blue area and two others that extend further into the green (fig. 4). Spectrophotometric curves show that the inks used are similar to those in other PIC plates, i.e. they have reflectance curves with broad-band characteristics. All tables are of the vanishing type and there is an attempt to differentiate between protan and deutan defects. Colorimetrically, tables I, II, VII and VIII have figure and background colours aligned mainly along the deutan isochromatic lines and only table III is a clear protan plate. Tables V, VI, IX, X and XI are ambiguous in design, i.e. they would be confused by most colour-deficient persons. Of the tables designed to detect blue-yellow deficiencies (tables V, VI, XI and XII), only the colours in table XII are aligned along tetartan confusion lines, while the other three tables are indefinite in their design. Thus the usefulness of these plates for detecting acquired dyschromatopsias is limited.

  2. Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved

    SciTech Connect

    Krainc, D.; Lipton, S.A.; Haas, M.; Ward, D.C.

    1995-10-10

    Human myocyte-specific enhancer binding factor 2C (hMEF2C) belongs to the MEF2 subfamily of the MADS (MCM1, AGAMOUS, DEF A, serum response factor) family of transcription factors. Members of the MADS family share a conserved domain - the MADS domain - that is necessary for DNA binding. Highly conserved versions of the MADS domain and of an adjacent domain that is known as the MEF2 domain are found in members of the MEF2 subfamily. Both of these domains are necessary for binding to the MEF2 regulatory element. This regulatory element is known to be functionally important in a variety of muscle-specific genes and possibly in the brain creatine kinase gene. The MEF2C gene product activates transcription by binding to the MEF2 element. hMEF2C is expressed at high levels in postmitotic neurons in the brain, where it is most abundant in the cerebral cortex, and is also expressed in differentiated myotubes. Several lines of evidence suggest the existence of a rat homologue of MEF2C, and a mouse homologue has been cloned. The mouse gene was mapped to mouse chromosome 13 in a region that is syntenic to human 5q13-q15. 12 refs., 1 fig.

  3. Association of the ABCG2 C421A polymorphism with prostate cancer risk and survival

    PubMed Central

    Gardner, Erin R.; Ahlers, Christoph M.; Shukla, Suneet; Sissung, Tristan M.; Ockers, Sandra B.; Price, Douglas K.; Hamada, Akinobu; Robey, Robert W.; Steinberg, Seth M.; Ambudkar, Suresh V.; Dahut, William L.; Figg, William D.

    2009-01-01

    Objective To determine if the C421A single nucleotide polymorphism (SNP) in the ATP-binding cassette transporter ABCG2 increases prostate cancer risk or affects survival. Patients, subjects and methods Numerous studies have suggested that dietary, hormonal and environmental factors all play a role in the initiation in prostate cancer; among these, the carcinogenic heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a known substrate of the ABCG2. A SNP of ABCG2, C421A, resulting in a glutamine to lysine change at amino acid 141, has been shown to result in decreased function of the protein. Due to the expression of ABCG2 in the prostate, together with the purported role of dietary carcinogens and steroids in the development and progression of prostate cancer, 311 individuals were genotyped for the ABCG2 C421A SNP, 170 patients with androgen-independent prostate cancer (AIPC) and 141 ‘healthy’ controls. We also evaluated the effect of this SNP on the intracellular accumulation of PhIP and testosterone in vitro. Results There were no significant differences in the prevalence of prostate cancer based on ABCG2 genetic variation in this population. However, survival was significantly longer for individuals with wild-type ABCG2, as compared with those hetero- or homozygous for the C421A SNP (7.4 years vs 5.3 years, P = 0.044). Conclusion Intracellular accumulation of PhIP was 80% higher in HEK293 cells transfected with Q141K ABCG2 than in wild-type cells, confirming that this SNP decreases transport of PhIP. In contrast, testosterone was not transported by either wild-type or variant transfected cells, nor did it act as in inhibitor of ABCG2 in subsequent transport assays. PMID:18710444

  4. RNA-Binding Protein AUF1 Promotes Myogenesis by Regulating MEF2C Expression Levels

    PubMed Central

    Panda, Amaresh C.; Abdelmohsen, Kotb; Yoon, Je-Hyun; Martindale, Jennifer L.; Yang, Xiaoling; Curtis, Jessica; Mercken, Evi M.; Chenette, Devon M.; Zhang, Yongqing; Schneider, Robert J.; Becker, Kevin G.; de Cabo, Rafael

    2014-01-01

    The mammalian RNA-binding protein AUF1 (AU-binding factor 1, also known as heterogeneous nuclear ribonucleoprotein D [hnRNP D]) binds to numerous mRNAs and influences their posttranscriptional fate. Given that many AUF1 target mRNAs encode muscle-specific factors, we investigated the function of AUF1 in skeletal muscle differentiation. In mouse C2C12 myocytes, where AUF1 levels rise at the onset of myogenesis and remain elevated throughout myocyte differentiation into myotubes, RNP immunoprecipitation (RIP) analysis indicated that AUF1 binds prominently to Mef2c (myocyte enhancer factor 2c) mRNA, which encodes the key myogenic transcription factor MEF2C. By performing mRNA half-life measurements and polysome distribution analysis, we found that AUF1 associated with the 3′ untranslated region (UTR) of Mef2c mRNA and promoted MEF2C translation without affecting Mef2c mRNA stability. In addition, AUF1 promoted Mef2c gene transcription via a lesser-known role of AUF1 in transcriptional regulation. Importantly, lowering AUF1 delayed myogenesis, while ectopically restoring MEF2C expression levels partially rescued the impairment of myogenesis seen after reducing AUF1 levels. We propose that MEF2C is a key effector of the myogenesis program promoted by AUF1. PMID:24891619

  5. First-principles study of stability, electronic structure and magnetic properties of Be2C nanoribbons

    NASA Astrophysics Data System (ADS)

    Zhang, Jianmin; Xu, Chunyan; Zheng, Huiling; Du, Xiaobo; Yan, Yu

    2017-02-01

    First-principles calculations are carried out to investigate the stability, electronic structure and magnetic properties of Be2C nanoribbons (Be2C-NRs) with their ribbon axis along the a and b axes. It is found that except for b-Be2C-NR with the C site terminated edge, a-Be2C-NRs and other b-Be2C-NRs possess good structural stabilities at room temperature. In addition, H passivation enables b-Be2C-NR with C site terminated edge to stabilize at room temperature by saturating the dangling bonds at edges. Furthermore, stable a-Be2C-NRs and b-Be2C-NRs are all nonmagnetic semiconductors and their band gaps are significantly dependent on the edge configuration and the ribbon width. In contrast, H passivated b-Be2C-NR with C site terminated edge is half-metallic with a magnetic ground state, irrespective of the ribbon width. In particular, H passivated b-Be2C-NR with C site terminated edge has a strong intra-edge ferromagnetic coupling interaction in the ground state, and an inter-edge ferromagnetic interaction is found in small-width H passivated nanoribbon. The calculated density of states and the spin density distribution show that the p-p hybridization interaction involving polarized electrons is responsible for intra-edge and inter-edge ferromagnetic coupling.

  6. Identification of Primary Gene Targets of TFAP2C in Hormone Responsive Breast Carcinoma Cells

    PubMed Central

    Woodfield, George W.; Chen, Yizhen; Bair, Thomas B.; Domann, Frederick E.; Weigel, Ronald J.

    2010-01-01

    The TFAP2C transcription factor is involved in mammary development, differentiation and oncogenesis. Previous studies established a role for TFAP2C in the regulation of ESR1 (ERα) and ERBB2 (Her2) in breast carcinomas. However, the role of TFAP2C in different breast cancer phenotypes has not been examined in detail. To develop a more complete characterization of TFAP2C target genes, ChIP-seq with anti-TFAP2C antibody and expression arrays with TFAP2C knock down were analyzed in MCF-7 breast carcinoma cells. Genomic sequences common to the ChIP-seq data set defined the consensus sequence for TFAP2C chromatin binding as the nine base sequence SCCTSRGGS (S=G/C, R=A/G), which closely matches the previously defined optimal in vitro binding site. Comparing expression arrays before and after knock down of TFAP2C with ChIP-seq data demonstrated a conservative estimate that 8% of genes altered by TFAP2C expression are primary target genes and includes genes that are both induced and repressed by TFAP2C. A set of 447 primary target genes of TFAP2C was identified, which included ESR1 (ERα), FREM2, RET, FOXA1, WWOX, GREB1, MYC and members of the retinoic acid response pathway. The identification of ESR1, WWOX, GREB1 and FOXA1 as primary targets confirmed the role of TFAP2C in hormone response. TFAP2C plays a critical role in gene regulation in hormone responsive breast cancer and its target genes are different than for the Her2 breast cancer phenotype. PMID:20629094

  7. Environmental Regulatory Update Table, October 1991

    SciTech Connect

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  8. Environmental Regulatory Update Table, November 1991

    SciTech Connect

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  9. Environmental regulatory update table, July 1991

    SciTech Connect

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-08-01

    This Environmental Regulatory Update Table (July 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  10. Environmental Regulatory Update Table, August 1991

    SciTech Connect

    Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

    1991-09-01

    This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  11. Environmental Regulatory Update Table, September 1991

    SciTech Connect

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  12. Environmental Regulatory Update Table, January 1991

    SciTech Connect

    Hawkins, G.T.; Houlberg, L.M.; Salk, M.S.

    1991-02-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  13. Environmental Regulatory Update Table, October 1990

    SciTech Connect

    Houlberg, L.M.; Noghrei-Nikbakht, P.A.; Salk, M.S.

    1990-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  14. Environmental Regulatory Update Table, December 1991

    SciTech Connect

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental regulatory update table, March 1989

    SciTech Connect

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-04-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  16. Environmental Regulatory Update Table, August 1990

    SciTech Connect

    Houlberg, L.M.; Nikbakht, A.; Salk, M.S.

    1990-09-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  17. Environmental Regulatory Update Table, September 1990

    SciTech Connect

    Houlberg, L.M.; Nikbakht, A.; Salk, M.S.

    1990-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  18. Environmental Regulatory Update Table, December 1989

    SciTech Connect

    Houlbert, L.M.; Langston, M.E. ); Nikbakht, A.; Salk, M.S. )

    1990-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental Regulatory Update Table, April 1989

    SciTech Connect

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    SciTech Connect

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H.

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  1. Preparation and properties of antibacterial TiO2@C/Ag core-shell composite

    NASA Astrophysics Data System (ADS)

    Tan, San-Xiang; Tan, Shao-Zao; Chen, Jing-Xing; Liu, Ying-Liang; Yuan, Ding-Sheng

    2009-08-01

    An environment-friendly hydrothermal method was used to prepare TiO2@C core-shell composite using TiO2 as core and sucrose as carbon source. TiO2@C served as a support for the immobilization of Ag by impregnation in silver nitrate aqueous solution. The chemical structures and morphologies of TiO2@C and TiO2@C/Ag composite were characterized by x-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, energy dispersive x-ray spectroscopy and Brunauer-Emmett-Teller (BET) analysis. The antibacterial properties of the TiO2@C/Ag core-shell composite against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were examined by the viable cell counting method. The results indicate that silver supported on the surface of TiO2@C shows excellent antibacterial activity.

  2. Foxp2 Controls Synaptic Wiring of Corticostriatal Circuits and Vocal Communication by Opposing Mef2C

    PubMed Central

    Chen, Yi-Chuan; Kuo, Hsiao-Ying; Bornschein, Ulrich; Takahashi, Hiroshi; Chen, Shih-Yun; Lu, Kuan-Ming; Yang, Hao-Yu; Chen, Gui-May; Lin, Jing-Ruei; Lee, Yi-Hsin; Chou, Yun-Chia; Cheng, Sin-Jhong; Chien, Cheng-Ting; Enard, Wolfgang; Hevers, Wulf; Pääbo, Svante; Graybiel, Ann M.; Liu, Fu-Chin

    2016-01-01

    Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder (ASD), in which language function can be severely affected. We demonstrate that in the striatum, the gene, Foxp2, negatively interacts with the synapse suppressor, Mef2C. We present causal evidence that Mef2C inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2C suppresses corticostriatal synapse formation and striatal spinogenesis, but can, itself, be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2C, and both intrastriatal and global decrease of Mef2C rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders. PMID:27595386

  3. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

    SciTech Connect

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M.H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric

    2014-10-02

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

  4. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

    PubMed Central

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M. H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric

    2013-01-01

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites. PMID:22116026

  5. PP2C gamma: a human protein phosphatase with a unique acidic domain.

    PubMed

    Travis, S M; Welsh, M J

    1997-08-04

    We have cloned a novel cDNA from human skeletal muscle which encodes a protein phosphatase with a unique acidic domain. It is 34% identical to mammalian PP2C alpha and PP2C beta and we call it PP2C gamma. It more closely resembles PP2Cs from Paramecium tetraurelia and Schizosaccharomyces pombe than mammalian PP2Cs. Northern blot analysis shows that PP2C gamma is widely expressed, and is most abundant in testis, skeletal muscle, and heart. Like known PP2Cs, recombinant PP2C gamma requires Mg2+ or Mn2+ for activity. Unlike any other known phosphatase, PP2C gamma has a highly acidic domain: 75% of the 54 residues are glutamate or aspartate.

  6. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases.

    PubMed

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X Edward; West, Graham M; Kovach, Amanda; Tan, M H Eileen; Suino-Powell, Kelly M; He, Yuanzheng; Xu, Yong; Chalmers, Michael J; Brunzelle, Joseph S; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R; Melcher, Karsten; Xu, H Eric

    2012-01-06

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

  7. Solar cell efficiency tables (version 49): Solar cell efficiency tables (version 49)

    SciTech Connect

    Green, Martin A.; Emery, Keith; Hishikawa, Yoshihiro; Warta, Wilhelm; Levi, Dean H.; Ho-Baillie, Anita W. Y.

    2016-11-28

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined, and new entries since June 2016 are reviewed.

  8. Solar cell efficiency tables (version 48): Solar cell efficiency tables (version 48)

    SciTech Connect

    Green, Martin A.; Emery, Keith; Hishikawa, Yoshihiro; Warta, Wilhelm

    2016-06-17

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined, and new entries since January 2016 are reviewed.

  9. The Demethylase JMJD2C Localizes to H3K4me3-Positive Transcription Start Sites and Is Dispensable for Embryonic Development

    PubMed Central

    Pedersen, Marianne Terndrup; Agger, Karl; Laugesen, Anne; Johansen, Jens V.; Cloos, Paul A. C.; Christensen, Jesper

    2014-01-01

    The histone demethylase JMJD2C, also known as KDM4C/GASC1, has activity against methylated H3K9 and H3K36 and is amplified and/or overexpressed in human cancers. By the generation of Jmjd2c knockout mice, we demonstrate that loss of Jmjd2c is compatible with cellular proliferation, embryonic stem cell (ESC) self-renewal, and embryonic development. Moreover, we report that JMJD2C localizes to H3K4me3-positive transcription start sites in both primary cells and in the human carcinoma KYSE150 cell line containing an amplification of the JMJD2C locus. Binding is dependent on the double Tudor domain of JMJD2C, which recognizes H3K4me3 but not H4K20me2/me3 in vitro, showing a binding specificity different from that of the double Tudor domains of JMJD2A and JMJD2B. Depletion of JMJD2C in KYSE150 cells has a modest effect on H3K9me3 and H3K36me3 levels but impairs proliferation and leads to deregulated expression of a subset of target genes involved in cell cycle progression. Taking these findings together, we show that JMJD2C is targeted to H3K4me3-positive transcription start sites, where it can contribute to transcriptional regulation, and report that the putative oncogene JMJD2C generally is not required for cellular proliferation or embryonic development. PMID:24396064

  10. Identification and biochemical characterization of Rap2C, a new member of the Rap family of small GTP-binding proteins.

    PubMed

    Paganini, Simona; Guidetti, Gianni Francesco; Catricalà, Silvia; Trionfini, Piera; Panelli, Simona; Balduini, Cesare; Torti, Mauro

    2006-01-01

    The Rap family of small GTP-binding proteins is composed by four different members: Rap1A, Rap1B, Rap2A and Rap2B. In this work we report the identification and characterization of a fifth member of this family of small GTPases. This new protein is highly homologous to Rap2A and Rap2B, binds labeled GTP on nitrocellulose, and is recognized by a specific anti-Rap2 antibody, but not by an anti-Rap1 antibody. The protein has thus been named Rap2C. Binding of GTP to recombinant purified Rap2C was Mg(2+)-dependent. However, accurate comparison of the kinetics of nucleotide binding and release revealed that Rap2C bound GTP less efficiently and possessed slower rate of GDP release compared to the highly homologous Rap2B. Moreover, in the presence of Mg(2+), the relative affinity of Rap2C for GTP was only about twofold higher than that for GDP, while, under the same conditions, Rap2B was able to bind GTP with about sevenfold higher affinity than GDP. When expressed in eukaryotic cells, Rap2C localized at the plasma membrane, as dictated by the presence of a CAAX motif at the C-terminus. We found that Rap2C represented the predominant Rap2 protein expressed in circulating mononuclear leukocytes, but was not present in platelets. Importantly, Rap2C was found to be expressed in human megakaryocytes, suggesting that the protein may be down-regulated during platelets generation. This work demonstrates that Rap2C is a new member of the Rap2 subfamily of proteins, able to bind guanine nucleotides with peculiar properties, and differently expressed by various hematopoietic subsets. This new protein may therefore contribute to the still poorly clarified cellular events regulated by this subfamily of GTP-binding proteins.

  11. Isolation and characterization of dehydration-responsive element-binding factor 2C (MsDREB2C) from Malus sieversii Roem.

    PubMed

    Zhao, Kai; Shen, Xinjie; Yuan, Huazhao; Liu, Yun; Liao, Xiong; Wang, Qi; Liu, Linlin; Li, Fang; Li, Tianhong

    2013-09-01

    DREB2 (dehydration-responsive element-binding factor 2)-type transcription factors play a critical role in the stress-related regulation network in plants. In this study, we isolated and characterized a DREB2 homolog from Malus sieversii Roem., designated MsDREB2C (GenBank accession No. JQ790526). MsDREB2C localized to the nucleus and transactivated reporter genes in yeast strain YGR-2. Quantitative real-time PCR analysis demonstrated that MsDREB2C was constitutively expressed and significantly induced by drought, salt, cold, heat and ABA. Transgenic Arabidopsis plants overexpressing MsDREB2C exhibited increased root and leaf growth and proline levels, and reduced water loss and stomatal aperture. The transcriptional level of genes that function downstream of dehydration-responsive elements was greater in the transgenic Arabidopsis plants than in wild-type plants under control and abiotic stress conditions. Furthermore, constitutive expression of MsDREB2C repressed the expression of pathogenesis-related (PR) genes and the activity of peroxidase in transgenic plants under control and pathogenic conditions. As a result, transgenic plants were more tolerant to drought, heat and cold, but more sensitive to Pst DC3000 (Pseudomonas syringae pv . tomato DC3000) infection than control plants. β-Glucuronidase expression analysis of the MsDREB2C promoter in transgenic tobacco plants showed that MsDREB2C was mainly expressed in the vascular tissues and seeds. Deletion analysis identified the regulatory regions responsible for the plant's response to drought (-831 to -680), ABA (-831 to -680 and -335 to -148), salt (-831 to -335), cold (-1,317 to -831 and -335 to -148) and heat (-335 to -148).

  12. Identification of a cys-ser substitution in the 5-HT{sub 2C} (HTR2C) receptor gene and allelic association to violent behavior and alcoholism

    SciTech Connect

    Lappalainen, J.; Ozaki, N.; Goldman, D.

    1994-09-01

    Several lines of evidence suggest that brain serotonergic functions, including behavioral and neurochemical responses to 5-HT{sub 2C} agonist, are abnormal in some individuals with alcoholism and aggressive behaviors. The aim of the present study was to identify coding sequence variants in the human 5-HT{sub 2C} receptor gene which may cause abnormal or variant function of this receptor. Using SSCP analysis, a non-conservative cys-ser substitution was found in the 5-HT{sub 2C} receptor (designated 5-HT{sub 2Ccys} and 5-HT{sub 2Cser}). The polymorphism was typed in CEPH families to genetically map the gene. To test for association of the variant to alcoholism, violent behavior and serotonin function, the 5-HT{sub 2C} genotypes of 151 non-related Finnish male alcoholic violent offenders and impulsive fire setters and 127 Finnish psychiatrically interviewed healthy male volunteers were determined. CSF 5-HIAA concentrations were available for 74 alcoholic violent offenders and 25 healthy volunteers. Linkage analysis placed the 5-HT{sub 2C} gene on Xq21, a region that has been previously shown to contain genes for several mental retardation syndromes. The 5-HT{sub 2Ccys}/5-HT{sub 2Cser} genotype frequencies in alcoholic violent offenders and controls differed significantly (0.90/0.10 and 0.82/0.18, respectively, P=0.048). The association was found to be strongest in the violent offenders who did not fulfill the criteria for antisocial personality disorder (5-HT{sub 2Ccys}/5-HT{sub 2Cser} 0.93/0.07, p=0.021). No association was found between CSF 5-HIAA concentrations and 5-HT{sub 2C} genotype. These results implicate a 5-HT{sub 2C} receptor amino acid substitution in predisposition to alcohol abuse and violent behavior in a subgroup of alcoholics.

