Sample records for cam kinase ii

  1. Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II

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    Souza, C.F. [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Carneiro, A.B.; Silveira, A.B. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); Laranja, G.A.T. [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); Silva-Neto, M.A.C. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); INCT, Entomologia Molecular (Brazil); Costa, S.C. Goncalves da [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Paes, M.C., E-mail: [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); INCT, Entomologia Molecular (Brazil)


    Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10 mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner . To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.

  2. The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway. (United States)

    Green, Jennifer L; Inoue, Takao; Sternberg, Paul W


    Inhibitors of Wnt signaling promote normal development and prevent cancer by restraining when and where the Wnt pathway is activated. ROR proteins, a class of Wnt-binding receptor tyrosine kinases, inhibit Wnt signaling by an unknown mechanism. To clarify how RORs inhibit the Wnt pathway, we examined the relationship between Wnts and the sole C. elegans ROR homolog, cam-1, during C. elegans vulval development, a Wnt-regulated process. We found that loss and overexpression of cam-1 causes reciprocal defects in Wnt-mediated cell-fate specification. Our molecular and genetic analyses revealed that the CAM-1 extracellular domain (ECD) is sufficient to non-autonomously antagonize multiple Wnts, suggesting that the CAM-1/ROR ECD sequesters Wnts. A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment.

  3. Behavioral modulation of neuronal calcium/calmodulin-dependent protein kinase II activity: differential effects on nicotine-induced spinal and supraspinal antinociception in mice. (United States)

    Damaj, M Imad


    Recent studies have implicated the involvement of Ca(2+)-dependent mechanisms, in particular calcium/calmodulin-dependent protein kinase II (CaM kinase II) in nicotine-induced antinociception using the tail-flick test. The spinal cord was suggested as a possible site of this involvement. The present study was undertaken to investigate the hypothesis that similar mechanisms exist for nicotine-induced antinociception in the hot-plate test, a response thought to be centrally mediated. In order to assess these mechanisms, i.c.v. administered CaM kinase II inhibitors were evaluated for their effects on antinociception produced by either i.c.v. or s.c. administration of nicotine in both tests. In addition, nicotine's analgesic effects were tested in mice lacking half of their CaM kinase II (CaM kinase II heterozygous) and compare it to their wild-type counterparts. Our results showed that although structurally unrelated CaM kinase II inhibitors blocked nicotine's effects in the tail-flick test in a dose-related manner, they failed to block the hot-plate responses. In addition, the antinociceptive effects of systemic nicotine in the tail-flick but not the hot-plate test were significantly reduced in CaM kinase II heterozygous mice. These observations indicate that in contrast to the tail-flick response, the mechanism of nicotine-induced antinociception in the hot-plate test is not mediated primarily via CaM kinase II-dependent mechanisms at the supraspinal level.

  4. Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and ROR2 kinase domains.

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    Travis W Bainbridge

    Full Text Available Receptor tyrosine kinase-like orphan receptors (ROR 1 and 2 are atypical members of the receptor tyrosine kinase (RTK family and have been associated with several human diseases. The vertebrate RORs contain an ATP binding domain that deviates from the consensus amino acid sequence, although the impact of this deviation on catalytic activity is not known and the kinase function of these receptors remains controversial. Recently, ROR2 was shown to signal through a Wnt responsive, β-catenin independent pathway and suppress a canonical Wnt/β-catenin signal. In this work we demonstrate that both ROR1 and ROR2 kinase domains are catalytically deficient while CAM-1, the C. elegans homolog of ROR, has an active tyrosine kinase domain, suggesting a divergence in the signaling processes of the ROR family during evolution. In addition, we show that substitution of the non-consensus residues from ROR1 or ROR2 into CAM-1 and MuSK markedly reduce kinase activity, while restoration of the consensus residues in ROR does not restore robust kinase function. We further demonstrate that the membrane-bound extracellular domain alone of either ROR1 or ROR2 is sufficient for suppression of canonical Wnt3a signaling, and that this domain can also enhance Wnt5a suppression of Wnt3a signaling. Based on these data, we conclude that human ROR1 and ROR2 are RTK-like pseudokinases.

  5. Thermodynamics of calmodulin trapping by Ca2+/calmodulin-dependent protein kinase II: subpicomolar Kd determined using competition titration calorimetry. (United States)

    Tse, Joyce K Y; Giannetti, Anthony M; Bradshaw, J Michael


    Calmodulin (CaM) trapping by Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a phenomenon whereby the affinity of CaM for CaMKII increases >1000-fold following CaMKII autophosphorylation. The molecular basis of this effect is not entirely understood. Binding of CaM to the phosphorylated and the unphosphorylated states of CaMKII is well mimicked by the interaction of CaM with two different length peptides taken from the CaM-binding region of CaMKII, peptides we refer to as the long and intermediate peptides. To better understand the conformational change accompanying CaM trapping, we have used isothermal titration calorimetry (ITC) to compare the binding thermodynamics of CaM to these peptides as well as to a shorter CaMKII-based peptide. Calorimetric analysis revealed that the enthalpy, rather than the entropy, distinguished binding of these three peptides. Furthermore, the heat capacity change was found to be similar for the long and intermediate peptides but smaller in magnitude for the short peptide. Direct titration of CaM with peptide provided the Kd value for the short peptide (Kd = 5.9 +/- 2.4 microM), but a novel, two-phased competitive binding strategy was necessary to ascertain the affinities of the intermediate (Kd = 0.17 +/- 0.06 nM) and long (Kd = 0.07 +/- 0.04 pM) peptides. To our knowledge, the Kd for the long peptide is the most potent measured to date using ITC. Together, the findings reported here support a model whereby the final conformational change accompanying CaM trapping buries little additional surface area but does involve formation of new hydrogen bonds and van der Waals contacts that contribute to formation of the high-affinity, CaM-trapped state.

  6. Nucleolin (C23), a physiological substrate for casein kinase II

    DEFF Research Database (Denmark)

    Schneider, H R; Issinger, O G


    Nucleolin (C23), a 110 kDa phosphoprotein, which is mainly found in the nucleolus has been shown to be a physiological substrate for casein kinase II (CKII). Nucleolin was identified and characterized by immunodetection using an anti-nucleolin antibody. Phosphopeptide patterns from nucleolin...... phosphorylated by purified casein kinase II and of phosphorylated nucleolin which had been isolated from tumor cells grown in the presence of [32P]-o-phosphate, were identical. The partial tryptic digest revealed nine phosphopeptides. Nucleolin isolated from Krebs II mouse ascites cells was phosphorylated...... by purified casein kinase II with about two moles phosphate per one mole of nucleolin....


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    Gheorghe Popescu


    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  8. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G


    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  9. The Rho kinases I and II regulate different aspects of myosin II activity

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R


    persistent ROCK II and guanine triphosphate-bound RhoA. In contrast, the microfilament cytoskeleton was enhanced by ROCK II down-regulation. Phagocytic uptake of fibronectin-coated beads was strongly down-regulated in ROCK II-depleted cells but not those lacking ROCK I. These effects originated in part from......The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... bundle assembly and smooth muscle contractility. Here, analysis of fibroblast adhesion to fibronectin revealed that although ROCK II was more abundant, its activity was always lower than ROCK I. Specific reduction of ROCK I by siRNA resulted in loss of stress fibers and focal adhesions, despite...


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    Full Text Available A computer assisted procedure for the cinematic analysis of the mechanism of a cam is essential in making a certain type of research operations. They mainly refer to the optimization of operations running on specific machinery, or to the re-design of the mechanism, in order to make the mechanism digital. This analysis seems even more important, when we consider the fact that most of the machines used in shoe industry nowadays use a cam mechanism. The paper is devided in two parts. In first part, it is elaborated a method of finding of a function G(x, belonging to a Fourier series, which approximates the numerical values {xi, yi}, with the biggest accuracy. Finding the function that approximates the most accurately the data set, for the position parameters of the follower S(ω, ( will lead to a complete kinematic and dynamic analysis of the cam mechanism. These values repeat with T = 2π period. In second part, the method is tasted using MatCAD work sessions which allow a numerical and graphical analysis of the mathematical relations involved, in order to test the reability of the method. The set of experimental data are resulted after measuring a cam mechanism of a machine used in shoemaking.

  11. A Review of CAM for Procedural Pain in Infancy: Part II. Other Interventions

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    Jennie C. I. Tsao


    Full Text Available This article is the second in a two-part series reviewing the empirical evidence for complementary and alternative medicine (CAM approaches for the management of pain related to medical procedures in infants up to 6 weeks of age. Part I of this series investigated the effects of sucrose with or without non-nutritive sucking (NNS. The present article examines other CAM interventions for procedural pain including music-based interventions, olfactory stimulation, kangaroo care and swaddling. Computerized databases were searched for relevant studies including prior reviews and primary trials. Preliminary support was revealed for the analgesic effects of the CAM modalities reviewed. However, the overall quality of the evidence for these approaches remains relatively weak. Additional well-designed trials incorporating rigorous methodology are required. Such investigations will assist in the development of evidence-based guidelines on the use of CAM interventions either alone or in concert with conventional approaches to provide safe, reliable analgesia for infant procedural pain.

  12. A mechanism for regulation of chloroplast LHC II kinase by plastoquinol and thioredoxin. (United States)

    Puthiyaveetil, Sujith


    State transitions are acclimatory responses to changes in light quality in photosynthesis. They involve the redistribution of absorbed excitation energy between photosystems I and II. In plants and green algae, this redistribution is produced by reversible phosphorylation of the chloroplast light harvesting complex II (LHC II). The LHC II kinase is activated by reduced plastoquinone (PQ) in photosystem II-specific low light. In high light, when PQ is also reduced, LHC II kinase becomes inactivated by thioredoxin. Based on newly identified amino acid sequence features of LHC II kinase and other considerations, a mechanism is suggested for its redox regulation.

  13. Inhibition of N1-Src kinase by a specific SH3 peptide ligand reveals a role for N1-Src in neurite elongation by L1-CAM (United States)

    Keenan, Sarah; Wetherill, Sarah J.; Ugbode, Christopher I.; Chawla, Sangeeta; Brackenbury, William J.; Evans, Gareth J. O.


    In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells. In cultured neurons, PDN1 fused to a fluorescent protein inhibited neurite outgrowth, an effect that was mimicked by shRNA targeting the N1-Src microexon. PDN1 also inhibited L1-CAM-dependent neurite elongation in cerebellar granule neurons, a pathway previously shown to be disrupted in Src−/− mice. PDN1 therefore represents a novel tool for distinguishing the functions of N1-Src and C-Src in neurons and is a starting point for the development of a small molecule inhibitor of N1-Src. PMID:28220894

  14. The Caenorhabditis elegans matrix non-peptidase MNP-1 is required for neuronal cell migration and interacts with the Ror receptor tyrosine kinase CAM-1. (United States)

    Craft, Teresa R; Forrester, Wayne C


    Directed cell migration is critical for metazoan development. During Caenorhabditis elegans development many neuronal, muscle and other cell types migrate. Multiple classes of proteins have been implicated in cell migration including secreted guidance cues, receptors for guidance cues and intracellular proteins that respond to cues to polarize cells and produce the forces that move them. In addition, cell surface and secreted proteases have been identified that may clear the migratory route and process guidance cues. We report here that mnp-1 is required for neuronal cell and growth cone migrations. MNP-1 is expressed by migrating cells and functions cell autonomously for cell migrations. We also find a genetic interaction between mnp-1 and cam-1, which encodes a Ror receptor tyrosine kinase required for some of the same cell migrations.

  15. The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II

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    Aristo Vojdani


    Full Text Available Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17, which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.

  16. Rat vas deferens SERCA2 is modulated by Ca{sup 2+}/calmodulin protein kinase II-mediated phosphorylation

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    Rodriguez, J.B.R.; Muzi-Filho, H. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Valverde, R.H.F. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Quintas, L.E.M. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Noel, F. [Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Einicker-Lamas, M. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ (Brazil); Cunha, V.M.N. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)


    Ca{sup 2+} pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca{sup 2+}-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca{sup 2+} (Ca{sub 0.5} = 780 nM) and a low sensitivity to vanadate (IC{sub 50} = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca{sup 2+} and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca{sup 2+} accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca{sup 2+} and CaM, possibly via CaMKII, in a process that results in stimulation of Ca{sup 2+} pumping activity.

  17. CARMENES input catalogue of M dwarfs II. High-resolution imaging with FastCam

    CERN Document Server

    Cortes-Contreras, M; Caballero, J A; Gauza, B; Montes, D; Alonso-Floriano, F J; Jeffers, S V; Morales, J C; Reiners, A; Ribas, I; Schoefer, P; Quirrenbach, A; Amado, P J; Mundt, R; Seifert, W


    Aims: We search for low-mass companions of M dwarfs and characterize their multiplicity fraction with the purpose of helping in the selection of the most appropriate targets for the CARMENES exoplanet survey. Methods: We obtained high-resolution images in the I band with the lucky imaging instrument FastCam at the 1.5 m Telescopio Carlos Sanchez for 490 mid- to late-M dwarfs. For all the detected binaries, we measured angular separations, position angles, and magnitude differences in the I band. We also calculated the masses of each individual component and estimated orbital periods, using the available magnitude and colour relations for M dwarfs and our own MJ-spectral type and mass-MI relations. To avoid biases in our sample selection, we built a volume-limited sample of M0.0-M5.0 dwarfs that is complete up to 86% within 14 pc. Results: From the 490 observed stars, we detected 80 companions in 76 systems, of which 30 are new discoveries. The multiplicity fraction in our observed sample is 16.7+-2.0% . In ou...

  18. Transient Receptor Potential Melastatin 7 Cation Channel Kinase: New Player in Angiotensin II-Induced Hypertension. (United States)

    Antunes, Tayze T; Callera, Glaucia E; He, Ying; Yogi, Alvaro; Ryazanov, Alexey G; Ryazanova, Lillia V; Zhai, Alexander; Stewart, Duncan J; Shrier, Alvin; Touyz, Rhian M


    Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein comprising a magnesium (Mg(2+))/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7 kinase-deficient mice (TRPM7Δkinase; heterozygous for TRPM7 kinase) and wild-type (WT) mice infused with angiotensin II (Ang II; 400 ng/kg per minute, 4 weeks). TRPM7 kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg(2+) was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (Phypertension is exaggerated, cardiac remodeling and left ventricular dysfunction are amplified, and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7 kinase expression/signaling, endothelial nitric oxide synthase downregulation, and proinflammatory vascular responses. Our findings identify TRPM7 kinase as a novel player in Ang II-induced hypertension and associated vascular and target organ damage.

  19. Replacement of tyrosine residues by phenylalanine in cytochrome P450cam alters the formation of Cpd II-like species in reactions with artificial oxidants. (United States)

    Spolitak, Tatyana; Dawson, John H; Ballou, David P


    Our previous rapid-scanning stopped-flow studies of the reaction of substrate-free cytochrome P450cam with peracids [Spolitak et al. (2005) J Biol Chem 280:20300-20309; (2006) J Inorg Biochem 100:2034-2044] spectrally characterized compound I [ferryl iron plus a porphyrin pi-cation radical (Fe(IV) = O/Por(+))], as well as Cpd ES (Fe(IV) = O/Tyr.). In the present studies, we report how the substitutions in Y75F, Y96F, and Y96F/Y75F P450cam variants permit the formation of a species we attribute to Cpd II (Fe(IV) = O) in reactions with peracids and cumene hydroperoxide. These variants produce changes in hydrogen bonding patterns and increased hydrophobicity that affect the ratio of heterolytic to homolytic pathways in reactions with cumene hydroperoxide, resulting in a shift of this ratio from 84/16 for WT to 72/28 for the Y96F/Y75F double mutant. Various ways of generating the Cpd II-like species were explored, and it was possible, especially with the more hydrophobic variants, to generate large fractions of the P450cam variants as Cpd II. The Cpd II-like species is ineffective at hydroxylating camphor, but can be readily reduced by ascorbate (as well as other peroxidase substrates) to ferric P450cam, which could then bind camphor to form the high-spin heme. The difference in the spectral properties of Cpd ES and Cpd II was rationalized as possibly being due to different states of protonation.

  20. CARMENES input catalogue of M dwarfs. II. High-resolution imaging with FastCam (United States)

    Cortés-Contreras, M.; Béjar, V. J. S.; Caballero, J. A.; Gauza, B.; Montes, D.; Alonso-Floriano, F. J.; Jeffers, S. V.; Morales, J. C.; Reiners, A.; Ribas, I.; Schöfer, P.; Quirrenbach, A.; Amado, P. J.; Mundt, R.; Seifert, W.


    Aims: We search for low-mass companions of M dwarfs and characterize their multiplicity fraction with the purpose of helping in the selection of the most appropriate targets for the CARMENES exoplanet survey. Methods: We obtained high-resolution images in the I band with the lucky imaging instrument FastCam at the 1.5 m Telescopio Carlos Sánchez for 490 mid- to late-M dwarfs. For all the detected binaries, we measured angular separations, position angles, and magnitude differences in the I band. We also calculated the masses of each individual component and estimated orbital periods, using the available magnitude and colour relations for M dwarfs and our own MJ-spectral type and mass-MI relations. To avoid biases in our sample selection, we built a volume-limited sample of M0.0-M5.0 dwarfs that is complete up to 86% within 14 pc. Results: From the 490 observed stars, we detected 80 companions in 76 systems, of which 30 are new discoveries. Another six companion candidates require additional astrometry to confirm physical binding. The multiplicity fraction in our observed sample is 16.7 ± 2.0%. The bias-corrected multiplicity fraction in our volume-limited sample is 19.5 ± 2.3% for angular separations of 0.2 to 5.0 arcsec (1.4-65.6 au), with a peak in the distribution of the projected physical separations at 2.5-7.5 au. For M0.0-M3.5 V primaries, our search is sensitive to mass ratios higher than 0.3 and there is a higher density of pairs with mass ratios over 0.8 compared to those at lower mass ratios. Binaries with projected physical separations shorter than 50 au also tend to be of equal mass. For 26 of our systems, we estimated orbital periods shorter than 50 a, 10 of which are presented here for the first time. We measured variations in angular separation and position angle that are due to orbital motions in 17 of these systems. The contribution of binaries and multiples with angular separations shorter than 0.2 arcsec, longer than 5.0 arcsec, and of

  1. Calmodulin kinase II inhibition protects against structural heart disease. (United States)

    Zhang, Rong; Khoo, Michelle S C; Wu, Yuejin; Yang, Yingbo; Grueter, Chad E; Ni, Gemin; Price, Edward E; Thiel, William; Guatimosim, Silvia; Song, Long-Sheng; Madu, Ernest C; Shah, Anisha N; Vishnivetskaya, Tatiana A; Atkinson, James B; Gurevich, Vsevolod V; Salama, Guy; Lederer, W J; Colbran, Roger J; Anderson, Mark E


    Beta-adrenergic receptor (betaAR) stimulation increases cytosolic Ca(2+) to physiologically augment cardiac contraction, whereas excessive betaAR activation causes adverse cardiac remodeling, including myocardial hypertrophy, dilation and dysfunction, in individuals with myocardial infarction. The Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a recently identified downstream element of the betaAR-initiated signaling cascade that is linked to pathological myocardial remodeling and to regulation of key proteins involved in cardiac excitation-contraction coupling. We developed a genetic mouse model of cardiac CaMKII inhibition to test the role of CaMKII in betaAR signaling in vivo. Here we show CaMKII inhibition substantially prevented maladaptive remodeling from excessive betaAR stimulation and myocardial infarction, and induced balanced changes in excitation-contraction coupling that preserved baseline and betaAR-stimulated physiological increases in cardiac function. These findings mark CaMKII as a determinant of clinically important heart disease phenotypes, and suggest CaMKII inhibition can be a highly selective approach for targeting adverse myocardial remodeling linked to betaAR signaling.

  2. Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase. (United States)

    Nishikawa, K; Toker, A; Wong, K; Marignani, P A; Johannes, F J; Cantley, L C


    Protein kinase Cmu (PKCmu), also named protein kinase D, is an unusual member of the PKC family that has a putative transmembrane domain and pleckstrin homology domain. This enzyme has a substrate specificity distinct from other PKC isoforms (Nishikawa, K., Toker, A., Johannes, F. J., Songyang, Z., and Cantley, L. C. (1997) J. Biol. Chem. 272, 952-960), and its mechanism of regulation is not yet clear. Here we show that PKCmu forms a complex in vivo with a phosphatidylinositol 4-kinase and a phosphatidylinositol-4-phosphate 5-kinase. A region of PKCmu between the amino-terminal transmembrane domain and the pleckstrin homology domain is shown to be involved in the association with the lipid kinases. Interestingly, a kinase-dead point mutant of PKCmu failed to associate with either lipid kinase activity, indicating that autophosphorylation may be required to expose the lipid kinase interaction domain. Furthermore, the subcellular distribution of the PKCmu-associated lipid kinases to the particulate fraction depends on the presence of the amino-terminal region of PKCmu including the predicted transmembrane region. These results suggest a novel model in which the non-catalytic region of PKCmu acts as a scaffold for assembly of enzymes involved in phosphoinositide synthesis at specific membrane locations.

  3. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II

    DEFF Research Database (Denmark)

    Elmlund, Hans; Baraznenok, Vera; Lindahl, Martin


    CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8......-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II....

  4. Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach. (United States)

    Al-Shboul, Othman; Mustafa, Ayman


    Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

  5. Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei (United States)

    Li, H.; Roux, S. J.


    A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

  6. Protein kinase C-beta II (PKC-betaII) expression in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise; Lindebjerg, Jan; Lahn, Michael;


    PURPOSE: Current development of targeted agents for the treatment of colorectal cancer include the clinical evaluation of kinase inhibitors, such as enzastaurin, a serine/threonine kinase inhibitor designed to suppress signaling through Protein Kinase C (PKC) and AKT pathways. Little is known abo...

  7. Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

    Directory of Open Access Journals (Sweden)

    Drescher Uwe


    Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

  8. Fibronectin matrix assembly requires distinct contributions from Rho kinases I and -II

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Ushakov, Dmitriy; Multhaupt, Hinke A B;


    Extracellular matrix is integral to tissue architecture and regulates many aspects of cell behavior. Fibronectin matrix assembly involves the actin cytoskeleton and the small GTPase RhoA, but downstream signaling is not understood. Here, down-regulation of either rho kinase isoform (ROCK I or -II...

  9. Cell organelles from crassulacean acid metabolism (CAM) plants : II. Compartmentation of enzymes of the crassulacean acid metabolism. (United States)

    Schnarrenberger, C; Groß, D; Burkhard, C; Herbert, M


    The intracellular distribution of enzymes involved in the Crassulacean acid metabolism (CAM) has been studied in Bryophyllum calycinum Salisb. and Crassula lycopodioides Lam. After separation of cell organelles by isopycnic centrifugation, enzymes of the Crassulacean acid metabolism were found in the following cell fractions: Phosphoenolpyruvate carboxylase in the chloroplasts; NAD-dependent malate dehydrogenase in the mitochondria and in the supernatant; NADP-dependent malate dehydrogenase and phosphoenolpyruvate carboxykinase in the chloroplasts; NADP-dependent malic enzyme in the supernatant and to a minor extent in the chloroplasts; NAD-dependent malic enzyme in the supernatant and to some degree in the mitochondria; and pyruvate; orthophosphate dikinase in the chloroplasts. The activity of the NAD-dependent malate dehydrogenase was due to three isoenzymes separated by (NH4)2SO4 gradient solubilization. These isoenzymes represented 17, 78, and 5% of the activity recovered, respectively, in the order of elution. The isoenzyme eluting first was associated with the mitochondria and the second isoenzyme was of cytosolic origin, while the intracellular location of the third isoenzyme was probably the peroxisome. Based on these findings, the metabolic path of Crassulacean acid metabolism within cells of CAM plants is discussed.

  10. Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II. (United States)

    Cingolani, Francesca; Casasampere, Mireia; Sanllehí, Pol; Casas, Josefina; Bujons, Jordi; Fabrias, Gemma


    Sphingosine kinase inhibitor (SKI) II has been reported as a dual inhibitor of sphingosine kinases (SKs) 1 and 2 and has been extensively used to prove the involvement of SKs and sphingosine-1-phosphate (S1P) in cellular processes. Dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and Cers. Both SKs and Des1 have interest as therapeutic targets. Here we show that SKI II is a noncompetitive inhibitor (Ki = 0.3 μM) of Des1 activity with effect also in intact cells without modifying Des1 protein levels. Molecular modeling studies support that the SKI II-induced decrease in Des1 activity could result from inhibition of NADH-cytochrome b5 reductase. SKI II, but not the SK1-specific inhibitor PF-543, provoked a remarkable accumulation of dhCers and their metabolites, while both SKI II and PF-543 reduced S1P to almost undetectable levels. SKI II, but not PF543, reduced cell proliferation with accumulation of cells in the G0/G1 phase. SKI II, but not PF543, induced autophagy. These overall findings should be taken into account when using SKI II as a pharmacological tool, as some of the effects attributed to decreased S1P may actually be caused by augmented dhCers and/or their metabolites.

  11. Membrane actions of 1α,25(OH)2D3 are mediated by Ca(2+)/calmodulin-dependent protein kinase II in bone and cartilage cells. (United States)

    Doroudi, Maryam; Plaisance, Marc C; Boyan, Barbara D; Schwartz, Zvi


    1α,25(OH)2D3 regulates osteoblasts and chondrocytes via its membrane-associated receptor, protein disulfide isomerase A3 (Pdia3) in caveolae. 1α,25(OH)2D3 binding to Pdia3 leads to phospholipase-A2 (PLA2)-activating protein (PLAA) activation, stimulating cytosolic PLA2 and resulting in prostaglandin E2 (PGE2) release and PKCα activation, subsequently stimulating differentiation. However, how PLAA transmits the signal to cPLA2 is unknown. Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) activation is required for PLA2 activation in vascular smooth muscle cells, suggesting a similar role in 1α,25(OH)2D3-dependent signaling. The aim of the present study is to evaluate the roles of CaM and CaMKII as mediators of 1α,25(OH)2D3-stimulated PLAA-dependent activation of cPLA2 and PKCα, and downstream biological effects. The results indicated that 1α,25(OH)2D3 and PLAA-peptide increased CaMKII activity within 9 min. Silencing Cav-1, Pdia3 or Plaa in osteoblasts suppressed this effect. Similarly, antibodies against Plaa or Pdia3 blocked 1α,25(OH)2D3-dependent CaMKII. Caveolae disruption abolished activation of CaMKII by 1α,25(OH)2D3 or PLAA. CaMKII-specific and CaM-specific inhibitors reduced cPLA2 and PKC activities, PGE2 release and osteoblast maturation markers in response to 1α,25(OH)2D3. Camk2a-silenced but not Camk2b-silenced osteoblasts showed comparable effects. Immunoprecipitation showed increased interaction of CaM and PLAA in response to 1α,25(OH)2D3. The results indicate that membrane actions of 1α,25(OH)2D3 via Pdia3 triggered the interaction between PLAA and CaM, leading to dissociation of CaM from caveolae, activation of CaMKII, and downstream PLA2 activation, and suggest that CaMKII plays a major role in membrane-mediated actions of 1α,25(OH)2D3.

  12. Cryogenic Cam Butterfly Valve (United States)

    McCormack, Kenneth J. (Inventor)


    A cryogenic cam butterfly valve has a body that includes an axially extending fluid conduit formed there through. A disc lug is connected to a back side of a valve disc and has a circular bore that receives and is larger than a cam of a cam shaft. The valve disc is rotatable for a quarter turn within the body about a lug axis that is offset from the shaft axis. Actuating the cam shaft in the closing rotational direction first causes the camming side of the cam of the cam shaft to rotate the disc lug and the valve disc a quarter turn from the open position to the closed position. Further actuating causes the camming side of the cam shaft to translate the valve disc into sealed contact with the valve seat. Opening rotational direction of the cam shaft reverses these motions.

  13. Excitation-Transcription Coupling in Parvalbumin-Positive Interneurons Employs a Novel CaM Kinase-Dependent Pathway Distinct from Excitatory Neurons. (United States)

    Cohen, Samuel M; Ma, Huan; Kuchibhotla, Kishore V; Watson, Brendon O; Buzsáki, György; Froemke, Robert C; Tsien, Richard W


    Properly functional CNS circuits depend on inhibitory interneurons that in turn rely upon activity-dependent gene expression for morphological development, connectivity, and excitatory-inhibitory coordination. Despite its importance, excitation-transcription coupling in inhibitory interneurons is poorly understood. We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB phosphorylation and gene expression. As in excitatory neurons, voltage-gated Ca(2+) influx through CaV1 channels triggers CaM nuclear translocation via local Ca(2+) signaling. However, PV+ interneurons are distinct in that nuclear signaling is mediated by γCaMKI, not γCaMKII. CREB phosphorylation also proceeds with slow, sigmoid kinetics, rate-limited by paucity of CaMKIV, protecting against saturation of phospho-CREB in the face of higher firing rates and bigger Ca(2+) transients. Our findings support the generality of CaM shuttling to drive nuclear CaMK activity, and they are relevant to disease pathophysiology, insofar as dysfunction of PV+ interneurons and molecules underpinning their excitation-transcription coupling both relate to neuropsychiatric disease.

  14. The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer–Villiger monooxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Isupov, Michail N.; Schröder, Ewald; Gibson, Robert P.; Beecher, Jean; Donadio, Giuliana; Saneei, Vahid; Dcunha, Stephlina A.; McGhie, Emma J.; Sayer, Christopher; Davenport, Colin F. [University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Lau, Peter C. [National Research Council Canada, 6100 Royalmount Avenue, Montreal, QC H4P 2R2 (Canada); Hasegawa, Yoshie; Iwaki, Hiroaki [Kansai University (Japan); Kadow, Maria; Balke, Kathleen; Bornscheuer, Uwe T. [Greifswald University, Felix-Hausdorff-Strasse 4, 17487 Greifswald (Germany); Bourenkov, Gleb [European Molecular Biology Laboratory (EMBL), Hamburg Outstation, Notkestrasse 85, 22607 Hamburg (Germany); Littlechild, Jennifer A., E-mail: [University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom)


    The first crystal structure of a type II Baeyer–Villiger monooxygenase reveals a different ring orientation of its FMN cofactor compared with other related bacterial luciferase-family enzymes. The three-dimensional structures of the native enzyme and the FMN complex of the overexpressed form of the oxygenating component of the type II Baeyer–Villiger 3,6-diketocamphane monooxygenase have been determined to 1.9 Å resolution. The structure of this dimeric FMN-dependent enzyme, which is encoded on the large CAM plasmid of Pseudomonas putida, has been solved by a combination of multiple anomalous dispersion from a bromine crystal soak and molecular replacement using a bacterial luciferase model. The orientation of the isoalloxazine ring of the FMN cofactor in the active site of this TIM-barrel fold enzyme differs significantly from that previously observed in enzymes of the bacterial luciferase-like superfamily. The Ala77 residue is in a cis conformation and forms a β-bulge at the C-terminus of β-strand 3, which is a feature observed in many proteins of this superfamily.

  15. Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II-induced inflammation and hypertension: regulation of oxidative stress. (United States)

    Ebrahimian, Talin; Li, Melissa Wei; Lemarié, Catherine A; Simeone, Stefania M C; Pagano, Patrick J; Gaestel, Matthias; Paradis, Pierre; Wassmann, Sven; Schiffrin, Ernesto L


    Vascular oxidative stress and inflammation play an important role in angiotensin II-induced hypertension, and mitogen-activated protein kinases participate in these processes. We questioned whether mitogen-activated protein kinase-activated protein kinase 2 (MK2), a downstream target of p38 mitogen-activated protein kinase, is involved in angiotensin II-induced vascular responses. In vivo experiments were performed in wild-type and Mk2 knockout mice infused intravenously with angiotensin II. Angiotensin II induced a 30 mm Hg increase in mean blood pressure in wild-type that was delayed in Mk2 knockout mice. Angiotensin II increased superoxide production and vascular cell adhesion molecule-1 in blood vessels of wild-type but not in Mk2 knockout mice. Mk2 knockdown by small interfering RNA in mouse mesenteric vascular smooth muscle cells caused a 42% reduction in MK2 protein and blunted the angiotensin II-induced 40% increase of MK2 expression. Mk2 knockdown blunted angiotensin II-induced doubling of intracellular adhesion molecule-1 expression, 2.4-fold increase of nuclear p65, and 1.4-fold increase in Ets-1. Mk2 knockdown abrogated the angiotensin II-induced 4.7-fold and 1.3-fold increase of monocyte chemoattractant protein-1 mRNA and protein. Angiotensin II enhanced reactive oxygen species levels (by 29%) and nicotinamide adenine dinucleotide phosphate oxidase activity (by 48%), both abolished by Mk2 knockdown. Reduction of MK2 blocked angiotensin II-induced p47phox translocation to the membrane, associated with a 53% enhanced catalase expression. Angiotensin II-induced increase of MK2 was prevented by the nicotinamide adenine dinucleotide phosphate oxidase inhibitor Nox2ds-tat. Mk2 small interfering RNA prevented the angiotensin II-induced 30% increase of proliferation. In conclusion, MK2 plays a critical role in angiotensin II signaling, leading to hypertension, oxidative stress via activation of p47phox and inhibition of antioxidants, and vascular inflammation

  16. Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice. (United States)

    Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji


    Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR.

  17. Roles of an unconventional protein kinase and myosin II in amoeba osmotic shock responses. (United States)

    Betapudi, Venkaiah; Egelhoff, Thomas T


    The contractile vacuole (CV) is a dynamic organelle that enables Dictyostelium amoeba and other protist to maintain osmotic homeostasis by expelling excess water. In the present study, we have uncovered a mechanism that coordinates the mechanics of the CV with myosin II, regulated by VwkA, an unconventional protein kinase that is conserved in an array of protozoa. Green fluorescent protein (GFP)-VwkA fusion proteins localize persistently to the CV during both filling and expulsion phases of water. In vwkA null cells, the established CV marker dajumin still localizes to the CV, but these structures are large, spherical and severely impaired for discharge. Furthermore, myosin II cortical localization and assembly are abnormal in vwkA null cells. Parallel analysis of wild-type cells treated with myosin II inhibitors or of myosin II null cells also results in enlarged CVs with impaired dynamics. We suggest that the myosin II cortical cytoskeleton, regulated by VwkA, serves a critical conserved role in the periodic contractions of the CV, as part of the osmotic protective mechanism of protozoa.

  18. Creatine kinase activity in patients with diabetes mellitus type I and type II. (United States)

    Jevrić-Causević, Adlija; Malenica, Maja; Dujić, Tanja


    Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  19. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors. (United States)

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E; Cuny, Gregory D; Uhlig, Holm H; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N


    RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers.

  20. Rho/Rho-dependent kinase affects locomotion and actin-myosin II activity of Amoeba proteus. (United States)

    Kłopocka, W; Redowicz, M J


    The highly motile free-living unicellular organism Amoeba proteus has been widely used as a model to study cell motility. However, the molecular mechanisms underlying its unique locomotion are still scarcely known. Recently, we have shown that blocking the amoebae's endogenous Rac- and Rho-like proteins led to distinct and irreversible changes in the appearance of these large migrating cells as well as to a significant inhibition of their locomotion. In order to elucidate the mechanism of the Rho pathway, we tested the effects of blocking the endogenous Rho-dependent kinase (ROCK) by anti-ROCK antibodies and Y-27632, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride, a specific inhibitor of ROCK, on migrating amoebae and the effect of the Rho and ROCK inhibition on the actin-activated Mg-ATPase of the cytosolic fraction of the amoebae. Amoebae microinjected with anti-ROCK inhibitors remained contracted and strongly attached to the glass surface and exhibited an atypical locomotion. Despite protruding many pseudopodia that were advancing in various directions, the amoebae could not effectively move. Immunofluorescence studies showed that ROCK-like protein was dispersed throughout the cytoplasm and was also found in the regions of actin-myosin II interaction during both isotonic and isometric contraction. The Mg-ATPase activity was about two- to threefold enhanced, indicating that blocking the Rho/Rho-dependent kinase activated myosin. It is possible then that in contrast to the vertebrate cells, the inactivation of Rho/Rho-dependent kinase in amoebae leads to the activation of myosin II and to the observed hypercontracted cells which cannot exert effective locomotion.

  1. Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Stanley K.L. [Singapore Immunology Network A-STAR (Singapore); Neo, Soek-Ying, E-mail: [Singapore Immunology Network A-STAR (Singapore); Yap, Yann-Wan [Singapore Immunology Network A-STAR (Singapore); Karuturi, R. Krishna Murthy; Loh, Evelyn S.L. [Genome Institute of Singapore A-STAR (Singapore); Liau, Kui-Hin [Department of General Surgery, Tan Tock Seng Hospital (Singapore); Ren, Ee-Chee, E-mail: [Singapore Immunology Network A-STAR (Singapore); Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)


    Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways. Herein we investigated the role of PI3K catalytic isoforms, particularly class II isoforms in HCC proliferation. Among the siRNAs tested against the eight known catalytic PI3K isoforms, specific ablation of class II PI3K alpha (PIK3C2{alpha}) was the most effective in impairing cell growth and this was accompanied by concomitant decrease in PIK3C2{alpha} mRNA and protein levels. Colony formation ability of cells deficient for PIK3C2{alpha} was markedly reduced and growth arrest was associated with increased caspase 3 levels. A small but significant difference in gene dosage and expression levels was detected between tumor and non-tumor tissues in a cohort of 19 HCC patients. Taken together, these data suggest for the first time that in addition to class I PI3Ks in cancer, class II PIK3C2{alpha} can modulate HCC cell growth.

  2. α-Calcium calmodulin kinase II modulates the temporal structure of hippocampal bursting patterns.

    Directory of Open Access Journals (Sweden)

    Jeiwon Cho

    Full Text Available The alpha calcium calmodulin kinase II (α-CaMKII is known to play a key role in CA1/CA3 synaptic plasticity, hippocampal place cell stability and spatial learning. Additionally, there is evidence from hippocampal electrophysiological slice studies that this kinase has a role in regulating ion channels that control neuronal excitability. Here, we report in vivo single unit studies, with α-CaMKII mutant mice, in which threonine 305 was replaced with an aspartate (α-CaMKII(T305D mutants, that indicate that this kinase modulates spike patterns in hippocampal pyramidal neurons. Previous studies showed that α-CaMKII(T305D mutants have abnormalities in both hippocampal LTP and hippocampal-dependent learning. We found that besides decreased place cell stability, which could be caused by their LTP impairments, the hippocampal CA1 spike patterns of α-CaMKII(T305D mutants were profoundly abnormal. Although overall firing rate, and overall burst frequency were not significantly altered in these mutants, inter-burst intervals, mean number of intra-burst spikes, ratio of intra-burst spikes to total spikes, and mean intra-burst intervals were significantly altered. In particular, the intra burst intervals of place cells in α-CaMKII(T305D mutants showed higher variability than controls. These results provide in vivo evidence that besides its well-known function in synaptic plasticity, α-CaMKII, and in particular its inhibitory phosphorylation at threonine 305, also have a role in shaping the temporal structure of hippocampal burst patterns. These results suggest that some of the molecular processes involved in acquiring information may also shape the patterns used to encode this information.

  3. Bcl10 is phosphorylated on Ser138 by Ca2+/calmodulin-dependent protein kinase II. (United States)

    Ishiguro, Kazuhiro; Ando, Takafumi; Goto, Hidemi; Xavier, Ramnik


    Ordered assembly of scaffold proteins Carma1-Bcl10-Malt1 determines NF-kappaB activation following T cell receptor (TCR) engagement. Carma1-Bcl10 interaction and the signaling pathway are controlled by Carma1 phosphorylation, which are induced by PKCtheta and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In addition to Carma1 phosphorylation, previous studies have demonstrated that Bcl10 is phosphorylated in the C-terminal Ser/Thr rich region following TCR engagement. However the kinases that phosphorylate Bcl10 are incompletely understood. Here we show that CaMKII phosphorylates Bcl10 on Ser138. Furthermore, a CaMKII inhibitor, KN93, and CaMKII siRNA substantially reduce Bcl10 phosphorylation induced by phorbol myristate acetate/ionomycin. S138A mutation prolongs Bcl10-induced NF-kappaB activation, suggesting that Bcl10 phosphorylation is involved in attenuation of NF-kappaB activation. These findings suggest that CaMKII modulates NF-kappaB activation via phosphorylating Bcl10 as well as Carma1.

  4. Isolation and characterization of recombinant human casein kinase II subunits alpha and beta from bacteria

    DEFF Research Database (Denmark)

    Grankowski, N; Boldyreff, B; Issinger, O G


    cDNA encoding the casein kinase II (CKII) subunits alpha and beta of human origin were expressed in Escherichia coli using expression vector pT7-7. Significant expression was obtained with E. coli BL21(DE3). The CKII subunits accounted for approximately 30% of the bacterial protein; however, most...... of the expressed proteins were produced in an insoluble form. The recombinant CKII alpha subunit was purified by DEAE-cellulose chromatography, followed by phosphocellulose and heparin-agarose chromatography. The recombinant CKII beta subunit was extracted from the insoluble pellet and purified in a single step...... on phosphocellulose. From 10 g bacterial cells, the yield of soluble protein was 12 mg alpha subunit and 5 mg beta subunit. SDS/PAGE analysis of the purified recombinant proteins indicated molecular masses of 42 kDa and 26 kDa for the alpha and beta subunits, respectively, in agreement with the molecular masses...

  5. Brain Region-Specific Effects of cGMP-Dependent Kinase II Knockout on AMPA Receptor Trafficking and Animal Behavior (United States)

    Kim, Seonil; Pick, Joseph E.; Abera, Sinedu; Khatri, Latika; Ferreira, Danielle D. P.; Sathler, Matheus F.; Morison, Sage L.; Hofmann, Franz; Ziff, Edward B.


    Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO…

  6. Consumer Health: CAM Claims (United States)

    Healthy Lifestyle Consumer health Don't take all CAM claims at face value. Do your homework when considering CAM therapies. By ... dose of skepticism. Federal Trade Commission. Accessed ...

  7. Hyperexcitability and changes in activities of Ca2+/calmodulin-dependent kinase II and mitogen-activated protein kinase in the hippocampus of rats exposed to 1-bromopropane. (United States)

    Fueta, Yukiko; Fukunaga, Kohji; Ishidao, Toru; Hori, Hajime


    Chronic inhalation of 1-bromopropane (1-BP), a substitute of ozone-depleting chlorofluorocarbons, has been suspected of having central neurotoxicity (Clinical Neurology and Neurosurgery 101 (1999) 199; Journal of Occupational Health 44 (2002) 1) for humans. In animal experiments, 1-BP inhalation (1500 ppm) caused hyperexcitability in the CA1 and the dentate gyrus (DG) [Journal of Occupational Health 42 (2000) 149, Journal of Occupational Health 44 (2002) 156]. We studied whether the hyperexcitability is associated with changes of Ca2+/calmodulin-dependent kinase II (CaMKII), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Male Wistar rats were exposed to 1-BP for 6 hours in a day in an exposure chamber with a concentration of 700 ppm for 8 weeks. After the inhalation, paired-pulse ratios of field excitatory postsynaptic potentials and population spikes (PSs) were analyzed in the CA1 and DG of hippocampal slices. Control rats were then given fresh air in the inhalation chamber. Semiquantitative immunoblotting analyses of protein kinases using antibodies against active and conventional protein kinases were done using the whole hippocampus. A paired-pulse ratio of PS was increased at the 5 ms interpulse interval in the CA1 and at the 10-20 ms interpulse intervals in the DG. The amount of active MAPK and total amount of CaMKIIalpha and beta were significantly increased by 28, 29, and 46% compared to control, respectively, without any change in PKC activity. In contrast, the amount of active CaMKIIbeta was decreased to 78%. These results suggest that modifications of intracellular signaling cascades are associated with hyperexcitability that occurred in the hippocampal formation of rats exposed to the chronic inhalation of 1-BP.

  8. Mechanical stress triggers cardiomyocyte autophagy through angiotensin II type 1 receptor-mediated p38MAP kinase independently of angiotensin II.

    Directory of Open Access Journals (Sweden)

    Li Lin

    Full Text Available Angiotensin II (Ang II type 1 (AT1 receptor is known to mediate a variety of physiological actions of Ang II including autophagy. However, the role of AT1 receptor in cardiomyocyte autophagy triggered by mechanical stress still remains elusive. The aim of this study was therefore to examine whether and how AT1 receptor participates in cardiomyocyte autophagy induced by mechanical stresses. A 48-hour mechanical stretch and a 4-week transverse aorta constriction (TAC were imposed to cultured cardiomyocytes of neonatal rats and adult male C57B/L6 mice, respectively, to induce cardiomyocyte hypertrophy prior to the assessment of cardiomyocyte autophagy using LC3b-II. Losartan, an AT1 receptor blocker, but not PD123319, the AT2 inhibitor, was found to significantly reduce mechanical stretch-induced LC3b-II upregulation. Moreover, inhibition of p38MAP kinase attenuated not only mechanical stretch-induced cardiomyocyte hypertrophy but also autophagy. To the contrary, inhibition of ERK and JNK suppressed cardiac hypertrophy but not autophagy. Intriguingly, mechanical stretch-induced autophagy was significantly inhibited by Losartan in the absence of Ang II. Taken together, our results indicate that mechanical stress triggers cardiomyocyte autophagy through AT1 receptor-mediated activation of p38MAP kinase independently of Ang II.

  9. Ca2+/calmodulin-dependent kinase II contributes to inhibitor of nuclear factor-kappa B kinase complex activation in Helicobacter pylori infection. (United States)

    Maubach, Gunter; Sokolova, Olga; Wolfien, Markus; Rothkötter, Hermann-Josef; Naumann, Michael


    Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor-kappa B (NF-κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF-κB-mediated inflammatory response. In our study, we investigated the role of Ca(2+) /calmodulin-dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3-Bcl10-MALT1 (CBM) complex in conjunction with H. pylori-induced activation of NF-κB via the inhibitor of nuclear factor-kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-κB in response to H. pylori infection, but not in response to TNF-α. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs α, δ, θ, nor the CBM complex itself is involved in the activation of NF-κB by H. pylori. The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer.

  10. Composite cam carrier

    Energy Technology Data Exchange (ETDEWEB)

    Wicks, Christopher Donald; Madin, Mark Michael


    A cam carrier assembly includes a cylinder head having valves and a camshaft having lobes. A cam carrier has a first side coupled with the cylinder head engaging around the valves and a second side with bearing surfaces supporting the camshaft. A series of apertures extend between the first and second sides for the lobes to interface with the valves. The cam carrier is made of carbon fiber composite insulating the camshaft from the cylinder head and providing substantial weight reduction to an upper section of an associated engine.