  13. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.

    PubMed

    Berglund, Eric D; Liu, Chen; Sohn, Jong-Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E; Vianna, Claudia R; Williams, Kevin W; Xu, Yong; Elmquist, Joel K

    2013-12-01

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

  14. Superconductivity of monolayer Mo2C: The key role of functional groups.

    PubMed

    Zhang, Jun-Jie; Dong, Shuai

    2017-01-21

    Monolayer Mo2C is a new member of two-dimensional materials. Here the electronic structure and lattice dynamics of monolayer Mo2C are calculated. According to the electron-phonon interaction, it is predicted that monolayer Mo2C could be a quasi-two-dimensional superconductor and the effects of functional-groups are crucially important considering its unsaturated surface. Despite the suppressed superconductivity by chalcogen adsorption, our most interesting prediction is that the electron-phonon interaction of monolayer Mo2C can be greatly enhanced by bromine absorption, suggesting that Mo2CBr2 as a good candidate for a nanoscale superconductor.

  15. The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate.

    PubMed

    Schüler, Andrea; Schwieger, Maike; Engelmann, Afra; Weber, Kristoffer; Horn, Stefan; Müller, Ursula; Arnold, Michael A; Olson, Eric N; Stocking, Carol

    2008-05-01

    Mef2c is a MADS (MCM1-agamous-deficient serum response factor) transcription factor best known for its role in muscle and cardiovascular development. A causal role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia (AML) has recently been demonstrated. Due to the pronounced monocytic component observed in Mef2c-induced AML, this study was designed to assess the importance of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells manipulated to constitutively express Mef2c demonstrated increased monopoiesis at the expense of granulopoiesis, whereas BM isolated from Mef2c(Delta/-) mice showed reduced levels of monocytic differentiation in response to cytokines. Mechanistic studies showed that loss of Mef2c expression correlated with reduced levels of transcripts encoding c-Jun, but not PU.1, C/EBPalpha, or JunB transcription factors. Inhibiting Jun expression by short-interfering RNA impaired Mef2c-mediated inhibition of granulocyte development. Moreover, retroviral expression of c-Jun in BM cells promoted monocytic differentiation. The ability of Mef2c to modulate cell-fate decisions between monocyte and granulocyte differentiation, coupled with its functional sensitivity to extracellular stimuli, demonstrate an important role in immunity--and, consistent with findings of other myeloid transcription factors, a target of oncogenic lesions in AML.

  16. Superconductivity of monolayer Mo2C: The key role of functional groups

    NASA Astrophysics Data System (ADS)

    Zhang, Jun-Jie; Dong, Shuai

    2017-01-01

    Monolayer Mo2C is a new member of two-dimensional materials. Here the electronic structure and lattice dynamics of monolayer Mo2C are calculated. According to the electron-phonon interaction, it is predicted that monolayer Mo2C could be a quasi-two-dimensional superconductor and the effects of functional-groups are crucially important considering its unsaturated surface. Despite the suppressed superconductivity by chalcogen adsorption, our most interesting prediction is that the electron-phonon interaction of monolayer Mo2C can be greatly enhanced by bromine absorption, suggesting that Mo2CBr2 as a good candidate for a nanoscale superconductor.

  17. A periodic table for cancer.

    PubMed

    Epstein, Richard J

    2015-01-01

    Cancers exhibit differences in metastatic behavior and drug sensitivity that correlate with certain tumor-specific variables such as differentiation grade, growth rate/extent and molecular regulatory aberrations. In practice, patient management is based on the past results of clinical trials adjusted for these biomarkers. Here, it is proposed that treatment strategies could be fine-tuned upfront simply by quantifying tumorigenic spatial (cell growth) and temporal (genetic stability) control losses, as predicted by genetic defects of cell-cycle-regulatory gatekeeper and genome-stabilizing caretaker tumor suppressor genes, respectively. These differential quantifications of tumor dysfunction may in turn be used to create a tumor-specific 'periodic table' that guides rational formulation of survival-enhancing anticancer treatment strategies.

  18. The taste of table salt.

    PubMed

    Roper, Stephen D

    2015-03-01

    Solutions of table salt (NaCl) elicit several tastes, including of course saltiness but also sweet, sour, and bitter. This brief review touches on some of the mileposts concerning what is known about taste transduction for the Na(+) ion, the main contributor to saltiness. Electrophysiological recordings, initially from single gustatory nerve fibers, and later, integrated impulse activity from gustatory nerves led researchers to predict that Na(+) ions interacted with a surface molecule. Subsequent studies have resolved that this molecule is likely to be an epithelial sodium channel, ENaC. Other Na(+) transduction mechanisms are also present in taste buds but have not yet been identified. The specific type(s) of taste cells responsible for salt taste also remains unknown.

  19. Transcriptional Regulation of the GPX1 Gene by TFAP2C and Aberrant CpG Methylation in Human Breast Cancer

    PubMed Central

    Kulak, Mikhail V.; Cyr, Anthony R.; Woodfield, George W.; Bogachek, Maria; Spanheimer, Philip M.; Li, Tiandao; Price, David H.; Domann, Frederick E.; Weigel, Ronald J.

    2012-01-01

    The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. TFAP2C is a transcription factor, which plays a critical role in the regulation of both estrogen receptor-alpha (ERα) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines. Comparing the genomic binding sites for TFAP2C, we identified that glutathione peroxidase (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene. Knock down of TFAP2C, but not the related factor TFAP2A, resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity correlated with endogenous GPX1 expression and overexpression of exogenous GPX1 induced GPX activity and significantly increased resistance to tert-butyl hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where GPX1 promoter methylation was associated with gene silencing, treatment with 5-aza-dC (an inhibitor of DNA methylation) allowed TFAP2C to bind to the GPX1 promoter resulting in activation of GPX1 RNA and protein expression. Methylation of the GPX1 promoter was identified in approximately 20% of primary breast cancers and a highly significant correlation between TFAP2C and GPX1 expression was confirmed when considering only those tumors with an unmethylated promoter, whereas the related factor, TFAP2A, failed to demonstrate a correlation. The results demonstrate that TFAP2C regulates the expression of GPX1, which influences the redox state and sensitivity to oxidative stress induced by peroxides. Given the established role of GPX1 in breast cancer, the results provide an important mechanism for TFAP2C

  20. Review of magnetic features observed in (A,A')Ni 2B 2C solid solutions

    NASA Astrophysics Data System (ADS)

    Kuznietz, Moshe; Gonçalves, António P.; Almeida, Manuel

    2002-08-01

    The nickel-borocarbides ANi 2B 2C [A=Y, Ln (lanthanide), An(actinide)], crystallizing in the body-centred tetragonal LuNi 2B 2C-type structure, are classified according to the existence or coexistence of superconducting and antiferromagnetic states (AF). The magnetic features observed in polycrystalline (A,A')Ni 2B 2C solid solutions, adopting the same crystal structure, are reviewed and discussed. Published data on the magnetism in (A,Ln)Ni 2B 2C systems (ANi 2B 2C nonmagnetic, A=Y,La,Lu) indicate a gradual rise in the threshold content, x( m), in (Y 1- xLn x)Ni 2B 2C (Ln=Gd,Tb,Dy,Ho,Er) for the establishment of AF states. (A,A')Ni 2B 2C systems with magnetic end compounds show gradual variation in magnetic features when A and A' are both heavy Ln. The behaviour of (A,A')Ni 2B 2C systems of light A (Pr or U) and heavy A' (Dy or Tm) depends on the magnetic structures of the end compounds. In intermediate compositions, incomplete moment compensation in (Pr,Dy)Ni 2B 2C decreases TN, while different moment directions in the end compounds in (U,Dy)Ni 2B 2C lead to a directional frustration of ordered moments. Such a frustration in (U,Tm)Ni 2B 2C is related to different magnetic structures of the end compounds.

  1. ‘Valley Pearl’ table grape

    Technology Transfer Automated Retrieval System (TEKTRAN)

    ‘Valley Pearl’ is an early to mid-season, white seedless table grape (Vitis vinifera L.) suitable for commercial table grape production where V. vinifera can be grown. Significant characteristics of ‘Valley Pearl’ are its high and consistent fruit production on spur pruned vines and large round berr...

  2. 46 CFR 67.550 - Fee table.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 68 29.00 Fishery endorsement do 12.00 Registry endorsement do none Recreational endorsement do none.... For the convenience of the user, the revised text is set forth as follows: § 67.550 Fee table. Table... ......do 12.00 Registry endorsement ......do none Recreational endorsement ......do none Note:...

  3. Relating Functional Groups to the Periodic Table

    ERIC Educational Resources Information Center

    Struyf, Jef

    2009-01-01

    An introduction to organic chemistry functional groups and their ionic variants is presented. Functional groups are ordered by the position of their specific (hetero) atom in the periodic table. Lewis structures are compared with their corresponding condensed formulas. (Contains 5 tables.)

  4. Sand and Water Table Buying Guide.

    ERIC Educational Resources Information Center

    Morris, Susan

    1990-01-01

    Discusses the importance of sand and water play for young children. Provides a partial list of materials and equipment used to provide sensory experiences at sand and water tables. Offers a buying guide listing manufacturers of sand and water tables, product descriptions, and ordering information. (DR)

  5. A New Compression Method for FITS Tables

    NASA Technical Reports Server (NTRS)

    Pence, William; Seaman, Rob; White, Richard L.

    2010-01-01

    As the size and number of FITS binary tables generated by astronomical observatories increases, so does the need for a more efficient compression method to reduce the amount disk space and network bandwidth required to archive and down1oad the data tables. We have developed a new compression method for FITS binary tables that is modeled after the FITS tiled-image compression compression convention that has been in use for the past decade. Tests of this new method on a sample of FITS binary tables from a variety of current missions show that on average this new compression technique saves about 50% more disk space than when simply compressing the whole FITS file with gzip. Other advantages of this method are (1) the compressed FITS table is itself a valid FITS table, (2) the FITS headers remain uncompressed, thus allowing rapid read and write access to the keyword values, and (3) in the common case where the FITS file contains multiple tables, each table is compressed separately and may be accessed without having to uncompress the whole file.

  6. Pinch Experiments in a Table Top Generator

    SciTech Connect

    Pavez, Cristian; Moreno, Jose; Soto, Leopoldo; Tarifeno, Ariel

    2009-01-21

    The design and construction of a table top multipurpose capacitor bank of hundred of Joules and hundred of kiloAmperes conceived to be used in small scale Z-pinch experiments is reported. A recent result on a Z-pinch gas embedded discharge using hollow conical electrodes done in a similar table top generator is also presented.

  7. 21 CFR 890.3760 - Powered table.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered table. 890.3760 Section 890.3760 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3760 Powered table. (a)...

  8. 21 CFR 890.3750 - Mechanical table.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Mechanical table. 890.3750 Section 890.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3750 Mechanical table....

  9. 21 CFR 890.3760 - Powered table.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered table. 890.3760 Section 890.3760 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3760 Powered table. (a)...

  10. 21 CFR 890.3750 - Mechanical table.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Mechanical table. 890.3750 Section 890.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3750 Mechanical table....

  11. 21 CFR 890.3750 - Mechanical table.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Mechanical table. 890.3750 Section 890.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3750 Mechanical table....

  12. 21 CFR 890.3760 - Powered table.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered table. 890.3760 Section 890.3760 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3760 Powered table. (a)...

  13. Solar cell efficiency tables (Version 31)

    SciTech Connect

    Green, Martin A.; Emery, Keith; Hishikawa, Yoshihiro; Warta, Wilhelm

    2007-01-01

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since July, 2008 are reviewed. Copyright © 2007 John Wiley & Sons, Ltd.

  14. 21 CFR 890.3760 - Powered table.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Powered table. 890.3760 Section 890.3760 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3760 Powered table. (a)...

  15. 21 CFR 890.3750 - Mechanical table.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Mechanical table. 890.3750 Section 890.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3750 Mechanical table....

  16. 21 CFR 890.3750 - Mechanical table.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Mechanical table. 890.3750 Section 890.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3750 Mechanical table....

  17. 21 CFR 890.3760 - Powered table.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Powered table. 890.3760 Section 890.3760 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3760 Powered table. (a)...

  18. 21 CFR 168.180 - Table sirup.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... added for nutritional purposes and artificial sweeteners are not considered to be suitable ingredients... CONSUMPTION SWEETENERS AND TABLE SIRUPS Requirements for Specific Standardized Sweeteners and Table Sirups... percent soluble sweetener solids by weight and is prepared with or without added water. It may contain...

  19. 21 CFR 168.180 - Table sirup.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... added for nutritional purposes and artificial sweeteners are not considered to be suitable ingredients... CONSUMPTION SWEETENERS AND TABLE SIRUPS Requirements for Specific Standardized Sweeteners and Table Sirups... percent soluble sweetener solids by weight and is prepared with or without added water. It may contain...

  20. 21 CFR 168.180 - Table sirup.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... added for nutritional purposes and artificial sweeteners are not considered to be suitable ingredients... CONSUMPTION SWEETENERS AND TABLE SIRUPS Requirements for Specific Standardized Sweeteners and Table Sirups... percent soluble sweetener solids by weight and is prepared with or without added water. It may contain...

  1. 21 CFR 892.1980 - Radiologic table.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Radiologic table. 892.1980 Section 892.1980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1980 Radiologic table. (a) Identification. A...

  2. 21 CFR 892.1980 - Radiologic table.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Radiologic table. 892.1980 Section 892.1980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1980 Radiologic table. (a) Identification. A...

  3. 21 CFR 892.1980 - Radiologic table.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Radiologic table. 892.1980 Section 892.1980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1980 Radiologic table. (a) Identification. A...

  4. 21 CFR 892.1980 - Radiologic table.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radiologic table. 892.1980 Section 892.1980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1980 Radiologic table. (a) Identification. A...

  5. 21 CFR 892.1980 - Radiologic table.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Radiologic table. 892.1980 Section 892.1980 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1980 Radiologic table. (a) Identification. A...

  6. 14 CFR 26.5 - Applicability table.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT CONTINUED AIRWORTHINESS AND SAFETY IMPROVEMENTS FOR TRANSPORT CATEGORY AIRPLANES General § 26.5 Applicability table. Table... Subpart B EAPAS/FTS Subpart C widespread fatigue damage Subpart D fuel tankflammability Subpart...

  7. Designing a Table both Swinging and Stable

    ERIC Educational Resources Information Center

    Frederickson, Greg N.

    2008-01-01

    Howard Eves captured people's imagination by proposing a hinged table whose top could swing around to be either an equilateral triangle or a square. But is Eves's mathematically motivated design actually good furniture design? This paper identifies potential design flaws in that hinged table and proposes an intriguing new design. Both the original…

  8. Online Periodic Table: A Cautionary Note

    ERIC Educational Resources Information Center

    Izci, Kemal; Barrow, Lloyd H.; Thornhill, Erica

    2013-01-01

    The purpose of this study was (a) to evaluate ten online periodic table sources for their accuracy and (b) to compare the types of information and links provided to users. Limited studies have been reported on online periodic table (Diener and Moore 2011; Slocum and Moore in "J Chem Educ" 86(10):1167, 2009). Chemistry students'…

  9. CREATING INPUT TABLES FROM WAPDEG FOR RIP

    SciTech Connect

    K.G. Mon

    1998-08-10

    The purpose of this calculation is to create tables for input into RIP ver. 5.18 (Integrated Probabilistic Simulator for Environmental Systems) from WAPDEG ver. 3.06 (Waste Package Degradation) output. This calculation details the creation of the RIP input tables for TSPA-VA REV.00.

  10. Benchmarking in Universities: League Tables Revisited

    ERIC Educational Resources Information Center

    Turner, David

    2005-01-01

    This paper examines the practice of benchmarking universities using a "league table" approach. Taking the example of the "Sunday Times University League Table", the author reanalyses the descriptive data on UK universities. Using a linear programming technique, data envelope analysis (DEA), the author uses the re-analysis to…

  11. The Stream Table in Physical Geography Instruction.

    ERIC Educational Resources Information Center

    Wikle, Thomas A.; Lightfoot, Dale R.

    1997-01-01

    Outlines a number of activities to be conducted with a stream table (large wooden box filled with sediment and designed for water to pass through) in class. Activities illustrate such fluvial processes as stream meandering, erosion, transportation, and deposition. Includes a diagram for constructing a stream table. (MJP)

  12. Web Thermo Tables (WTT) - Professional Edition

    National Institute of Standards and Technology Data Gateway

    SRD 203 NIST/TRC Web Thermo Tables (WTT) - Professional Edition (Online Subscription)   WTT - Professional Edition, a Web version of the TRC Thermodynamic Tables, represents a complete collection of critically evaluated thermodynamic property data primarily for pure organic compounds. As of Nov. 2011, WTT contains information on 23999 compounds.

  13. Web Thermo Tables (WTT) - Lite Edition

    National Institute of Standards and Technology Data Gateway

    SRD 202 NIST/TRC Web Thermo Tables (WTT) - Lite Edition (Online Subscription)   WTT - Lite Edition, a Web version of the TRC Thermodynamic Tables, represents a collection of critically evaluated thermodynamic property data for 150 commonly-used (primarily organic) pure compounds.

  14. Some Reflections on the Periodic Table and Its Use.

    ERIC Educational Resources Information Center

    Fernelius, W. Conard

    1986-01-01

    Discusses early periodic tables; effect on the periodic table of atomic numbers; the periodic table in relation to electron distribution in the atoms of elements; terms and concepts related to the table; and the modern basis of the periodic table. Additional comments about these and other topics are included. (JN)

  15. Single-crystal X-ray and powder neutron diffraction of ThB 2C (ThB 2C-type)

    NASA Astrophysics Data System (ADS)

    Rogl, Peter; Fischer, Peter

    1989-02-01

    The crystal structure of ThB 2C was determined using single-crystal X-ray and powder neutron diffraction data. ThB 2C crystallizes in the rhombohedral space group R overline3m with a = 0.66761(23), c = 1.13760(31) nm, {c}/{a} = 1.704, V = 0.4391 nm 3, Z = 9 . X-ray intensity data were obtained from a four-circle diffractometer; the structure was solved by Patterson methods and refined by full-matrix least-squares calculation. R = {∑|ΔF|}/{∑|F o| } = 0.034 for an asymmetric set of 219 independent reflections (| Fo| > 2 σ( Fo)). Precise nonmetal atom parameters and bond distances have been derived from room-temperature neutron powder diffraction data employing the Rietveld-Young profile analysis method. The reliability value of the neutron refinement was RI = 0.067. The crystal structure of ThB 2C is a new structure type with slightly puckered 6 3-Th-metal layers alternating with nonmetal layers each composed of hexagons of boron atoms, the hexagons being linked by carbon atoms. Boron atoms are in a triangular prismatic metal surrounding of a tetrakaidekahedral coordination |Th 6B 2C 1|B, whereas carbon atoms occupy the center points of quadratic bipyramids |Th 4B 2|C. The crystal structure of ThB 2C derives from the AlB 2-type structure with carbon atoms entering the boron nets to form a 2∞ - (6B) · (6B(3C)) 2 layer.

  16. Draft genome sequence of Lactobacillus plantarum strains E2C2 and E2C5 isolated from human stool culture.

    PubMed

    Suryavanshi, Mangesh V; Paul, Dhiraj; Doijad, Swapnil P; Bhute, Shrikant S; Hingamire, Tejashri B; Gune, Rahul P; Shouche, Yogesh S

    2017-01-01

    Probiotic Lactobacillus species offer various health benefits, thus have been employed in treatment and prevention of various diseases. Due to the differences in the isolation source and the site of action, most of the lactobacilli tested in-vitro for probiotics properties fail to extend similar effects in-vivo. Consequently, the search of autochthonous, efficacious and probably population specific probiotics is a high priority in the probiotics research. In this regards, whole genome sequencing of as many Lactobacillus as possible will help to deepen our understanding of biology and their health effects. Here, we provide the genomic insights of two coherent oxalic acid tolerant Lactobacillus species (E2C2 and E2C5) isolated from two different healthy human gut flora. These two isolates were found to have higher tolerance towards oxalic acid (300 mM sodium oxalate). The draft genome of strain E2C2 consists of 3,603,563 bp with 3289 protein-coding genes, 94 RNA genes, and 43.99% GC content, while E2C5 contained 3,615,168 bp, 3293 coding genes (93.4% of the total genes), 95 RNA genes and 43.97% GC content. Based on 16S rRNA gene sequence analysis followed by in silico DNA-DNA hybridization studies, both the strains were identified as Lactobacillus plantarum belonging to family Lactobacillaceae within the phylum Firmicutes. Both the strains were genomically identical, sharing 99.99% CDS that showed 112 SNPs. Both the strains also exhibited deconjugation activity for the bile salts while genome analysis revealed that the L. plantarum strains E2C2 and E2C5 also have the ability to produce vitamins, biotin, alpha- and beta- glucosidase suggesting potential probiotic activities of the isolates. The description presented here is based on the draft genomes of strains E2C2 and E2C5 which are submitted to GenBank under the accession numbers LSST00000000.1 and LTCD00000000.1, respectively.

  17. 5-HT(2C) agonists as therapeutics for the treatment of schizophrenia.