  11. Increased calcium/calmodulin-dependent protein kinase II activity by morphine-sensitization in rat hippocampus. (United States)

    Kadivar, Mehdi; Farahmandfar, Maryam; Ranjbar, Faezeh Esmaeli; Zarrindast, Mohammad-Reza


    Repeated exposure to drugs of abuse, such as morphine, elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect long-lasting changes in some of the important molecules involved in memory processing such as calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we investigated the effect of morphine sensitization on mRNA expression of α and β isoforms and activity of CaMKII in the hippocampus of male rats. Animals were treated for 3 days with saline or morphine (20mg/kg) and following a washout period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The results indicate that morphine administration in pre-treated animals produces behavioral sensitization, as determined by significant increase in locomotion and oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA expression of both α and β isoforms of CaMKII in the hippocampus. The present study also showed that induction of morphine sensitization significantly increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent activities of CaMK II in the rat hippocampus. However, acute administration of morphine (5mg/kg) did not alter either α and β CaMKII mRNA expression or CaMKII activity in the hippocampus. The stimulation effects of morphine sensitization on mRNA expression and activity of CaMKII were completely abolished by administration of naloxone, 30min prior to s.c. injections of morphine (20mg/kg/day×3 days). Our data demonstrated that induction of morphine sensitization could effectively modulate the activity and the mRNA expression of CaMKII in the hippocampus and this effect of morphine was exerted by the activation of opioid receptors.

  12. Role of EGFR transactivation in angiotensin II signaling to extracellular regulated kinase in preglomerular smooth muscle cells. (United States)

    Andresen, Bradley T; Linnoila, Jenny J; Jackson, Edwin K; Romero, Guillermo G


    Angiotensin (Ang) II promotes the phosphorylation of extracellular regulated kinase (ERK); however, the mechanisms leading to Ang II-induced ERK phosphorylation are debated. The currently accepted theory involves transactivation of epidermal growth factor receptor (EGFR). We have shown that generation of phosphatidic acid (PA) is required for the recruitment of Raf to membranes and the activation of ERK by multiple agonists, including Ang II. In the present report, we confirm that phospholipase D-dependent generation of PA is required for Ang II-mediated phosphorylation of ERK in Wistar-Kyoto and spontaneously hypertensive rat preglomerular smooth muscle cells (PGSMCs). However, EGF stimulation does not activate phospholipase D or generate PA. These observations indicate that EGF recruits Raf to membranes via a mechanism that does not involve PA, and thus, Ang II-mediated phosphorylation of ERK is partially independent of EGFR-mediated signaling cascades. We hypothesized that phosphoinositide-3-kinase (PI3K) can also act to recruit Raf to membranes; therefore, inhibition of PI3K should inhibit EGF signaling to ERK. Wortmannin, a PI3K inhibitor, inhibited EGF-mediated phosphorylation of ERK (IC50, approximately 14 nmol/L). To examine the role of the EGFR in Ang II-mediated phosphorylation of ERK we utilized 100 nmol/L wortmannin to inhibit EGFR signaling to ERK and T19N RhoA to block Ang II-mediated ERK phosphorylation. Wortmannin treatment inhibited EGF-mediated but not Ang II-mediated phosphorylation of ERK. Furthermore, T19N RhoA inhibited Ang II-mediated ERK phosphorylation, whereas T19N RhoA had significantly less effect on EGF-mediated ERK phosphorylation. We conclude that transactivation of the EGFR is not primarily responsible for Ang II-mediated activation of ERK in PGSMCs.

  13. Syndecan-2 regulates melanin synthesis via protein kinase C βII-mediated tyrosinase activation. (United States)

    Jung, Hyejung; Chung, Heesung; Chang, Sung Eun; Choi, Sora; Han, Inn-Oc; Kang, Duk-Hee; Oh, Eok-Soo


    Syndecan-2, a transmembrane heparan sulfate proteoglycan that is highly expressed in melanoma cells, regulates melanoma cell functions (e.g. migration). Since melanoma is a malignant tumor of melanocytes, which largely function to synthesize melanin, we investigated the possible involvement of syndecan-2 in melanogenesis. Syndecan-2 expression was increased in human skin melanoma tissues compared with normal skin. In both mouse and human melanoma cells, siRNA-mediated knockdown of syndecan-2 was associated with reduced melanin synthesis, whereas overexpression of syndecan-2 increased melanin synthesis. Similar effects were also detected in human primary epidermal melanocytes. Syndecan-2 expression did not affect the expression of tyrosinase, a key enzyme in melanin synthesis, but instead enhanced the enzymatic activity of tyrosinase by increasing the membrane and melanosome localization of its regulator, protein kinaseII. Furthermore, UVB caused increased syndecan-2 expression, and this up-regulation of syndecan-2 was required for UVB-induced melanin synthesis. Taken together, these data suggest that syndecan-2 regulates melanin synthesis and could be a potential therapeutic target for treating melanin-associated diseases.

  14. Cyclin-dependent kinase 9 links RNA polymerase II transcription to processing of ribosomal RNA. (United States)

    Burger, Kaspar; Mühl, Bastian; Rohrmoser, Michaela; Coordes, Britta; Heidemann, Martin; Kellner, Markus; Gruber-Eber, Anita; Heissmeyer, Vigo; Strässer, Katja; Eick, Dirk


    Ribosome biogenesis is a process required for cellular growth and proliferation. Processing of ribosomal RNA (rRNA) is highly sensitive to flavopiridol, a specific inhibitor of cyclin-dependent kinase 9 (Cdk9). Cdk9 has been characterized as the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Here we studied the connection between RNAPII transcription and rRNA processing. We show that inhibition of RNAPII activity by α-amanitin specifically blocks processing of rRNA. The block is characterized by accumulation of 3' extended unprocessed 47 S rRNAs and the entire inhibition of other 47 S rRNA-specific processing steps. The transcription rate of rRNA is moderately reduced after inhibition of Cdk9, suggesting that defective 3' processing of rRNA negatively feeds back on RNAPI transcription. Knockdown of Cdk9 caused a strong reduction of the levels of RNAPII-transcribed U8 small nucleolar RNA, which is essential for 3' rRNA processing in mammalian cells. Our data demonstrate a pivotal role of Cdk9 activity for coupling of RNAPII transcription with small nucleolar RNA production and rRNA processing.

  15. CAM and NK Cells

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Takeda


    Full Text Available It is believed that tumor development, outgrowth and metastasis are under the surveillance of the immune system. Although both innate and acquired immune systems play roles, innate immunity is the spearhead against tumors. Recent studies have revealed the critical role of natural killer (NK cells in immune surveillance and that NK cell activity is considerably influenced by various agents, such as environmental factors, stress, foods and drugs. Some of these NK cell stimulants have been used in complementary and alternative medicine (CAM since ancient times. Therefore, the value of CAM should be re-evaluated from this point of view. In this review, we overview the intimate correlation between NK cell functions and CAM agents, and discuss possible underlying mechanisms mediating this. In particular, neuro-immune crosstalk and receptors for CAM agents are the most important and interesting candidates for such mechanisms.

  16. Oxidized calmodulin kinase II regulates conduction following myocardial infarction: a computational analysis.

    Directory of Open Access Journals (Sweden)

    Matthew D Christensen


    Full Text Available Calmodulin kinase II (CaMKII mediates critical signaling pathways responsible for divergent functions in the heart including calcium cycling, hypertrophy and apoptosis. Dysfunction in the CaMKII signaling pathway occurs in heart disease and is associated with increased susceptibility to life-threatening arrhythmia. Furthermore, CaMKII inhibition prevents cardiac arrhythmia and improves heart function following myocardial infarction. Recently, a novel mechanism for oxidative CaMKII activation was discovered in the heart. Here, we provide the first report of CaMKII oxidation state in a well-validated, large-animal model of heart disease. Specifically, we observe increased levels of oxidized CaMKII in the infarct border zone (BZ. These unexpected new data identify an alternative activation pathway for CaMKII in common cardiovascular disease. To study the role of oxidation-dependent CaMKII activation in creating a pro-arrhythmia substrate following myocardial infarction, we developed a new mathematical model of CaMKII activity including both oxidative and autophosphorylation activation pathways. Computer simulations using a multicellular mathematical model of the cardiac fiber demonstrate that enhanced CaMKII activity in the infarct BZ, due primarily to increased oxidation, is associated with reduced conduction velocity, increased effective refractory period, and increased susceptibility to formation of conduction block at the BZ margin, a prerequisite for reentry. Furthermore, our model predicts that CaMKII inhibition improves conduction and reduces refractoriness in the BZ, thereby reducing vulnerability to conduction block and reentry. These results identify a novel oxidation-dependent pathway for CaMKII activation in the infarct BZ that may be an effective therapeutic target for improving conduction and reducing heterogeneity in the infarcted heart.

  17. Function of cGMP-dependent protein kinase II in volume load-induced diuresis. (United States)

    Schramm, Andrea; Schinner, Elisabeth; Huettner, Johannes P; Kees, Frieder; Tauber, Philipp; Hofmann, Franz; Schlossmann, Jens


    Atrial natriuretic peptide (ANP)/cGMPs cause diuresis and natriuresis. Their downstream effectors beyond cGMP remain unclear. To elucidate a probable function of cGMP-dependent protein kinase II (cGKII), we investigated renal parameters in different conditions (basal, salt diets, starving, water load) using a genetically modified mouse model (cGKII-KO), but did not detect any striking differences between WT and cGKII-KO. Thus, cGKII is proposed to play only a marginal role in the adjustment of renal concentration ability to varying salt loads without water restriction or starving conditions. When WT mice were subjected to a volume load (performed by application of a 10-mM glucose solution (3% of BW) via feeding needle), they exhibited a potent diuresis. In contrast, urine volume was decreased significantly in cGKII-KO. We showed that AQP2 plasma membrane (PM) abundance was reduced for about 50% in WT upon volume load, therefore, this might be a main cause for the enhanced diuresis. In contrast, cGKII-KO mice almost completely failed to decrease AQP2-PM distribution. This significant difference between both genotypes is not induced by an altered p-Ser256-AQP2 phosphorylation, as phosphorylation at this site decreases similarly in WT and KO. Furthermore, sodium excretion was lowered in cGKII-KO mice during volume load. In summary, cGKII is only involved to a minor extent in the regulation of basal renal concentration ability. By contrast, cGKII-KO mice are not able to handle an acute volume load. Our results suggest that membrane insertion of AQP2 is inhibited by cGMP/cGKII.

  18. Functional analysis of Trichoderma reesei CKIIα2, a catalytic subunit of casein kinase II. (United States)

    Wang, Mingyu; Yang, Hui; Zhang, Meiling; Liu, Kuimei; Wang, Hanbin; Luo, Yi; Fang, Xu


    Trichoderma reesei is the most important industrial cellulase-producing filamentous fungus. Although its molecular physiology has been investigated, the signal transduction pathways are not fully understood. In particular, the role of casein kinase II (CKII) is not yet clear. In this work, we carried out functional investigations on a catalytic subunit of CKII, CKIIα2. Comparison of the phenotypic features of T. reesei parent and Δck2α2 strains showed significant changes following ck2α2 disruption. T. reesei Δck2α2 form significantly smaller mycelial pellets in glucose-containing liquid minimum media, have shorter and fewer branch hyphae, produce smaller amounts of chitinases, produce more spores, show more robust growth on glucose-containing agar plates, and consume glucose at a significantly higher rate. Suggestions can be made that CKIIα2 governs chitinase expression, and the disruption of ck2α2 results in lower levels of chitinase production, leading to a weaker cell wall disruption capability, further resulting in weaker hyphal branching, which eventually leads to smaller mycelial pellets in liquid media. Further conclusions can be made that CKIIα2 is involved in repression of sporulation and glucose metabolism, which is consistent with the proposal that CKIIα2 represses global metabolism. These observations make the deletion of ck2α2 a potentially beneficial genetic disruption for T. reesei during industrial applications, as smaller mycelial pellets, more spores and more robust glucose metabolism are all desired traits for industrial fermentation. This work reports novel unique functions of a CKII catalytic subunit and is also the first genetic and physiological investigation on CKII in T. reesei.

  19. Type II kinase inhibitors show an unexpected inhibition mode against Parkinson's disease-linked LRRK2 mutant G2019S. (United States)

    Liu, Min; Bender, Samantha A; Cuny, Gregory D; Sherman, Woody; Glicksman, Marcie; Ray, Soumya S


    A number of well-known type II inhibitors (ATP-noncompetitive) that bind kinases in their DFG-out conformation were tested against wild-type LRRK2 and the most common Parkinson's disease-linked mutation, G2019S. We found that traditional type II inhibitors exhibit surprising variability in their inhibition mechanism between the wild type (WT) and the G2019S mutant of LRRK2. The type II kinase inhibitors were found to work in an ATP-competitive fashion against the G2019S mutant, whereas they appear to follow the expected noncompetitive mechanism against WT. Because the G2019S mutation lies in the DXG motif (DYG in LRRK2 but DFG in most other kinases) of the activation loop, we explored the structural consequence of the mutation on loop dynamics using an enhanced sampling method called metadynamics. The simulations suggest that the G2019S mutation stabilizes the DYG-in state of LRRK2 through a series of hydrogen bonds, leading to an increase in the conformational barrier between the active and inactive forms of the enzyme and a relative stabilization of the active form. The conformational bias toward the active form of LRRK2 mutants has two primary consequences. (1) The mutant enzyme becomes hyperactive, a known contributor to the Parkinsonian phenotype, as a consequence of being "locked" into the activated state, and (2) the mutation creates an unusual allosteric pocket that can bind type II inhibitors but in an ATP-competitive fashion. Our results suggest that developing type II inhibitors, which are generally considered superior to type I inhibitors because of desirable selectivity profiles, might be especially challenging for the G2019S LRRK2 mutant.

  20. Hepatocyte Growth Factor Inhibits Apoptosis by the Profibrotic Factor Angiotensin II via Extracellular Signal-regulated Kinase 1/2 in Endothelial Cells and Tissue Explants (United States)


    II via Extracellular Signal-regulated Kinase 1/2 in Endothelial Cells and Tissue Explants Young H. Lee, Ana P. Marquez , Ognoon Mungunsukh, and Regina...L., Gonzalez- Garcia , M., Page, C., Herrera, R., and Nunez, G. (1997). Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt... Marquez , A. P., and Day, R. M. (2010). Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial

  1. PreCam

    Energy Technology Data Exchange (ETDEWEB)

    Allam, Sahar S. [Fermilab; Tucker, Douglas L. [Fermilab


    The Dark Energy Survey (DES) will be taking the next step in probing the properties of Dark Energy and in understanding the physics of cosmic acceleration. A step towards the photometric calibration of DES is to have a quick, bright survey in the DES footprint (PreCam), using a pre-production set of the Dark Energy Camera (DECam) CCDs and a set of 100 mm×100 mm DES filters. The objective of the PreCam Survey is to create a network of calibrated DES grizY standard stars that will be used for DES nightly calibrations and to improve the DES global relative calibrations. Here, we describe the first year of PreCam observation, results, and photometric calibrations.

  2. Investigation of Neuronal Cell Type-Specific Gene Expression of Ca2+/Calmodulin-dependent Protein Kinase II.

    Directory of Open Access Journals (Sweden)

    Mima Kazuko


    Full Text Available The promoter activity of the rat Ca2+/calmodulin-dependent protein kinase II gene was analyzed using the luciferase reporter gene in neuronal and non-neuronal cell lines. Neuronal cell type-specific promoter activity was found in the 5'-flanking region of &agr; and &bgr; isoform genes of the kinase. Silencer elements were also found further upstream of promoter regions. A brain-specific protein bound to the DNA sequence of the 5'-flanking region of the gene was found by gel mobility shift analysis in the nuclear extract of the rat brain, including the cerebellum, forebrain, and brainstem, but not in that of non-neuronal tissues, including liver, kidney and spleen. The luciferase expression system and gel shift analysis can be used as an additional and better index by which to monitor gene expression in most cell types.

  3. Endogenous type II cGMP-dependent protein kinase exists as a dimer in membranes and can Be functionally distinguished from the type I isoforms

    NARCIS (Netherlands)

    A.B. Vaandrager (Arie); M.J. Edixhoven (Marcel); A.G. Bot (Alice); M.A. Kroos (Marian); T. Jarchau; S. Lohmann; H.G. Genieser; H.R. de Jonge (Hugo)


    textabstractIn mammalian tissues two types of cGMP-dependent protein kinase (cGK) have been identified. In contrast to the dimeric cGK I, cGK II purified from pig intestine was shown previously to behave as a monomer. However, recombinant rat cGK II was found to have hy

  4. Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion


    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  5. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion


    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  6. A dynamic model of interactions of Ca2+, calmodulin, and catalytic subunits of Ca2+/calmodulin-dependent protein kinase II.

    Directory of Open Access Journals (Sweden)

    Shirley Pepke


    Full Text Available During the acquisition of memories, influx of Ca2+ into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca2+influx during the first few seconds of activity is interpreted within the Ca2+-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity,including Ca2+/calmodulin-dependent protein kinase II (CaMKII, are regulated by calmodulin, a small protein that can bindup to 4 Ca2+ ions. As a first step toward clarifying how the Ca2+-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca2+, calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca2+ play a significant role in activation of CaMKII in the physiological regime,supporting the notion that processing of Ca2+ signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca2+ is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca2+ transients arises from the kinetics of interaction of fluctuating Ca2+with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic

  7. Application of an Online-Coupled Regional Climate Model, WRF-CAM5, over East Asia for Examination of Ice Nucleation Schemes: Part II. Sensitivity to Heterogeneous Ice Nucleation Parameterizations and Dust Emissions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yang; Chen, Ying; Fan, Jiwen; Leung, Lai-Yung


    Aerosol particles can affect cloud microphysical properties by serving as ice nuclei (IN). Large uncertainties exist in the ice nucleation parameterizations (INPs) used in current climate models. In this Part II paper, to examine the sensitivity of the model predictions to different heterogeneous INPs, WRF-CAM5 simulation using the INP of Niemand et al. (N12) [1] is conducted over East Asia for two full years, 2006 and 2011, and compared with simulation using the INP of Meyers et al. (M92) [2], which is the original INP used in CAM5. M92 calculates the nucleated ice particle concentration as a function of ice supersaturation, while N12 represents the nucleated ice particle concentration as a function of temperature and the number concentrations and surface areas of dust particles. Compared to M92, the WRF-CAM5 simulation with N12 produces significantly higher nucleated ice crystal number concentrations (ICNCs) in the northern domain where dust sources are located, leading to significantly higher cloud ice number and mass concentrations and ice water path, but the opposite is true in the southern domain where temperatures and moistures play a more important role in ice formation. Overall, the simulation with N12 gives lower downward shortwave radiation but higher downward longwave radiation, cloud liquid water path, cloud droplet number concentrations, and cloud optical depth. The increase in cloud optical depth and the decrease in downward solar flux result in a stronger shortwave and longwave cloud forcing, and decreases temperature at 2-m and precipitation. Changes in temperature and radiation lower surface concentrations of OH, O3, SO42-, and PM2.5, but increase surface concentrations of CO, NO2, and SO2 over most of the domain. By acting as cloud condensation nuclei (CCN) and IN, dust particles have different impacts on cloud water and ice number concentrations, radiation, and temperature at 2-m and

  8. Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

    Energy Technology Data Exchange (ETDEWEB)

    Muchir, Antoine, E-mail: [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Wu, Wei [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Sera, Fusako; Homma, Shunichi [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Worman, Howard J., E-mail: [Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY (United States); Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY (United States)


    Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna{sup H222P/H222P} mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna{sup H222P/H222P} mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna{sup H222P/H222P} mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna{sup H222P/H222P} mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left

  9. Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells. (United States)

    Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F


    Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function.

  10. Polarized targeting of L1-CAM regulates axonal and dendritic bundling in vitro. (United States)

    Barry, Joshua; Gu, Yuanzheng; Gu, Chen


    Proper axonal and dendritic bundling is essential for the establishment of neuronal connections and the synchronization of synaptic inputs, respectively. Cell adhesion molecules of the L1-CAM (L1-cell adhesion molecule) family regulate axon guidance and fasciculation, neuron migration, dendrite morphology, and synaptic plasticity. It remains unclear how these molecules play so many different roles. Here we show that polarized axon-dendrite targeting of an avian L1-CAM protein, NgCAM (neuron-glia cell adhesion molecule), can regulate the switch of bundling of the two major compartments of rat hippocampal neurons. Using a new in-vitro model for studying neurite-neurite interactions, we found that expressed axonal NgCAM induced robust axonal bundling via the trans-homophilic interaction of immunoglobulin domains. Interestingly, dendritic bundling was induced by the dendritic targeting of NgCAM, caused by either deleting its fibronectin repeats or blocking activities of protein kinases. Consistent with the NgCAM results, expression of mouse L1-CAM also induced axonal bundling and blocking kinase activities disrupted its axonal targeting. Furthermore, the trans-homophilic interaction stabilized the bundle formation, probably through recruiting NgCAM proteins to contact sites and promoting guided axon outgrowth. Taken together, our results suggest that precise localization of L1-CAM is important for establishing proper cell-cell contacts in neural circuits.

  11. The octopamine receptor OAMB mediates ovulation via Ca2+/calmodulin-dependent protein kinase II in the Drosophila oviduct epithelium.

    Directory of Open Access Journals (Sweden)

    Hyun-Gwan Lee

    Full Text Available Ovulation is an essential physiological process in sexual reproduction; however, the underlying cellular mechanisms are poorly understood. We have previously shown that OAMB, a Drosophila G-protein-coupled receptor for octopamine (the insect counterpart of mammalian norepinephrine, is required for ovulation induced upon mating. OAMB is expressed in the nervous and reproductive systems and has two isoforms (OAMB-AS and OAMB-K3 with distinct capacities to increase intracellular Ca2+ or intracellular Ca2+ and cAMP in vitro. Here, we investigated tissue specificity and intracellular signals required for OAMB's function in ovulation. Restricted OAMB expression in the adult oviduct epithelium, but not the nervous system, reinstated ovulation in oamb mutant females, in which either OAMB isoform was sufficient for the rescue. Consistently, strong immunoreactivities for both isoforms were observed in the wild-type oviduct epithelium. To delineate the cellular mechanism by which OAMB regulates ovulation, we explored protein kinases functionally interacting with OAMB by employing a new GAL4 driver with restricted expression in the oviduct epithelium. Conditional inhibition of Ca2+/Calmodulin-dependent protein kinase II (CaMKII, but not protein kinase A or C, in the oviduct epithelium inhibited ovulation. Moreover, constitutively active CaMKII, but not protein kinase A, expressed only in the adult oviduct epithelium fully rescued the oamb female's phenotype, demonstrating CaMKII as a major downstream molecule conveying the OAMB's ovulation signal. This is consistent with the ability of both OAMB isoforms, whose common intracellular signal in vitro is Ca2+, to reinstate ovulation in oamb females. These observations reveal the critical roles of the oviduct epithelium and its cellular components OAMB and CaMKII in ovulation. It is conceivable that the OAMB-mediated cellular activities stimulated upon mating are crucial for secretory activities suitable for egg

  12. Roller Cam Positioners

    Energy Technology Data Exchange (ETDEWEB)

    Bowden, Gordon B.


    Roller Cam Positioners could support the LCLS undulator sections allowing micron sized alignment adjustment of each undulator in 5 degrees of freedom. The supports are kinematic with the number of degrees of freedom matched to the number of constraints. Ton loads are supported on simple ball bearings. Motion is intrinsically bounded. Positioning mechanisms are based on pure rolling motion with sub-micron hysteresis and micron resolution. This note describes a general purpose positioning mechanism suitable for undulator support.