    PubMed

    Rosenzweig-Lipson, Sharon; Comery, Thomas A; Marquis, Karen L; Gross, Jonathan; Dunlop, John

    2012-01-01

    The 5-HT(2C) receptor is a highly complex, highly regulated receptor which is widely distributed throughout the brain. The 5-HT(2C) receptor couples to multiple signal transduction pathways leading to engagement of a number of intracellular signaling molecules. Moreover, there are multiple allelic variants of the 5-HT(2C) receptor and the receptor is subject to RNA editing in the coding regions. The complexity of this receptor is further emphasized by the studies suggesting the utility of either agonists or antagonists in the treatment of schizophrenia. While several 5-HT(2C) agonists have demonstrated clinical efficacy in obesity (lorcaserin, PRX-000933), the focus of this review is on the therapeutic potential of 5-HT(2C) agonists in schizophrenia. To this end, the preclinical profile of 5-HT(2C) agonists from a neurochemical, electrophysiological, and a behavioral perspective is indicative of antipsychotic-like efficacy without extrapyramidal symptoms or weight gain. Recently, the selective 5-HT(2C) agonist vabicaserin demonstrated clinical efficacy in a Phase II trial in schizophrenia patients without weight gain and with low EPS liability. These data are highly encouraging and suggest that 5-HT(2C) agonists are potential therapeutics for the treatment of psychiatric disorders.

  18. Establishing a Research Center: The Minority Male Community College Collaborative (M2C3)

    ERIC Educational Resources Information Center

    Wood, J. Luke; Urias, Marissa Vasquez; Harris, Frank, III

    2016-01-01

    This chapter describes the establishment of the Minority Male Community College Collaborative (M2C3), a research and practice center at San Diego State University. M2C3 partners with community colleges across the United States to enhance access, achievement, and success among men of color. This chapter begins with a description of the national…

  19. Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family.

    PubMed

    Lu, Gang; Wang, Yibin

    2008-02-01

    1. The Type 2C protein phosphatases (PP2C) represent a highly conserved gene family in the mammalian genome. Recent studies have revealed that PP2C isoforms possess unique patterns of tissue and subcellular distribution associated with diverse functionalities. 2. The functional importance of PP2C isoforms has been shown in a plethora of signalling networks controlling cell differentiation, proliferation, growth, survival and metabolism. However, little is known about the regulatory mechanisms of PP2C at the molecular level. It is uncertain how PP2C isoforms are recruited, activated and inactivated during signalling transduction processes. 3. In the present paper, an overview of the critical functions of individual PP2C isoforms in regulating cellular signalling events will be provided, along with our perspectives on the challenging issues to be addressed. It is clear that a better understanding of the complex biological effects elicited by specific signalling pathways involving PP2C isoforms has great potential for developing novel therapies for a variety of human diseases, including cancer, diabetes and neural disorders, as well as cardiovascular diseases.

  20. A PP2C-1 Allele Underlying a Quantitative Trait Locus Enhances Soybean 100-Seed Weight.

    PubMed

    Lu, Xiang; Xiong, Qing; Cheng, Tong; Li, Qing-Tian; Liu, Xin-Lei; Bi, Ying-Dong; Li, Wei; Zhang, Wan-Ke; Ma, Biao; Lai, Yong-Cai; Du, Wei-Guang; Man, Wei-Qun; Chen, Shou-Yi; Zhang, Jin-Song

    2017-03-28

    Cultivated soybeans may lose some useful genetic locus during domestication. Introgression of genes from wild soybeans may broaden the genetic background and improve soybean agronomic traits. Here, through whole-genome sequencing of an RIL population derived from a cross between a wild soybean ZYD7 and a cultivated soybean HN44, and mapping of QTLs for seed weight, we discover that a phosphatase 2C-1 (PP2C-1) allele from wild soybean ZYD7 contributes to the increase of seed weight/size in transgenic plants. The PP2C-1 may achieve this function by enhancing cell size of integument and activating a subset of seed trait-related genes. The PP2C-1 was further found to associate with a transcription factor GmBZR1 and facilitate accumulation of dephosphorylated GmBZR1. In contrast, a PP2C-2 allele with variations of a few amino acids at N-terminus does not exhibit this function. Moreover, the GmBZR1 can promote seed weight/size in transgenic plants. Through analysis of cultivated soybean accessions, we find that 40% of the examined accessions do not have the PP2C-1 allele, suggesting that these accessions can be improved through introduction of the PP2C-1 allele. Our study identifies an elite allele PP2C-1, which can enhance seed weight/size. Manipulation of the allele by molecule-assisted breeding may increase production in soybean and other legumes/crops.

  1. Structural and electronic studies of metal carbide clusterfullerene Sc2C2@Cs-C72

    NASA Astrophysics Data System (ADS)

    Feng, Yongqiang; Wang, Taishan; Wu, Jingyi; Feng, Lai; Xiang, Junfeng; Ma, Yihan; Zhang, Zhuxia; Jiang, Li; Shu, Chunying; Wang, Chunru

    2013-07-01

    We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed.We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed. Electronic supplementary information (ESI) available: Experimental details, HPLC chromatogram, and DFT calculations. CCDC 917712. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3nr01739g

  2. Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

    PubMed Central

    González, Débora; Torrens, Marta; Farré, Magí

    2015-01-01

    Background. 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. Objectives. To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. Methods. Twenty healthy recreational 2C-B users (12 women) self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech), subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires), and cardiovascular effects (blood pressure and heart rate). Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. Conclusions. The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties. PMID:26543863

  3. The alpha(2C)-adrenergic receptor mediates hyperactivity of coloboma mice, a model of attention deficit hyperactivity disorder.

    PubMed

    Bruno, Kristy J; Hess, Ellen J

    2006-09-01

    Drugs that modify noradrenergic transmission such as atomoxetine and clonidine are increasingly prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). However, the therapeutic targets of these compounds are unknown. Norepinephrine is also implicated in the hyperactivity exhibited by coloboma mice. To identify the receptor subtypes that regulate the hyperactivity, coloboma mice were systematically challenged with adrenergic drugs. The beta-adrenergic receptor antagonist propranolol and the alpha(1)-adrenergic receptor antagonist prazosin each had little effect on the hyperactivity. Conversely, the alpha(2)-adrenergic receptor antagonist yohimbine reduced the activity of coloboma mice but not control mice. Subtype-selective blockade of alpha(2C)-, but not alpha(2A)- or alpha(2B)-adrenergic receptors, ameliorated hyperactivity of coloboma mice without affecting activity of control mice, suggesting that alpha(2C)-adrenergic receptors mediate the hyperactivity. Localized in the basal ganglia, alpha(2C)-adrenergic receptors are in a prime position to impact locomotor activity and are, therefore, potential targets of pharmacotherapy for ADHD.

  4. Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.

    PubMed

    Baker, Jennifer L; Dunn, Katherine A; Mingrone, Joseph; Wood, Bernard A; Karpinski, Beverly A; Sherwood, Chet C; Wildman, Derek E; Maynard, Thomas M; Bielawski, Joseph P

    2016-06-01

    Genes encoding nuclear receptors (NRs) are attractive as candidates for investigating the evolution of gene regulation because they (1) have a direct effect on gene expression and (2) modulate many cellular processes that underlie development. We employed a three-phase investigation linking NR molecular evolution among primates with direct experimental assessment of NR function. Phase 1 was an analysis of NR domain evolution and the results were used to guide the design of phase 2, a codon-model-based survey for alterations of natural selection within the hominids. By using a series of reliability and robustness analyses we selected a single gene, NR2C1, as the best candidate for experimental assessment. We carried out assays to determine whether changes between the ancestral and extant NR2C1s could have impacted stem cell pluripotency (phase 3). We evaluated human, chimpanzee, and ancestral NR2C1 for transcriptional modulation of Oct4 and Nanog (key regulators of pluripotency and cell lineage commitment), promoter activity for Pepck (a proxy for differentiation in numerous cell types), and average size of embryological stem cell colonies (a proxy for the self-renewal capacity of pluripotent cells). Results supported the signal for alteration of natural selection identified in phase 2. We suggest that adaptive evolution of gene regulation has impacted several aspects of pluripotentiality within primates. Our study illustrates that the combination of targeted evolutionary surveys and experimental analysis is an effective strategy for investigating the evolution of gene regulation with respect to developmental phenotypes.

  5. Deliberate and Crisis Action Planning and Execution Segments Increment 2A (DCAPES Inc 2A)

    DTIC Science & Technology

    2016-03-01

    Defense Acquisition Management Information Retrieval (DAMIR) UNCLASSIFIED DCAPES Inc 2A 2016 MAR UNCLASSIFIED 2 Table of Contents Common...M - Millions of Dollars MAIS - Major Automated Information System MAIS OE - MAIS Original Estimate MAR – MAIS Annual Report MDA - Milestone...Logistics DCAPES Inc 2A 2016 MAR UNCLASSIFIED 3 Lt Col Christopher Thrower 201 East Moore Drive Bldg 856, Room 154 Maxwell Air Force Base-Gunter AFB, AL

  6. Pivot tables for mortality analysis, or who needs life tables anyway?

    PubMed

    Wesley, David; Cox, Hugh F

    2007-01-01

    Actuarial life-table analysis has long been used by life insurance medical directors for mortality abstraction from clinical studies. Ironically, today's life actuary instead uses pivot tables to analyze mortality. Pivot tables (a feature/function in MS Excel) collapse various dimensions of data that were previously arranged in an "experience study" format. Summary statistics such as actual deaths, actual and expected mortality (usually measured in dollars), and calculated results such as actual to expected ratios, are then displayed in a 2-dimensional grid. The same analytic process, excluding the dollar focus, can be used for clinical mortality studies. For raw survival data, especially large datasets, this combination of experience study data and pivot tables has clear advantages over life-table analysis in both accuracy and flexibility. Using the SEER breast cancer data, we compare the results of life-table analysis and pivot-table analysis.

  7. 1998 Anthropometric Survey of U.S. Army Personnel: Bivariate Frequency Tables

    DTIC Science & Technology

    1990-05-01

    Back Length, Omphalion Males Females 37 38 39 Table 31 Table 32 Table 33 Chest Circumference/ Waist Circumference , Natural Indentation Males...Females 40 41 42 Table 34 Table 35 Table 36 Chest Circumference/ Waist Circumference , Omphalion Males Females 43 44 45 Table 37 Table...Table 191 Table 192 Vertical Chest Circumference/ Waist Circumference , Natural Indentation Males Females 199 200 201 Table 193 Table 194

  8. Molecular Determinants of the Human α2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

    PubMed Central

    Pullikuth, Ashok K.; Guidry, Jessie J.

    2015-01-01

    The human α2C-adrenergic receptor (α2C-AR) is localized intracellularly at physiologic temperature. Decreasing the environmental temperature strongly stimulates the receptor transport to the cell surface. In contrast, rat and mouse α2C-AR plasma membrane levels are less sensitive to decrease in temperature, whereas the opossum α2C-AR cell surface levels are not changed in these conditions. Structural analysis demonstrated that human α2C-AR has a high number of arginine residues in the third intracellular loop and in the C-terminus, organized as putative RXR motifs. Although these motifs do not affect the receptor subcellular localization at 37°C, deletion of the arginine clusters significantly enhanced receptor plasma membrane levels at reduced temperature. We found that this exaggerated transport of the human receptor is mediated by two functional arginine clusters, one in the third intracellular loop and one in the C-terminus. This effect is mediated by interactions with COPI vesicles, but not by 14-3-3 proteins. In rat α2C-AR, the arginine cluster from the third intracellular loop is shifted to the left due to three missing residues. Reinsertion of these residues in the rat α2C-AR restored the same temperature sensitivity as in the human receptor. Proteomic and coimmunoprecipitation experiments identified pontin as a molecule having stronger interactions with human α2C-AR compared with rat α2C-AR. Inhibition of pontin activity enhanced human receptor plasma membrane levels and signaling at 37°C. Our results demonstrate that human α2C-AR has a unique temperature-sensitive traffic pattern within the G protein–coupled receptor class due to interactions with different molecular chaperones, mediated in part by strict spatial localization of specific arginine residues. PMID:25680754

  9. GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity

    PubMed Central

    Magee, Michael S.; Kraft, Crystal L.; Abraham, Tara S.; Baybutt, Trevor R.; Marszalowicz, Glen P.; Li, Peng; Waldman, Scott A.

    2016-01-01

    ABSTRACT Adoptive T-cell therapy (ACT) is an emerging paradigm in which T cells are genetically modified to target cancer-associated antigens and eradicate tumors. However, challenges treating epithelial cancers with ACT reflect antigen targets that are not tumor-specific, permitting immune damage to normal tissues, and preclinical testing in artificial xenogeneic models, preventing prediction of toxicities in patients. In that context, mucosa-restricted antigens expressed by cancers exploit anatomical compartmentalization which shields mucosae from systemic antitumor immunity. This shielding may be amplified with ACT platforms employing antibody-based chimeric antigen receptors (CARs), which mediate MHC-independent recog-nition of antigens. GUCY2C is a cancer mucosa antigen expressed on the luminal surfaces of the intestinal mucosa in mice and humans, and universally overexpressed by colorectal tumors, suggesting its unique utility as an ACT target. T cells expressing CARs directed by a GUCY2C-specific antibody fragment recognized GUCY2C, quantified by expression of activation markers and cytokines. Further, GUCY2C CAR-T cells lysed GUCY2C-expressing, but not GUCY2C-deficient, mouse colorectal cancer cells. Moreover, GUCY2C CAR-T cells reduced tumor number and morbidity and improved survival in mice harboring GUCY2C-expressing colorectal cancer metastases. GUCY2C-directed T cell efficacy reflected CAR affinity and surface expression and was achieved without immune-mediated damage to normal tissues in syngeneic mice. These observations highlight the potential for therapeutic translation of GUCY2C-directed CAR-T cells to treat metastatic tumors, without collateral autoimmunity, in patients with metastatic colorectal cancer. PMID:27853651

  10. Characterization of the postjunctional α2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins

    PubMed Central

    Görnemann, T; von Wenckstern, H; Kleuser, B; Villalón, C M; Centurión, D; Jähnichen, S; Pertz, H H

    2007-01-01

    Background and purpose: In terms of postjunctional α2-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the α2-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. Experimental approach: α-adrenoceptor-mediated vasoconstriction was studied using a tissue bath protocol. mRNA profile and relative quantification of α2-adrenoceptor subtypes were determined in porcine pulmonary veins using reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. Key results: In porcine pulmonary veins, noradrenaline, phenylephrine (α1-adrenoceptor agonist), UK14304 and clonidine (α2-adrenoceptor agonists) caused concentration-dependent contractions. The rank order of agonist potency was: NA≈UK14304≈clonidine > phenylephrine. UK14304 responses were antagonised by MK912 (noncompetitive antagonist parameter pD'2: 10.1), rauwolscine (pKB: 9.5), yohimbine (pKB: 9.1), WB4101 (pKB: 8.7), ARC239 (pKB: 7.5), prazosin (pKB: 7.1) and BRL44408 (pKB: 7.0). Antagonist potencies fitted best with radioligand binding data (pKi) at the human recombinant α2C-adrenoceptor (r2 = 0.96, P = 0.0001). Correlation with α2B-adrenoceptors was lower (r2 = 0.74, P > 0.01) and no correlation was obtained with α2A-adrenoceptors. Moreover, RT-PCR studies in porcine pulmonary veins showed mRNA signals for α2A- and α2C-adrenoceptors, but not for α2B-adrenoceptors, whilst real-time PCR studies indicated a prominent expression of α2C-adrenoceptor mRNA. Conclusions and Implications: Postjunctional α2C-adrenoceptors mediated contraction in porcine pulmonary veins. α1-Adrenoceptors also seem to be present in this tissue. Since α2-adrenoceptor responsiveness is increased when pulmonary vascular tone is elevated, α2C-adrenoceptor antagonists may be beneficial in diseases such as pulmonary hypertension or congestive heart failure. PMID:17375080

  11. 50 CFR Table 2c to Part 660... - 2010, and Beyond, Open Access and Limited Entry Allocations by Species or Species Goup (weights...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false 2010, and Beyond, Open Access and Limited... Part 660, Subpart G—2010, and Beyond, Open Access and Limited Entry Allocations by Species or Species... Whiting Trawl, 2.2 mt for limited entry fixed gear, 2.5 mt for directed open access, 4.9 mt for...

  12. CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel

    PubMed Central

    Motsinger-Reif, Alison A.; Drobish, Amy; Winham, Stacey J.; McLeod, Howard L.; Carey, Lisa A.; Dees, E. Claire

    2013-01-01

    Paclitaxel is one of the most frequently used chemotherapeutic agents for the treatment of breast cancer patients. Using a candidate gene approach, we hypothesized that polymorphisms in genes relevant to the metabolism and transport of paclitaxel are associated with treatment efficacy and toxicity. Patient and tumor characteristics and treatment outcomes were collected prospectively for breast cancer patients treated with paclitaxel-containing regimens in the neoadjuvant setting. Treatment response was measured before and after each phase of treatment by clinical tumor measurement and categorized according to RECIST criteria, while toxicity data were collected from physician notes. The primary endpoint was achievement of clinical complete response (cCR) and secondary endpoints included clinical response rate (complete response + partial response) and grade 3+ peripheral neuropathy. The genotypes and haplotypes assessed were CYP1B1*3, CYP2C8*3, CYP3A4*1B/CYP3A5*3C, and ABCB1*2. A total of 111 patients were included in this study. Overall, cCR was 30.1 % to the paclitaxel component. CYP2C8*3 carriers (23/111, 20.7 %) had higher rates of cCR (55 % vs. 23 %; OR = 3.92 [95 % CI: 1.46–10.48], corrected p = 0.046). In the secondary toxicity analysis, we observed a trend toward greater risk of severe neuropathy (22 % vs. 8 %; OR = 3.13 [95 % CI: 0.89–11.01], uncorrected p = 0.075) in subjects carrying the CYP2C8*3 variant. Other polymorphisms interrogated were not significantly associated with response or toxicity. Patients carrying CYP2C8*3 are more likely to achieve clinical complete response from neoadjuvant paclitaxel treatment, but may also be at increased risk of experiencing severe peripheral neurotoxicity. PMID:22527101

  13. 40 CFR Table 3 to Subpart Ooo - Fugitive Emission Limits

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Nonmetallic Mineral Processing Plants Subpt. OOO, Table 3 Table 3 to Subpart OOO—Fugitive Emission Limits Table 3 to Subpart...

  14. Thalmann Algorithm Decompression Table Generation Software Design Document

    DTIC Science & Technology

    2010-09-01

    Decompression Table Generation Software Design Document Navy Experimental Diving Unit Author...TITLE (Include Security Classification) (U) THALMANN ALGORITHM DECOMPRESSION TABLE GENERATION SOFTWARE DESIGN DOCUMENT 12. PERSONAL AUTHOR(S...1 2. Decompression Table Generator (TBLP7R

  15. INTRODUCTION Outline of Round Tables Outline of Round Tables

    NASA Astrophysics Data System (ADS)

    Abarzhi, Snezhana I.; Sreenivasan, Katepalli R.

    2010-12-01

    The Second International Conference and Advanced School 'Turbulent Mixing and Beyond', TMB-2009, was held at the Abdus Salam International Centre for Theoretical Physics, (ICTP), Trieste, Italy on 27 July-7 August 2009. TMB-2009 united over 180 participants ranging from students to members of the National Academies of Sciences and Engineering, and including researchers at experienced and early stages of their carriers from leading scientific institutions in academia, national laboratories, corporations and industry worldwide. Responding to the community's inquiry and reaffirming the practices established at TMB-2007, two Round Tables were organized for the participants of TMB-2009 on 30 July 2009 and 6 August 2009 in the Oppenheimer Room at the Centre. The goals of the Round Tables were to encourage the information exchange among the members of the interdisciplinary and international TMB community, promote discussions regarding the state-of-the-art in TMB-related scientific areas, identify directions for frontier research, and articulate recommendations for future developments. This article is a summary of the collective work of the Round Table participants (listed alphabetically below by their last names), whose contributions form its substance and, as such, are greatly appreciated. Abarzhi, Snezhana I (University of Chicago, USA) Andrews, Malcolm (Los Alamos National Laboratory, USA) Belotserkovskii, Oleg (Institute for Computer Aided Design of the Russian Academy of Sciences, Russia) Bershadskii, Alexander (ICAR, Israel) Brandenburg, Axel (Nordita, Denmark) Chumakov, Sergei (Stanford University, USA) Desai, Tara (University of Milano-Bicocca, Italy) Galperin, Boris (University of South Florida, USA) Gauthier, Serge (Commissariat à l'Energie Atomique, France) Gekelman, Walter (University of California at Los Angeles, USA) Gibson, Carl (University of California at San Diego, USA) Goddard III, William A (California Institute of Technology, USA) Grinstein, Fernando

  16. Room-temperature synthesis of crystalline molybdenum and tungsten carbides, Mo sub 2 C and W sub 2 C, via chemical-reduction methods. Technical report

    SciTech Connect

    Zeng, D.; Hampden-Smith, M.J.