  13. Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by assembling a hexokinase II-Src complex on the mitochondrial surface. (United States)

    Pantic, B; Trevisan, E; Citta, A; Rigobello, M P; Marin, O; Bernardi, P; Salvatori, S; Rasola, A


    The biological functions of myotonic dystrophy protein kinase (DMPK), a serine/threonine kinase whose gene mutations cause myotonic dystrophy type 1 (DM1), remain poorly understood. Several DMPK isoforms exist, and the long ones (DMPK-A/B/C/D) are associated with the mitochondria, where they exert unknown activities. We have studied the isoform A of DMPK, which we have found to be prevalently associated to the outer mitochondrial membrane. The kinase activity of mitochondrial DMPK protects cells from oxidative stress and from the ensuing opening of the mitochondrial permeability transition pore (PTP), which would otherwise irreversibly commit cells to death. We observe that DMPK (i) increases the mitochondrial localization of hexokinase II (HK II), (ii) forms a multimeric complex with HK II and with the active form of the tyrosine kinase Src, binding its SH3 domain and (iii) it is tyrosine-phosphorylated by Src. Both interaction among these proteins and tyrosine phosphorylation of DMPK are increased under oxidative stress, and Src inhibition selectively enhances death in DMPK-expressing cells after HK II detachment from the mitochondria. Down-modulation of DMPK abolishes the appearance of muscle markers in in vitro myogenesis, which is rescued by oxidant scavenging. Our data indicate that, together with HK II and Src, mitochondrial DMPK is part of a multimolecular complex endowed with antioxidant and pro-survival properties that could be relevant during the function and differentiation of muscle fibers.

  14. Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors that do not require binding into the canonical ATP hinge region

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Yu Mi; Clare, Michael; Ensinger, Carol L.; Hood, Molly M.; Lord, John W.; Lu, Wei-Ping; Miller, David F.; Patt, William C.; Smith, Bryan D.; Vogeti, Lakshminarayana; Kaufman, Michael D.; Petillo, Peter A.; Wise, Scott C.; Abendroth, Jan; Chun, Lawrence; Clark, Robin; Feese, Michael; Kim, Hidong; Stewart, Lance; Flynn, Daniel L. (Deciphera); (Emerald); (Cocrystal)


    Switch control pocket inhibitors of p38-alpha kinase are described. Durable type II inhibitors were designed which bind to arginines (Arg67 or Arg70) that function as key residues for mediating phospho-threonine 180 dependant conformational fluxing of p38-alpha from an inactive type II state to an active type I state. Binding to Arg70 in particular led to potent inhibitors, exemplified by DP-802, which also exhibited high kinase selectivity. Binding to Arg70 obviated the requirement for binding into the ATP Hinge region. X-ray crystallography revealed that DP-802 and analogs induce an enhanced type II conformation upon binding to either the unphosphorylated or the doubly phosphorylated form of p38-alpha kinase.

  15. Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors that do not require binding into the canonical ATP hinge region. (United States)

    Ahn, Yu Mi; Clare, Michael; Ensinger, Carol L; Hood, Molly M; Lord, John W; Lu, Wei-Ping; Miller, David F; Patt, William C; Smith, Bryan D; Vogeti, Lakshminarayana; Kaufman, Michael D; Petillo, Peter A; Wise, Scott C; Abendroth, Jan; Chun, Lawrence; Clark, Robin; Feese, Michael; Kim, Hidong; Stewart, Lance; Flynn, Daniel L


    Switch control pocket inhibitors of p38-alpha kinase are described. Durable type II inhibitors were designed which bind to arginines (Arg67 or Arg70) that function as key residues for mediating phospho-threonine 180 dependant conformational fluxing of p38-alpha from an inactive type II state to an active type I state. Binding to Arg70 in particular led to potent inhibitors, exemplified by DP-802, which also exhibited high kinase selectivity. Binding to Arg70 obviated the requirement for binding into the ATP Hinge region. X-ray crystallography revealed that DP-802 and analogs induce an enhanced type II conformation upon binding to either the unphosphorylated or the doubly phosphorylated form of p38-alpha kinase.

  16. Thyroid Disease and Complementary and Alternative Medicine (CAM) (United States)

    ... Alternative Medicine (CAM) Thyroid Disease and Complementary and Alternative Medicine (CAM) WHAT IS COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)? Complementary and Alternative Medicine (CAM) is defined ...

  17. Dynamics of glucose-induced membrane recruitment of protein kinase C beta II in living pancreatic islet beta-cells. (United States)

    Pinton, Paolo; Tsuboi, Takashi; Ainscow, Edward K; Pozzan, Tullio; Rizzuto, Rosario; Rutter, Guy A


    The mechanisms by which glucose may affect protein kinase C (PKC) activity in the pancreatic islet beta-cell are presently unclear. By developing adenovirally expressed chimeras encoding fusion proteins between green fluorescent protein and conventional (betaII), novel (delta), or atypical (zeta) PKCs, we show that glucose selectively alters the subcellular localization of these enzymes dynamically in primary islet and MIN6 beta-cells. Examined by laser scanning confocal or total internal reflection fluorescence microscopy, elevated glucose concentrations induced oscillatory translocations of PKCbetaII to spatially confined regions of the plasma membrane. Suggesting that increases in free cytosolic Ca(2+) concentrations ([Ca(2+)](c)) were primarily responsible, prevention of [Ca(2+)](c) increases with EGTA or diazoxide completely eliminated membrane recruitment, whereas elevation of cytosolic [Ca(2+)](c) with KCl or tolbutamide was highly effective in redistributing PKCbetaII both to the plasma membrane and to the surface of dense core secretory vesicles. By contrast, the distribution of PKCdelta.EGFP, which binds diacylglycerol but not Ca(2+), was unaffected by glucose. Measurement of [Ca(2+)](c) immediately beneath the plasma membrane with a ratiometric "pericam," fused to synaptic vesicle-associated protein-25, revealed that depolarization induced significantly larger increases in [Ca(2+)](c) in this domain. These data demonstrate that nutrient stimulation of beta-cells causes spatially and temporally complex changes in the subcellular localization of PKCbetaII, possibly resulting from the generation of Ca(2+) microdomains. Localized changes in PKCbetaII activity may thus have a role in the spatial control of insulin exocytosis.

  18. Hydrophobic motif site-phosphorylated protein kinaseII between mTORC2 and Akt regulates high glucose-induced mesangial cell hypertrophy. (United States)

    Das, Falguni; Ghosh-Choudhury, Nandini; Mariappan, Meenalakshmi M; Kasinath, Balakuntalam S; Choudhury, Goutam Ghosh


    PKCβII controls the pathologic features of diabetic nephropathy, including glomerular mesangial cell hypertrophy. PKCβII contains the COOH-terminal hydrophobic motif site Ser-660. Whether this hydrophobic motif phosphorylation contributes to high glucose-induced mesangial cell hypertrophy has not been determined. Here we show that, in mesangial cells, high glucose increased phosphorylation of PKCβII at Ser-660 in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. Using siRNAs to downregulate PKCβII, dominant negative PKCβII, and PKCβII hydrophobic motif phosphorylation-deficient mutant, we found that PKCβII regulates activation of mechanistic target of rapamycin complex 1 (mTORC1) and mesangial cell hypertrophy by high glucose. PKCβII via its phosphorylation at Ser-660 regulated phosphorylation of Akt at both catalytic loop and hydrophobic motif sites, resulting in phosphorylation and inactivation of its substrate PRAS40. Specific inhibition of mTORC2 increased mTORC1 activity and induced mesangial cell hypertrophy. In contrast, inhibition of mTORC2 decreased the phosphorylation of PKCβII and Akt, leading to inhibition of PRAS40 phosphorylation and mTORC1 activity and prevented mesangial cell hypertrophy in response to high glucose; expression of constitutively active Akt or mTORC1 restored mesangial cell hypertrophy. Moreover, constitutively active PKCβII reversed the inhibition of high glucose-stimulated Akt phosphorylation and mesangial cell hypertrophy induced by suppression of mTORC2. Finally, using renal cortexes from type 1 diabetic mice, we found that increased phosphorylation of PKCβII at Ser-660 was associated with enhanced Akt phosphorylation and mTORC1 activation. Collectively, our findings identify a signaling route connecting PI3-kinase to mTORC2 to phosphorylate PKCβII at the hydrophobic motif site necessary for Akt phosphorylation and mTORC1 activation, leading to mesangial cell hypertrophy.

  19. Neuronal calcium/calmodulin-dependent protein kinase II mediates nicotine reward in the conditioned place preference test in mice. (United States)

    Jackson, Kia J; Muldoon, Pretal P; Walters, Carrie; Damaj, Mohamad Imad


    Several recent studies have indicated the involvement of calcium-dependent mechanisms, in particular the abundant calcium-activated kinase, calcium/calmodulin-dependent kinase II (CaMKII), in behaviors associated with nicotine dependence in mice. Behavioral and biochemical studies have shown that CaMKII is involved in acute and chronic nicotine behaviors and nicotine withdrawal; however, evidence of a role for CaMKII in nicotine reward is lacking. Thus, the goal of the current study was to examine the role of CaMKII in nicotine reward. Using pharmacological and genetic tools, we tested nicotine conditioned place preference (CPP) in C57Bl/6 mice after administration of CaMKII antagonists and in α-CaMKII wild-type (+/+) and heterozygote (±) mice. CaMKII antagonists blocked expression of nicotine CPP, and the preference score was significantly reduced in α-CaMKII ± mice compared with their +/+ counterparts. Further, we assessed CaMKII activity in the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex, and hippocampus after nicotine CPP and found significant increases in CaMKII activity in the mouse VTA and NAc that were blocked by CaMKII antagonists. The findings from this study show that CaMKII mediates nicotine reward and suggest that increases in CaMKII activity in the VTA and NAc are relevant to nicotine reward behaviors.

  20. Hydraulic involute cam actuator (United States)

    Love, Lonnie J.; Lind, Randall F.


    Mechanical joints are provided in which the angle between a first coupled member and a second coupled member may be varied by mechanical actuators. In some embodiments the angle may be varied around a pivot axis in one plane and in some embodiments the angle may be varied around two pivot axes in two orthogonal planes. The joints typically utilize a cam assembly having two lobes with an involute surface. Actuators are configured to push against the lobes to vary the rotation angle between the first and second coupled member.

  1. Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain

    DEFF Research Database (Denmark)

    Pandey, A.; Dan, I.; Kristiansen, T.Z.;


    activates the JNK kinase pathway but not p38 or ERK pathways. PAK5 transcript is predominantly expressed in brain as revealed by Northern blot and in situ hybridization. The expression pattern of PAK5 is distinct from that of PAK4 and PAK6, suggesting a functional division among PAK-II subfamily kinases......The p21-activated kinase (PAK) family of protein kinases has recently attracted considerable attention as an effector of Rho family of small G proteins and as an upstream regulator of MAPK signalling pathways during cellular events such as re-arrangement of the cytoskeleton and apoptosis. We have...... that PAK5 preferentially binds to CDC42 in the presence of GTP and that CRIB motif is essential for this interaction. PAK5 is a functional protein kinase but unlike PAK-I family kinases (PAK1, 2, and 3), the kinase activity of PAK5 does not seem to require the binding of CDC42. Overexpression of PAK5...

  2. Growth-dependent modulation of casein kinase II and its substrate nucleolin in primary human cell cultures and HeLa cells

    DEFF Research Database (Denmark)

    Schneider, H R; Issinger, O G


    We have previously provided evidence that casein kinase II (CKII) and its substrate nucleolin increase concomitantly during certain development stages during embryogenesis (Schneider et al., Eur. J. Biochem. 161, 733-738). We now show that during normal growth of primary cell cultures and HeLa...

  3. cGMP stimulation of cystic fibrosis transmembrane conductance regulator Cl- channels co-expressed with cGMP-dependent protein kinase type II but not type Ibeta

    NARCIS (Netherlands)

    A.B. Vaandrager (Arie); S.M. Lohmann (Suzanne); H.R. de Jonge (Hugo); W.C. Poller; B.C. Tilly (Bernard); A. Smolenski; S. Schneider-Rasp; A.G. Bot (Alice); M.J. Edixhoven (Marcel); B.J. Scholte (Bob); T. Jarchau; U. Walter


    textabstractIn order to investigate the involvement of cGMP-dependent protein kinase (cGK) type II in cGMP-provoked intestinal Cl- secretion, cGMP-dependent activation and phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels was ana

  4. Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II

    NARCIS (Netherlands)

    P.J. French (Pim); J. Bijman (Jan); M.J. Edixhoven (Marcel); A.B. Vaandrager (Arie); B.J. Scholte (Bob); S.M. Lohmann (Suzanne); A.C. Nairn; H.R. de Jonge (Hugo)


    textabstractType II cGMP-dependent protein kinase (cGKII) isolated from pig intestinal brush borders and type I alpha cGK (cGKI) purified from bovine lung were compared for their ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl- channel in excis

  5. The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury

    Institute of Scientific and Technical Information of China (English)

    Xuewen Liu; Cui Ma; Ruixian Xing; Weiwei Zhang; Buxian Tian; Xidong Li; Qiushi Li; Yanhui Zhang


    In this study, primary cultured cerebral cortical neurons of Sprague-Dawley neonatal rats were treated with 0.25, 0.5, and 1.0 μM calmodulin-dependent protein kinase II inhibitor KN-93 after 50 μM N-methyl-D-aspartic acid-induced injury. Results showed that, compared with N-methyl-Daspartic acid-induced injury neurons, the activity of cells markedly increased, apoptosis was significantly reduced, leakage of lactate dehydrogenase decreased, and intracellular Ca2+ concentrations in neurons reduced after KN-93 treatment. The expression of caspase-3, phosphorylated calmodulin-dependent protein kinase II and total calmodulin-dependent protein kinase II protein decreased after KN-93 treatment. And the effect was apparent at a dose of 1.0 μM KN-93. Experimental findings suggest that KN-93 can induce a dose-dependent neuroprotective effect, and that the underlying mechanism may be related to the down-regulation of caspase-3 and calmodulin- dependent protein kinase II expression.

  6. Extracellular signal regulated kinase and SMAD signaling both mediate the angiotensin II driven progression towards overt heart failure in homozygous TGR(mRen2)27

    NARCIS (Netherlands)

    de Boer, RA; Pokharel, S; Flesch, M; van Kampen, DA; Suurmeijer, AJH; Boomsma, F; van Gilst, WH; van Veldhuisen, DJ; Pinto, YM


    Angiotensin (Ang) II is a key player in left ventricular (LV) remodeling and cardiac fibrosis. Its effects are thought to be transferred at least in part by mitogen-activated protein kinases (MAPK), transforming growth factor (TGF) beta(1), and the Smad pathway. In this study we sought to elucidate

  7. CAD/CAM data management (United States)

    Bray, O. H.


    The role of data base management in CAD/CAM, particularly for geometric data is described. First, long term and short term objectives for CAD/CAM data management are identified. Second, the benefits of the data base management approach are explained. Third, some of the additional work needed in the data base area is discussed.

  8. The Ca²⁺-calmodulin-Ca²⁺/calmodulin-dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes. (United States)

    Toledo, Flavia D; Pérez, Leonardo M; Basiglio, Cecilia L; Ochoa, Justina E; Sanchez Pozzi, Enrique J; Roma, Marcelo G


    Oxidative stress (OS) is a common event in most hepatopathies, leading to mitochondrial permeability transition pore (MPTP) formation and further exacerbation of both OS from mitochondrial origin and cell death. Intracellular Ca²⁺ increase plays a permissive role in these events, but the underlying mechanisms are poorly known. We examined in primary cultured rat hepatocytes whether the Ca²⁺/calmodulin (CaM)-dependent protein kinase II (CaMKII) signaling pathway is involved in this process, by using tert-butyl hydroperoxide (tBOOH) as a pro-oxidant, model compound. tBOOH (500 μM, 15 min) induced MPTP formation, as assessed by measuring mitochondrial membrane depolarization as a surrogate marker, and increased lipid peroxidation in a cyclosporin A (CsA)-sensitive manner, revealing the involvement of MPTPs in tBOOH-induced radical oxygen species (ROS) formation. Intracellular Ca²⁺ sequestration with BAPTA/AM, CaM blockage with W7 or trifluoperazine, and CaMKII inhibition with KN-62 all fully prevented tBOOH-induced MPTP opening and reduced tBOOH-induced lipid peroxidation to a similar extent to CsA, suggesting that Ca²⁺/CaM/CaMKII signaling pathway fully mediates MPTP-mediated mitochondrial ROS generation. tBOOH-induced apoptosis, as shown by flow cytometry of annexin V/propidium iodide, mitochondrial release of cytochrome c, activation of caspase-3 and increase in the Bax-to-Bcl-xL ratio, and the Ca²⁺/CaM/CaMKII signaling antagonists fully prevented these effects. Intramitochondrial CaM and CaMKII were partially involved in tBOOH-induced MPTP formation, since W7 and KN-62 both attenuated the tBOOH-induced, MPTP-mediated swelling of isolated mitochondria. We concluded that Ca²⁺/CaM/CaMKII signaling pathway is a key mediator of OS-induced MPTP formation and the subsequent exacerbation of OS from mitochondrial origin and apoptotic cell death.

  9. Expression of Calmodulin and Myosin Light Chain Kinase during Larval Settlement of the Barnacle Balanus amphitrite

    KAUST Repository

    Chen, Zhang-Fan


    Barnacles are one of the most common organisms in intertidal areas. Their life cycle includes seven free-swimming larval stages and sessile juvenile and adult stages. The transition from the swimming to the sessile stages, referred to as larval settlement, is crucial for their survivor success and subsequent population distribution. In this study, we focused on the involvement of calmodulin (CaM) and its binding proteins in the larval settlement of the barnacle, Balanus (= Amphibalanus) amphitrite. The full length of CaM gene was cloned from stage II nauplii of B. amphitrite (referred to as Ba-CaM), encoding 149 amino acid residues that share a high similarity with published CaMs in other organisms. Quantitative real-time PCR showed that Ba-CaM was highly expressed in cyprids, the stage at which swimming larvae are competent to attach and undergo metamorphosis. In situ hybridization revealed that the expressed Ba-CaM gene was localized in compound eyes, posterior ganglion and cement glands, all of which may have essential functions during larval settlement. Larval settlement assays showed that both the CaM inhibitor compound 48/80 and the CaM-dependent myosin light chain kinase (MLCK) inhibitor ML-7 effectively blocked barnacle larval settlement, whereas Ca 2+/CaM-dependent kinase II (CaMKII) inhibitors did not show any clear effects. The subsequent real-time PCR assay showed a higher expression level of Ba-MLCK gene in larval stages than in adults, suggesting an important role of Ba-MLCK gene in larval development and competency. Overall, the results suggest that CaM and CaM-dependent MLCK function during larval settlement of B. amphitrite. © 2012 Chen et al.

  10. On understanding the very different science premises meaningful to CAM versus orthodox medicine: Part II--applications of Part I fundamentals to five different space-time examples. (United States)

    Tiller, William A


    In Part I of this pair of articles, the fundamental experimental observations and theoretical perspectives were provided for one to understand the key differences between our normal, uncoupled state of physical reality and the human consciousness-induced coupled state of physical reality. Here in Part II, the thermodynamics of complementary and alternative medicine, which deals with the partially coupled state of physical reality, is explored via the use of five different foci of relevance to today's science and medicine: (1) homeopathy; (2) the placebo effect; (3) long-range, room temperature, macroscopic size-scale, information entanglement; (4) an explanation for dark matter/energy plus human levitation possibility; and (5) electrodermal diagnostic devices. The purpose of this pair of articles is to clearly differentiate the use and limitations of uncoupled state physics in both nature and today's orthodox medicine from coupled state physics in tomorrow's complementary and alternative medicine.

  11. Optimisation Methods for Cam Mechanisms

    Directory of Open Access Journals (Sweden)

    Claudia–Mari Popa


    Full Text Available In this paper we present the criteria which represent the base of optimizing the cam mechanisms and also we perform the calculations for several types of mechanisms. We study the influence of the constructive parameters in case of the simple machines with rotation cam and follower (flat or curve of translation on the curvature radius and that of the transmission angle. As it follows, we present the optimization calculations of the cam and flat rotation follower mechanisms, as well as the calculations for optimizing the cam mechanisms by circular groove followers’ help. For an easier interpretation of the results, we have visualized the obtained cam in AutoCAD according to the script files generated by a calculation program.

  12. Rad Pole Cam Development

    Energy Technology Data Exchange (ETDEWEB)

    Heckendorn, F. M.; Odell, D. M. C; Harpring, L. J.; Peterson, K. D.


    The RadPoleCam was developed to provide Department Of Energy (DOE) first responders the capability to assess the radiological and visual condition of remote or inaccessible locations. Real time gamma isotopic identification is provided to the first responder in the form of audio feedback (i.e. spoken through head phones) from a gamma detector mounted on a collapsible pole that can extend from 1 to 9 meters (6 to 29 feet). Simultaneously, selectable direct and side looking visual images are provided from the 5cm (2in) diameter, waterproof probe tip. The lightweight, self contained, ruggedized, system will provide a rapidly deployable field system for visual and radiological search and assessment of confined spaces and extended reach locations.

  13. Immunohistochemical locali- zation of Ca2+/calmodulin- dependent kinase in tobacco

    Institute of Scientific and Technical Information of China (English)


    The existence of Ca2+/calmodulin-dependent kinase (CaM kinase, CaMK) in tobacco is verified immuno- logically and its distribution in different tissues of tobacco is studied. It has been demonstrated that CaMK is mainly distributed in early developing anthers, developing ovules and embryos, lateral root primordium, apical meristem and leaf primordium of buds and mesophyll cells and developing vascular bundles of leaves. There is enormous CaM kinase distributed in leaf epidermis fair cells and guard cells of stomas too. Little kinase is found in mature stem or root cells. The distribution properties of CaM kinase in tobacco are consistent with those of CaM, suggesting that there exists the Ca2+ signal transduction pathway mediated by CaM kinase in tobacco and it plays an important role in the plant growth and development.

  14. Monoclonal antibody against brain calmodulin-dependent protein kinase type II detects putative conformational changes induced by Ca/sup 2 +/-calmodulin

    Energy Technology Data Exchange (ETDEWEB)

    LeVine, H. III; Su, J.L.; Sahyoun, N.E.


    A mouse monoclonal IgG1 antibody has been generated against the soluble form of the calmodulin-dependent protein kinase type II. This antibody recognizes both the soluble and cytoskeletal forms of the enzyme, requiring Ca/sup 2 +/ for the interaction. Other divalent cations such as Zn/sup 2 +/, Mn/sup 2 +/, Cd/sup 2 +/, Co/sup 2 +/, and Ni/sup 2 +/ will substitute for Ca/sup 2 +/, while Mg/sup 2 +/ and Ba/sup 2 +/ will not. The antibody reacts with both the ..cap alpha..- and ..beta..-subunits on Western blots in a similar Ca/sup 2 +/-dependent fashion but with a lower sensitivity. The affinity of the antibody for the kinase is 0.13 nM determined by displacement of /sup 125/I Bolton-Hunter-labeled kinase with unlabeled enzyme. Calmodulin and antibody reciprocally potentiate each other's interaction with the enzyme. This is illustrated both by direct binding studies and by a decrease of the K/sub m app/ for calmodulin and an increase in the V/sub max/ for the autophosphorylation reaction of the enzyme. The antibody thus appears to recognize and stabilize a conformation of the kinase which favors calmodulin binding although it does not itself activate the kinase in the absence of calmodulin. Since the M/sub r/ 30,000 catalytic fragment of the kinase is not immunoreactive, either the antibody combining site of the kinase must be present in the noncatalytic portion of the protein along with the calmodulin binding site or proteolysis interferes with the putative Ca/sup 2 +/-dependent conformational change. Thus, monoclonal antibodies can be useful tools in elucidating the mechanism by which Ca/sup 2 +/ and calmodulin act on the kinase molecule.

  15. Early interference with p44/42 mitogen-activated protein kinase signaling in hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension. (United States)

    Yu, Yang; Xue, Bao-Jian; Zhang, Zhi-Hua; Wei, Shun-Guang; Beltz, Terry G; Guo, Fang; Johnson, Alan Kim; Felder, Robert B


    Blood-borne angiotensin II (ANG II) can upregulate p44/42 mitogen-activated protein kinase (MAPK) signaling and ANG II type-1 receptors in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center. We tested the hypothesis that brain p44/42 MAPK signaling contributes to the development of ANG II-induced hypertension. The ANG II infusion (120 ng/kg per min, subcutaneously) induced increases in phosphorylated p44/42 MAPK and ANG II type-1 receptors in the PVN after 1 week, before the onset of hypertension, that were sustained as hypertension developed during a 2- or 3-week infusion protocol. Bilateral PVN microinjections of small interfering RNAs for p44/42 MAPK, at the onset of the ANG II infusion or 1 week later, prevented the early increase in p44/42 MAPK activity. The early treatment normalized ANG II type-1 receptor expression in the PVN and attenuated the hypertensive response to the 2-week infusion of ANG II. The later small interfering RNA microinjections had a transient effect on ANG II type-1 receptor expression in PVN and no effect on the hypertensive response to the 3-week infusion of ANG II. The early treatment also normalized the pressure response to ganglionic blockade. The ANG II infusion induced increases in mRNA for proinflammatory cytokines that were not affected by either small interfering RNA treatment. These results suggest that the full expression of ANG II-induced hypertension depends on p44/42 MAPK-mediated effects. A potential role for p44/42 MAPK in modulating the ANG II-induced central inflammatory response might also be considered. MAPK signaling in PVN may be a novel target for early intervention in the progression of ANG II-dependent hypertension.

  16. Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice. (United States)

    Wincott, Charlotte M; Kim, Seonil; Titcombe, Roseann F; Tukey, David S; Girma, Hiwot K; Pick, Joseph E; Devito, Loren M; Hofmann, Franz; Hoeffer, Charles; Ziff, Edward B


    Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.

  17. Pavlovian fear conditioning regulates Thr286 autophosphorylation of Ca2+/calmodulin-dependent protein kinase II at lateral amygdala synapses. (United States)

    Rodrigues, Sarina M; Farb, Claudia R; Bauer, Elizabeth P; LeDoux, Joseph E; Schafe, Glenn E


    Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role in synaptic plasticity and memory formation in a variety of learning systems and species. The present experiments examined the role of CaMKII in the circuitry underlying pavlovian fear conditioning. First, we reveal by immunocytochemical and tract-tracing methods that alphaCaMKII is postsynaptic to auditory thalamic inputs and colocalized with the NR2B subunit of the NMDA receptor. Furthermore, we show that fear conditioning results in an increase of the autophosphorylated (active) form of alphaCaMKII in lateral amygdala (LA) spines. Next, we demonstrate that intra-amygdala infusion of a CaMK inhibitor, 1-[NO-bis-1,5-isoquinolinesulfonyl]-N-methyl-l-tyrosyl-4-phenylpiperazine, KN-62, dose-dependently impairs the acquisition, but not the expression, of auditory and contextual fear conditioning. Finally, in electrophysiological experiments, we demonstrate that an NMDA receptor-dependent form of long-term potentiation at thalamic input synapses to the LA is impaired by bath application of KN-62 in vitro. Together, the results of these experiments provide the first comprehensive view of the role of CaMKII in the amygdala during fear conditioning.

  18. Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells. (United States)

    Lipschutz, Joshua H; Li, Shixiong; Arisco, Amy; Balkovetz, Daniel F


    The tight junction of the epithelial cell determines the characteristics of paracellular permeability across epithelium. Recent work points toward the claudin family of tight junction proteins as leading candidates for the molecular components that regulate paracellular permeability properties in epithelial tissues. Madin-Darby canine kidney (MDCK) strain I and II cells are models for the study of tight junctions and based on transepithelial electrical resistance (TER) contain "tight" and "leaky" tight junctions, respectively. Overexpression studies suggest that tight junction leakiness in these two strains of MDCK cells is conferred by expression of the tight junction protein claudin-2. Extracellular signal-regulated kinase (ERK) 1/2 activation by hepatocyte growth factor treatment of MDCK strain II cells inhibited claudin-2 expression and transiently increased TER. This process was blocked by the ERK 1/2 inhibitor U0126. Transfection of constitutively active mitogen-activated protein kinase/extracellular signal-regulated kinase kinase into MDCK strain II cells also inhibited claudin-2 expression and increased TER. MDCK strain I cells have higher levels of active ERK 1/2 than do MDCK strain II cells. U0126 treatment of MDCK strain I cells decreased active ERK 1/2 levels, induced expression of claudin-2 protein, and decreased TER by approximately 20-fold. U0126 treatment also induced claudin-2 expression and decreased TER in a high resistance mouse cortical collecting duct cell line (94D). These data show for the first time that the ERK 1/2 signaling pathway negatively controls claudin-2 expression in mammalian renal epithelial cells and provide evidence for regulation of tight junction paracellular transport by alterations in claudin composition within tight junction complexes.

  19. 2-Cam LWIR imaging Stokes polarimeter (United States)

    Kudenov, Michael W.; Dereniak, Eustace L.; Pezzaniti, Larry; Gerhart, Grant R.


    A 2-Cam micro-bolometer imaging polarimeter operating in the LWIR is presented. The system is capable of snapshot imaging Stokes polarimetry in any one channel (S I, S II, or S 3) by taking two simultaneous measurements of a scene. For measurements of S I or S II, the instrument relies on a specially optimized wire-grid beam-splitter. For measurements of S 3, a form birefringent quarter-wave retarder is inserted into the optical path. Specifics associated with the design of the wire-grid beam-splitter and the form birefringent quarter-wave retarder will be overviewed, with inclusion of RCWA simulations. Calibration and simulation procedures, as well as calibration targets, will be highlighted, and initial data from the instrument are presented.

  20. Production of superoxide from photosystem II-light harvesting complex II supercomplex in STN8 kinase knock-out rice mutants under photoinhibitory illumination. (United States)

    Poudyal, Roshan Sharma; Nath, Krishna; Zulfugarov, Ismayil S; Lee, Choon-Hwan


    When phosphorylation of Photosystem (PS) II core proteins is blocked in STN8 knock-out mutants of rice (Oryza sativa) under photoinhibitory illumination, the mobilization of PSII supercomplex is prevented. We have previously proposed that more superoxide (O2(-)) is produced from PSII in the mutant (Nath et al., 2013, Plant J. 76, 675-686). Here, we clarify the type and site for the generation of reactive oxygen species (ROS). Using both histochemical and fluorescence probes, we observed that, compared with wild-type (WT) leaves, levels of ROS, including O2(-) and hydrogen peroxide (H2O2), were increased when leaves from mutant plants were illuminated with excess light. However, singlet oxygen production was not enhanced under such conditions. When superoxide dismutase was inhibited, O2(-) production was increased, indicating that it is the initial event prior to H2O2 production. In thylakoids isolated from WT leaves, kinase was active in the presence of ATP, and spectrophotometric analysis of nitrobluetetrazolium absorbance for O2(-) confirmed that PSII-driven superoxide production was greater in the mutant thylakoids than in the WT. This contrast in levels of PSII-driven superoxide production between the mutants and the WT plants was confirmed by conducting protein oxidation assays of PSII particles from osstn8 leaves under strong illumination. Those assays also demonstrated that PSII-LHCII supercomplex proteins were oxidized more in the mutant, thereby implying that PSII particles incur greater damage even though D1 degradation during PSII-supercomplex mobilization is partially blocked in the mutant. These results suggest that O2(-) is the major form of ROS produced in the mutant, and that the damaged PSII in the supercomplex is the primary source of O2(-).

  1. Phosphorylation of calcium calmodulin-dependent protein kinase II following lateral fluid percussion brain injury in rats. (United States)

    Folkerts, Michael M; Parks, Elizabeth A; Dedman, John R; Kaetzel, Marcia A; Lyeth, Bruce G; Berman, Robert F


    Traumatic brain injury (TBI) can dramatically increase levels of intracellular calcium ([Ca(2+)](i)). One consequence of increased [Ca(2+)](i) would be altered activity and function of calcium-regulated proteins, including calcium-calmodulin-dependent protein kinase II (CaMKII), which is autophosphorylated on Thr(286)(pCaMKII(286)) in the presence of calcium and calmodulin. Therefore, we hypothesized that TBI would result in increased levels of pCaMKII(286), and that such increases would occur early after injury in brain regions known to be damaged following lateral fluid percussion TBI (i.e., hippocampus and cortex). In order to test this hypothesis, immunostaining of CaMKII was examined in rat hippocampus and cortex after lateral fluid percussion (LFP) injury using an antibody directed against pCaMKII(286). LFP injury produced a marked increase in pCaMKII(286) immunostaining in the hippocampus and overlying cortex 30 min after TBI. The pattern of increased immunostaining was uneven, and unexpectedly absent in some hippocampal CA3 pyramidal neurons. This suggests that phosphatase activity may also increase following TBI, resulting in dephosphorylation of pCaMKII(286) in subpopulations of CA3 pyramidal neurons. Western blotting confirmed a rapid increase in levels of pCaMKII(286) at 10 and 30 min after brain injury, and that it was transient and no longer significantly elevated when examined at 3, 8, and 24 h. These results demonstrate that TBI alters the autophosphorylation state of CaMKII, an important neuronal regulator of critical cell functions, including enzyme activities, cell structure, gene expression, and neuronal plasticity, and provide a molecular mechanism that is likely to contribute to cell injury and impaired plasticity after TBI.

  2. CAD/CAM for optomechatronics (United States)

    Zhou, Haiguang; Han, Min


    We focus at CAD/CAM for optomechatronics. We have developed a kind of CAD/CAM, which is not only for mechanics but also for optics and electronic. The software can be used for training and education. We introduce mechanical CAD, optical CAD and electrical CAD, we show how to draw a circuit diagram, mechanical diagram and luminous transmission diagram, from 2D drawing to 3D drawing. We introduce how to create 2D and 3D parts for optomechatronics, how to edit tool paths, how to select parameters for process, how to run the post processor, dynamic show the tool path and generate the CNC programming. We introduce the joint application of CAD&CAM. We aim at how to match the requirement of optical, mechanical and electronics.

  3. Scleroderma, Stress and CAM Utilization

    Directory of Open Access Journals (Sweden)

    Ka-Kit Hui


    Full Text Available Scleroderma is an autoimmune disease influenced by interplay among genetic and environmental factors, of which one is stress. Complementary and alternative medicine (CAM is frequently used to treat stress and those diseases in which stress has been implicated. Results are presented from a survey of patients with scleroderma. Respondents were a convenient sample of those attending a national conference in Las Vegas in 2002. Findings implicate stress in the onset, continuation and exacerbation of scleroderma. The implication is that CAM providers may be filling an important patient need in their provision of services that identify and treat stress and its related disorders.

  4. Mechanical properties and DIC analyses of CAD/CAM materials (United States)

    Roperto, Renato; Akkus, Anna; Akkus, Ozan; Porto-Neto, Sizenando; Teich, Sorin; Lang, Lisa; Campos, Edson


    Background This study compared two well-known computer-aided-design/computer-aided-manufactured (CAD/CAM) blocks (Paradigm MZ100 [3M ESPE] and Vitablocs Mark II [Vita] in terms of fracture toughness (Kic), index of brittleness (BI) and stress/strain distributions. Material and Methods Three-point bending test was used to calculate the fracture toughness, and the relationship between the Kic and the Vickers hardness was used to calculate the index of brittleness. Additionally, digital image correlation (DIC) was used to analyze the stress/strain distribution on both materials. Results The values for fracture toughness obtained under three-point bending were 1.87Pa√m (±0.69) for Paradigm MZ100 and 1.18Pa√m (±0.17) for Vitablocs Mark II. For the index of brittleness, the values for Paradigm and Vitablocs were 73.13μm-1/2 (±30.72) and 550.22μm-1/2 (±82.46). One-way ANOVA was performed to find differences (α=0.05) and detected deviation between the stress/strain distributions on both materials. Conclusions Both CAD/CAM materials tested presented similar fracture toughness, but, different strain/stress distributions. Both materials may perform similarly when used in CAD/CAM restorations. Key words:Ceramic, CAD/CAM, hybrid materials, composite resin, fracture toughness. PMID:27957262

  5. Casein kinase II induced polymerization of soluble TDP-43 into filaments is inhibited by heat shock proteins.

    Directory of Open Access Journals (Sweden)

    Yari Carlomagno

    Full Text Available BACKGROUND: Trans-activation Response DNA-binding Protein-43 (TDP-43 lesions are observed in Amyotrophic Lateral Sclerosis (ALS, Frontotemporal Lobar Degeneration with ubiquitin inclusions (FTLD-TDP and 25-50% of Alzheimer's Disease (AD cases. These abnormal protein inclusions are composed of either amorphous TDP-43 aggregates or highly ordered filaments. The filamentous TDP-43 accumulations typically contain clean 10-12 nm filaments though wider 18-20 nm coated filaments may be observed. The TDP-43 present within these lesions is phosphorylated, truncated and ubiquitinated, and these modifications appear to be abnormal as they are linked to both a cellular heat shock response and microglial activation. The mechanisms associated with this abnormal TDP-43 accumulation are believed to result in a loss of TDP-43 function, perhaps due to the post-translational modifications or resulting from physical sequestration of the TDP-43. The formation of TDP-43 inclusions involves cellular translocation and conversion of TDP-43 into fibrillogenic forms, but the ability of these accumulations to sequester normal TDP-43 and propagate this behavior between neurons pathologically is mostly inferred. The lack of methodology to produce soluble full length TDP-43 and recapitulate this polymerization into filaments as observed in disease has limited our understanding of these pathogenic cascades. RESULTS: The protocols described here generate soluble, full-length and untagged TDP-43 allowing for a direct assessment of the impact of various posttranslational modifications on TDP-43 function. We demonstrate that Casein Kinase II (CKII promotes the polymerization of this soluble TDP-43 into 10 nm diameter filaments that resemble the most common TDP-43 structures observed in disease. Furthermore, these filaments are recognized as abnormal by Heat Shock Proteins (HSPs which can inhibit TDP-43 polymerization or directly promote TDP-43 filament depolymerization. CONCLUSION

  6. The detection of EpCAM

    NARCIS (Netherlands)

    Wit, De Sanne; Dalum, Van Guus; Lenferink, Aufried T.M.; Tibbe, Arjan G.J.; Hiltermann, T.J.N.; Groen, Harry J.M.; Rijn, Van C.J.M.; Terstappen, Leon W.M.M.


    EpCAM expressing circulating tumor cells, detected by CellSearch, are predictive of short survival in several cancers and may serve as a liquid biopsy to guide therapy. Here we investigate the presence of EpCAM+ CTC detected by CellSearch and EpCAM- CTC discarded by CellSear

  7. Phosphorylation of the PCNA binding domain of the large subunit of replication factor C by Ca2+/calmodulin-dependent protein kinase II inhibits DNA synthesis

    DEFF Research Database (Denmark)

    Maga, G; Mossi, R; Fischer, R


    that the PCNA binding domain is phosphorylated by the Ca2+/calmodulin-dependent protein kinase II (CaMKII), an enzyme required for cell cycle progression in eukaryotic cells. The DNA binding domain, on the other hand, is not phosphorylated. Phosphorylation by CaMKII reduces the binding of PCNA to RF......Replication factor C (RF-C) is a heteropentameric protein essential for DNA replication and DNA repair. It is a molecular matchmaker required for loading of the proliferating cell nuclear antigen (PCNA) sliding clamp onto double-strand DNA and for PCNA-dependent DNA synthesis by DNA polymerases...

  8. Bonding Effectiveness of Luting Composites to Different CAD/CAM Materials



    PURPOSE: To evaluate the influence of different surface treatments of six novel CAD/CAM materials on the bonding effectiveness of two luting composites. MATERIALS AND METHODS: Six different CAD/CAM materials were tested: four ceramics - Vita Mark II; IPS Empress CAD and IPS e.max CAD; Celtra Duo - one hybrid ceramic, Vita Enamic, and one composite CAD/CAM block, Lava Ultimate. A total of 60 blocks (10 per material) received various mechanical surface treatments: 1. 600-grit SiC ...

  9. Protein kinase A type I activates a CRE-element more efficiently than protein kinase A type II regardless of C subunit isoform

    Directory of Open Access Journals (Sweden)

    Kvissel Anne-Katrine


    Full Text Available Abstract Background Protein kinase A type I (PKAI and PKAII are expressed in most of the eukaryotic cells examined. PKA is a major receptor for cAMP and specificity is achieved partly through tissue-dependent expression and subcellular localization of subunits with different biochemical properties. In addition posttranslational modifications help fine tune PKA activity, distribution and interaction in the cell. In spite of this the functional significance of two forms of PKA in one cell has not been fully determined. Here we have tested the ability of PKAI and PKAII formed by expression of the regulatory (R subunits RIα or RIIα in conjunction with Cα1 or Cβ2 to activate a co-transfected luciferace reporter gene, controlled by the cyclic AMP responsive element-binding protein (CREB in vivo. Results We show that PKAI when expressed at equal levels as PKAII was significantly (p Conclusion We suggest that differential effects of PKAI and PKAII in inducing Cre-luciferace activity depend on R and not C subunit identity.

  10. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G


    subunits are highly conserved during evolution. The relationship between CK-2 alpha from humans and plants is still 73%. Similar relationships are reported for the beta-subunit. Chromosomal assignment of CK-2 alpha shows two gene loci, one of which is a pseudogene. They are located on different chromosomes......, no genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2......-subunit affecting: (i) stability, (ii) enzyme specificity and (iii) enzyme activity. The question where CK-2 and its subunits are located throughout the cell cycle has also been addressed, mainly because of the large discrepancies that still exist between results obtained by different investigators. Tissue...

  11. Casein kinase II is required for proper cell division and acts as a negative regulator of centrosome duplication in Caenorhabditis elegans embryos (United States)

    Medley, Jeffrey C.; Kabara, Megan M.; Stubenvoll, Michael D.; DeMeyer, Lauren E.


    ABSTRACT Centrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein kinase II (CK2) in early Caenorhabditis elegans embryos. The catalytic subunit (KIN-3/CK2α) of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner. PMID:27881437

  12. Olmesartan inhibits angiotensin II-Induced migration of vascular smooth muscle cells through Src and mitogen-activated protein kinase pathways. (United States)

    Kyotani, Yoji; Zhao, Jing; Tomita, Sayuko; Nakayama, Hitoshi; Isosaki, Minoru; Uno, Masayuki; Yoshizumi, Masanori


    Clinical studies have shown that angiotensin-receptor blockers (ARBs) reduce the risk of cardiovascular diseases in hypertensive patients. It is assumed that the reduction of the risk by ARBs may be attributed in part to the inhibition of angiotensin II (AII)-induced vascular smooth muscle cell (VSMC) migration associated with atherosclerosis. However, the effect of ARBs on AII-induced changes in intracellular signaling and resultant cell migration has not been well established. Here, we investigated the effect of olmesartan, an ARB, on AII-induced extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) activation and rat aortic smooth muscle cell (RASMC) migration. Olmesartan inhibited AII-induced ERK1/2 and JNK activation at lower concentrations (10 nM). On the other hand, PP2, a Src tyrosine kinase inhibitor, also inhibited AII-induced ERK1/2 and JNK activation, but its effect on ERK1/2 was less pronounced than that of olmesartan. Olmesartan, U0126 (an ERK1/2 inhibitor), SP600125 (a JNK inhibitor), and PP2 potently inhibited AII-induced RASMC migration. From these findings, it was inferred that angiotensin-receptor blockade by olmesartan results in the inhibition of AII-induced activation of Src, ERK1/2, and JNK in RASMC. Olmesartan may be a potent inhibitor of AII-induced VSMC migration, which may be involved in the progression of atherosclerosis.

  13. Phosphorylation and mRNA splicing of collapsin response mediator protein-2 determine inhibition of rho-associated protein kinase (ROCK) II function in carcinoma cell migration and invasion

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Couchman, John R; Yoneda, Atsuko


    migration and invasion. Furthermore, the interaction of CRMP-2 and ROCK II is partially regulated by glycogen synthase kinase (GSK)-3 phosphorylation of CRMP-2, downstream of PI3K. Inhibition of PI3K reduced interaction of CRMP-2 with ROCK II, an effect rescued by simultaneous inhibition of GSK3. Inhibition...... II-CRMP-2 interactions. Using phosphorylation-mimetic and -resistant CRMP-2L constructs, it was revealed that phosphorylation of CRMP-2L negatively regulates its inhibitory function in ROCK-dependent haptotactic cell migration, as well as invasion of human colon carcinoma cells. Collectively......The Rho-associated protein kinases (ROCK I and II) are central regulators of important cellular processes such as migration and invasion downstream of the GTP-Rho. Recently, we reported collapsin response mediator protein (CRMP)-2 as an endogenous ROCK II inhibitor. To reveal how the CRMP-2-ROCK II...

  14. Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a noncanonical CTD-interacting domain fold. (United States)

    Mühlbacher, Wolfgang; Mayer, Andreas; Sun, Mai; Remmert, Michael; Cheung, Alan C M; Niesser, Jürgen; Soeding, Johannes; Cramer, Patrick


    CTDK-I is a yeast kinase complex that phosphorylates the C-terminal repeat domain (CTD) of RNA polymerase II (Pol II) to promote transcription elongation. CTDK-I contains the cyclin-dependent kinase Ctk1 (homologous to human CDK9/CDK12), the cyclin Ctk2 (human cyclin K), and the yeast-specific subunit Ctk3, which is required for CTDK-I stability and activity. Here we predict that Ctk3 consists of a N-terminal CTD-interacting domain (CID) and a C-terminal three-helix bundle domain. We determine the X-ray crystal structure of the N-terminal domain of the Ctk3 homologue Lsg1 from the fission yeast Schizosaccharomyces pombe at 2.0 Å resolution. The structure reveals eight helices arranged into a right-handed superhelical fold that resembles the CID domain present in transcription termination factors Pcf11, Nrd1, and Rtt103. Ctk3 however shows different surface properties and no binding to CTD peptides. Together with the known structure of Ctk1 and Ctk2 homologues, our results lead to a molecular framework for analyzing the structure and function of the CTDK-I complex.

  15. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  16. Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation. (United States)

    Hintermair, Corinna; Heidemann, Martin; Koch, Frederic; Descostes, Nicolas; Gut, Marta; Gut, Ivo; Fenouil, Romain; Ferrier, Pierre; Flatley, Andrew; Kremmer, Elisabeth; Chapman, Rob D; Andrau, Jean-Christophe; Eick, Dirk


    Eukaryotic RNA polymerase II (Pol II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1). Differential phosphorylation of Ser2, Ser5, and Ser7 in the 5' and 3' regions of genes coordinates the binding of transcription and RNA processing factors to the initiating and elongating polymerase complexes. Here, we report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. ChIPseq analyses indicate an increase of Thr4-P levels in the 3' region of genes occurring subsequently to an increase of Ser2-P levels. A Thr4/Ala mutant of Pol II displays a lethal phenotype. This mutant reveals a global defect in RNA elongation, while initiation is largely unaffected. Since Thr4 replacement mutants are viable in yeast we conclude that this amino acid has evolved an essential function(s) in the CTD of Pol II for gene transcription in mammalian cells.

  17. Mangiferin, a natural xanthone, protects murine liver in Pb(II induced hepatic damage and cell death via MAP kinase, NF-κB and mitochondria dependent pathways.

    Directory of Open Access Journals (Sweden)

    Pabitra Bikash Pal

    Full Text Available One of the most well-known naturally occurring environmental heavy metals, lead (Pb has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II] in the form of Pb(NO32 (at a dose of 5 mg/kg body weight, 6 days, orally induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally, on the other hand, diminished the formation of reactive oxygen species (ROS and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT and alkaline phosphatase (ALP]. Mangiferin also reduced Pb(II induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II-induced activation of mitogen-activated protein kinases (MAPKs (phospho-ERK 1/2, phosphor-JNK phospho- p38, nuclear translocation of NF-κB and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II. Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II induced hepatic dysfunction.