    1992-05-22

    The species MOC13(TBF)3, MOC14(THF)2 and WC14 have been reduced in THF solution with LiBEt3H to give black, homogeneous solutions. The black product could be separated from the other reaction by-products to give either a colloidal black solution or an agglomerated black precipitate. TEM of the dried colloidal solutions showed the presence of monodispersed 1-2nm sized particles which gave a broad electron diffraction rings corresponding to a d-spacing of -2.4 Anstrom Energy dispersive spectroscopy showed only the presence of Mo or W depending on which starting material was used. The black precipitates were shown to be agglomerates of the 1-2nm crystallites. X-ray powder diffraction data also showed a broad peak centered at 2.4 Anstrom for Mo2C and 2.3 Anstrom for W2C. On heating the peaks sharpened and a number of other lower intensity peaks emerged that were consistent with the presence of crystalline M2C (M = Mo, 500 deg C or W, 450 deg C) rather than the expected metal products. The identity Of M2C was confirmed by elemental analysis and by TGA oxidation experiments.

  17. A Classification Table for Achondrites

    NASA Technical Reports Server (NTRS)

    Chennaoui-Aoudjehane, H.; Larouci, N.; Jambon, A.; Mittlefehldt, D. W.

    2014-01-01

    Classifying chondrites is relatively easy and the criteria are well documented. It is based on mineral compositions, textural characteristics and more recently, magnetic susceptibility. It can be more difficult to classify achondrites, especially those that are very similar to terrestrial igneous rocks, because mineralogical, textural and compositional properties can be quite variable. Achondrites contain essentially olivine, pyroxenes, plagioclases, oxides, sulphides and accessory minerals. Their origin is attributed to differentiated parents bodies: large asteroids (Vesta); planets (Mars); a satellite (the Moon); and numerous asteroids of unknown size. In most cases, achondrites are not eye witnessed falls and some do not have fusion crust. Because of the mineralogical and magnetic susceptibility similarity with terrestrial igneous rocks for some achondrites, it can be difficult for classifiers to confirm their extra-terrestrial origin. We -as classifiers of meteorites- are confronted with this problem with every suspected achondrite we receive for identification. We are developing a "grid" of classification to provide an easier approach for initial classification. We use simple but reproducible criteria based on mineralogical, petrological and geochemical studies. We presented the classes: acapulcoites, lodranites, winonaites and Martian meteorites (shergottite, chassignites, nakhlites). In this work we are completing the classification table by including the groups: angrites, aubrites, brachinites, ureilites, HED (howardites, eucrites, and diogenites), lunar meteorites, pallasites and mesosiderites. Iron meteorites are not presented in this abstract.

  18. High TFAP2C/low CD44 expression is associated with an increased rate of pathologic complete response following neoadjuvant chemotherapy in breast cancer

    PubMed Central

    Spanheimer, Philip M.; Askeland, Ryan W.; Kulak, Mikhail V.; Wu, Tong; Weigel, Ronald J.

    2013-01-01

    Background In luminal breast cancer cell lines, TFAP2C regulates expression of key genes in the estrogen receptor–associated cluster and represses basal-associated genes including CD44. We examined the effect of TFAP2C overexpression in a basal cell line and characterized the expression of TFAP2C and CD44 in breast cancer specimens to determine if expression was associated with clinical response. Methods MDA-MB-231 breast cancer cells were treated with a TFAP2C-containing plasmid and evaluated for effects on CD44 expression. Pretreatment biopsy cores from patients receiving neoadjuvant chemotherapy for breast cancer were evaluated for TFAP2A, p53, TFAP2C, and CD44 expression by immunohistochemistry. Results Overexpression of TFAP2C in MDA-MB-231 cells resulted in decreased expression of CD44 mRNA and protein, P< 0.05. A pathologic complete response (pCR) following neoadjuvant chemotherapy was achieved in 17% of patients (4/23). Average expression for TFAP2C by immunohistochemistry in patients with a pCR was 93%, compared with 46% in patients with residual disease, P= 0.016; and in tumors that stained at ≥80% for TFAP2C, 4 of 9 (44%) achieved pCR, compared with 0 of 14 below 80%, P= 0.01. Additionally, in tumors that stained ≤80% for CD44, 4 of 10 (40%) achieved pCR, compared with 0 of 13 >80%, P = 0.02. In tumors that stained high for TFAP2C (≥80%) and low for CD44 (≥80%), 4 of 7 (57%) achieved pCR, compared with 0 of 16 in all other groups (P= 0.004). Conclusions TFAP2C repressed CD44 expression in basal-derived breast cancer. In primary breast cancer specimens, high TFAP2C and low CD44 expression were associated with pCR after neoadjuvant chemotherapy and could be predictive of tumors that have improved response to neoadjuvant chemotherapy. PMID:23764310

  19. Visualize Your Data with Google Fusion Tables

    NASA Astrophysics Data System (ADS)

    Brisbin, K. E.

    2011-12-01

    Google Fusion Tables is a modern data management platform that makes it easy to host, manage, collaborate on, visualize, and publish tabular data online. Fusion Tables allows users to upload their own data to the Google cloud, which they can then use to create compelling and interactive visualizations with the data. Users can view data on a Google Map, plot data in a line chart, or display data along a timeline. Users can share these visualizations with others to explore and discover interesting trends about various types of data, including scientific data such as invasive species or global trends in disease. Fusion Tables has been used by many organizations to visualize a variety of scientific data. One example is the California Redistricting Map created by the LA Times: http://goo.gl/gwZt5 The Pacific Institute and Circle of Blue have used Fusion Tables to map the quality of water around the world: http://goo.gl/T4SX8 The World Resources Institute mapped the threat level of coral reefs using Fusion Tables: http://goo.gl/cdqe8 What attendees will learn in this session: This session will cover all the steps necessary to use Fusion Tables to create a variety of interactive visualizations. Attendees will begin by learning about the various options for uploading data into Fusion Tables, including Shapefile, KML file, and CSV file import. Attendees will then learn how to use Fusion Tables to manage their data by merging it with other data and controlling the permissions of the data. Finally, the session will cover how to create a customized visualization from the data, and share that visualization with others using both Fusion Tables and the Google Maps API.

  20. The double sheath system and tendon gliding in zone 2C.

    PubMed

    Tang, J B

    1995-06-01

    Anatomical structures, the morphology of gliding tunnel, the gliding amplitude of tendons and the range of finger motion after sheath incision in zone 2C were studied in 40 fingers of ten preserved cadaver hands. The tendon of FDS in zone 2C courses around that of FDP, and FDS serves functionally as a second sheath for FDP. This "double sheath" system in zone 2C accounts for the poor results of tendon repair in zone 2C. The tendon repairs in zone 2C glide into zone 2D during finger flexion. Therefore, the condition of the gliding tunnel of zone 2D is also important to the function of tendon repairs in zone 2C. The range of motion was shown to be insignificantly influenced by partial incision of the A2 pulley, and this did not decrease the total strength of the sheath markedly. These suggest that partial incision or enlargement of the A2 pulley can be carried out for tendon repairs in zone 2C without causing mechanical problems of function.

  1. Design, synthesis, and application of OB2C combinatorial peptide and peptidomimetic libraries.

    PubMed

    Liu, Ruiwu; Shih, Tsung-Chieh; Deng, Xiaojun; Anwar, Lara; Ahadi, Sara; Kumaresan, Pappanaicken; Lam, Kit S

    2015-01-01

    The "one-bead two-compound" (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover "death ligands." Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3'-diaminobenzidine as a substrate. Two novel synthetic "death ligands" against Molt-4 cells were discovered using this OB2C library approach.

  2. MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders

    PubMed Central

    Harrington, Adam J; Raissi, Aram; Rajkovich, Kacey; Berto, Stefano; Kumar, Jaswinder; Molinaro, Gemma; Raduazzo, Jonathan; Guo, Yuhong; Loerwald, Kris; Konopka, Genevieve; Huber, Kimberly M; Cowan, Christopher W

    2016-01-01

    Numerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) – a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission. In addition, we find that MEF2C regulates E/I synapse density predominantly as a cell-autonomous, transcriptional repressor. Analysis of differential gene expression in Mef2c mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the Mef2c mutant mice displayed numerous behaviors reminiscent of autism, ID and SCZ, suggesting that perturbing MEF2C function in neocortex can produce autistic- and ID-like behaviors in mice. DOI: http://dx.doi.org/10.7554/eLife.20059.001 PMID:27779093

  3. Serotonin2c receptor constitutive activity: in vivo direct and indirect evidence and functional significance.

    PubMed

    Navailles, Sylvia; Lagière, Mélanie; Guthrie, Martin; De Deurwaerdère, Philippe

    2013-06-01

    Serotonin2c (5-HT2c) receptors are widely expressed in the central nervous system where they play a pivotal role in the regulation of neuronal network excitability. Along with this fundamental physiological function, 5-HT2c receptors are thought to be implicated in the pathophysiology of several neuropsychiatric disorders and have become a major pharmacological target for the development of improved treatments of these disorders. In the past decade, many studies have focused on the constitutive activity of 5-HT2c receptors and the therapeutic potential of drugs acting as inverse agonists. Although the constitutive activity of the 5-HT2c receptor has been clearly described in vitro, the transposition of this concept to living animals is often difficult to ascertain. Nevertheless, cumulating evidence has demonstrated the functional relevance of such property in regulating physiological systems in vivo both at the level of the central and peripheral nervous systems. The present review provides an update of the growing number of studies that show, by means of pharmacological tools, the participation of the constitutive activity of 5-HT2c receptors in the control of various biochemical and behavioural functions in vivo and emphasizes the functional organization of this constitutive control together with the phasic and tonic (involving the spontaneous release of 5-HT) modalities of the 5-HT2c receptor in the brain.

  4. Synthesis and evaluation of methylated arylazepine compounds for PET imaging of 5-HT(2c) receptors.

    PubMed

    Granda, Michael L; Carlin, Stephen M; Moseley, Christian K; Neelamegam, Ramesh; Mandeville, Joseph B; Hooker, Jacob M

    2013-02-20

    The serotonin 5-HT(2c) receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT(2c) in these diseases, a method for measuring 5-HT(2c )density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT(2c) but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT(2c) ligands, may be a suitable method for producing new radiotracers for 5-HT(2c). The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 ± 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT(2c) ligands as radiotracers for PET.

  5. Synthesis and Evaluation of Methylated Arylazepine Compounds for PET Imaging of 5-HT2c Receptors

    PubMed Central

    2012-01-01

    The serotonin 5-HT2c receptor is implicated in a number of diseases including obesity, depression, anxiety, and schizophrenia. In order to ascribe the role of 5-HT2c in these diseases, a method for measuring 5-HT2c density and function in vivo, such as with positron emission tomography (PET), must be developed. Many high-affinity and relatively selective ligands exist for 5-HT2c but cannot be accessed with current radiosynthetic methods for use as PET radiotracers. We propose that N-methylation of an arylazepine moiety, a frequent structural feature in 5-HT2c ligands, may be a suitable method for producing new radiotracers for 5-HT2c. The impact of N-methylation has not been previously reported. For the agonists that we selected herein, N-methylation was found to increase affinity up to 8-fold without impairing selectivity. Compound 5, an N-methylated azetidine-derived arylazepine, was found to be brain penetrant and reached a brain/blood ratio of 2.05:1. However, our initial test compound was rapidly metabolized within 20 min of administration and exhibited high nonspecific binding. N-Methylation, with 16 ± 3% isolated radiochemical yield (decay corrected), is robust and may facilitate screening other 5-HT2c ligands as radiotracers for PET. PMID:23421677

  6. Substrate analysis of Arabidopsis PP2C-type protein phosphatases.

    PubMed

    Umbrasaite, Julija; Schweighofer, Alois; Meskiene, Irute

    2011-01-01

    Protein phosphorylation by protein kinases can be reversed by the action of protein phosphatases. In plants, the Ser/Thr-specific phosphatases dominate among the protein phosphatase families with the type 2C protein phosphatases (PP2Cs) being the most abundant among them. PP2Cs are monomeric enzymes that require metal cations for their activity and are insensitive to known phosphatase inhibitors. PP2Cs were shown to counteract the mitogen-activated protein kinase (MAP kinase/MAPK) activities in plants and to regulate developmental and stress signaling pathways. Studies of PP2C activities can be performed in vitro using recombinant proteins. The potential substrates of PP2Cs can be tested for dephosphorylation by the phosphatase in vitro. We have found that the stress-induced PP2Cs from alfalfa and Arabidopsis interact with stress-activated MAPKs in yeast two-hybrid (Y2H) screens. Consequently, recombinant MAPKs were employed as substrates for dephosphorylation by selected PP2Cs from different family clusters. The members of the PP2C phosphatase family demonstrated specificity toward the substrate already in vitro, supporting the notion that protein phosphatases are specific enzymes. The PP2C from Arabidopsis thaliana cluster B, Arabidopsis PP2C-type phosphatase (AP2C1), and its homolog from Medicago sativa, Medicago PP2C-type phosphatase (MP2C), were able to dephosphorylate and inactivate MAPKs, whereas the ABSCISIC ACID (ABA)-INSENSITIVE 2 (ABI2) and HOMOLOGY TO ABI1 (HAB1) PP2Cs from the distinct Arabidopsis cluster A were not able to do so. The method described here can be used for the determination of PP2C protein activity and for studying the effect of mutations introduced into their catalytic domains.

  7. Preparation and electrochemical analysis of electrodeposited MnO2/C composite for advanced capacitor electrode

    NASA Astrophysics Data System (ADS)

    Kim, In-Tae; Kouda, Nobuo; Yoshimoto, Nobuko; Morita, Masayuki

    2015-12-01

    Mesoporous carbon (MPC) with uniform inner mesopore structure and high specific surface area prepared by an MgO-templated method has been employed for a substrate of MnO2/C composite. The MnO2/C composite was synthesized by anodic or cathodic electrodeposition of MnO2 from MnSO4 or KMnO4 precursor, respectively, on the MPC substrate. The XRD patterns of the composite confirmed that MnO2 was effectively deposited on the substrate under both anodic and cathodic electrodeposition processes. From the SEM images, sheet-like MnO2 was deposited by anodic deposition (a-MnO2/C) while needle-like MnO2 deposition was observed for the cathodic deposition (c-MnO2/C). The voltammetric experiments showed that the capacitive behavior of the composite depended on the preparation method. The difference in the specific capacitance between a-MnO2/C and c-MnO2/C is considered to be mainly due to the shape of MnO2 deposited on the MPC substrate. The electrochemical capacitance of c-MnO2/C was much higher than that of the substrate carbon. The observed capacitance increase in c-MnO2/C was attributed to the pseudo-capacitance of MnO2 that utilized effectively in controlled pore structure of MPC. The composite electrode, prepared by the cathodic deposition (c-MnO2/C), showed high specific capacitance and good durability for constant-current charge-discharge cycling.

  8. Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response.

    PubMed

    Halberstadt, Adam L; Geyer, Mark A

    2014-02-01

    N-benzyl substitution markedly enhances the affinity of phenethylamine hallucinogens at the 5-HT(2A) receptor. N-benzyl substituted derivatives of 2,5-dimethoxy-4-iodophenethylamine (2C-I), such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) and N-(2,3-methylenedioxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBMD), have appeared recently as designer drugs, but have not been characterized behaviorally. The head twitch response (HTR) is induced by 5-HT(2A) receptor activation in rats and mice, and is widely used as a behavioral proxy for hallucinogen effects in humans. Nevertheless, it is not clear whether phenethylamine hallucinogens reliably provoke this behavior. Hence, we investigated whether 2C-I, 25I-NBOMe and 25I-NBMD induce head twitches in C57BL/6J mice. The HTR was assessed using a head-mounted magnet and a magnetometer coil. 2C-I (1-10 mg/kg SC), 25I-NBOMe (0.1-1 mg/kg SC), and 25I-NBMD (1-10 mg/kg SC) induced the HTR. 25I-NBOMe displayed 14-fold higher potency than 2C-I, and the selective 5-HT(2A) antagonist M100,907 completely blocked the HTR induced by all three compounds. These findings show that phenethylamine hallucinogens induce the HTR by activating 5-HT(2A) receptors. Our results demonstrate that 25I-NBOMe is a highly potent derivative of 2C-I, confirming previous in vitro findings that N-benzyl substitution increases 5-HT(2A) affinity. Given the high potency and ease of synthesis of N-benzylphenethylamines, it is likely that the recreational use of these hallucinogens will become more widespread in the future.

  9. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    SciTech Connect

    Witek, Matthew; Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A.; Snook, Adam E.

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  10. Inactive alleles of cytochrome P450 2C19 may be positively selected in human evolution

    PubMed Central

    2014-01-01

    Background Cytochrome P450 CYP2C19 metabolizes a wide range of pharmacologically active substances and a relatively small number of naturally occurring environmental toxins. Poor activity alleles of CYP2C19 are very frequent worldwide, particularly in Asia, raising the possibility that reduced metabolism could be advantageous in some circumstances. The evolutionary selective forces acting on this gene have not previously been investigated. We analyzed CYP2C19 genetic markers from 127 Gambians and on 120 chromosomes from Yoruba, Europeans and Asians (Japanese + Han Chinese) in the Hapmap database. Haplotype breakdown was explored using bifurcation plots and relative extended haplotype homozygosity (REHH). Allele frequency differentiation across populations was estimated using the fixation index (FST) and haplotype diversity with coalescent models. Results Bifurcation plots suggested conservation of alleles conferring slow metabolism (CYP2C19*2 and *3). REHH was high around CYP2C19*2 in Yoruba (REHH 8.3, at 133.3 kb from the core) and to a lesser extent in Europeans (3.5, at 37.7 kb) and Asians (2.8, at −29.7 kb). FST at the CYP2C19 locus was low overall (0.098). CYP2C19*3 was an FST outlier in Asians (0.293), CYP2C19 haplotype diversity < = 0.037, p <0.001. Conclusions We found some evidence that the slow metabolizing allele CYP2C19*2 is subject to positive selective forces worldwide. Similar evidence was also found for CYP2C19*3 which is frequent only in Asia. FST is low at the CYP2C19 locus, suggesting balancing selection overall. The biological factors responsible for these selective pressures are currently unknown. One possible explanation is that early humans were exposed to a ubiquitous novel toxin activated by CYP2C19. The genetic adaptation took place within the last 10,000 years which coincides with the development of systematic agricultural practices. PMID:24690327

  11. Clinically significant CYP2C inhibition by noscapine but not by glucosamine.

    PubMed

    Rosenborg, S; Stenberg, M; Otto, S; Ostervall, J; Masquelier, M; Yue, Q-Y; Bertilsson, L; Eliasson, E

    2010-09-01

    Noscapine and glucosamine reportedly interact with warfarin. We investigated the effects of these drugs on various cytochrome P450 (CYP) activity markers. Twelve healthy subjects were phenotyped at baseline and during separate treatments with noscapine and glucosamine. Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Noscapine-dependent inhibition of CYP2C9 may explain the interaction with warfarin.

  12. The periodic table: icon and inspiration.

    PubMed

    Poliakoff, Martyn; Tang, Samantha

    2015-03-13

    To start this discussion meeting on the new chemistry of the elements held on 12 May 2014, Martyn Poliakoff, Foreign Secretary of the Royal Society, was invited to give the opening remarks. As a chemist and a presenter of the popular online video channel 'The periodic table of videos', Martyn communicates his personal and professional interest in the elements to the public, who in turn use these videos both as an educational resource and for entertainment purposes. Ever since Mendeleev's first ideas for the periodic table were published in 1869, the table has continued to grow as new elements have been discovered, and it serves as both icon and inspiration; its form is now so well established that it is recognized the world over as a symbol for science. This paper highlights but a few of the varied forms that the table can take, such as an infographic, which can convey the shortage of certain elements with great impact.

  13. Theodore William Richards and the Periodic Table

    ERIC Educational Resources Information Center

    Conant, James B.

    1970-01-01

    Discusses the contribution of Theodore Richards to the accurate determination of atomic weights of copper and other elements; his major contribution was to the building of the definitive periodic table of the elements. (BR)

  14. Toward an Organic Chemist's Periodic Table.

    ERIC Educational Resources Information Center

    Hall, H. K., Jr.

    1980-01-01

    An analogy between electron transfer reactions of the elements and those of organic molecules is offered. Examples of organic electron transfer reactions are presented. The rationale of constructing an organic chemists' periodic table is also discussed. (HM)

  15. Data Tables - Environments and Contaminants - Contaminated Lands

    EPA Pesticide Factsheets

    This document contains a table with the percentage of children ages 0 to 17 years living within one mile of Superfund and Corrective Action sites that may not have all human health protective measures in place in 2009.

  16. Ecological periodic tables: In principle and practice

    EPA Science Inventory

    The chemical periodic table, the Linnaean system of classification and the Hertzsprung-Russell diagram are iconic information organizing structure in chemistry, biology and astronomy, respectively, because they are simple, exceptionally useful and they foster the expansion of sci...

  17. Computation of group table alphanumeric display

    NASA Technical Reports Server (NTRS)

    Allen, G. P.; Evans, D. D.

    1971-01-01

    Computer program, using only group elements as input data, provides machine computation of group tables used for proving theorems and algorithms of finite groups. Program is written for second generation computers.

  18. Selective 5-hydroxytryptamine 2C receptor agonists derived from the lead compound tranylcypromine: identification of drugs with antidepressant-like action.

    PubMed

    Cho, Sung Jin; Jensen, Niels H; Kurome, Toru; Kadari, Sudhakar; Manzano, Michael L; Malberg, Jessica E; Caldarone, Barbara; Roth, Bryan L; Kozikowski, Alan P

    2009-04-09

    We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT(2C) agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT(2C) agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT(2C) receptor agonists with selectivity over both 5-HT(2A) and 5-HT(2B) receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT(2A) and 5-HT(2B), respectively (EC(50) = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.