  18. Mangiferin, a Natural Xanthone, Protects Murine Liver in Pb(II) Induced Hepatic Damage and Cell Death via MAP Kinase, NF-κB and Mitochondria Dependent Pathways (United States)

    Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.


    One of the most well-known naturally occurring environmental heavy metals, lead (Pb) has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II)] in the form of Pb(NO3)2 (at a dose of 5 mg/kg body weight, 6 days, orally) induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally), on the other hand, diminished the formation of reactive oxygen species (ROS) and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT) and alkaline phosphatase (ALP)]. Mangiferin also reduced Pb(II) induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II)-induced activation of mitogen-activated protein kinases (MAPKs) (phospho-ERK 1/2, phosphor-JNK phospho- p38), nuclear translocation of NF-κB and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II) induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II). Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II) induced hepatic dysfunction. PMID:23451106

  19. Theoretical investigation, biological evaluation and VEGFR2 kinase studies of metal(II) complexes derived from hydrotris(methimazolyl)borate. (United States)

    Jayakumar, S; Mahendiran, D; Srinivasan, T; Mohanraj, G; Kalilur Rahiman, A


    The reaction of soft tripodal scorpionate ligand, sodium hydrotris(methimazolyl)borate with M(ClO4)2·6H2O [MMn(II), Ni(II), Cu(II) or Zn(II)] in methanol leads to the cleavage of B-N bond followed by the formation of complexes of the type [M(MeimzH)4](ClO4)2·H2O (1-4), where MeimzH=methimazole. All the complexes were fully characterized by spectro-analytical techniques. The molecular structure of the zinc(II) complex (4) was determined by X-ray crystallography, which supports the observed deboronation reaction in the scorpionate ligand with tetrahedral geometry around zinc(II) ion. The electronic spectra of complexes suggested tetrahedral geometry for manganese(II) and nickel(II) complexes, and square-planar geometry for copper(II) complex. Frontier molecular orbital analysis (HOMO-LUMO) was carried out by B3LYP/6-31G(d) to understand the charge transfer occurring in the molecules. All the complexes exhibit significant antimicrobial activity against Gram (-ve) and Gram (+ve) bacterial as well as fungal strains, which are quite comparable to standard drugs streptomycin and clotrimazole. The copper(II) complex (3) showed excellent free radical scavenging activity against DPPH in all concentration with IC50 value of 30μg/mL, when compared to the other complexes. In the molecular docking studies, all the complexes showed hydrophobic, π-π and hydrogen bonding interactions with BSA. The cytotoxic activity of the complexes against human hepatocellular liver carcinoma (HepG2) cells was assessed by MTT assay, which showed exponential responses toward increasing concentration of complexes.

  20. Hazmat Cam Wireless Video System

    Energy Technology Data Exchange (ETDEWEB)

    Kevin L. Young


    This paper describes the Hazmat Cam Wireless Video System and its application to emergency response involving chemical, biological or radiological contamination. The Idaho National Laboratory designed the Hazmat Cam Wireless Video System to assist the National Guard Weapons of Mass Destruction - Civil Support Teams during their mission of emergency response to incidents involving weapons of mass destruction. The lightweight, handheld camera transmits encrypted, real-time video from inside a contaminated area, or hot-zone, to a command post located a safe distance away. The system includes a small wireless video camera, a true-diversity receiver, viewing console, and an optional extension link that allows the command post to be placed up to five miles from danger. It can be fully deployed by one person in a standalone configuration in less than 10 minutes. The complete system is battery powered. Each rechargeable camera battery powers the camera for 3 hours with the receiver and video monitor battery lasting 22 hours on a single charge. The camera transmits encrypted, low frequency analog video signals to a true-diversity receiver with three antennas. This unique combination of encryption and transmission technologies delivers encrypted, interference-free images to the command post under conditions where other wireless systems fail. The lightweight camera is completely waterproof for quick and easy decontamination after use. The Hazmat Cam Wireless Video System is currently being used by several National Guard Teams, the US Army, and by fire fighters. The system has been proven to greatly enhance situational awareness during the crucial, initial phase of a hazardous response allowing commanders to make better, faster, safer decisions.

  1. Effect of Anacyclus pyrethrum on pentylenetetrazole-induced kindling, spatial memory, oxidative stress and rho-kinase II expression in mice. (United States)

    Pahuja, Monika; Mehla, Jogender; Reeta, K H; Tripathi, Manjari; Gupta, Yogendra Kumar


    Anacyclus pyrethrum (A. pyrethrum) has been reported to exhibit anticonvulsant activity. In the present study, the effect of hydro-alcoholic extract of A. pyrethrum root (HEAP) on pentylenetetrazole (PTZ) induced kindling, spatial memory, oxidative stress and rho kinase (ROCK II) was assessed. Male albino mice (25-30 g) were used in the study. PTZ (35 mg/kg, i.p. on alternate days) was injected to induce kindling and PTZ (70 mg/kg, i.p) challenge was given 7 days post-kindling. HEAP was administered orally daily in the doses of 100, 250 and 500 mg/kg along with PTZ injections during the kindling process and continued till PTZ challenge post kindling. Spatial memory was assessed using Morris water maze test. Oxidative stress parameters [malondialdehyde (MDA) and reduced glutathione (GSH)] and ROCK II expression were estimated in whole brain at the end of the study. Pre-treatment with HEAP (250 and 500 mg/kg) showed significant increase in the myoclonic jerk latency and delay in the development of kindling. A significant decrease in mortality was observed at higher doses of HEAP (250 and 500 mg/kg). Pre-treatment with HEAP significantly increased the number of platform crossings and decreased the escape latency, as opposed to the PTZ group, thus showing protection against memory deficit. HEAP pre-treatment also attenuated the oxidative stress induced by PTZ kindling. PTZ induced kindling increased the ROCK II expression whereas, HEAP pre-treatment attenuated the increase in ROCK II expression. To conclude, HEAP pre-treatment showed antiepileptic effect and also showed protection against cognitive impairment by decreasing oxidative stress and ROCK II expression in PTZ kindled mice.

  2. AMP-activated protein kinase inhibits TGF-β-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition. (United States)

    Lee, Jang Han; Kim, Ji Hyun; Kim, Ja Seon; Chang, Jai Won; Kim, Soon Bae; Park, Jung Sik; Lee, Sang Koo


    The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-β (TGF-β), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-β (10 ng/ml), angiotensin II (1 μM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1β riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-β, angiotensin II, aldosterone, high glucose, and urinary albumin.

  3. Phosphorylation at Ser²⁶ in the ATP-binding site of Ca²⁺/calmodulin-dependent kinase II as a mechanism for switching off the kinase activity. (United States)

    Yilmaz, Mehtap; Gangopadhyay, Samudra S; Leavis, Paul; Grabarek, Zenon; Morgan, Kathleen G


    CaMKII (Ca²⁺/calmodulin-dependent kinase II) is a serine/threonine phosphotransferase that is capable of long-term retention of activity due to autophosphorylation at a specific threonine residue within each subunit of its oligomeric structure. The γ isoform of CaMKII is a significant regulator of vascular contractility. Here, we show that phosphorylation of CaMKII γ at Ser²⁶, a residue located within the ATP-binding site, terminates the sustained activity of the enzyme. To test the physiological importance of phosphorylation at Ser²⁶, we generated a phosphospecific Ser²⁶ antibody and demonstrated an increase in Ser²⁶ phosphorylation upon depolarization and contraction of blood vessels. To determine if the phosphorylation of Ser²⁶ affects the kinase activity, we mutated Ser²⁶ to alanine or aspartic acid. The S26D mutation mimicking the phosphorylated state of CaMKII causes a dramatic decrease in Thr²⁸⁷ autophosphorylation levels and greatly reduces the catalytic activity towards an exogenous substrate (autocamtide-3), whereas the S26A mutation has no effect. These data combined with molecular modelling indicate that a negative charge at Ser²⁶ of CaMKII γ inhibits the catalytic activity of the enzyme towards its autophosphorylation site at Thr²⁸⁷ most probably by blocking ATP binding. We propose that Ser²⁶ phosphorylation constitutes an important mechanism for switching off CaMKII activity.

  4. L-type calcium channels and calcium/calmodulin-dependent kinase II differentially mediate behaviors associated with nicotine withdrawal in mice. (United States)

    Jackson, K J; Damaj, M I


    Smoking is a widespread health problem. Because the nicotine withdrawal syndrome is a major contributor to continued smoking and relapse, it is important to understand the molecular and behavioral mechanisms of nicotine withdrawal to generate more effective smoking cessation therapies. Studies suggest a role for calcium-dependent mechanisms, such as L-type calcium channels and calcium/calmodulin-dependent protein kinase II (CaMKII), in the effects of nicotine dependence; however, the role of these mechanisms in nicotine-mediated behaviors is unclear. Thus, the goal of this study was to elucidate the role of L-type calcium channels and CaMKII in nicotine withdrawal behaviors. Using both pharmacological and genetic methods, our results show that L-type calcium channels are involved in physical, but not affective, nicotine withdrawal behaviors. Although our data do provide evidence of a role for CaMKII in nicotine withdrawal behaviors, our pharmacological and genetic assessments yielded different results concerning the specific role of the kinase. Pharmacological data suggest that CaMKII is involved in somatic signs and affective nicotine withdrawal, and activity level is decreased after nicotine withdrawal, whereas the genetic assessments yielded results suggesting that CaMKII is involved only in the anxiety-related response, yet the kinase activity may be increased after nicotine withdrawal; thus, future studies are necessary to clarify the precise behavioral specifics of the relevance of CaMKII in nicotine withdrawal behaviors. Overall, our data show that L-type calcium channels and CaMKII are relevant in nicotine withdrawal and differentially mediate nicotine withdrawal behaviors.

  5. Phosphorylation of calcium/calmodulin-stimulated protein kinase II at T286 enhances invasion and migration of human breast cancer cells (United States)

    Chi, Mengna; Evans, Hamish; Gilchrist, Jackson; Mayhew, Jack; Hoffman, Alexander; Pearsall, Elizabeth Ann; Jankowski, Helen; Brzozowski, Joshua Stephen; Skelding, Kathryn Anne


    Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional kinase that controls a range of cellular functions, including proliferation, differentiation and apoptosis. The biological properties of CaMKII are regulated by multi-site phosphorylation. However, the role that CaMKII phosphorylation plays in cancer cell metastasis has not been examined. We demonstrate herein that CaMKII expression and phosphorylation at T286 is increased in breast cancer when compared to normal breast tissue, and that increased CAMK2 mRNA is associated with poor breast cancer patient prognosis (worse overall and distant metastasis free survival). Additionally, we show that overexpression of WT, T286D and T286V forms of CaMKII in MDA-MB-231 and MCF-7 breast cancer cells increases invasion, migration and anchorage independent growth, and that overexpression of the T286D phosphomimic leads to a further increase in the invasive, migratory and anchorage independent growth capacity of these cells. Pharmacological inhibition of CaMKII decreases MDA-MB-231 migration and invasion. Furthermore, we demonstrate that overexpression of T286D, but not WT or T286V-CaMKII, leads to phosphorylation of FAK, STAT5a, and Akt. These results demonstrate a novel function for phosphorylation of CaMKII at T286 in the control of breast cancer metastasis, offering a promising target for the development of therapeutics to prevent breast cancer metastasis. PMID:27605043

  6. Ca²⁺/calmodulin-dependent protein kinase II contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available We have recently shown that p38MAP kinase (p38MAPK stimulates ROS generation via the activation of NADPH oxidase during neonatal hypoxia-ischemia (HI brain injury. However, how p38MAPK is activated during HI remains unresolved and was the focus of this study. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII plays a key role in brain synapse development, neural transduction and synaptic plasticity. Here we show that CaMKII activity is stimulated in rat hippocampal slice culture exposed to oxygen glucose deprivation (OGD to mimic the condition of HI. Further, the elevation of CaMKII activity, correlated with enhanced p38MAPK activity, increased superoxide generation from NADPH oxidase as well as necrotic and apoptotic cell death. All of these events were prevented when CaMKII activity was inhibited with KN93. In a neonatal rat model of HI, KN93 also reduced brain injury. Our results suggest that CaMKII activation contributes to the oxidative stress associated with neural cell death after HI.

  7. Onzichtbare beugels dankzij CAD-CAM

    NARCIS (Netherlands)

    F.R. de Winter


    De introductie van de cad-cam-techniek in de tandheelkunde heeft in de orthodontie geleid tot het orthodontisch verplaatsen van gebitselementen met een serie opeenvolgende dieptrekplaten, ontworpen en gefabriceerd met behulp van cad-cam. Daarbij is iedere plaat een kleine stap in de richting van de

  8. L1CAM Binds ErbB Receptors through Ig-Like Domains Coupling Cell Adhesion and Neuregulin Signalling (United States)

    Grijota-Martinez, Carmen; Lakomá, Jarmila; Baars, Sigrid; Garcia-Alonso, Luis; Cabedo, Hugo


    During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a system works in coordination is not well understood. Cross-regulatory interactions between different signalling pathways and redundancy between them can increase precision and fidelity of guidance systems. Immunoglobulin superfamily proteins of the NCAM and L1 families couple specific substrate recognition and cell adhesion with the activation of receptor tyrosine kinases. Thus it has been shown that L1CAM-mediated cell adhesion promotes the activation of the EGFR (erbB1) from Drosophila to humans. Here we explore the specificity of the molecular interaction between L1CAM and the erbB receptor family. We show that L1CAM binds physically erbB receptors in both heterologous systems and the mammalian developing brain. Different Ig-like domains located in the extracellular part of L1CAM can support this interaction. Interestingly, binding of L1CAM to erbB enhances its response to neuregulins. During development this may synergize with the activation of erbB receptors through L1CAM homophilic interactions, conferring diffusible neuregulins specificity for cells or axons that interact with the substrate through L1CAM. PMID:22815787

  9. Beta 2 subunit-containing nicotinic receptors mediate acute nicotine-induced activation of calcium/calmodulin-dependent protein kinase II-dependent pathways in vivo. (United States)

    Jackson, K J; Walters, C L; Damaj, M I


    Nicotine is the addictive component of tobacco, and successful smoking cessation therapies must address the various processes that contribute to nicotine addiction. Thus, understanding the nicotinic acetylcholine receptor (nAChR) subtypes and subsequent molecular cascades activated after nicotine exposure is of the utmost importance in understanding the progression of nicotine dependence. One possible candidate is the calcium/calmodulin-dependent protein kinase II (CaMKII) pathway. Substrates of this kinase include the vesicle-associated protein synapsin I and the transcription factor cAMP response element-binding protein (CREB). The goal of these studies was to examine these postreceptor mechanisms after acute nicotine treatment in vivo. We first show that administration of nicotine increases CaMKII activity in the ventral tegmental area (VTA), nucleus accumbens (NAc), and amygdala. In beta2 nAChR knockout (KO) mice, nicotine does not induce an increase in kinase activity, phosphorylated (p)Synapsin I, or pCREB. In contrast, alpha7 nAChR KO mice show nicotine-induced increases in CaMKII activity and pCREB, similar to their wild-type littermates. Moreover, we show that when animals are pretreated with the CaMKII inhibitors 4-[(2S)-2-[(5-isoquinolinylsulfonyl) methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl]phenyl isoquinolinesulfonic acid ester (KN-62) and N-[2-[[[3-(4-chlorophenyl)-2 propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphonamide (KN-93), nicotine-induced increase in the kinase activity and pCREB was attenuated in the VTA and NAc, whereas pretreatment with (2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, phosphate) (KN-92), the inactive analog, did not alter the nicotine-induced increase in pCREB. Taken together, these data suggest that the nicotine-induced increase in CaMKII activity may correlate with the nicotine-induced increase in pSynapsin I and pCREB in the VTA and NAc via beta2

  10. Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels.

    Directory of Open Access Journals (Sweden)

    Huy Q Nguyen

    Full Text Available The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.

  11. Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels (United States)

    Nguyen, Huy Q.; Nye, Jonathan; Buster, Daniel W.; Klebba, Joseph E.; Rogers, Gregory C.; Bosco, Giovanni


    The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein. PMID:25723539

  12. Central SDF-1/CXCL12 expression and its cardiovascular and sympathetic effects: the role of angiotensin II, TNF-α, and MAP kinase signaling. (United States)

    Wei, Shun-Guang; Zhang, Zhi-Hua; Yu, Yang; Felder, Robert B


    The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptors are expressed by neurons and glial cells in cardiovascular autonomic regions of the brain, including the hypothalamic paraventricular nucleus (PVN), and contribute to neurohumoral excitation in rats with ischemia-induced heart failure. The present study examined factors regulating the expression of SDF-1 in the PVN and mechanisms mediating its sympatho-excitatory effects. In urethane anesthetized rats, a 4-h intracerebroventricular (ICV) infusion of angiotensin II (ANG II) or tumor necrosis factor-α (TNF-α) in doses that increase mean blood pressure (MBP) and sympathetic drive increased the expression of SDF-1 in PVN. ICV administration of SDF-1 increased the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK), JNK, and p38 MAPK in PVN, along with MBP, heart rate (HR), and renal sympathetic nerve activity (RSNA), but did not affect total p44/42 MAPK, JNK, and p38 MAPK levels. ICV pretreatment with the selective p44/42 MAPK inhibitor PD98059 prevented the SDF-1-induced increases in MBP, HR, and RSNA; ICV pretreatment with the selective JNK and p38 MAPK inhibitors attenuated but did not block these SDF-1-induced excitatory responses. ICV PD98059 also prevented the sympatho-excitatory response to bilateral PVN microinjections of SDF-1. ICV pretreatment with SDF-1 short-hairpin RNA significantly reduced ANG II- and TNF-α-induced phosphorylation of p44/42 MAPK in PVN. These findings identify TNF-α and ANG II as drivers of SDF-1 expression in PVN and suggest that the full expression of their cardiovascular and sympathetic effects depends upon SDF-1-mediated activation of p44/42 MAPK signaling.

  13. Validation of aerosols, reactive gases and greenhouse gases in the CAMS forecasts, analyses and reanalyses (United States)

    Eskes, Henk; Basart, Sara; Blechschmidt, Anne; Chabrillat, Simon; Clark, Hannah; Cuevas, Emilio; Engelen, Richard; Kapsomenakis, John; Katragkou, Eleni; Mantzius Hansen, Kaj; Niemeijer, Sander; Ramonet, Michel; Schulz, Michael; Sudarchikova, Natalia; Wagner, Annette; Warneke, Thorsten


    The Atmosphere Monitoring Service of the European Copernicus Programme (CAMS) is an operational service providing analyses, reanalyses and daily forecasts of aerosols, reactive gases and greenhouse gases on a global scale, and air quality forecasts and reanalyses on a regional scale. CAMS is based on the systems developed during the European MACC I-II-III (Monitoring Atmospheric Composition and Climate) research projects. In CAMS data assimilation techniques are applied to combine in-situ and remote sensing observations with global and European-scale models of atmospheric reactive gases, aerosols and greenhouse gases. The global component is based on the Integrated Forecast System of the ECMWF, and the regional component on an ensemble of 7 European air quality models. CAMS is implemented by ECMWF, and the transition from MACC to CAMS is currently being implemented (2015-2016). CAMS has a dedicated validation activity, a partnership of 13 institutes co-ordinated by KNMI, to document the quality of the atmospheric composition products. In our contribution we discuss this validation activity, including the measurement data sets, validation requirements, the operational aspects, the upgrade procedure, the validation reports and scoring methods, and the model configurations and assimilation systems validated. Of special concern are the forecasts of high pollution concentration events (fires, dust storms, air pollution events, volcano ash and SO2). A few interesting validation results will be shown.

  14. Strategies for the Design of a Slide-o-Cam Transmission

    CERN Document Server

    Chablat, Damien


    The optimization of the pressure angle in a cam-follower transmission is reported in this paper. This transmission is based on Slide-o-Cam, a cam mechanism with multiple rollers mounted on a common translating follower. The design of Slide-o-Cam, a transmission intended to produce a sliding motion from a turning drive, or vice versa, was reported elsewhere. This transmission provides pure-rolling motion, thereby reducing the friction of rack-and-pinions and linear drives. The pressure angle is a suitable performance index for this transmission because it determines the amount of force transmitted to the load vs. that transmitted to the machine frame. Two alternative design strategies are studied, namely, (i) increase the number of lobes on each cam or (ii) increase the number of cams. This device is intended to replace the current ball-screws in Orthoglide, a three-DOF parallel robot for the production of translational motions, currently under development at Ecole Centrale de Nantes for machining applications...

  15. Materials for chairside CAD/CAM restorations. (United States)

    Fasbinder, Dennis J


    Chairside computer-aided design/computer-aided manufacturing (CAD/CAM) systems have become considerably more accurate, efficient, and prevalent as the technology has evolved in the past 25 years. The initial restorative material option for chairside CAD/CAM restorations was limited to ceramic blocks. Restorative material options have multiplied and now include esthetic ceramics, high-strength ceramics, and composite materials for both definitive and temporary restoration applications. This article will review current materials available for chairside CAD/CAM restorations.

  16. CAM Stochastic Volatility Model for Option Pricing

    Directory of Open Access Journals (Sweden)

    Wanwan Huang


    Full Text Available The coupled additive and multiplicative (CAM noises model is a stochastic volatility model for derivative pricing. Unlike the other stochastic volatility models in the literature, the CAM model uses two Brownian motions, one multiplicative and one additive, to model the volatility process. We provide empirical evidence that suggests a nontrivial relationship between the kurtosis and skewness of asset prices and that the CAM model is able to capture this relationship, whereas the traditional stochastic volatility models cannot. We introduce a control variate method and Monte Carlo estimators for some of the sensitivities (Greeks of the model. We also derive an approximation for the characteristic function of the model.

  17. Aberrant calcium/calmodulin-dependent protein kinase II (CaMKII) activity is associated with abnormal dendritic spine morphology in the ATRX mutant mouse brain. (United States)

    Shioda, Norifumi; Beppu, Hideyuki; Fukuda, Takaichi; Li, En; Kitajima, Isao; Fukunaga, Kohji


    In humans, mutations in the gene encoding ATRX, a chromatin remodeling protein of the sucrose-nonfermenting 2 family, cause several mental retardation disorders, including α-thalassemia X-linked mental retardation syndrome. We generated ATRX mutant mice lacking exon 2 (ATRX(ΔE2) mice), a mutation that mimics exon 2 mutations seen in human patients and associated with milder forms of retardation. ATRX(ΔE2) mice exhibited abnormal dendritic spine formation in the medial prefrontal cortex (mPFC). Consistent with other mouse models of mental retardation, ATRX(ΔE2) mice exhibited longer and thinner dendritic spines compared with wild-type mice without changes in spine number. Interestingly, aberrant increased calcium/calmodulin-dependent protein kinase II (CaMKII) activity was observed in the mPFC of ATRX(ΔE2) mice. Increased CaMKII autophosphorylation and activity were associated with increased phosphorylation of the Rac1-guanine nucleotide exchange factors (GEFs) T-cell lymphoma invasion and metastasis 1 (Tiam1) and kalirin-7, known substrates of CaMKII. We confirmed increased phosphorylation of p21-activated kinases (PAKs) in mPFC extracts. Furthermore, reduced protein expression and activity of protein phosphatase 1 (PP1) was evident in the mPFC of ATRX(ΔE2) mice. In cultured cortical neurons, PP1 inhibition by okadaic acid increased CaMKII-dependent Tiam1 and kalirin-7 phosphorylation. Together, our data strongly suggest that aberrant CaMKII activation likely mediates abnormal spine formation in the mPFC. Such morphological changes plus elevated Rac1-GEF/PAK signaling seen in ATRX(ΔE2) mice may contribute to mental retardation syndromes seen in human patients.

  18. Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kouchi, Zen, E-mail: [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Fujiwara, Yuki [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Yamaguchi, Hideki [Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-city, Saitama 332-0012 (Japan); Nakamura, Yoshikazu; Fukami, Kiyoko [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan)


    Highlights: {yields} We analyzed Phosphatidylinositol 5-phosphate kinase II{beta} (PIPKII{beta}) function in cancer. {yields} PIPKII{beta} is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. {yields} PIPKII{beta} suppresses cellular motility through E-cadherin induction in SW480 cells. {yields} Nuclear PIP{sub 2} but not plasma membrane-localized PIP{sub 2} mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1{alpha},25-dihydroxyvitamin D{sub 3} (1{alpha},25(OH){sub 2}D{sub 3}) has anti-cancer activity in several colon cancers. 1{alpha},25(OH){sub 2}D{sub 3} induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKII{beta}) but not PIPKII{alpha} is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLC{delta}1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P{sub 2}) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLC{delta}1 PHD inhibited 1{alpha},25(OH){sub 2}D{sub 3}-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P{sub 2} production mediates E-cadherin expression through PIPKII{beta} in a VDR-dependent manner. PIPKII{beta} is also involved in the suppression of the cell motility induced by 1{alpha},25(OH){sub 2}D{sub 3}. These results indicate that PIPKII{beta}-mediated PI(4,5)P{sub 2} signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

  19. IBD and Complementary and Alternative Medicine (CAM) (United States)

    ... interventions that focus on the interplay between emotional, mental, social, spiritual, and behavioral factors and their influence on health. Examples include prayer, tai chi, hypnosis, meditation, biofeedback, and yoga. Some techniques that were considered CAM in the ...

  20. AFSC/FMA/CAMS Data Objects (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The CAMS system consists of a set of tables and packages that provide authentication services to all other North Pacific Groundfish and Halibut Observing Program...

  1. Patients’ views of CAM as spiritual practice

    DEFF Research Database (Denmark)

    Ulrich, Anita; Evron, Lotte; Ostenfeld-Rosenthal, Ann


    Objectives: This paper explores Danish cancer patients’ narratives on spiritual beliefs, practices and the relationship these practices may have to complementary and alternative medicine (CAM). Design: Narrative inquiry was used to understand how spiritual beliefs and practices might be related t....... For some individuals a belief in the ‘spiritual’ role of CAM per se may be analogous to religious belief.......Objectives: This paper explores Danish cancer patients’ narratives on spiritual beliefs, practices and the relationship these practices may have to complementary and alternative medicine (CAM). Design: Narrative inquiry was used to understand how spiritual beliefs and practices might be related...... to CAM. Thirty-two cancer patients, family, friends and alternative practitioners were followed up over a two year period by face to face interview, telephone and focus groups. Results: Although religious and spiritual issues were not manifestly expressed by many of the subjects, these issues were...

  2. Knowledge and training needs among Danish nurses about CAM

    DEFF Research Database (Denmark)

    Lunde, Anita


    to explore nurses’ knowledge about CAM and their needs for training. Methods: Similar to international investigations a Danish “CAM-knowledge” questionnaire was developed that included multiple choice, yes/no and 5 points scale answers. Validity was established through initial pilot testing. Contacts...... of CAM also tend to have a theoretical background of CAM. Around 75 % of the nurses agree or partly agree that it is important for nurses to receive education about CAM and that nurses have knowledge about CAM that enables them to advise patients. Training needs concerning CAM were indicated by 52....... Conclusion: Among Danish nurses CAM knowledge can be described as minor or average and a minority already has CAM education. Additional CAM training would be welcomed by more than half of the respondents in this survey....

  3. Model Documentation for the MiniCAM

    Energy Technology Data Exchange (ETDEWEB)

    Brenkert, Antoinette L.; Smith, Steven J.; Kim, Son H.; Pitcher, Hugh M.


    The MiniCAM, short for the Mini-Climate Assessment Model, is an integrated assessment model of moderate complexity focused on energy and agriculture sectors. The model produces emissions of greenhouse gases (carbon dioxide, methane and nitrous oxide) and other radiatively important substances such as sulfur dioxide. Through incorporation of the simple climate model MAGICC, the consequences of these emissions for climate change and sea-level rise can be examined. The MiniCAM is designed to be fast and flexible.

  4. Chiropractic and CAM Utilization: A Descriptive Review

    Directory of Open Access Journals (Sweden)

    Meeker William C


    Full Text Available Abstract Objective To conduct a descriptive review of the scientific literature examining use rates of modalities and procedures used by CAM clinicians to manage chronic LBP and other conditions Data Sources A literature of PubMed and MANTIS was performed using the key terms Chiropractic; Low Back Pain; Utilization Rate; Use Rate; Complementary and Alternative Medicine; and Health Services in various combinations. Data Selection A total of 137 papers were selected, based upon including information about chiropractic utilization, CAM utilization and low back pain and other conditions. Data Synthesis Information was extracted from each paper addressing use of chiropractic and CAM, and is summarized in tabular form. Results Thematic analysis of the paper topics indicated that there were 5 functional areas covered by the literature: back pain papers, general chiropractic papers, insurance-related papers, general CAM-related papers; and worker's compensation papers. Conclusion Studies looking at chiropractic utilization demonstrate that the rates vary, but generally fall into a range from around 6% to 12% of the population, most of whom seek chiropractic care for low back pain and not for organic disease or visceral dysfunction. CAM is itself used by people suffering from a variety of conditions, though it is often used not as a primary intervention, but rather as an additional form of care. CAM and chiropractic often offer lower costs for comparable results compared to conventional medicine.

  5. Genomic analyses of the CAM plant pineapple. (United States)

    Zhang, Jisen; Liu, Juan; Ming, Ray


    The innovation of crassulacean acid metabolism (CAM) photosynthesis in arid and/or low CO2 conditions is a remarkable case of adaptation in flowering plants. As the most important crop that utilizes CAM photosynthesis, the genetic and genomic resources of pineapple have been developed over many years. Genetic diversity studies using various types of DNA markers led to the reclassification of the two genera Ananas and Pseudananas and nine species into one genus Ananas and two species, A. comosus and A. macrodontes with five botanical varieties in A. comosus. Five genetic maps have been constructed using F1 or F2 populations, and high-density genetic maps generated by genotype sequencing are essential resources for sequencing and assembling the pineapple genome and for marker-assisted selection. There are abundant expression sequence tag resources but limited genomic sequences in pineapple. Genes involved in the CAM pathway has been analysed in several CAM plants but only a few of them are from pineapple. A reference genome of pineapple is being generated and will accelerate genetic and genomic research in this major CAM crop. This reference genome of pineapple provides the foundation for studying the origin and regulatory mechanism of CAM photosynthesis, and the opportunity to evaluate the classification of Ananas species and botanical cultivars.

  6. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity (United States)

    Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.


    casein kinase II (CKII) inhibitor, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3-fold at 24 h post-infection. In contrast, 100 μm of the CKII inhibitor reduced the titre of the M type only 1.3-fold at 48 h post-infection. Our data suggest that the different growth of U- and M-type IHNV in RTG-2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.

  7. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity. (United States)

    Park, J W; Moon, C H; Harmache, A; Wargo, A R; Purcell, M K; Bremont, M; Kurath, G


    casein kinase II (CKII) inhibitor, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3-fold at 24 h post-infection. In contrast, 100 μm of the CKII inhibitor reduced the titre of the M type only 1.3-fold at 48 h post-infection. Our data suggest that the different growth of U- and M-type IHNV in RTG-2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.

  8. Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II {beta} subunit (CSNK2B)

    Energy Technology Data Exchange (ETDEWEB)

    Albertella, M.R.; Jones, H.; Thomson, W. [Oxford Univ. (United Kingdom)] [and others


    A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An {approximately}220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II{beta} subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product. 49 refs., 8 figs.

  9. Theoretical calculations, DNA interaction, topoisomerase I and phosphatidylinositol-3-kinase studies of water soluble mixed-ligand nickel(II) complexes. (United States)

    Gurumoorthy, Perumal; Mahendiran, Dharmasivam; Kalilur Rahiman, Aziz


    Eight water soluble mixed-ligand nickel(II) complexes of the type [NiL(1-4)(diimine)H2O]·(ClO4)2, (1-8) where L(1-4) = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) were synthesized and characterized by elemental analysis and spectroscopic methods. The uncoordinated perchlorate anions was ascertained form IR spectra of the complexes, and the absorption spectra reveal the octahedron geometry around nickel(II) ion with tridentate Schiff base ligand, diimine and a coordinated water molecule. Cyclic voltammograms of the complexes indicate the one-electron irreversible processes in the cathodic and anodic region. In vitro antioxidant activity proved the significant radical scavenging activity of the complexes against DPPH radical. The groove/electrostatic binding nature of complexes with CT-DNA (calf thymus deoxyribonucleic acid) were affirmed by absorption, hydrodynamic and voltammetric titration experiments and docking analysis. All the complexes exhibit significant cleavage activity on plasmid DNA via hydrolytic and oxidatively, in which the oxidative mechanism involves hydroxyl radicals and supports the possibility of minor-groove binding. The complex 4 shows significant topoisomerase I (Topo-I) inhibitory activity. The molecular modeling analysis of complexes with phosphatidylinositol-3-kinase (PI3K) receptor indicate the hydrogen bonding with Met1039, Asp837 and Leu1027, and hydrophobic interactions with Ser488, Asn498, Asp500, Gln662, Lys668, Ile844, Ile847, Ile850, Val941, Leu942, Leu1020, Met1034, Leu1035, Thr1037, Met1039, Gln1041 and Ile1051 of subdomain IIA of BSA. The complexes show σ-π interaction between diimines and amino groups of Leu1030 and Arg839.

  10. Pharmacological and safety evaluation of CIGB-300, a casein kinase 2 inhibitor peptide, administered intralesionally to patients with cervical cancer stage IB2/II

    Directory of Open Access Journals (Sweden)

    Soriano-García JL


    Full Text Available CIGB-300 is a pro-apoptotic casein kinase 2 inhibitor peptide with potential anticancer action. An open-label and dose scaling Phase I trial was carried out to investigate the peptide tumor uptake, pharmacokinetics, toxicity, and levels of a CIGB-300 response biomarker in patients with cervical cancer stage IB2/II. Fourteen patients were included; six of them received 35 mg, 6 received 70 mg and the two remaining patients received 245 mg of CIGB-300 prior chemoradiotherapy. CIGB-300 was applied by intratumor injections during 5-consecutive days. For pharmacokinetic and biodistribution studies, the peptide was radiolabeled with 99mTc in the first administration and whole body gammagraphy and plasma testing were done during 48 h. Data showed that the maximum tolerated dose was 70 mg for CIGB-300 in this clinical setting. Furthermore, an allergic-like syndrome was identified as the dose limiting toxicity, which was well-correlated with plasmatic histamine levels. Importantly, the mean tumor uptake was 14.9 mg and 10.4 mg for CIGB-300 doses of 35 and 70 mg, respectively. Also, the kidneys were the main target organ for drug elimination. Finally, treatment with CIGB-300 significantly reduced the B23/nucleophosmin levels in tumor specimens. CIGB-300 meets potentialities to be tested in future trials in a neoadjuvant setting prior to chemoradiotherapy in cervical cancer.

  11. cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits. (United States)

    Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B


    Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response.

  12. Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia. (United States)

    Chen, Yan; Yang, Cheng; Wang, Zaijie Jim


    Repeated administration of opioids not only leads to tolerance and dependence, but also results in nociceptive enhancement called opioid-induced hyperalgesia (OIH). Nociceptive mediators involved in OIH generation remain poorly understood. In the present study, we tested the hypothesis that Ca(2+)/calmodulin-depent protein kinase II (CaMKIIalpha) is critical for OIH. Opioid-induced hyperalgesia was produced by repeated morphine administration or pellet implantation in mice. Correlating with the development of tactile allodynia and thermal hyperalgesia, spinal CaMKIIalpha activity was significantly increased in OIH. KN93, a CaMKII inhibitor, dose- and time-dependently reversed OIH and CaMKII activation without impairing locomotor coordination. To elucidate the specific CaMKII isoform involved, we targeted CaMKIIalpha by using small interfering RNA and demonstrated that knockdown of spinal CaMKIIalpha attenuated OIH. Furthermore, morphine failed to induce OIH in CaMKIIalpha(T286A) point mutant mice, although wild-type littermate mice developed robust OIH after repeated treatments with morphine. These data implicate, for the first time, an essential role of CaMKIIalpha as a cellular mechanism leading to and maintaining opioid-induced hyperalgesia.

  13. Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

    Directory of Open Access Journals (Sweden)

    Hyun-Soo Kim


    Full Text Available Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02, casein kinase II (CKII, and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.

  14. Muestreo en transecto de formaciones vegetales de fanerófitos y caméfitos (MIFC (II: estudio de los sabinares de la Reserva Biológica de Doñana (RBD (España

    Directory of Open Access Journals (Sweden)

    Cámara Artigas, Rafael


    Full Text Available In this document the savin juniper forest or bosque de naves of Juniperus phoenicea subsp. turbinata (Guss. Nyman has been characterized in the Doñana Biological Reserve (DRB, by using a plant inventory methodology in linear transects. In this case, the inventory of phanerophytes and chamaephytes (MIFC in the area surrounding the lagoons of Charco del Toro (CHT and Navazo del Toro (NVT has been consi - dered. They have identified 5 different groups according to their constituent elements and their variables of vertical and horizontal structure (coverage. These are geo - botanically related with the aeolian mantle units of Doñana, as well as with the beha - vior of high transmissivity and hydrodynamic subsurface of the surface formations on which they are distributed. The group considered as savin juniper type formation is located in the Upper Dry Aeolian Mantle (UDAM where the sabinar de El Ojillo is found (Group 1: NVTV 19.Se estudia el bosque de sabinar o «bosque de naves» de Juniperus phoenicea subsp. turbinata (Guss. Nyman de la Reserva Biológica de Doñana (RBD, en el entorno de las lagunas de Charco del Toro (CHT y Navazo del Toro (NVT utilizando el Método de Inventario de Fanerófitos y Caméfitos (MIFC. Se identifican cinco grupos de sabinares en función de sus elementos constitutivos y la estructura vertical y horizontal (cobertura. Geobotánicamente los sabinares se relacionan con los mantos eólicos litorales de Doñana que tienen una alta conductividad hidráulica y ausencia de una dinámica hídrica subsuperficial. El grupo considerado como formación sabinar-tipo se localiza en el Alto Manto Eólico Seco (AMEs en el paraje del sabinar de El Ojillo (Grupo 1: NVTv 19. [fr] La forêt de genévriers ou forêt de navires de Juniperus phoenicea subsp. turbinata (Guss. Nyman a été caractérisée dans la Réserve Biologique de Doñana (RBD en utilisant une méthodologie d’inventaire végétal en transects linéaires consid

  15. Transparency in Dutch CAM practices: a comparison between CAM and GP physicians.

    NARCIS (Netherlands)

    Heiligers, P.; Dulmen, S. van


    Introduction: CAM (Complementary and Alternative Medicine) is increasing worldwide because the demand is growing. Transparency is needed to provide more objective information about CAM services, to date largely unknown by a majority of care users and mainstream care providers. Despite the fact that

  16. A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma

    NARCIS (Netherlands)

    F. Morschhauser; J.F. Seymour; H.C. Kluin-Nelemans (Hanneke); A. Grigg; M. Wolf; M. Pfreundschuh (Michael); H. Tilly (Herve); J. Raemaekers; M.B. van 't Veer (Mars); N. Milpied; G. Cartron; A. Pezzutto; A. Spencer; F. Reyes; M. Dreyling (Martin)


    textabstractBackground: Protein kinase C beta (PKCβ), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses

  17. A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma

    NARCIS (Netherlands)

    Morschhauser, F.; Seymour, J. F.; Kluin-Nelemans, H. C.; Grigg, A.; Wolf, M.; Pfreundschuh, M.; Tilly, H.; Raemaekers, J.; van 't Veer, M. B.; Milpied, N.; Cartron, G.; Pezzutto, A.; Spencer, A.; Reyes, F.; Dreyling, M.


    Background: Protein kinase C beta (PKC beta), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signali

  18. Next Generation CAD/CAM/CAE Systems (United States)

    Noor, Ahmed K. (Compiler); Malone, John B. (Compiler)


    This document contains presentations from the joint UVA/NASA Workshop on Next Generation CAD/CAM/CAE Systems held at NASA Langley Research Center in Hampton, Virginia on March 18-19, 1997. The presentations focused on current capabilities and future directions of CAD/CAM/CAE systems, aerospace industry projects, and university activities related to simulation-based design. Workshop attendees represented NASA, commercial software developers, the aerospace industry, government labs, and academia. The workshop objectives were to assess the potential of emerging CAD/CAM/CAE technology for use in intelligent simulation-based design and to provide guidelines for focused future research leading to effective use of CAE systems for simulating the entire life cycle of aerospace systems.

  19. Possible interaction of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II on reversal of spatial memory impairment induced by morphine. (United States)

    Farahmandfar, Maryam; Kadivar, Mehdi; Naghdi, Nasser


    The opioid system plays an important role in learning and memory by modulation of different molecules in the brain. The aim of the present study was to investigate the role of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II (CaMKII) on the morphine-induced modulation of spatial memory consolidation in male rats. Spatial memory was assessed in Morris water maze task by a single training session of eight trials followed by a probe trial and visible test 24h later. Our data indicated that post-training administration of L-arginine, a nitric oxide precursor (6 and 9 µg/rat, intra-CA1) significantly decreased amnesia induced by morphine (10 mg/kg) in spatial memory consolidation. A reversal effect of L-arginine on morphine-induced amnesia prevented by KN-93 (N-[2-(N-(4-chlorocinnamyl)-N-methylaminomethyl) phenyl]-N-[2-hydroxyethyl] methoxybenzenesulfnamide), CaMKII inhibitor, (10 nmol/0.5 µl/site). In addition, post-training injection of L-NAME, (NG-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (10 and 15 µg/rat) or KN-93 (10 nmol/0.5 µl/site) with lower dose of morphine (2.5 mg/kg), which did not induce amnesia by itself, caused inhibition of memory consolidation. We also showed that co-administration of L-arginine (9 µg/rat) and morphine (10 mg/kg) significantly increased CaMKII activity in the rat hippocampus. On the other hand, administration of L-NAME (10 µg/rat) led to a decrease in the haippocampal activity of CaMKII in morphine-treated (2.5mg/kg) animals. These results indicate that acute single exposure to morphine can modulate consolidation of spatial memory, which may be mediated by a hippocampal nitrergic system and CaMKII activity.

  20. Age-dependent targeting of protein phosphatase 1 to Ca2+/calmodulin-dependent protein kinase II by spinophilin in mouse striatum.

    Directory of Open Access Journals (Sweden)

    Anthony J Baucum

    Full Text Available Mechanisms underlying age-dependent changes of dendritic spines on striatal medium spiny neurons are poorly understood. Spinophilin is an F-actin- and protein phosphatase 1 (PP1-binding protein that targets PP1 to multiple downstream effectors to modulate dendritic spine morphology and function. We found that calcium/calmodulin-dependent protein kinase II (CaMKII directly and indirectly associates with N- and C-terminal domains of spinophilin, but F-actin can displace CaMKII from the N-terminal domain. Spinophilin co-localizes PP1 with CaMKII on the F-actin cytoskeleton in heterologous cells, and spinophilin co-localizes with synaptic CaMKII in neuronal cultures. Thr286 autophosphorylation enhances the binding of CaMKII to spinophilin in vitro and in vivo. Although there is no change in total levels of Thr286 autophosphorylation, maturation from postnatal day 21 into adulthood robustly enhances the levels of CaMKII that co-immunoprecipitate with spinophilin from mouse striatal extracts. Moreover, N- and C-terminal domain fragments of spinophilin bind more CaMKII from adult vs. postnatal day 21 striatal lysates. Total levels of other proteins that interact with C-terminal domains of spinophilin decrease during maturation, perhaps reducing competition for CaMKII binding to the C-terminal domain. In contrast, total levels of α-internexin and binding of α-internexin to the spinophilin N-terminal domain increases with maturation, perhaps bridging an indirect interaction with CaMKII. Moreover, there is an increase in the levels of myosin Va, α-internexin, spinophilin, and PP1 in striatal CaMKII immune complexes isolated from adult and aged mice compared to those from postnatal day 21. These changes in spinophilin/CaMKII interactomes may contribute to changes in striatal dendritic spine density, morphology, and function during normal postnatal maturation and aging.

  1. VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shang; Dang, Yuan Ye; Oi Lam Che, Ginny [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China); Kwan, Yiu Wa [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Chan, Shun Wan [State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong (China); Leung, George Pak Heng [Pharmacology and Pharmacy, Faculty of Medicine, The University of Hong Kong, Hong Kong (China); Lee, Simon Ming Yuen, E-mail: [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China); Hoi, Maggie Pui Man, E-mail: [State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao (China)


    In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities. - Highlights: • In vivo VRI model • Rescue effects of calycosin • Calycosin EC survival pathways.

  2. Regulation of voltage-gated Ca(2+) currents by Ca(2+)/calmodulin-dependent protein kinase II in resting sensory neurons. (United States)

    Kostic, Sandra; Pan, Bin; Guo, Yuan; Yu, Hongwei; Sapunar, Damir; Kwok, Wai-Meng; Hudmon, Andy; Wu, Hsiang-En; Hogan, Quinn H


    Calcium/calmodulin-dependent protein kinase II (CaMKII) is recognized as a key element in encoding depolarization activity of excitable cells into facilitated voltage-gated Ca(2+) channel (VGCC) function. Less is known about the participation of CaMKII in regulating VGCCs in resting cells. We examined constitutive CaMKII control of Ca(2+) currents in peripheral sensory neurons acutely isolated from dorsal root ganglia (DRGs) of adult rats. The small molecule CaMKII inhibitor KN-93 (1.0μM) reduced depolarization-induced ICa by 16-30% in excess of the effects produced by the inactive homolog KN-92. The specificity of CaMKII inhibition on VGCC function was shown by the efficacy of the selective CaMKII blocking peptide autocamtide-2-related inhibitory peptide in a membrane-permeable myristoylated form, which also reduced VGCC current in resting neurons. Loss of VGCC currents is primarily due to reduced N-type current, as application of mAIP selectively reduced N-type current by approximately 30%, and prior N-type current inhibition eliminated the effect of mAIP on VGCCs, while prior block of L-type channels did not reduce the effect of mAIP on total ICa. T-type currents were not affected by mAIP in resting DRG neurons. Transduction of sensory neurons in vivo by DRG injection of an adeno-associated virus expressing AIP also resulted in a loss of N-type currents. Together, these findings reveal a novel molecular adaptation whereby sensory neurons retain CaMKII support of VGCCs despite remaining quiescent.