  19. Selective 5-Hydroxytrytamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine – Identification of Drugs with Antidepressant-Like Action

    PubMed Central

    Cho, Sung Jin; Jensen, Niels H.; Kurome, Toru; Kadari, Sudhakar; Manzano, Michael L.; Malberg, Jessica E.; Caldarone, Barbara; Roth, Bryan L.; Kozikowski, Alan P.

    2009-01-01

    We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2-phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted benzene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37 with 120- and 14-fold selectivity over 5-HT2A and 5-HT2B, respectively (EC50 = 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10–60 mg/kg) decreased immobility time in the mouse forced swim test. PMID:19284718

  20. Structural relationship between a bacterial developmental protein and eukaryotic PP2C protein phosphatases.

    PubMed

    Adler, E; Donella-Deana, A; Arigoni, F; Pinna, L A; Stragler, P

    1997-01-01

    Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the phosphoprotein SpoIIAA triggers the cell type-specific activation of a sporulation transcription factor. Here we report that SpoIIE displays sequence similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and that residues common to these proteins are required for the function of both SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C protein phosphatases are structurally related, and reveal a striking formal similarity between the SpoIIAA regulatory circuit and that of mammalian mitochondrial pyruvate dehydrogenase. This similarity may reflect an evolutionarily conserved mechanism of biological regulation based on the interplay of His protein kinase-like Ser kinases and PP2C-like protein phosphatases.

  1. Synthesis of MoS(2)-C one-dimensional nanostructures with improved lithium storage properties.

    PubMed

    Zhang, Chaofeng; Wang, Zhiyu; Guo, Zaiping; Lou, Xiong Wen David

    2012-07-25

    Uniform one-dimensional (1D) MoS2-C composite nanostructures including nanorods and nanotubes have been produced through a sulfidation reaction in H2S flow using MoOx/polyaniline hybrid nanostructures as the precursor. These MoS2-C 1D nanostructures exhibit greatly enhanced electrochemical performance as anode materials for lithium-ion batteries. Typically, stable capacity retention of 776 mA h g(-1) can be achieved after 100 cycles for MoS2-C nanotubes. Even cycled at a high current density of 1000 mA g(-1), these structures can still deliver high capacities of 450-600 mA h g(-1). The unique 1D nanostructure and the extra carbon in the hybrid structure are beneficial to the greatly improved electrochemical performance of these MoS2-C nanocomposites.

  2. Solar Cell Efficiency Tables (Version 33)

    SciTech Connect

    Green, M. A.; Emery, K.; Hishikawa, Y.; Warta, W.

    2009-01-01

    Consolidated tables showing an extensive listing of the highest independently confirmed efficiencies for solar cells and modules are presented. Guidelines for inclusion of results into these tables are outlined and new entries since July 2008 are reviewed. Efficiencies are updated to the new reference solar spectrum tabulated in IEC 60904-3 Ed. 2 revised in April 2008 and an updated list of recognised test centres is also included.

  3. Online Periodic Table: A Cautionary Note

    NASA Astrophysics Data System (ADS)

    Izci, Kemal; Barrow, Lloyd H.; Thornhill, Erica

    2013-08-01

    The purpose of this study was (a) to evaluate ten online periodic table sources for their accuracy and (b) to compare the types of information and links provided to users. Limited studies have been reported on online periodic table (Diener and Moore 2011; Slocum and Moore in J Chem Educ 86(10):1167, 2009). Chemistry students' understanding of periodic table is vital for their success in chemistry, and the online periodic table has the potential to advance learners' understanding of chemical elements and fundamental chemistry concepts (Brito et al. in J Res Sci Teach 42(1):84-111, 2005). The ten sites were compared for accuracy of data with the Handbook of Chemistry and Physics (HCP, Haynes in CRC handbook of chemistry and physics: a ready-reference book of chemical and physical data. CRC Press, Boca Raton 2012). The 10 sites are the most visited periodic table Web sites available. Four different elements, carbon, gold, argon, and plutonium, were selected for comparison, and 11 different attributes for each element were identified for evaluating accuracy. A wide variation of accuracy was found among the 10 periodic table sources. Chemicool was the most accurate information provider with 66.67 % accuracy when compared to the HCP. The 22 types of information including meaning of name and use in industry and society provided by these sites were, also, compared. WebElements, "Chemicool", "Periodic Table Live", and "the Photographic Periodic Table of the Elements" were the most information providers, providing 86.36 % of information among the 10 Web sites. "WebElements" provides the most links among the 10 Web sites. It was concluded that if an individual teacher or student desires only raw physical data from element, the Internet might not be the best choice.

  4. IUPAC Periodic Table of the Isotopes

    USGS Publications Warehouse

    Holden, N.E.; Coplen, T.B.; Böhlke, J.K.; Wieser, M.E.; Singleton, G.; Walczyk, T.; Yoneda, S.; Mahaffy, P.G.; Tarbox, L.V.

    2011-01-01

    For almost 150 years, the Periodic Table of the Elements has served as a guide to the world of elements by highlighting similarities and differences in atomic structure and chemical properties. To introduce students, teachers, and society to the existence and importance of isotopes of the chemical elements, an IUPAC Periodic Table of the Isotopes (IPTI) has been prepared and can be found as a supplement to this issue.

  5. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    PubMed

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests.

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

    PubMed

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

    2005-10-15

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

  7. Phylodynamics of Hepatitis C Virus Subtype 2c in the Province of Córdoba, Argentina

    PubMed Central

    Mengarelli, Silvia; Farías, Adrián A.; Fay, Fabián; Pisano, María B.; Elbarcha, Osvaldo; Contigiani, Marta S.; Campos, Rodolfo H.

    2011-01-01

    The Hepatitis C Virus Genotype 2 subtype 2c (HCV-2c) is detected as a low prevalence subtype in many countries, except in Southern Europe and Western Africa. The current epidemiology of HCV in Argentina, a low-prevalence country, shows the expected low prevalence for this subtype. However, this subtype is the most prevalent in the central province of Córdoba. Cruz del Eje (CdE), a small rural city of this province, shows a prevalence for HCV infections of 5%, being 90% of the samples classified as HCV-2c. In other locations of Córdoba Province (OLC) with lower prevalence for HCV, HCV-2c was recorded in about 50% of the samples. The phylogenetic analysis of samples from Córdoba Province consistently conformed a monophyletic group with HCV-2c sequences from all the countries where HCV-2c has been sequenced. The phylogeographic analysis showed an overall association between geographical traits and phylogeny, being these associations significant (α = 0.05) for Italy, France, Argentina (places other than Córdoba), Martinique, CdE and OLC. The coalescence analysis for samples from CdE, OLC and France yielded a Time for the Most Common Recent Ancestor of about 140 years, whereas its demographic reconstruction showed a “lag” phase in the viral population until 1880 and then an exponential growth until 1940. These results were also obtained when each geographical area was analyzed separately, suggesting that HCV-2c came into Córdoba province during the migration process, mainly from Europe, which is compatible with the history of Argentina of the early 20th century. This also suggests that the spread of HCV-2c occurred in Europe and South America almost simultaneously, possibly as a result of the advances in medicine technology of the first half of the 20th century. PMID:21611129

  8. Structural determinants of D-cycloserine efficacy at the NR1/NR2C NMDA receptors

    PubMed Central

    Dravid, Shashank M.; Burger, Pieter B.; Prakash, Anand; Geballe, Matthew T.; Yadav, Roopali; Le, Phuong; Vellano, Kimberly; Snyder, James P.; Traynelis, Stephen F.

    2010-01-01

    We have studied relative efficacies of NR1 agonists glycine and D-cycloserine (DCS), and found efficacy to be dependent on the NR2 subunit. DCS shows partial agonism at NR1/NR2B but has higher relative efficacy than glycine at NR1/NR2C receptor. Molecular dynamics (MD) simulations of the NR1/NR2B and NR1/NR2C agonist binding domain dimer suggest only subtle differences in the interactions of DCS with NR1 binding site residues relative to glycine. The most pronounced differences were observed in the NR1/NR2C simulation between the orientation of helix F and G of the NR1 subunit. Interestingly, Helix F was previously proposed to influence receptor gating and to adopt an orientation depending on agonist efficacy. MD simulations and site-directed mutagenesis further suggest a role for residues at the agonist binding domain dimer interface in regulating DCS efficacy. To relate the structural rearrangements to receptor gating, we recorded single-channel currents from outside-out patches containing a single active NR1/NR2C receptor. DCS increased the mean open time and open probability of NR1/NR2C receptors in comparison to glycine. Maximum likelihood fitting of a gating model for NR1/NR2C receptor activation to the single channel data suggests that DCS specifically accelerates the rate constant governing a fast gating step and reduces the closing rate. These changes appear to reflect a decreased activation energy for a pregating step and increased stability of the open states. We suggest that the higher efficacy of DCS at NR1/NR2C receptors involves structural rearrangements at the dimer interface and an effect on NR1/NR2C receptor pre-gating conformational changes. PMID:20164358

  9. An ANFIS-based on B2C electronic commerce transaction

    NASA Astrophysics Data System (ADS)

    Lin, Juan; Liu, Chenlian; Guo, Yongning

    2014-10-01

    The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.

  10. An ANFIS-based on B2C electronic commerce transaction

    SciTech Connect

    Lin, Juan; Liu, Chenlian; Guo, Yongning

    2014-10-06

    The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.

  11. Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes

    PubMed Central

    Villagra, David; Goethe, John; Schwartz, Harold I; Szarek, Bonnie; Kocherla, Mohan; Gorowski, Krystyna; Windemuth, Andreas; Ruaño, Gualberto

    2011-01-01

    Aims We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores. Methods A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices. The data were used to create distributions and rankings of innate drug metabolism capacity to which individuals can be compared. Drug-specific indices are a combination of the drug metabolism indices with substrate-specific coefficients. Results The combinatory drug metabolism indices proved useful in positioning individuals relative to a population with regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific indices generate pharmacogenetic guidance of immediate clinical relevance, and can be further modified to incorporate covariates in particular clinical cases. Conclusions We believe that this combinatory approach represents an improvement over the current gene-by-gene reporting by providing greater scope while still allowing for the resolution of a single-gene index when needed. This method will result in novel clinical and research applications, facilitating the translation from pharmacogenomics to personalized medicine, particularly in psychiatry where many drugs are metabolized or activated by multiple CYP450 isoenzymes. PMID:21861665

  12. Counteractive roles of protein phosphatase 2C (PP2C) and a MAP kinase kinase homolog in the osmoregulation of fission yeast.

    PubMed

    Shiozaki, K; Russell, P

    1995-02-01

    With the goal of discovering the cellular functions of type 2C protein phosphatases, we have cloned and analyzed two ptc (phosphatase two C) genes, ptc2+ and ptc3+, from the fission yeast Schizosaccharomyces pombe. Together with the previously identified ptc1+ gene, the enzymes encoded by these genes account for approximately 90% of the measurable PP2C activity in fission yeast cells. No obvious growth defects result from individual disruptions of ptc genes, but a delta ptc1 delta ptc3 double mutant displays aberrant cell morphology and temperature-sensitive cell lysis that is further accentuated in a delta ptc1 delta ptc2 delta ptc3 triple mutant. These phenotypes are almost completely suppressed by the presence of osmotic stabilizers, strongly indicating that PP2C has an important role in osmoregulation. Genetic suppression of delta ptc1 delta ptc3 lethality identified two loci, mutations of which render cells hypersensitive to high-osmolarity media. One locus is identical to wis1+, encoding a MAP kinase kinase (MEK) homolog. The Wis1 sequence is most closely related to the Saccharomyces cerevisiae MEK encoded by PBS2, which is required for osmoregulation. These data indicate that divergent yeasts have functionally conserved MAP kinase pathways, which are required to increase intracellular osmotic concentrations in response to osmotic stress. Moreover, our observations implicate PP2C enzymes as also having an important role in signal transduction processes involved in osmoregulation, probably acting to negatively regulate the osmosensing signal that is transmitted through Wis1 MAP kinase kinase.

  13. Ultrasmall and phase-pure W2C nanoparticles for efficient electrocatalytic and photoelectrochemical hydrogen evolution

    NASA Astrophysics Data System (ADS)

    Gong, Qiufang; Wang, Yu; Hu, Qi; Zhou, Jigang; Feng, Renfei; Duchesne, Paul N.; Zhang, Peng; Chen, Fengjiao; Han, Na; Li, Yafei; Jin, Chuanhong; Li, Yanguang; Lee, Shuit-Tong

    2016-10-01

    Earlier research has been primarily focused on WC as one of the most promising earth-abundant electrocatalysts for hydrogen evolution reaction (HER), whereas the other compound in this carbide family--W2C--has received far less attention. Our theoretical calculations suggest that such a focus is misplaced and W2C is potentially more HER-active than WC. Nevertheless, the preparation of phase pure and sintering-free W2C nanostructures represents a formidable challenge. Here we develop an improved carburization method and successfully prepare ultrasmall and phase-pure W2C nanoparticles. When evaluated for HER electrocatalysis, W2C nanoparticles exhibit a small onset overpotential of 50 mV, a Tafel slope of 45 mV dec-1 and outstanding long-term cycling stability, which are dramatically improved over all existing WC-based materials. In addition, the integration of W2C nanoparticles with p-type Si nanowires enables highly active and sustainable solar-driven hydrogen production. Our results highlight the great potential of this traditionally non-popular material in HER electrocatalysis.

  14. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    SciTech Connect

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo; Hidalgo, Cecilia; Lavandero, Sergio

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  15. Association of CYP2C9*2 with Bosentan-Induced Liver Injury

    PubMed Central

    Markova, Svetlana M.; De Marco, Teresa; Bendjilali, Nasrine; Kobashigawa, Erin A.; Mefford, Joel; Sodhi, Jasleen; Le, Hoa; Zhang, Chenghong; Halladay, Jason; Rettie, Allan E.; Khojasteh, Cyrus; McGlothlin, Dana; Wu, Alan H.B.; Hsueh, Wen-Chi; Witte, John S.; Schwartz, Janice B.; Kroetz, Deanna L.

    2013-01-01

    Bosentan (Tracleer®) is an endothelin receptor antagonist prescribed for the treatment of pulmonary arterial hypertension (PAH). Its use is limited by drug-induced liver injury (DILI). To identify genetic markers of DILI, association analyses were performed on 56 Caucasian PAH patients receiving bosentan. Twelve functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, SLCO1B3) implicated in bosentan pharmacokinetics were tested for associations with ALT, AST and DILI. After adjusting for BMI, CYP2C9*2 was the only polymorphism associated with ALT, AST and DILI (β = 2.16, P = 0.024; β = 1.92, P = 0.016; OR 95% CI = 2.29 - ∞, P = 0.003, respectively). Bosentan metabolism in vitro by CYP2C9*2 was significantly reduced compared to CYP2C9*1 and was comparable to CYP2C9*3. These results suggest that CYP2C9*2 is a potential genetic marker for prediction of bosentan-induced liver injury and warrants investigation for the optimization of bosentan treatment. PMID:23863877

  16. First astronomical detection of the cumulene carbon chain molecule H2C6 in TMC-1.

    PubMed

    Langer, W D; Velusamy, T; Kuiper, T B; Peng, R; McCarthy, M C; Travers, M J; Kovacs, A; Gottlieb, C A; Thaddeus, P

    1997-05-01

    The cumulene carbenes are important components of hydrocarbon chemistry in low-mass star-forming cores. Here we report the first astronomical detection of the long-chain cumulene carbene H2C6 in the interstellar cloud TMC-1, from observations of two of its rotational transitions: J(K,K') = 7(1,7) --> 6(1,6) at 18.8 GHz and 8(1,8) --> 7(1,7) at 21.5 GHz, using NASA's Deep Space Network 70 m antenna at Goldstone, California. In addition we also observed the shorter cumulene carbene H2C4 at the same position. The fractional abundance of H2C6 relative to H2 is about 4.7 x 10(-11) and that of H2C4 is about 4.1 x 10(-9). The abundance of H2C6 is in fairly good agreement with gas-phase chemical models for young molecular cloud cores, but the abundance of H2C4 is significantly larger than predicted.

  17. Association of CYP2C9*2 with bosentan-induced liver injury.

    PubMed

    Markova, S M; De Marco, T; Bendjilali, N; Kobashigawa, E A; Mefford, J; Sodhi, J; Le, H; Zhang, C; Halladay, J; Rettie, A E; Khojasteh, C; McGlothlin, D; Wu, A H B; Hsueh, W-C; Witte, J S; Schwartz, J B; Kroetz, D L

    2013-12-01

    Bosentan (Tracleer) is an endothelin receptor antagonist prescribed for the treatment of pulmonary arterial hypertension (PAH). Its use is limited by drug-induced liver injury (DILI). To identify genetic markers of DILI, association analyses were performed on 56 Caucasian PAH patients receiving bosentan. Twelve functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, and SLCO1B3) implicated in bosentan pharmacokinetics were tested for associations with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and DILI. After adjusting for body mass index, CYP2C9*2 was the only polymorphism associated with ALT, AST, and DILI (β = 2.16, P = 0.024; β = 1.92, P = 0.016; odds ratio 95% CI = 2.29-∞, P = 0.003, respectively). Bosentan metabolism by CYP2C9*2 in vitro was significantly reduced compared with CYP2C9*1 and was comparable to that by CYP2C9*3. These results suggest that CYP2C9*2 is a potential genetic marker for prediction of bosentan-induced liver injury and warrants investigation for the optimization of bosentan treatment.

  18. A new 2D monolayer BiXene, M2C (M = Mo, Tc, Os).

    PubMed

    Sun, Weiwei; Li, Yunguo; Wang, Baotian; Jiang, Xue; Katsnelson, Mikhail I; Korzhavyi, Pavel; Eriksson, Olle; Di Marco, Igor

    2016-08-25

    The existence of BiXenes, a new family of 2D monolayers, is hereby predicted. Theoretically, BiXenes have 1H symmetry (P6[combining macron]m2) and can be formed from the 4d/5d binary carbides. As the name suggests, they are close relatives of MXenes, which instead have 1T symmetry (P3[combining macron]m1). The newly found BiXenes, as well as some new MXenes, are shown to have formation energies close to that of germanene, which suggests that these materials should be possible to be synthesised. Among them, we illustrate that 1H-Tc2C and 1T-Mo2C are dynamically stable at 0 K, while 1H-Mo2C, 1T-Tc2C, 1H-Os2C, and 1T-Rh2C are likely to be stabilised via strain or temperature. In addition, the nature of the chemical bonding is analysed, emphasizing that the covalency between the transition metal ions and carbon is much stronger in BiXenes than in MXenes. The emergence of BiXenes can not only open up a new era of conducting 2D monolayers, but also provide good candidates for carrier materials aimed at energy storage and spintronic devices that have already been unveiled in MXenes.

  19. Evidence for Circulation of Bovine Viral Diarrhoea Virus Type 2c in Ruminants in Southern Italy.

    PubMed

    Decaro, N; Lucente, M S; Lanave, G; Gargano, P; Larocca, V; Losurdo, M; Ciambrone, L; Marino, P A; Parisi, A; Casalinuovo, F; Buonavoglia, C; Elia, G

    2016-11-23

    Recently, bovine viral diarrhoea virus type 2c (BVDV-2c) was responsible for a severe outbreak in cattle in northern Europe. Here, we present the results of an epidemiological survey for pestiviruses in ruminants in southern Italy. Pooled serum samples were obtained from 997 bovine, 800 ovine, 431 caprine and eight bubaline farms, and pestiviral RNA was detected by molecular methods in 44 farms consisting of 16 cattle and one buffalo herds and of 21 sheep and six goat flocks. Twenty-nine and 15 farms were infected by BVDV-1 and BVDV-2 strains, respectively. BVDV-1 strains were recovered mainly from cattle and were heterogeneous, belonging to the subtypes 1b, 1u, 1e, 1g and 1h. In contrast, all BVDV-2 viruses but two were detected in sheep or goats and were characterized as BVDV-2c by sequence analysis of 5'UTR. These strains displayed high genetic identity to BVDV-2c circulating in cattle in northern Europe and were more distantly related to a BVDV-2c isolate recovered from a cattle herd in southern Italy more than 10 years before. The circulation of a BVDV-2c in small ruminants suggests the need for a continuous surveillance for the emergence of pestivirus-induced clinical signs in southern Italian farms.

  20. Decreased serotonin2C receptor responses in male patients with schizophrenia.

    PubMed

    Lee, Myung Ae; Jayathilake, Karuna; Sim, Min Young; Meltzer, Herbert Y

    2015-03-30

    Serotonin (5-HT)2C receptors in brain affect psychosis, reward, substance abuse, anxiety, other behaviors, appetite, body temperature, and other physiological measures. They also have been implicated in antipsychotic drug efficacy and side effects. We previously reported that the hyperthermia following administration of MK-212, a predominantly 5-HT(2C) receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT(2C) receptor responsiveness. We have now studied the responses to oral MK-212 and placebo in a larger sample of unmedicated male SCH (n = 69) and normal controls (CON) (n = 33), and assessed the influence of comorbid substance abuse (SA) on oral body temperature, behavioral responses, etc. The placebo-adjusted oral body temperature response to MK-212 was significantly lower in SCH compared to CON and not significantly different between the SCH with or without SA. Some behavioral responses to MK-212, e.g. self-rated feelings of increased anxiety, depression and decreased calmness, or good overall feeling, were significantly lower in the SCH patients compared to CON. These results add to the evidence for diminished 5-HT(2C) receptor responsiveness in SCH patients compared to CON and are consistent with reported association of HTR(2C) polymorphisms, leading to decreased expression or function of the HTR(2C) in patients with SCH.

  1. MicroRNA-23a reduces slow myosin heavy chain isoforms composition through myocyte enhancer factor 2C (MEF2C) and potentially influences meat quality.

    PubMed

    Shen, Linyuan; Chen, Lei; Zhang, Shunhua; Zhang, Yi; Wang, Jingyong; Zhu, Li

    2016-06-01

    MicroRNAs (miRNAs) are non-coding small RNAs that participate in the regulation of a variety of biological processes. Muscle fiber types were very important to meat quality traits, however, the molecular mechanism by which miRNAs regulate the muscle fiber type composition is not fully understood. The aim of this study was to investigate whether miRNA-23a can affect muscle fiber type composition. Luciferase reporter assays proved that miRNA-23a directly targets the 3' untranslated region (UTRs) of MEF2c. Overexpression of miRNA-23a significantly suppressed the expression of MEF2c both in mRNA and protein levels, thus caused down-regulation of the expression of some key downstream genes of MEF2c (PGC1-α, NRF1 and mtTFA). More interestingly, overexpression of miRNA-23a significantly restrained the myogenic differentiation and decreased the ratio of slow myosin heavy chain in myoblasts (p<0.05). Our findings hinted a novel role of miRNA-23a in the epigenetic regulation of meat quality via decreasing the ratio of slow myosin heavy chain isoforms.

  2. RADIOACTIVE CHEMICAL ELEMENTS IN THE ATOMIC TABLE.

    SciTech Connect

    HOLDEN, N.E.

    2005-08-13

    In the 1949 Report of the Atomic Weights Commission, a series of new elements were added to the Atomic Weights Table. Since these elements had been produced in the laboratory and were not discovered in nature, the atomic weight value of these artificial products would depend upon the production method. Since atomic weight is a property of an element as it occurs in nature, it would be incorrect to assign an atomic weight value to that element. As a result of that discussion, the Commission decided to provide only the mass number of the most stable (longest-lived) known isotope as the number to be associated with these entries in the Atomic Weights Table. As a function of time, the mass number associated with various elements has changed as longer-lived isotopes of a particular elements has been found in nature, or as improved half-life values of an element's isotopes might cause a shift in the longest-lived isotope from one mass number to another. In the 1957 Report of the Atomic Weights Commission, it was decided to discontinue the listing of the mass number in the Atomic Weights Table on the grounds that the kind of information supplied by the mass number is inconsistent with the primary purpose of the Table, i.e., to provide accurate values of ''these constants'' for use in chemical calculations. In addition to the Table of Atomic Weights, the Commission included an auxiliary Table of Radioactive Elements for the first time, where the entry would be the isotope of that element which was most stable, i.e., it had the longest known half-life. In their 1973 report, the Commission noted that the users of the Atomic Weights Table were dissatisfied with the omission of values in the Table for some elements and it was decided to reintroduce the mass number for elements. In their 1983 report, the Commission decided that radioactive elements were considered to lack a characteristic terrestrial isotopic composition, from which an atomic weight value could be calculated to

  3. Nrf2-Mediated HO-1 Induction Contributes to Antioxidant Capacity of a Schisandrae Fructus Ethanol Extract in C2C12 Myoblasts

    PubMed Central

    Kang, Ji Sook; Han, Min Ho; Kim, Gi-Young; Kim, Cheol Min; Kim, Byung Woo; Hwang, Hye Jin; Choi, Yung Hyun

    2014-01-01

    This study was designed to confirm the protective effect of Schisandrae Fructus, which are the dried fruits of Schisandra chinensis (Turcz.) Baill, against oxidative stress-induced cellular damage and to elucidate the underlying mechanisms in C2C12 myoblasts. Preincubating C2C12 cells with a Schisandrae Fructus ethanol extract (SFEE) significantly attenuated hydrogen peroxide (H2O2)-induced inhibition of growth and induced scavenging activity against intracellular reactive oxygen species (ROS) induced by H2O2. SFEE also inhibited comet tail formation and phospho-histone γH2A.X expression, suggesting that it prevents H2O2-induced cellular DNA damage. Furthermore, treating C2C12 cells with SFEE significantly induced heme oxygenase-1 (HO-1) and phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2). However, zinc protoporphyrin IX, a potent inhibitor of HO-1 activity, significantly reversed the protective effects of SFEE against H2O2-induced growth inhibition and ROS generation in C2C12 cells. Additional experiments revealed that the potential of the SFEE to induce HO-1 expression and protect against H2O2-mediated cellular damage was abrogated by transient transfection with Nrf2-specific small interfering RNA, suggesting that the SFEE protected C2C12 cells against oxidative stress-induced injury through the Nrf2/HO-1 pathway. PMID:25493944

  4. 40 CFR Appendix to Subpart Cc of... - Tables

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 11 2013-07-01 2013-07-01 false Tables Appendix to Subpart CC of Part... to Subpart CC of Part 63—Tables Table 1—Hazardous Air Pollutants Chemical name CAS No.a Benzene 71432... salts, esters, or derivatives. Table 2—Leak Definitions for Pumps and Valves Standard a Phase...

  5. 40 CFR Table 3 to Subpart Ooo - Fugitive Emission Limits

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 6 2011-07-01 2011-07-01 false Fugitive Emission Limits 3 Table 3 to... Processing Plants Subpt. OOO, Table 3 Table 3 to Subpart OOO—Fugitive Emission Limits Table 3 to Subpart OOO...; andPeriodic inspections of water sprays according to § 60.674(b) and § 60.676(b); and A...

  6. 21 CFR 880.6140 - Medical chair and table.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Devices § 880.6140 Medical chair and table. (a) Identification. A medical chair or table is a device intended for medical purposes that consists of a chair or table without wheels and not electrically powered... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical chair and table. 880.6140 Section...

  7. 40 CFR Table 2 to Subpart Aaaaa of... - Operating Limits

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 13 2010-07-01 2010-07-01 false Operating Limits 2 Table 2 to Subpart.... AAAAA, Table 2 Table 2 to Subpart AAAAA of Part 63—Operating Limits As required in § 63.7090(b), you must meet each operating limit in the following table that applies to you. For . . . You must . . ....

  8. [COSMOS motion design optimization in the CT table].

    PubMed

    Shang, Hong; Huang, Jian; Ren, Chao

    2013-03-01

    Through the CT Table dynamic simulation by COSMOS Motion, analysis the hinge of table and the motor force, then optimize the position of the hinge of table, provide the evidence of selecting bearing and motor, meanwhile enhance the design quality of the CT table and reduce the product design cost.

  9. 44 CFR 208.12 - Maximum Pay Rate Table.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... tables/SSR/HTML/0290.asp. (ii) Engineers and Canine Handlers. DHS uses the latest General Schedule pay... rates used in the initial Table can be found at http://www.opm.gov/oca/03tables/html/gs.asp. (iii...://www.opm.gov/oca/03tables/locdef.asp. (3) Review and update. DHS will review and update the...

  10. 44 CFR 208.12 - Maximum Pay Rate Table.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... tables/SSR/HTML/0290.asp. (ii) Engineers and Canine Handlers. DHS uses the latest General Schedule pay... rates used in the initial Table can be found at http://www.opm.gov/oca/03tables/html/gs.asp. (iii...://www.opm.gov/oca/03tables/locdef.asp. (3) Review and update. DHS will review and update the...

  11. 44 CFR 208.12 - Maximum Pay Rate Table.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... tables/SSR/HTML/0290.asp. (ii) Engineers and Canine Handlers. DHS uses the latest General Schedule pay... rates used in the initial Table can be found at http://www.opm.gov/oca/03tables/html/gs.asp. (iii...://www.opm.gov/oca/03tables/locdef.asp. (3) Review and update. DHS will review and update the...

  12. 44 CFR 208.12 - Maximum Pay Rate Table.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... tables/SSR/HTML/0290.asp. (ii) Engineers and Canine Handlers. DHS uses the latest General Schedule pay... rates used in the initial Table can be found at http://www.opm.gov/oca/03tables/html/gs.asp. (iii...://www.opm.gov/oca/03tables/locdef.asp. (3) Review and update. DHS will review and update the...

  13. 44 CFR 208.12 - Maximum Pay Rate Table.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... tables/SSR/HTML/0290.asp. (ii) Engineers and Canine Handlers. DHS uses the latest General Schedule pay... rates used in the initial Table can be found at http://www.opm.gov/oca/03tables/html/gs.asp. (iii...://www.opm.gov/oca/03tables/locdef.asp. (3) Review and update. DHS will review and update the...

  14. CRF Type 2 Receptors Mediate the Metabolic Effects of Ghrelin in C2C12 cells

    PubMed Central

    Gershon, Eran; Vale, Wylie W

    2014-01-01

    Objective Ghrelin is known to regulate appetite control and cellular metabolism. The Corticotropin-Releasing Factor (CRF) family is also known to regulate energy balance. In this study, we investigated the links between ghrelin and the CRF family in C2C12 cells, a mouse myoblast cell line. Design and methods C2C12 cells were treated with ghrelin in the presence or absence of CRF receptor antagonists and then subjected to different metabolic analyses. Results Ghrelin enhanced glucose uptake by C2C12 cells, induced GLUT4 translocation to the cell surface and decreased RBP4 expression. A CRF-R2 selective antagonist, anti-sauvagine-30, blocked ghrelin-induced glucose uptake, Ghrelin upregulated CRF-R2 but not CRF-R1 levels. Moreover, ghrelin-treated C2C12 cells displayed a cAMP and pERK activation in response to Ucn3, a CRF-R2 specific ligand, but not in response to CRF or stressin, CRF-R1 specific ligands. Ghrelin also induced UCP2 and UCP3 expression, which were blocked by anti-sauvagine-30. Ghrelin did not induce fatty acids uptake by C2C12 cells or ACC expression. Even though C2C12 cells clearly exhibited responses to ghrelin, the known ghrelin receptor, GHSR1a, was not detectable in C2C12 cells. Conclusion Our results suggest that, ghrelin plays a role in regulating muscle glucose and, raise the possibility that suppression of the CRF-R2 pathway might provide benefits in high ghrelin states. PMID:23804489

  15. Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals

    PubMed Central

    Isaza, Carlos; Henao, Julieta; Martínez, José H Isaza; Arias, Juan C Sepúlveda; Beltrán, Leonardo

    2007-01-01

    Background Omeprazole is metabolized by the hepatic cytochrome P450 (CYP) 2C19 enzyme to 5-hydroxyomeprazole. CYP2C19 exhibits genetic polymorphisms responsible for the presence of poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers (EMs). The defective mutations of the enzyme and their frequencies change between different ethnic groups; however, the polymorphism of the CYP2C19 gene has not been studied in Colombian mestizos. The aim of this study was to evaluate the genotype and phenotype status of CYP2C19 in Colombian mestizos, in order to contribute to the use of appropriate strategies of drug therapy for this population. Methods 189 subjects were genotyped using the multiplex SNaPshot technique and a subgroup of 44 individuals received 20 mg of omeprazole followed by blood collection at 3 hours to determine the omeprazole hydroxylation index by HPLC. Results 83.6%, 15.3% and 1.1% of the subjects were genotyped as EMs, IMs and PMs, respectively. The frequencies of the CYP2C29*1 and CYP2C19*2 alleles were 91.3% and 8.7% respectively whereas the *3, *4, *5, *6 and *8 alleles were not found. No discrepancies were found between the genotype and phenotype of CYP2C19. Conclusion The frequency of poor metabolizers (1.1%) in the Colombian mestizos included in this study is similar to that in Bolivian mestizos (1%) but lower than in Mexican-Americans (3.2%), West Mexicans (6%), Caucasians (5%) and African Americans (5.4%). The results of this study will be useful for drug dosage recommendations in Colombian mestizos. PMID:17623107

  16. Serotonergic modulation in neuropathy induced by oxaliplatin: effect on the 5HT2C receptor.

    PubMed

    Baptista-de-Souza, Daniela; Di Cesare Mannelli, Lorenzo; Zanardelli, Matteo; Micheli, Laura; Nunes-de-Souza, Ricardo Luiz; Canto-de-Souza, Azair; Ghelardini, Carla

    2014-07-15

    Fluoxetine has been shown to be effective in clinical and experimental studies of neuropathic pain. Besides to increase serotonin levels in the synaptic cleft, fluoxetine is able to block the serotonergic 5-HT2C receptor subtype, which in turn has been involved in the modulation of neuropathic pain. This study investigated the effect of repeated treatments with fluoxetine on the neuropathic nociceptive response induced by oxaliplatin and the effects of both treatments on 5-HT2C receptor mRNA expression and protein levels in the rat spinal cord (SC), rostral ventral medulla (RVM), midbrain periaqueductal gray (PAG) and amygdala (Amy). Nociception was assessed by paw-pressure, cold plate and Von Frey tests. Fluoxetine prevented mechanical hypersensitivity and pain threshold alterations induced by oxaliplatin but did not prevent the impairment in weight gain induced by this anticancer drug. Ex vivo analysis revealed that oxaliplatin increased the 5-HT2C receptor mRNA expression and protein levels in the SC and PAG. Similar effects were observed in fluoxetine-treated animals but only within the PAG. While oxaliplatin decreased the 5-HT2C mRNA expression levels in the Amy, fluoxetine increased their protein levels in this area. Fluoxetine impaired the oxaliplatin effects on the 5-HT2C receptor mRNA expression in the SC and Amy and protein levels in the SC. All treatments increased of 5-HT2C receptor mRNA expression and protein levels in the PAG. These results suggest that the effects of fluoxetine on neuropathic pain induced by oxaliplatin are associated with quantitative changes in the 5-HT2C receptors located within important areas of the nociceptive system.

  17. Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia.

    PubMed

    Martins, Luiza Conceição Amorim; Rocha, Natália Pessoa; Torres, Karen Cecília Lima; Dos Santos, Rodrigo Ribeiro; França, Giselle Sabrina; de Moraes, Edgar Nunes; Mukhamedyarov, Marat Alexandrovich; Zefirov, Andrey Lvovich; Rizvanov, Albert Anatolyevich; Kiyasov, Andrey Pavlovich; Vieira, Luciene Bruno; Guimarães, Melissa Monteiro; Yalvaç, Mehmet Emir; Teixeira, Antônio Lúcio; Bicalho, Maria Aparecida Camargo; Janka, Zoltán; Romano-Silva, Marco Aurélio; Palotás, András; Reis, Helton José

    2012-10-15

    Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well.

  18. Renewal Tables: Tables of Functions Arising in Renewal Theory.

    DTIC Science & Technology

    1981-09-01

    A 0 1 1 v AN I- _A -N0 A4 ’ V z -- N 3~~ 44271-.5 ItN - - - 4*N N *N523P- 23A - N2A 2 - -- - - -2 - -~ - - - - 3 -- o 4 N 4 ~’ A4 𔃾 .3 -3 4 a4 4- 44...34 -- - - - - - - - - - - - - - - - - - - 5521.5VS’ AZA A S A A V S A S O S 5 S V S S A 2 S ’ A (I4 06 Q 0 041004 10 - -A - t ~ -ON- 32~~ 4 j3 2 23 3...N ’a I -- -VA4~~U-2 - - -~ - - - �~~~~~~~~~~ -2 -- - - -4 - N2A -𔃾 4 4 N A 4 4 4 4 4 ~ 3 4 ~ S 24-.N9A4242N9A~~~~ 3 2 42 4 2N . U4 . NA 3 4. . AA

  19. 40 CFR Table 1 to Subpart Eeeeee... - Applicability of General Provisions to Subpart EEEEEE

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sources. 63.9(a), (b)(1), (b)(2), (b)(5), (c), (d), (h)(1)-(h)(3), (h)(5), (h)(6), (i), (j) Notification...), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12) (b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes. 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c)(3), (c)(4), (d) Reserved No. 63.2 Definitions Yes....

  20. 40 CFR Table 2 to Subpart Nnnnnn... - Applicability of General Provisions to Subpart NNNNNN

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... continuous emissions monitoring system. 63.9(h)(1)-(h)(3), (h)(6) Yes. 63.10(a), (b)(1), (b)(2)(xii), (b)(2...)(1), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12), (b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes. 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c)(3), (c)(4), (d) Reserved No. 63.2 Definitions Yes....

  1. 40 CFR Table 2 to Subpart Nnnnnn... - Applicability of General Provisions to Subpart NNNNNN

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... continuous emissions monitoring system. 63.9(h)(1)-(h)(3), (h)(6) Yes. 63.10(a), (b)(1), (b)(2)(xii), (b)(2...)(1), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12), (b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes. 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c)(3), (c)(4), (d) Reserved No. 63.2 Definitions Yes....

  2. 40 CFR Table 1 to Subpart Qqqqqq... - Applicability of General Provisions to Subpart QQQQQQ

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Subject Applies to subpart QQQQQQ? Explanation 63.1(a)(1), (a)(2), (a)(3), (a)(4), (a)(6), (a)(10)-(a)(12)(b)(1), (b)(3), (c)(1), (c)(2), (c)(5), (e) Applicability Yes 63.1(a)(5), (a)(7)-(a)(9), (b)(2), (c... Requirements Yes 63.6(e)(3)(i), (e)(3)(iii)-(e)(3)(ix), (f), (g), (h)(1), (h)(2), (h)(4),...

  3. CYP2C19 polymorphisms in acute coronary syndrome patients undergoing clopidogrel therapy in Zhengzhou population.

    PubMed

    Guo, Y M; Zhao, Z C; Zhang, L; Li, H Z; Li, Z; Sun, H L

    2016-05-25

    The goal of this study was to explore the polymorphisms of CYP2C19 (CYP2C19*2, CYP2C19*3) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on clopidogrel therapy in Zhengzhou city for guidance on clinical medication and reduction in the incidence of thromboembolic events. Two hundred and thirty-four ACS patients undergoing PCI were included in the study, including 171 males (average age = 64.13 ± 12 years) and 63 females (average age = 67.86 ± 10.20 years). Pyrosequencing analysis detected CYP2C19*2/*3 genotypes, which were divided into wild-type homozygous C/C, mutant heterozygous C/T, and mutant homozygous T/T. This study further explored the relationship between CYP2C19 polymorphisms and clopidogrel resistance in ACS patients. Gene frequencies of C/C, C/T, and T/T for CYP2C19*2 were 39.74, 50, and 10.26%, respectively, while the frequencies of C/C, C/T, and T/T for CYP2C19*3 were 94.02, 5.55, and 0.43%, respectively. According to platelet aggregation analysis, 203 cases normally responded to clopidogrel (86.8%) and 31 cases were clopidogrel resistant (13.2%). There was a correlation between gender and genotype distribution but none between age and genotype. In addition, patients with clopidogrel resistance were treated with ticagrelor antiplatelet therapy instead of clopidogrel, and only 1 case in all patients suffered thrombotic events during a 3-12 month follow-up. In conclusion, CYP2C19*2/*3 polymorphisms may be associated with clopidogrel resistance. Wild-type homozygote and single mutant heterozygote of CYP2C19*2/*3 can be given a normal dose of clopidogrel, while carriers with single mutant homozygote or double mutant heterozygote require ticagrelor antiplatelet therapy as an alternative.

  4. Apparatus for Teaching Physics: Air Table Experiments Without an Air Table.

    ERIC Educational Resources Information Center

    Minnix, Richard B.; Carpenter, D. Rae, Jr.

    1985-01-01

    Describes a new method and apparatus (consisting of a steel sheet, electromagnet, base, balls, and carbon paper) used to perform mechanics experiments which, until now, required use of an air table. Also compares the apparatus to an air table, explores its range of uses, and examines rotational dynamics. (DH)

  5. MTR, TRA603. INCANAL CONVEYOR TABLE, SAW TABLE, AND STORAGE AREA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. IN-CANAL CONVEYOR TABLE, SAW TABLE, AND STORAGE AREA RACKS. DISCHARGE MECHANISM. BLAW-KNOX 3150-579-1, 12/1950. INL INDEX NO. 531-603-40-098-100302, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. 40 CFR Table A to Subpart D of... - Table A to Subpart D of Part 192

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Table A to Subpart D of Part 192 A Table A to Subpart D of Part 192 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM...

  7. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease.

    PubMed

    Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A; Beelen, Dietrich W; Rebmann, Vera

    2016-10-27

    Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.

  8. Controlled growth of ultrathin Mo2C superconducting crystals on liquid Cu surface

    NASA Astrophysics Data System (ADS)

    Geng, Dechao; Zhao, Xiaoxu; Li, Linjun; Song, Peng; Tian, Bingbing; Liu, Wei; Chen, Jianyi; Shi, Dong; Lin, Ming; Zhou, Wu; Loh, Kian Ping

    2017-03-01

    Exhibiting thickness-dependent change in the critical temperature (T c) for the onset of superconductivity, Mo2C has emerged as an important new member in the family of two-dimensional atomic crystals. Controllable growth in terms of morphology and thickness is necessary to elucidate its intrinsic properties at the 2D limit. Here we demonstrate the chemical vapor deposition of ultrathin Mo2C crystals on liquid Cu surface where the morphology of the crystals can be controlled by tuning the carbon supersaturation. A unique staggered carbon vacancy ordering is discovered in Mo2C crystals having particular geometries. Thickness engineering of the crystal can be achieved by controlling the thickness of the Cu catalyst layer, which affords a facile route to grow ultrathin 2D samples. Ultrathin Mo2C crystals so obtained, have been characterized using aberration corrected scanning transmission electron microscopy annular dark field imaging, where the co-existence of both AA and AB stacking modes is observed. The high crystallinity of the Mo2C crystals synthesized in this work is attested by its characteristic sharp superconducting transition.

  9. Feature extraction of fog from multi-spectral infrared images of FY-2C geostationary satellite

    NASA Astrophysics Data System (ADS)

    Fan, Hong; Liu, Tang-you; Xu, Wu-jun

    2007-12-01

    FY-2C is geostationary satellite which is researched and developed by China. The primary advantage of geostationary satellite is the ability to characterize the radiance by obtaining numerous views of a specific earth location at any time of a day. This allows the production of a composite image to monitor short-term weather better. This paper describes a technique that uses multi-spectral infrared composite images of FY-2C to estimate particles emission and recognize fog at night. Radiations of particles detected by FY-2C at different wavelengths are analyzed combined with solar spectral irradiance. Having several spectral bands makes the analysis algorithms more complex and inefficient, thus it is important to choose the most respective bands. By applying Karhunen-Loeve transform to raw data of FY-2C, the infrared images are analyzed. By comparing Eigen image of these infrared images with visible image in the same batch, it is concluded that data of IR3 contribute to the first Eigen image mostly, which shows that the newly added IR3 channel of FY-2C has greatly improved the ability of distinguishing short time weather phenomena. Producing composite images by calculation and analysis at sequential period of time can clearly show changes of fog coverage. The improvement of the geostationary satellite instruments that have come to pass will encourage more widespread use of these derived products in the coming years.

  10. Ultrasmall and phase-pure W2C nanoparticles for efficient electrocatalytic and photoelectrochemical hydrogen evolution

    PubMed Central

    Gong, Qiufang; Wang, Yu; Hu, Qi; Zhou, Jigang; Feng, Renfei; Duchesne, Paul N.; Zhang, Peng; Chen, Fengjiao; Han, Na; Li, Yafei; Jin, Chuanhong; Li, Yanguang; Lee, Shuit-Tong

    2016-01-01

    Earlier research has been primarily focused on WC as one of the most promising earth-abundant electrocatalysts for hydrogen evolution reaction (HER), whereas the other compound in this carbide family—W2C—has received far less attention. Our theoretical calculations suggest that such a focus is misplaced and W2C is potentially more HER-active than WC. Nevertheless, the preparation of phase pure and sintering-free W2C nanostructures represents a formidable challenge. Here we develop an improved carburization method and successfully prepare ultrasmall and phase-pure W2C nanoparticles. When evaluated for HER electrocatalysis, W2C nanoparticles exhibit a small onset overpotential of 50 mV, a Tafel slope of 45 mV dec−1 and outstanding long-term cycling stability, which are dramatically improved over all existing WC-based materials. In addition, the integration of W2C nanoparticles with p-type Si nanowires enables highly active and sustainable solar-driven hydrogen production. Our results highlight the great potential of this traditionally non-popular material in HER electrocatalysis. PMID:27752046

  11. HDAC5 controls MEF2C-driven sclerostin expression in osteocytes.

    PubMed

    Wein, Marc N; Spatz, Jordan; Nishimori, Shigeki; Doench, John; Root, David; Babij, Philip; Nagano, Kenichi; Baron, Roland; Brooks, Daniel; Bouxsein, Mary; Pajevic, Paola Divieti; Kronenberg, Henry M

    2015-03-01

    Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by the gene SOST) inhibits osteoblastic bone formation and is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report that histone deacetylase 5 (HDAC5) negatively regulates sclerostin levels in osteocytes in vitro and in vivo. HDAC5 shRNA increases, whereas HDAC5 overexpression decreases SOST expression in the novel murine Ocy454 osteocytic cell line. HDAC5 knockout mice show increased levels of SOST mRNA, more sclerostin-positive osteocytes, decreased Wnt activity, low trabecular bone density, and reduced bone formation by osteoblasts. In osteocytes, HDAC5 binds and inhibits the function of MEF2C, a crucial transcription factor for SOST expression. Using chromatin immunoprecipitation, we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic enhancer 45 kB downstream from the transcription start site. HDAC5 deficiency increases SOST enhancer MEF2C chromatin association and H3K27 acetylation and decreases recruitment of corepressors NCoR and HDAC3. HDAC5 associates with and regulates the transcriptional activity of this enhancer, suggesting direct regulation of SOST gene expression by HDAC5 in osteocytes. Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes.

  12. Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).

    PubMed

    Shou, H; Eloyan, A; Lee, S; Zipunnikov, V; Crainiceanu, A N; Nebel, N B; Caffo, B; Lindquist, M A; Crainiceanu, C M

    2013-12-01

    This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

  13. Re-engineering of CYP2C9 to probe acid-base substrate selectivity.

    PubMed

    Tai, Guoying; Dickmann, Leslie J; Matovic, Nicholas; DeVoss, James J; Gillam, Elizabeth M J; Rettie, Allan E

    2008-10-01

    A common feature of many CYP2C9 ligands is their weak acidity. As revealed by crystallography, the structural basis for this behavior involves a charge-pairing interaction between an anionic moiety on the substrate and an active site R108 residue. In the present study we attempted to re-engineer CYP2C9 to better accept basic ligands by charge reversal at this key residue. We expressed and purified the R108E and R108E/D293N mutants and compared their ability with that of native CYP2C9 to interact with (S)-warfarin, diclofenac, pyrene, propranolol, and ibuprofen amine. As expected, the R108E mutant maintained all the native enzyme's pyrene 1-hydroxylation activity, but catalytic activity toward diclofenac and (S)-warfarin was abrogated. In contrast, the double mutant displayed much less selectivity in its behavior toward these control ligands. Neither of the mutants displayed significant enhancement of propranolol metabolism, and all three preparations exhibited a type II (inhibitor) rather than type I (substrate) spectrum with ibuprofen amine, although binding became progressively weaker with the single and double mutants. Collectively, these data underscore the importance of the amino acid at position 108 in the acid substrate selectivity of CYP2C9, highlight the accommodating nature of the CYP2C9 active site, and provide a cautionary note regarding facile re-engineering of these complex cytochrome P450 active sites.

  14. Electron affinity of trans-2-C4F8 from electron attachment-detachment kinetics.

    PubMed

    Van Doren, Jane M; Condon, Laura R; DeSouza-Goding, Antonet; Miller, Thomas M; Bopp, Joseph C; Viggiano, A A

    2010-01-28

    Electron attachment and detachment kinetics of 2-C(4)F(8) were studied over the temperature range 298-487 K with a flowing-afterglow Langmuir-probe apparatus. Only parent anions were formed in the attachment process throughout this temperature range. At the highest temperatures, thermal electron detachment of the parent anions is important. Analysis of the 2-C(4)F(8) gas showed an 82/18 mixture of trans/cis isomers. The kinetic data at the higher temperatures were used to determine the electron affinity EA(trans-2-C(4)F(8)) = 0.79 +/- 0.06 eV after making some reasonable assumptions. The same quantity was calculated using the G3(MP2) compound method, yielding 0.74 eV. The kinetic data were not sufficient to establish a reliable value for EA(cis-2-C(4)F(8)), but G3(MP2) calculations give a value 0.017 eV greater than that for trans-2-C(4)F(8). MP2 and density functional theory were used to study the structural properties of the neutral and anion isomers.

  15. Clinical Application of CYP2C19 Pharmacogenetics Toward More Personalized Medicine

    PubMed Central

    Lee, Su-Jun

    2013-01-01

    More than 30 years of genetic research on the CYP2C19 gene alone has identified approximately 2,000 reference single nucleotide polymorphisms (rsSNPs) containing 28 registered alleles in the P450 Allele Nomenclature Committee and the number continues to increase. However, knowledge of CYP2C19 SNPs remains limited with respect to biological functions. Functional information on the variant is essential for justifying its clinical use. Only common variants (minor allele frequency >5%) that represent CYP2C19*2, *3, *17, and others have been mostly studied. Discovery of new genetic variants is outstripping the generation of knowledge on the biological meanings of existing variants. Alternative strategies may be needed to fill this gap. The present study summarizes up-to-date knowledge on functional CYP2C19 variants discovered in phenotyped humans studied at the molecular level in vitro. Understanding the functional meanings of CYP2C19 variants is an essential step toward shifting the current medical paradigm to highly personalized therapeutic regimens. PMID:23378847

  16. Type 2C Protein Phosphatase Is a Key Regulator of Antiviral Extreme Resistance Limiting Virus Spread

    PubMed Central

    Seo, Jang-Kyun; Kwon, Sun-Jung; Cho, Won Kyong; Choi, Hong-Soo; Kim, Kook-Hyung

    2014-01-01

    Effector-triggered immunity (ETI) is an active immune response triggered by interactions between host resistance proteins and their cognate effectors. Although ETI is often associated with the hypersensitive response (HR), various R genes mediate an HR-independent process known as extreme resistance (ER). In the soybean-Soybean mosaic virus (SMV) pathosystem, the strain-specific CI protein of SMV functions as an effector of Rsv3-mediated ER. In this study, we used the soybean (Rsv3)-SMV (CI) pathosystem to gain insight into the molecular signaling pathway involved in ER. We used genome-wide transcriptome analysis to identify a subset of the type 2C protein phophatase (PP2C) genes that are specifically up-regulated in Rsv3-mediated ER. Gain-of-function analysis of the most significantly expressed soybean PP2C gene, GmPP2C3a, showed that ABA-induced GmPP2C3a functions as a key regulator of Rsv3-mediated ER. Our results further suggest that the primary mechanism of ER against viruses is the inhibition of viral cell-to-cell movement by callose deposition in an ABA signaling-dependent manner. PMID:25082428

  17. DRAGON, a GPI-anchored membrane protein, inhibits BMP signaling in C2C12 myoblasts.

    PubMed

    Kanomata, Kazuhiro; Kokabu, Shoichiro; Nojima, Junya; Fukuda, Toru; Katagiri, Takenobu

    2009-06-01

    Bone morphogenetic proteins (BMPs) induce osteoblastic differentiation of myoblasts via binding to cell surface receptors. Repulsive guidance molecules (RGMs) have been identified as BMP co-receptors. We report here that DRAGON/RGMb, a member of the RGM family, suppressed BMP signaling in C2C12 myoblasts via a novel mechanism. All RGMs were expressed in C2C12 cells that were differentiated into myocytes and osteoblastic cells, but RGMc was not detected in immature cells. In C2C12 cells, only DRAGON suppressed ALP and Id1 promoter activities induced by BMP-4 or by constitutively activated BMP type I receptors. This inhibition by DRAGON was dependent on the secretory form of the von Willbrand factor type D domain. DRAGON even suppressed BMP signaling induced by constitutively activated Smad1. Over-expression of neogenin did not alter the inhibitory capacity of DRAGON. Taken together, these findings indicate that DRAGON may be an inhibitor of BMP signaling in C2C12 myoblasts. We also suggest that a novel molecule(s) expressed on the cell membrane may mediate the signal transduction of DRAGON in order to suppress BMP signaling in C2C12 myoblasts.

  18. Critical behavior and magnetocaloric effect in layered structure Tb2C

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao; Matsuishi, Satoru; Hosono, Hideo

    2016-08-01

    The critical behavior and magnetocaloric effects of the layered structure Tb2C have been investigated using magnetization measurements around the Curie temperature. Analyzing temperature and field dependence of magnetization reveals that the Tb2C system undergoes a second-order magnetic phase transition at T C  =  266 K. Critical exponents obtained from modified Arrott, Kouvel-Fisher (KF) and scaling plots are consistent with each other. The critical exponents suggest that the magnetic phase transition in Tb2C can be described by the mean-field model. The exchange energy declines as J(r) ~ r -4.547, indicating that long-range interaction dominates the exchange interaction. Consequently, the field dependence magnetic entropy change (ΔS M) of Tb2C, calculated using the Maxwell relation, clearly demonstrates that the relationship between  -ΔS M and (H/T C)2/3 obeys the mean-field theory, supporting our conclusion of the ferromagnetism phase transition in Tb2C following the mean-field theory.

  19. Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C.

    PubMed

    Schwieger, Maike; Schüler, Andrea; Forster, Martin; Engelmann, Afra; Arnold, Michael A; Delwel, Ruud; Valk, Peter J; Löhler, Jürgen; Slany, Robert K; Olson, Eric N; Stocking, Carol

    2009-09-17

    Acute myelogenous leukemia is driven by leukemic stem cells (LSCs) generated by mutations that confer (or maintain) self-renewal potential coupled to an aberrant differentiation program. Using retroviral mutagenesis, we identified genes that generate LSCs in collaboration with genetic disruption of the gene encoding interferon response factor 8 (Irf8), which induces a myeloproliferation in vivo. Among the targeted genes, we identified Mef2c, encoding a MCM1-agamous-deficiens-serum response factor transcription factor, and confirmed that overexpression induced a myelomonocytic leukemia in cooperation with Irf8 deficiency. Strikingly, several of the genes identified in our screen have been reported to be up-regulated in the mixed-lineage leukemia (MLL) subtype. High MEF2C expression levels were confirmed in acute myelogenous leukemia patient samples with MLL gene disruptions, prompting an investigation of the causal interplay. Using a conditional mouse strain, we demonstrated that Mef2c deficiency does not impair the establishment or maintenance of LSCs generated in vitro by MLL/ENL fusion proteins; however, its loss led to compromised homing and invasiveness of the tumor cells. Mef2c-dependent targets included several genes encoding matrix metalloproteinases and chemokine ligands and receptors, providing a mechanistic link to increased homing and motility. Thus, MEF2C up-regulation may be responsible for the aggressive nature of this leukemia subtype.

  20. Canine parvovirus type 2c infection in a kitten associated with intracranial abscess and convulsions.

    PubMed

    Decaro, Nicola; Desario, Costantina; Amorisco, Francesca; Losurdo, Michele; Colaianni, Maria Loredana; Greco, Maria Fiorella; Buonavoglia, Canio

    2011-04-01

    A case of canine parvovirus type 2c (CPV-2c) infection in a 3-month-old feral kitten with a cerebral abscess and neurological disease is reported. The cat displayed ataxia and convulsions together with signs of gastroenteritis and profound alteration of the total and differential white blood cell counts. A parvovirus strain was detected by a TaqMan assay in the blood and faeces of the affected kitten, which was characterised as CPV by means of molecular assays but did not react with any of the CPV type-specific probes. By sequence and phylogenetic analyses of the VP2-protein gene, the CPV-2c strain displayed a non-coding mutation in the probe-binding region. Although the role of CPV-2c in this particular case is unclear, it is possible that it predisposed the kitten to the clinical signs seen. Continuous surveillance is needed to monitor future spreading of this CPV-2c mutant, and any associated clinical signs, in the dog and cat population.

  1. STILTS: Starlink Tables Infrastructure Library Tool Set

    NASA Astrophysics Data System (ADS)

    Taylor, Mark

    2011-05-01

    The STIL Tool Set is a set of command-line tools based on STIL, the Starlink Tables Infrastructure Library. It deals with the processing of tabular data; the package has been designed for, but is not restricted to, astronomical tables such as object catalogues. Some of the tools are generic and can work with multiple formats (including FITS, VOTable, CSV, SQL and ASCII), and others are specific to the VOTable format. In some ways, STILTS forms the command-line counterpart of the GUI table analysis tool TOPCAT. The package is robust, fully documented, and designed for efficiency, especially with very large datasets. Facilities offered include: format conversioncrossmatchingplottingcolumn calculation and rearrangementrow selectionsdata and metadata manipulation and displaysortingstatistical calculationshistogram calculationdata validationVO service accessA powerful and extensible expression language is used for specifying data calculations. These facilities can be put together in very flexible and efficient ways. For tasks in which the data can be streamed, the size of table STILTS can process is effectively unlimited. For other tasks, million-row tables usually do not present a problem. STILTS is written in pure Java (J2SE1.5 or later), and can be run from the command line or from Jython, or embedded into java applications. It is released under the GPL.

  2. Harnessing Knowledge on Very Important Pharmacogenes CYP2C9 and CYP2C19 Variation for Precision Medicine in Resource-Limited Global Conflict Zones.

    PubMed

    Barlas, İbrahim Ömer; Sezgin, Orhan; Dandara, Collet; Türköz, Gözde; Yengel, Emre; Cindi, Zinhle; Ankaralı, Handan; Şardaş, Semra

    2016-10-01

    Pharmacogenomics harnesses the utility of a patient's genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to neighboring countries in the Middle East. The growing permanence of refugees and mass migrations is a call to shift our focus in the life sciences community from old models of pharmaceutical innovation. These seismic social changes demand faster decisions for "population-to-population bridging," whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/refugee populations whose profiles are dynamic, such as in the Eastern Mediterranean region at present. Thus, it is important to characterize and report on the prevalence of pharmacogenes that affect commonly used medications and predict if population changes may call for attention to particular differences that may impact health of patients. Thus, we report here on four single-nucleotide polymorphism (SNP) variations in CYP2C9 and CYP2C19 genes among Mersin-Turkish healthy volunteers in the Mersin Province in the Eastern Mediterranean region that is currently hosting a vast number of migrant populations from Syria. Both CYP2C9 and CYP2C19 are very important pharmacogene molecular targets. We compare and report here on the observed SNP genetic variation in our sample with data on 12 world populations from dbSNP and discuss the feasibility of forecasting the pharmacokinetics of drugs utilized by migrant

  3. Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats.

    PubMed

    Shimokawa, Takaomi; Tsutsui, Hidenobu; Miura, Takeshi; Nishinaka, Toru; Terada, Tomoyuki; Takama, Masashi; Yoshida, Shuhei; Tanba, Takao; Tojo, Ayumi; Yamagata, Masayo; Yukimura, Tokihito

    2016-06-15

    Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.

  4. A genetic variant of HTR2C may play a role in the manifestation of Tourette syndrome.

    PubMed

    Dehning, Sandra; Müller, Norbert; Matz, Judith; Bender, Andreas; Kerle, Irina; Benninghoff, Jens; Musil, Richard; Spellmann, Ilja; Bondy, Brigitta; Möller, Hans-Juergen; Riedel, Michael; Zill, Peter

    2010-02-01

    Gilles de la Tourette syndrome (GTS) (MIM 137580) is a complex neuropsychiatric disorder probably originating from a disturbed interplay of several neurotransmitter systems in the prefrontal-limbic-basal ganglia loop. Polygenetic multifactorial inheritance has been postulated; nevertheless, no confirmed susceptible genes have been identified yet. As neuroimaging studies allude to dopaminergic and serotonergic dysfunction in GTS and serotonin as an important factor for dopamine release, genotyping of common polymorphisms in the serotonergic receptor (HTR1A: C-1019G; HTR2A: T102C, His452Tyr, A-1438G; HTR2C: C-759T, G-697C) and transporter genes (SLC6A4) was carried out in 87 patients with GTS, compared with 311 matched controls. We found a nominally significant association between both polymorphisms in the HTR2C and the GTS, which was more pronounced in male patients. Analysis of the further serotonergic polymorphisms did not reveal any significant result. A modified function of these promoter polymorphisms may contribute to the complex interplay of serotonin and dopamine and then to the manifestation of GTS.

  5. MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive nonfluent aphasia.

    PubMed

    Allegri, Ricardo F; Bartoloni, Leonardo; Iturry, Mónica; Romero, Carlos; Begué, Christián; Sevlever, Gustavo; Taratuto, Ana Lía

    2014-01-01

    We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype by histotyping.

  6. Magnetic properties of Y1- xGdxCo2B2C series of borocarbides

    NASA Astrophysics Data System (ADS)

    Bud'ko, S. L.; Giordanengo, B.; Sulpice, A.; Fontes, M. B.; Baggio-Saitovitch, E. M.

    1995-04-01

    Magnetic properties of Y1- xGdxCo2B2C series of compounds were studied. Two magnetically ordered phases were observed for 0.7 ≤ x ≤ 1. Change of the magnetic ordering temperatures T 1 and T 2 with the Gd concentration is argued to be related to the dilution of magnetic Gd by nonmagnetic Y and to the reduction of the distance between ( Y1- xGdx) C planes. However, significant contribution to the changes in T 1 between pure GdNi2B2C and GdCo2B2C samples is suggested to be due to the different 3 d band filling in these compounds.

  7. Catalytic mechanism and kinase interactions of ABA-signaling PP2C phosphatases.

    PubMed

    Zhou, X Edward; Soon, Fen-Fen; Ng, Ley-Moy; Kovach, Amanda; Suino-Powell, Kelly M; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H Eric; Melcher, Karsten

    2012-05-01

    Abscisic acid (ABA) is an essential hormone that controls plant growth, development and responses to abiotic stresses. ABA signaling is mediated by type 2C protein phosphatases (PP2Cs), including HAB1 and ABI2, which inhibit stress-activated SnRK2 kinases and whose activity is regulated by ABA and ABA receptors. Based on biochemical data and our previously determined crystal structures of ABI2 and the SnRK2.6-HAB1 complex, we present the catalytic mechanism of PP2C and provide new insight into PP2C-SnRK2 interactions and possible roles of other SnRK2 kinases in ABA signaling.

  8. Selective deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) surfaces

    NASA Astrophysics Data System (ADS)

    Xiong, Ke; Yu, Weiting; Chen, Jingguang G.

    2014-12-01

    The selective deoxygenation of aldehydes and alcohols without cleaving the Csbnd C bond is crucial for upgrading bio-oil and other biomass-derived molecules to useful fuels and chemicals. In this work, propanal, 1-propanol, furfural and furfuryl alcohol were selected as probe molecules to study the deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) prepared over a Mo(1 1 0) surface. The reaction pathways were investigated using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS). The deoxygenation of propanal and 1-propanol went through a similar intermediate (propoxide or η2(C,O)-propanal) to produce propene. The deoxygenation of furfural and furfuryl alcohol produced a surface intermediate similar to adsorbed 2-methylfuran. The comparison of these results revealed the promising deoxygenation performance of Mo2C, as well as the effect of the furan ring on the selective deoxygenation of the Cdbnd O and Csbnd OH bonds.

  9. D2d(23)-C84 versus Sc2C2@D2d(23)-C84: Impact of Endohedral Sc2C2 Doping on Chemical Reactivity in the Photolysis of Diazirine.

    PubMed

    Yamada, Michio; Tanabe, Yukiko; Dang, Jing-Shuang; Sato, Satoru; Mizorogi, Naomi; Hachiya, Makoto; Suzuki, Mitsuaki; Abe, Tsuneyuki; Kurihara, Hiroki; Maeda, Yutaka; Zhao, Xiang; Lian, Yongfu; Nagase, Shigeru; Akasaka, Takeshi

    2016-12-21

    We compared the chemical reactivity of D2d(23)-C84 and that of Sc2C2@D2d(23)-C84, both having the same carbon cage geometry, in the photolysis of 2-adamantane-2,3'-[3H]-diazirine, to clarify metal-atom doping effects on the chemical reactivity of the carbon cage. Experimental and computational studies have revealed that the chemical reactivity of the D2d(23)-C84 carbon cage is altered drastically by endohedral Sc2C2 doping. The reaction of empty D2d(23)-C84 with the diazirine under photoirradiation yields two adamantylidene (Ad) adducts. NMR spectroscopic studies revealed that the major Ad monoadduct (C84(Ad)-A) has a fulleroid structure and that the minor Ad monoadduct (C84(Ad)-B) has a methanofullerene structure. The latter was also characterized using X-ray crystallography. C84(Ad)-A is stable under photoirradiation, but it interconverted to C84(Ad)-B by heating at 80 °C. In contrast, the reaction of endohedral Sc2C2@D2d(23)-C84 with diazirine under photoirradiation affords four Ad monoadducts (Sc2C2@C84(Ad)-A, Sc2C2@C84(Ad)-B, Sc2C2@C84(Ad)-C, and Sc2C2@C84(Ad)-D). The structure of Sc2C2@C84(Ad)-C was characterized using X-ray crystallography. Thermal interconversion of Sc2C2@C84(Ad)-A and Sc2C2@C84(Ad)-B to Sc2C2@C84(Ad)-C was also observed. The reaction mechanisms of the Ad addition and thermal interconversion were elucidated from theoretical calculations. Calculation results suggest that C84(Ad)-B and Sc2C2@C84(Ad)-C are thermodynamically favorable products. Their different chemical reactivities derive from Sc2C2 doping, which raises the HOMO and LUMO levels of the D2d(23)-C84 carbon cage.

  10. Hepatic cytochrome P450 enzymes belonging to the CYP2C subfamily from an Australian marsupial, the koala (Phascolarctos cinereus).

    PubMed

    Jones, Brett R; El-Merhibi, Adaweyah; Ngo, Suong N T; Stupans, Ieva; McKinnon, Ross A

    2008-09-01

    Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a diverse array of xenobiotics and endogenous substrates. We have previously reported that the obligate Eucalyptus feeder koala (Phascolarctos cinereus) exhibits a higher hepatic CYP2C activity as compared to non-Eucalyptus feeders human or rat, with stimulation of CYP2C activity by cineole. In the present study, we examine CYP2C expression by immunohistochemistry and describe the identification and cloning of koala CYP2Cs. Utilising anti-rat CYP2C6 antibody, the expression of CYP2C was found to be uniform across the hepatic sections, being consistent with that observed in human and rat. Two 1647 and 1638 bp koala liver CYP2C complete cDNAs, designated CYP2C47 and CYP2C48 respectively, were cloned by cDNA library screening. The koala CYP2C cDNAs encode a protein of 495 amino acids. Three additional partial CYP2C sequences were also identified from the koala, indicating the multiplicity of the CYP2C subfamily in this unique marsupial species. The results of this study demonstrate the presence of koala hepatic CYP2Cs that share several common features with other published CYP2Cs; however CYP2C47 and CYP2C48 contain four extra amino acid residues at the NH2-terminal, a transmembrane anchor which was reported being a fundamentally conserved structure core of all eukaryote CYP enzymes.

  11. Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain.

    PubMed

    Booth Depaz, Iris M; Toselli, Francesca; Wilce, Peter A; Gillam, Elizabeth M J

    2015-03-01

    Cytochrome P450 enzymes from the CYP2C subfamily play a prominent role in the metabolic clearance of many drugs. CYP2C enzymes have also been implicated in the metabolism of arachidonic acid to vasoactive epoxyeicosatrienoic acids. CYP2C8, CYP2C9, and CYP2C19 are expressed in the adult liver at significant levels; however, the expression of CYP2C enzymes in extrahepatic tissues such as the brain is less well characterized. Form-specific antibodies to CYP2C9 and CYP2C19 were prepared by affinity purification of antibodies raised to unique peptides. CYP2C9 and CYP2C19 were located in microsomal fractions of all five human brain regions examined, namely the frontal cortex, hippocampus, basal ganglia, amygdala, and cerebellum. Both CYP2C9 and CYP2C19 were detected predominantly within the neuronal soma but with expression extending down axons and dendrites in certain regions. Finally, a comparison of cortex samples from alcoholics and age-matched controls suggested that CYP2C9 expression was increased in alcoholics.

  12. CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP.

    PubMed

    Huezo-Diaz, Patricia; Perroud, Nader; Spencer, Edgar P; Smith, Rebecca; Sim, Sarah; Virding, Susanne; Uher, Rudolf; Gunasinghe, Cerisse; Gray, Jo; Campbell, Desmond; Hauser, Joanna; Maier, Wolfgang; Marusic, Andrej; Rietschel, Marcella; Perez, Jorge; Giovannini, Caterina; Mors, Ole; Mendlewicz, Julien; McGuffin, Peter; Farmer, Anne E; Ingelman-Sundberg, Magnus; Craig, Ian W; Aitchison, Katherine J

    2012-03-01

    In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

  13. Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite.

    PubMed

    Boulenc, Xavier; Djebli, Nassim; Shi, Juan; Perrin, Laurent; Brian, William; Van Horn, Robert; Hurbin, Fabrice

    2012-01-01

    Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses. CYP2C19 involvements were estimated to be from 58 to 67% in intermediate metabolizers (IMs), from 58 to 72% in extensive metabolizers (EMs), and from 56 to 74% in ultrarapid metabolizers (UMs), depending on the study and the dose. For this purpose, a static model was proposed to estimate the net contribution of a given enzyme to the secondary metabolite formation. This static model was compared with a dynamic approach (Simcyp model) and showed good consistency. In parallel, in vitro investigations showed that omeprazole is a mechanism-based inhibitor of CYP2C19 with K(I) of 8.56 μM and K(inact) of 0.156 min(-1). These values were combined with the net CYP2C19 contribution to the active metabolite formation, through a static approach, to predict the inhibitory effect at 80-mg omeprazole doses in EM, IM, and UM CYP2C19 populations, with good consistency, compared with observed clinical values.

  14. The Periodic Round Table (by Gary Katz)

    NASA Astrophysics Data System (ADS)

    Rodgers, Reviewed By Glen E.

    2000-02-01

    Unwrapping and lifting the Periodic Round Table out of its colorful box is an exciting experience for a professional chemist or a chemistry student. Touted as a "new way of looking at the elements", it is certainly thatat least at first blush. The "table" consists of four sets of two finely finished hardwood discs each with the following elemental symbols and their corresponding atomic numbers pleasingly and symmetrically wood-burned into their faces. The four sets of two discs are 1 1/2, 3, 4 1/2, and 6 in. in diameter, each disc is 3/4 in. thick, and therefore the entire "round table" stands 6 in. high and is 6 in. in diameter at its base. The eight beautifully polished discs (represented below) are held together by center dowels that allow each to be rotated separately.

  15. Ancient Maya Astronomical Tables from Xultun, Guatemala

    NASA Astrophysics Data System (ADS)

    Saturno, William A.; Stuart, David; Aveni, Anthony F.; Rossi, Franco

    2012-05-01

    Maya astronomical tables are recognized in bark-paper books from the Late Postclassic period (1300 to 1521 C.E.), but Classic period (200 to 900 C.E.) precursors have not been found. In 2011, a small painted room was excavated at the extensive ancient Maya ruins of Xultun, Guatemala, dating to the early 9th century C.E. The walls and ceiling of the room are painted with several human figures. Two walls also display a large number of delicate black, red, and incised hieroglyphs. Many of these hieroglyphs are calendrical in nature and relate astronomical computations, including at least two tables concerning the movement of the Moon, and perhaps Mars and Venus. These apparently represent early astronomical tables and may shed light on the later books.

  16. Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users.

    PubMed

    Shram, M J; Schoedel, K A; Bartlett, C; Shazer, R L; Anderson, C M; Sellers, E M

    2011-05-01

    Lorcaserin is a selective and potent serotonin 2C receptor subtype (5-HT(2C)) agonist under development for the treatment of obesity. This study assessed the drug's abuse potential on the basis of its pharmacological profile. For this purpose, a double-blind, double-dummy, placebo-controlled, randomized seven-way crossover study with single oral doses of lorcaserin (20, 40, and 60 mg), zolpidem (15 and 30 mg), ketamine (100 mg), and placebo was conducted in recreational polydrug users (N = 35). Subjective and objective measures were assessed up to 24 h after the dose. We found that zolpidem and ketamine had significantly higher peak scores relative to placebo on the primary measures as well as on most of the secondary measures. The subjective effects of a 20-mg dose of lorcaserin were similar to those of placebo, whereas supratherapeutic doses of lorcaserin were associated with significant levels of dislike by users as compared with placebo, zolpidem, and ketamine. Perceptual effects were minimal after administration of lorcaserin and significantly lower than after administration of either ketamine or zolpidem. The findings suggest that, at supratherapeutic doses, lorcaserin is associated with distinct, primarily negative, subjective effects and has low abuse potential.

  17. Modelling the B2C Marketplace: Evaluation of a Reputation Metric for e-Commerce

    NASA Astrophysics Data System (ADS)

    Gutowska, Anna; Sloane, Andrew

    This paper evaluates recently developed novel and comprehensive reputation metric designed for the distributed multi-agent reputation system for the Business-to-Consumer (B2C) E-commerce applications. To do that an agent-based simulation framework was implemented which models different types of behaviours in the marketplace. The trustworthiness of different types of providers is investigated to establish whether the simulation models behaviour of B2C e-Commerce systems as they are expected to behave in real life.

  18. DOPEX-1D2C: A one-dimensional, two-constraint radiation shield optimization code

    NASA Technical Reports Server (NTRS)

    Lahti, G. P.

    1973-01-01

    A one-dimensional, two-constraint radiation sheild weight optimization procedure and a computer program, DOPEX-1D2C, is described. The DOPEX-1D2C uses the steepest descent method to alter a set of initial (input) thicknesses of a spherical shield configuration to achieve a minimum weight while simultaneously satisfying two dose-rate constraints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. Code input instruction, a FORTRAN-4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is less than 1/2 minute on an IBM 7094.

  19. Mathematics of Periodic Tables for Benzenoid Hydrocarbons.

    PubMed

    Dias, Jerry Ray

    2007-01-01

    The upper and lower bounds for invariants of polyhex systems based on the Harary and Harborth inequalities are studied. It is shown that these invariants are uniquely correlated by the Periodic Table for Benzenoid Hydrocarbons. A modified periodic table for total resonant sextet (TRS) benzenoids based on the invariants of Ds and r(empty) is presented; Ds is the number of disconnections among the empty rings for fused TRS benzenoid hydrocarbons. This work represents a contribution toward deciphering the topological information content of benzenoid formulas.

  20. 40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the...

  1. 40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the...

  2. 40 CFR Table 5 to Subpart Sssss of... - Initial Compliance With Emission Limits

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... continuous process unit that is subject to the THC emission concentration limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen The 3-hour block average THC emission concentration measured during the...

  3. 40 CFR Table 5 to Subpart Sssss of... - Initial Compliance With Emission Limits

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... continuous process unit that is subject to the THC emission concentration limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen The 3-hour block average THC emission concentration measured during the...

  4. 40 CFR Table 5 to Subpart Sssss of... - Initial Compliance With Emission Limits

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... continuous process unit that is subject to the THC emission concentration limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen The 3-hour block average THC emission concentration measured during the...

  5. 40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the...

  6. 40 CFR Table 5 to Subpart Sssss of... - Initial Compliance With Emission Limits

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... continuous process unit that is subject to the THC emission concentration limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen The 3-hour block average THC emission concentration measured during the...

  7. 40 CFR Table 4 to Subpart Sssss to... - Requirements for Performance Tests

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... OM&M plan; and (6) If complying with the THC concentration or THC percentage reduction limits... continuous process unit that is subject to the THC emission limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart a. Measure THC concentrations at the outlet of the control device or in the...

  8. 40 CFR Table 5 to Subpart Sssss of... - Initial Compliance With Emission Limits

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... continuous process unit that is subject to the THC emission concentration limit listed in item 2.a., 3.a., 4, or 5 of Table 1 to this subpart The average THC concentration must not exceed 20 ppmvd, corrected to 18 percent oxygen The 3-hour block average THC emission concentration measured during the...

  9. Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

    PubMed

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-07-01

    Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans.

  10. 77 FR 2573 - International Product Change-Global Plus 1C and 2C Negotiated Service Agreements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... International Product Change--Global Plus 1C and 2C Negotiated Service Agreements AGENCY: Postal Service TM... Regulatory Commission to add Global Plus 1C and 2C Negotiated Service Agreements to the Competitive Products... of United States Postal Service to Add Global Plus 1C and 2C Negotiated Service Agreements to...

  11. User-Interface Design Characteristics of Fortune 500 B2C E-Commerce Sites and Industry Differences

    ERIC Educational Resources Information Center

    Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.

    2006-01-01

    This study examined the user-interface design characteristics of 107 Fortune 500 B2C e-commerce Web sites and industry differences. Data were collected from corporate homepages, B2C product/service pages, B2C interactive shopping pages, as well as customer satisfaction of 321 online shoppers. The findings indicate that (a) to attract online…

  12. 77 FR 21782 - International Conference on Harmonisation; Draft Guidance for Industry on E2C(R2) Periodic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-11

    ... and combines two ICH guidances, ``E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety Data Management: Periodic... Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852....

  13. Dosing algorithms for vitamin K antagonists across VKORC1 and CYP2C9 genotypes.

    PubMed

    Baranova, E V; Verhoef, T I; Ragia, G; le Cessie, S; Asselbergs, F W; de Boer, A; Manolopoulos, V G; Maitland-van der Zee, A H

    2017-03-01

    Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.

  14. Nanoparticle-mediated intracellular lipid accumulation during C2C12 cell differentiation

    SciTech Connect

    Tsukahara, Tamotsu; Haniu, Hisao

    2011-03-25

    Research highlights: {yields} HTT2800 has a significant effect on intracellular lipid accumulation. {yields} HTT2800 reduced muscle-specific genes and led to the emergence of adipocyte-related genes. {yields} HT2800 converts the differentiation pathway of C2C12 myoblasts to that of adipoblast-like cells. -- Abstract: In this report, we sought to elucidate whether multiwall carbon nanotubes are involved in the modulation of the proliferation and differentiation of the skeletal muscle cell line C2C12. Skeletal muscle is a major mass peripheral tissue that accounts for 40% of total body weight and 50% of energy consumption. We focused on the differentiation pathway of myoblasts after exposure to a vapor-grown carbon fiber, HTT2800, which is one of the most highly purified carbon nanotubes. This treatment leads in parallel to the expression of a typical adipose differentiation program. We found that HTT2800 stimulated intracellular lipid accumulation in C2C12 cells. We have also shown by quantified PCR analysis that the expression of adipose-related genes was markedly upregulated during HTT2800 exposure. Taken together, these results suggest that HTT2800 specifically converts the differentiation pathway of C2C12 myoblasts to that of adipoblast-like cells.

  15. Surface morphology of orthorhombic Mo2C catalyst and high coverage hydrogen adsorption

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Tian, Xinxin; Yang, Yong; Li, Yong-Wang; Wang, Jianguo; Beller, Matthias; Jiao, Haijun

    2016-09-01

    High coverage hydrogen adsorption on twenty two terminations of orthorhombic Mo2C has been systematically studied by using density functional theory and ab initio thermodynamics. Hydrogen stable coverage on the surfaces highly depends on temperatures and H2 partial pressure. The estimated hydrogen desorption temperatures under ultra-high vacuum condition on Mo2C are in reasonable agreement with the available temperature-programmed desorption data. Obviously, hydrogen adsorption can affect the surface stability and therefore modify the surface morphology of Mo2C. Upon increasing the chemical potential of hydrogen which can be achieved by increasing the H2 partial pressure and/or decreasing the temperature, the proportions of the (001), (010), (011) and (100) surfaces increase, while those of the (101), (110) and (111) surfaces decrease. Among these surfaces, the (100) surface is most sensitive upon hydrogen adsorption and the (111) surface is most exposed under a wide range of conditions. Our study clearly reveals the role of hydrogen on the morphology of orthorhombic Mo2C catalyst in conjugation with hydro-treating activity.

  16. ABA Inducible Rice Protein Phosphatase 2C Confers ABA Insensitivity and Abiotic Stress Tolerance in Arabidopsis

    PubMed Central

    Singh, Amarjeet; Jha, Saroj K.; Bagri, Jayram; Pandey, Girdhar K.

    2015-01-01

    Arabidopsis PP2C belonging to group A have been extensively worked out and known to negatively regulate ABA signaling. However, rice (Oryza sativa) orthologs of Arabidopsis group A PP2C are scarcely characterized functionally. We have identified a group A PP2C from rice (OsPP108), which is highly inducible under ABA, salt and drought stresses and localized predominantly in the nucleus. Genetic analysis revealed that Arabidopsis plants overexpressing OsPP108 are highly insensitive to ABA and tolerant to high salt and mannitol stresses during seed germination, root growth and overall seedling growth. At adult stage, OsPP108 overexpression leads to high tolerance to salt, mannitol and drought stresses with far better physiological parameters such as water loss, fresh weight, chlorophyll content and photosynthetic potential (Fv/Fm) in transgenic Arabidopsis plants. Expression profile of various stress marker genes in OsPP108 overexpressing plants revealed interplay of ABA dependent and independent pathway for abiotic stress tolerance. Overall, this study has identified a potential rice group A PP2C, which regulates ABA signaling negatively and abiotic stress signaling positively. Transgenic rice plants overexpressing this gene might provide an answer to the problem of low crop yield and productivity during adverse environmental conditions. PMID:25886365

  17. Thermal ramp tritium release in COBRA-1A2 C03 beryllium pebbles

    SciTech Connect

    Baldwin, D.L.

    1998-03-01

    Tritium release kinetics, using the method of thermal ramp heating at three linear ramp rates, were measured on the COBRA-1A2 C03 1-mm beryllium pebbles. This report includes a brief discussion of the test, and the test data in graph format.

  18. The Development of B2C E-Commerce in Greece: Current Situation and Future Potential.

    ERIC Educational Resources Information Center

    Kardaras, Dimitris; Papathanassiou, Eleutherios

    2000-01-01

    Reports on the results of a survey of 120 companies in Greece that evaluated the potential of business to customer (B2C) Internet applications and investigated how the Internet and e-commerce can offer new opportunities for businesses to improve their customers' satisfaction. Discusses electronic commerce problems and future technology. (Contains…

  19. The Arabidopsis Protein Phosphatase PP2C38 Negatively Regulates the Central Immune Kinase BIK1.

    PubMed

    Couto, Daniel; Niebergall, Roda; Liang, Xiangxiu; Bücherl, Christoph A; Sklenar, Jan; Macho, Alberto P; Ntoukakis, Vardis; Derbyshire, Paul; Altenbach, Denise; Maclean, Dan; Robatzek, Silke; Uhrig, Joachim; Menke, Frank; Zhou, Jian-Min; Zipfel, Cyril

    2016-08-01

    Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component.

  20. The Arabidopsis Protein Phosphatase PP2C38 Negatively Regulates the Central Immune Kinase BIK1

    PubMed Central

    Liang, Xiangxiu; Bücherl, Christoph A.; Sklenar, Jan; Macho, Alberto P.; Ntoukakis, Vardis; Derbyshire, Paul; Altenbach, Denise; Robatzek, Silke; Uhrig, Joachim; Menke, Frank; Zhou, Jian-Min

    2016-01-01

    Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component. PMID:27494702