  3. CAM practitioners in the Australian health workforce: an underutilized resource

    Directory of Open Access Journals (Sweden)

    Grace Sandra


    Full Text Available Abstract Background CAM practitioners are a valuable but underutilizes resource in Australian health care. Despite increasing public support for complementary and alternative medicine (CAM little is known about the CAM workforce. Apart from the registered professions of chiropractic, osteopathy and Chinese medicine, accurate information about the number of CAM practitioners in the workforce has been difficult to obtain. It appears that many non-registered CAM practitioners, although highly qualified, are not working to their full capacity. Discussion Increasing public endorsement of CAM stands in contrast to the negative attitude toward the CAM workforce by some members of the medical and other health professions and by government policy makers. The marginalisation of the CAM workforce is evident in prejudicial attitudes held by some members of the medical and other health professions and its exclusion from government policy making. Inconsistent educational standards has meant that non-registered CAM practitioners, including highly qualified and competent ones, are frequently overlooked. Legitimising their contribution to the health workforce could alleviate workforce shortages and provide opportunities for redesigned job roles and new multidisciplinary teams. Priorities for better utilisation of the CAM workforce include establishing a guaranteed minimum education standard for more CAM occupation groups through national registration, providing interprofessional education that includes CAM practitioners, developing courses to upgrade CAM practitioners' professional skills in areas of indentified need, and increasing support for CAM research. Summary Marginalisation of the CAM workforce has disadvantaged those qualified and competent CAM practitioners who practise evidence-informed medicine on the basis of many years of university training. Legitimising and expanding the important contribution of CAM practitioners could alleviate projected health

  4. Georeferencing CAMS data: Polynomial rectification and beyond (United States)

    Yang, Xinghe

    The Calibrated Airborne Multispectral Scanner (CAMS) is a sensor used in the commercial remote sensing program at NASA Stennis Space Center. In geographic applications of the CAMS data, accurate geometric rectification is essential for the analysis of the remotely sensed data and for the integration of the data into Geographic Information Systems (GIS). The commonly used rectification techniques such as the polynomial transformation and ortho rectification have been very successful in the field of remote sensing and GIS for most remote sensing data such as Landsat imagery, SPOT imagery and aerial photos. However, due to the geometric nature of the airborne line scanner which has high spatial frequency distortions, the polynomial model and the ortho rectification technique in current commercial software packages such as Erdas Imagine are not adequate for obtaining sufficient geometric accuracy. In this research, the geometric nature, especially the major distortions, of the CAMS data has been described. An analytical step-by-step geometric preprocessing has been utilized to deal with the potential high frequency distortions of the CAMS data. A generic sensor-independent photogrammetric model has been developed for the ortho-rectification of the CAMS data. Three generalized kernel classes and directional elliptical basis have been formulated into a rectification model of summation of multisurface functions, which is a significant extension to the traditional radial basis functions. The preprocessing mechanism has been fully incorporated into the polynomial, the triangle-based finite element analysis as well as the summation of multisurface functions. While the multisurface functions and the finite element analysis have the characteristics of localization, piecewise logic has been applied to the polynomial and photogrammetric methods, which can produce significant accuracy improvement over the global approach. A software module has been implemented with full

  5. Web-based CAD and CAM for optomechatronics (United States)

    Han, Min; Zhou, Hai-Guang


    CAD & CAM technologies are being used in design and manufacturing process, and are receiving increasing attention from industries and education. We have been researching to develop a new kind of software that is for web-course CAD & CAM. It can be used either in industries or in training, it is supported by IE. Firstly, we aim at CAD/CAM for optomechatronics. We have developed a kind of CAD/CAM, which is not only for mechanics but also for optics and electronic. That is a new kind of software in China. Secondly, we have developed a kind of software for web-course CAD & CAM, we introduce the basis of CAD, the commands of CAD, the programming, CAD/CAM for optomechatronics, the joint application of CAD & CAM. We introduce the functions of MasterCAM, show the whole processes of CAD/CAM/CNC by examples. Following the steps showed on the web, the trainer can not miss. CAD & CAM are widely used in many areas, development of web-course CAD & CAM is necessary for long- distance education and public education. In 1992, China raised: CAD technique, as an important part of electronic technology, is a new key technique to improve the national economic and the modernization of national defence. As so for, the education. Of CAD & CAM is mainly involved in manufacturing industry in China. But with the rapidly development of new technology, especially the development of optics and electronics, CAD & CAM will receive more attention from those areas.

  6. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)


    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

  7. Integrated design of cam mechanisms and servo-control systems

    Institute of Scientific and Technical Information of China (English)

    姚燕安[1; 颜鸿森[2; 张策[3; 邹慧君[4


    Traditionally, in a cam mechanism, the cam is driven by an actuator at a constant speed. The motion characteristics of the follower are determined once the cam profile is designed. This paper presents a novel theory named "integrated design of cam mechanisms and servo-control systems" whose basic idea is varying the input speed trajectory of the cam by a microcomputer-controlled servomotor to improve kinematic and dynamic characteristics of the follower system. The philosophy of the theory is developing superior machines by taking advantage of the flexibility of servo-control systems to compensate for disadvantages of rigid cam mechanisms. The systematic design criteria of the cam-servo-integrated system are developed and an approach based on optimal-control theory is presented for to select suitable cam speed functions, hence the basis of the theory is formed.

  8. Complementary and Alternative Medicine (CAM) Treatments and Pediatric Psychopharmacology (United States)

    Rey, Joseph M.; Walter, Garry; Soh, Nerissa


    Children and adolescents often use complementary and alternative medicine (CAM) treatments outside their indications, particularly to lose weight. Some of the herbal remedies and dietary supplements that may of relevance for psychopharmacological practice are discussed with respect to CAM treatments.

  9. DFM/CAPP/CAM System in a Concurrent Engineering Environment

    Institute of Scientific and Technical Information of China (English)


    In this paper the importance of DFM/CAPP/CAM system in Concurrent Engineering (CE) is discussed. Based on the analyses of the character of concurrent product design and manufacturing process design, the workflow of DFM/CAPP/CAM system in CE is given. DFM/CAPP/CAM theories, methods and functions are investigated in a delicate and all-round way, and are implemented in the developed DFM/CAPP/CAM system.

  10. Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase Ⅳ expression in nucleus accumbens of rats: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei-liang BIAN; Gui-qin XIE; Sheng-zhong CUI; Mei-ling WU; Yue-hua LI; Ling-li QUE; Xiao-ru YUAN


    Aim: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase Ⅳ (CaM kinase Ⅳ) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of non-selective opioid antagonist (naloxone) on the CaM kinase Ⅳ expression in the NAc and ethanol consumption of rats were also observed. Methods: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase Ⅳ levels in the NAc were analyzed using Western blotting. Results: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase Ⅳ expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenu-ated ethanol intake of rats and antagonized the decrease of CaM kinase Ⅳ in the nuclei of NAc neurons. The cytosolic CaM kinase Ⅳ protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. Conclusion: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase Ⅳ signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase Ⅳ in the NAc.

  11. CAD/CAM. High-Technology Training Module. (United States)

    Zuleger, Robert

    This high technology training module is an advanced course on computer-assisted design/computer-assisted manufacturing (CAD/CAM) for grades 11 and 12. This unit, to be used with students in advanced drafting courses, introduces the concept of CAD/CAM. The content outline includes the following seven sections: (1) CAD/CAM software; (2) computer…

  12. Education and Training Packages for CAD/CAM. (United States)

    Wright, I. C.


    Discusses educational efforts in the fields of Computer Assisted Design and Manufacturing (CAD/CAM). Describes two educational training initiatives underway in the United Kingdom, one of which is a resource materials package for teachers of CAD/CAM at the undergraduate level, and the other a training course for managers of CAD/CAM systems. (TW)

  13. Current techniques in CAD/CAM denture fabrication. (United States)

    Baba, Nadim Z; AlRumaih, Hamad S; Goodacre, Brian J; Goodacre, Charles J


    Recently, the use of computer-aided design/computer-aided manufacturing (CAD/CAM) to produce complete dentures has seen exponential growth in the dental market, and the number of commercially available CAD/CAM denture systems grows every year. The purpose of this article is to describe the clinical and laboratory procedures of 5 CAD/CAM denture systems.

  14. Faint stars and OmegaCAM

    NARCIS (Netherlands)

    Kuijken, K; Cristiani, S; Renzini, A; Williams, RE


    OmegaCAM will be the wide-field imager on the VLT Survey Telescope. In this contribution I present applications of this instrument to the study of faint stellar populations. Two projects are highlighted: a proper motion study to uncover the galactic halo population, and a microlensing study towards


    Directory of Open Access Journals (Sweden)

    E. B. Romanova


    Full Text Available The subject matter of the paper is the process of data translation between computer-aided design system for electronic devices PADS VX and system for technological preparation of production of printed circuit boards CAM350 10. The object of this study is two-way translation of data in these systems. Experimental researches are applied as research methods based on repeated playback of forward and reverse data translation process between PADS and CAM350 systems. The aim is to examine the challenges of data exchange between systems and to find out the ways of their solution. The basis of the work is functionality analysis of PADS and CAM350 systems while data translation, which was carried out in the course of operating experience of these systems. The paper presents advantages and disadvantages of translation methods and their comparison. Errors arising in the process are analyzed. Possible reasons of errors origination are described. The main results are recommendations for data exchange between PADS and CAM350 systems. The proposed recommendations give the possibility to optimize the exchange of data between these systems. Practical significance of the work lies in the implementation of results at LLC «Abeo». Recommendations have been used in the development of dozens of different electronic devices. The use of these results made it possible to reduce the production run-up time, to increase data transmission correctness, thereby improving the quality of products and reduction of their cost.

  16. Bridging CAM practice and research: teaching CAM practitioners about research methodology. (United States)

    Zick, Suzanna M; Benn, Rita


    The National Institutes of Health (NIH) is continuing to provide funds directed to support research in complementary and alternative medicine (CAM). CAM providers typically have insufficient knowledge of scientific language or research methodology to develop rigorous proposals. Their ability to contribute meaningfully as advisors, teachers, or research partners in academic settings, is hence limited. To address this issue, we have developed and implemented a 7-week course designed to teach community-based CAM providers: (1) to understand scientific terminology, research design and grantsmanship; (2) to critically evaluate the research literature; and (3) to design pilot studies in areas of their interest. In this article, we describe the recruitment process for selecting course participants, the course design and instructional process and the evaluation results based on qualitative and quantitative methodology. We offer suggestions for developing training opportunities both at the local and national level that would increase the expertise of CAM providers in participating and seeking funded research.

  17. Impact of future climate policy scenarios on air quality and aerosol-cloud interactions using an advanced version of CESM/CAM5: Part II. Future trend analysis and impacts of projected anthropogenic emissions (United States)

    Glotfelty, Timothy; Zhang, Yang


    Following a comprehensive evaluation of the Community Earth System Model modified at the North Carolina State University (CESM-NCSU), Part II describes the projected changes in the future state of the atmosphere under the representative concentration partway scenarios (RCP4.5 and 8.5) by 2100 for the 2050 time frame and examine the impact of climate change on future air quality under both scenarios, and the impact of projected emission changes under the RCP4.5 scenario on future climate through aerosol direct and indirect effects. Both the RCP4.5 and RCP8.5 simulations predict similar changes in air quality by the 2050 period due to declining emissions under both scenarios. The largest differences occur in O3, which decreases by global mean of 1.4 ppb under RCP4.5 but increases by global mean of 2.3 ppb under RCP8.5 due to differences in methane levels, and PM10, which decreases by global mean of 1.2 μg m-3 under RCP4.5 and increases by global mean of 0.2 μg m-3 under RCP8.5 due to differences in dust and sea-salt emissions under both scenarios. Enhancements in cloud formation in the Arctic and Southern Ocean and increases of aerosol optical depth (AOD) in central Africa and South Asia dominate the change in surface radiation in both scenarios, leading to global average dimming of 1.1 W m-2 and 2.0 W m-2 in the RCP4.5 and RCP8.5 scenarios, respectively. Declines in AOD, cloud formation, and cloud optical thickness from reductions of emissions of primary aerosols and aerosol precursors under RCP4.5 result in near surface warming of 0.2 °C from a global average increase of 0.7 W m-2 in surface downwelling solar radiation. This warming leads to a weakening of the Walker Circulation in the tropics, leading to significant changes in cloud and precipitation that mirror a shift in climate towards the negative phase of the El Nino Southern Oscillation.

  18. Complementary and alternative medicine use of women with breast cancer : Self-help CAM attracts other women than guided CAM therapies

    NARCIS (Netherlands)

    Lo-Fo-Wong, Deborah N. N.; Ranchor, Adelita V.; de Haes, Hanneke C. J. M.; Sprangers, Mirjam A. G.; Henselmans, Inge


    Objective: Examine stability of use of complementary and alternative medicine (CAM) of breast cancer patients, reasons for CAM use, and sociodemographic, clinical, and psychological predictors of CAM use. Methods: CAM use was assessed after adjuvant therapy and six months later. Following the CAM He

  19. Phosphatidylinositol 3-kinase in myogenesis. (United States)

    Kaliman, P; Zorzano, A


    Phosphatidylinositol 3-kinase (PI 3-kinase) has been cloned and characterized in a wide range of organisms. PI 3-kinases are activated by a diversity of extracellular stimuli and are involved in multiple cell processes such as cell proliferation, protein trafficking, cell motility, differentiation, regulation of cytoskeletal structure, and apoptosis. It has recently been shown that PI 3-kinase is a crucial second messenger in the signaling of myogenesis. Two structurally unrelated highly specific inhibitors of PI 3-kinase-wortmannin and LY294002-block the morphological and biochemical differentiation program of different skeletal-muscle cell models. Moreover, L6E9 myoblasts overexpressing a dominant-negative mutant of PI 3-kinase p85 regulatory subunit (Δp85) are unable to differentiate. Furthermore, PI 3-kinase is specifically involved in the insulinlike growth factor (IGF)-dependent myogenic pathway. Indeed, the ability of IGF-I, des-1,3-IGF-I, and IGF-II to promote cell fusion and muscle-specific protein expression is impaired after treatment with PI 3-kinase inhibitors or in cells overexpressing Δp85. The identification of additional key downstream elements of the IGF/PI 3-kinase myogenic cascade is crucial to a detailed understanding of the process of muscle differentiation and may generate new tools for skeletal and cardiac muscle regeneration therapies. (Trends Cardiovasc Med 1997;7:198-202). © 1997, Elsevier Science Inc.

  20. Stain susceptibility of composite and ceramic CAD/CAM blocks versus direct resin composites with different resinous matrices. (United States)

    Alharbi, Amal; Ardu, Stefano; Bortolotto, Tissiana; Krejci, Ivo


    To evaluate the stain susceptibility of CAD/CAM blocks and direct composite after long term exposure to various staining agents. 40 disk-shaped samples were fabricated from each of nine materials; six CAD/CAM (Vitablocs Mark II, Paradigm MZ100, Experimental Vita Hybrid Ceramic, Vita Enamic, Experimental Kerr and Lava Ultimate) and three direct composites (Filtek Supreme, Venus Diamond and Filtek Silorane). Samples were randomly divided into five groups (n = 8) according to different staining solutions (distilled water, tea, red wine, coffee and artificial saliva). Initial L*a*b* values were assessed using a calibrated digital spectrophotometer. Specimens were immersed in staining solutions and stored in an incubator at 37 °C for 120 days. L*a*b* values were assessed again and color change (∆E) was calculated as difference between recorded L*a*b* values. ANOVA, and Duncan test were used to identify differences between groups (α = 0.05). Significant differences in ∆E values were detected between materials (p = 0.000). Among all staining solutions, the highest ∆E value was observed with red wine. The new CAD/CAM blocks (Vita Enamic, Vita Hybrid Ceramic and Lava Ultimate) showed the highest resistance to staining compared to the MZ100 composite resin blocks. Filtek Silorane, a direct composite, showed high stain resistance values compared to CAD/CAM materials and other direct composites. Ceramic and composite CAD/CAM blocks had lower staining susceptibility than methacrylate based direct composite. Staining susceptibility of the new resin based CAD/CAM materials Vita Enamic and Lava Ultimate was comparable to feldspathic ceramic blocks (Vitablocs Mark II). Filtek Silorane showed promising results that were comparable to some CAD/CAM blocks.

  1. Introduction to Analytical Methods for Internal Combustion Engine Cam Mechanisms

    CERN Document Server

    Williams, J J


    Modern design methods of Automotive Cam Design require the computation of a range of parameters. This book provides a logical sequence of steps for the derivation of the relevant equations from first principles, for the more widely used cam mechanisms. Although originally derived for use in high performance engines, this work is equally applicable to the design of mass produced automotive and other internal combustion engines.   Introduction to Analytical Methods for Internal Combustion Engine Cam Mechanisms provides the equations necessary for the design of cam lift curves with an associated smooth acceleration curve. The equations are derived for the kinematics and kinetics of all the mechanisms considered, together with those for cam curvature and oil entrainment velocity. This permits the cam shape, all loads, and contact stresses to be evaluated, and the relevant tribology to be assessed. The effects of asymmetry on the manufacture of cams for finger follower and offset translating curved followers is ...

  2. Research on the processing speed of cam grinding (United States)

    Peng, Baoying; Han, Qiushi


    Cam Grinding is a special kind of non-circular machining. The processing speed of cam grinding has a major influence on cam machining precision. In this paper, decomposed the X-axis feed speed and C-axis velocity by the tangential speed and normal speed in accordance with the curvature circle at the point of cam profile grinding. Proposed the cam grinding processing speed model and linear velocity calculation formula, the processing experiment on the CNC camshaft grinding machine results show that the cam grinding speed model is correct. Constant angular speed grinding and constant linear speed grinding are analyzed respectively, which provides a theoretical basis for cam grinding processing speed optimization.

  3. Attenuation of endothelin-1-induced calcium response by tyrosine kinase inhibitors in vascular smooth muscle cells. (United States)

    Liu, C Y; Sturek, M


    Although tyrosine kinases play an important role in cell growth and have been implicated in regulation of smooth muscle contraction, their role in agonist-induced myoplasmic Ca2+ responses is unclear. We examined effects of the tyrosine kinase inhibitors genistein and methyl 2,5-dihydroxycinnamate (MDHC) on the endothelin-1 (ET-1)-induced Ca2+ response and determined underlying mechanisms for the effects. Freshly isolated smooth muscle cells from porcine coronary arteries were loaded with fura 2 ester, and myoplasmic free Ca2+ (Ca2+ (m)) concentration was estimated with fura 2 microfluorometry. Both genistein and MDHC inhibited the initial transient Cam2+ response to ET by 54 and 81%, respectively (P latent period from ET-1 application to the beginning of the Cam2+ response being increased from 1.08 +/- 0.17 to 2.65 +/- 0.52 min (P < 0.05). In the absence of extracellular Ca2+, genistein inhibited the ET-1-induced Cam2+ response by 93% (P < 0.05). The Cam2+ responses to caffeine (5 mM) or inositol trisphosphate (IP3) applied intracellularly via a patch-clamp pipette were not affected by genistein. Both genistein and MDHC also abolished the sustained Cam2+ response to ET-1. However, the Cam2+ response to depolarization by 80 mM K+ was not inhibited by MDHC and only inhibited 22% by genistein (P < 0.05). These results indicate that 1) activation of tyrosine kinases is an important regulatory mechanism for the ET-1-induced Cam2+ response in vascular smooth muscle and 2) tyrosine kinases mediate ET-1-induced Ca2+ release with no direct effect on IP3-mediated Ca2+ release. Thus ET-1-mediated signaling upstream of IP3 interaction with the Ca2+ stores is regulated by tyrosine kinases.

  4. Formal Management of CAD/CAM Processes (United States)

    Kohlhase, Michael; Lemburg, Johannes; Schröder, Lutz; Schulz, Ewaryst

    Systematic engineering design processes have many aspects in common with software engineering, with CAD/CAM objects replacing program code as the implementation stage of the development. They are, however, currently considerably less formal. We propose to draw on the mentioned similarities and transfer methods from software engineering to engineering design in order to enhance in particular the reliability and reusability of engineering processes. We lay out a vision of a document-oriented design process that integrates CAD/CAM documents with requirement specifications; as a first step towards supporting such a process, we present a tool that interfaces a CAD system with program verification workflows, thus allowing for completely formalised development strands within a semi-formal methodology.

  5. CAD/CAM-assisted breast reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Melchels, Ferry; Hutmacher, Dietmar Werner [Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059 (Australia); Wiggenhauser, Paul Severin; Schantz, Jan-Thorsten [Department of Plastic and Hand Surgery, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Warne, David; Barry, Mark [High Performance Computing and Research Support, Queensland University of Technology, Gardens Point Road, Brisbane, QLD 4000 (Australia); Ong, Fook Rhu; Chong, Woon Shin, E-mail:, E-mail: [Singapore Polytechnic, 500 Dover Road, 139651 Singapore (Singapore)


    The application of computer-aided design and manufacturing (CAD/CAM) techniques in the clinic is growing slowly but steadily. The ability to build patient-specific models based on medical imaging data offers major potential. In this work we report on the feasibility of employing laser scanning with CAD/CAM techniques to aid in breast reconstruction. A patient was imaged with laser scanning, an economical and facile method for creating an accurate digital representation of the breasts and surrounding tissues. The obtained model was used to fabricate a customized mould that was employed as an intra-operative aid for the surgeon performing autologous tissue reconstruction of the breast removed due to cancer. Furthermore, a solid breast model was derived from the imaged data and digitally processed for the fabrication of customized scaffolds for breast tissue engineering. To this end, a novel generic algorithm for creating porosity within a solid model was developed, using a finite element model as intermediate.

  6. CAM and Post-Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Alex Hankey


    Full Text Available In the form of the Transcendental Meditation program CAM offers a method of eliminating deep-rooted stress, the efficacy of which has been demonstrated in several related studies. Any discussion of CAM and post-traumatic stress disorder should include a study of its application to Vietnam War Veterans in which improvements were observed on all variables, and several participants were able to return to work after several years of being unable to hold a job. The intervention has been studied for its impact on brain and autonomic nervous system function. It has been found to be highly effective against other stress-related conditions such as hypertension, and to improve brain coherence—a measure of effective brain function. It should be considered a possible ‘new and improved mode of treatment’ for PTSD, and further studies of its application made.

  7. CAM/LIFTER forces and friction (United States)

    Gabbey, D. J.; Lee, J.; Patterson, D. J.


    This report details the procedures used to measure the cam/lifter forces and friction. The present effort employed a Cummins LTA-10, and focuses on measurements and dynamic modeling of the injector train. The program was sponsored by the US Department of Energy in support of advanced diesel engine technology. The injector train was instrumented to record the instantaneous roller speed, roller pin friction torque, pushrod force, injector link force, and cam speed. These measurements, together with lift profiles for pushrod and injector link displacement, enabled the friction work loss in the injector train to be determined. Other significant design criteria such as camshaft roller follower slippage and maximum loads on components were also determined. Future efforts will concentrate on the dynamic model, with tests run as required for correlation.

  8. Chiropractic and CAM Utilization: A Descriptive Review


    Meeker William C; Lawrence Dana J


    Abstract Objective To conduct a descriptive review of the scientific literature examining use rates of modalities and procedures used by CAM clinicians to manage chronic LBP and other conditions Data Sources A literature of PubMed and MANTIS was performed using the key terms Chiropractic; Low Back Pain; Utilization Rate; Use Rate; Complementary and Alternative Medicine; and Health Services in various combinations. Data Selection A total of 137 papers were selected, based upon including inform...

  9. An investigation of cam-roller mechanism applied in sphere cam engine

    Institute of Scientific and Technical Information of China (English)

    张雷; 潘存云; 徐小军; 徐海军; 张正洲


    As an alternative power source for hybrid electrical vehicle(HEV), electric generating system(EGS) driven by sphere cam engine(SCE) is said to own higher power density and integration. In this work, the structure and working principle of EGS were introduced, based on which the advantages of EGS were displayed. The profile of sphere cam was achieved after the desired motion of piston was given. After establishing the dynamic model of power transmission mechanism, the characteristics of cam-roller mechanism were studied. The results show that the optimal cam profile of SCE is a sinusoid curve which has two peaks and two valleys and a mean pressure angle of 47.19°. Because of the special cam shape, the trace of end surface center of piston is an eight-shape curve on a specific sphere surface. SCE running at speed of 3000 r/min can generate the power of 33.81 kW, which could satisfy the need of HEVs. However, the force between cylinder and piston skirt caused by Coriolis acceleration can reach up to 1182 N, which leads to serious wear between cylinder liner and piston skirt and may shorten the lifespan of SCE.

  10. The NectarCAM camera project

    CERN Document Server

    Glicenstein, J-F; Barrio, J-A; Blanch, O; Boix, J; Bolmont, J; Boutonnet, C; Cazaux, S; Chabanne, E; Champion, C; Chateau, F; Colonges, S; Corona, P; Couturier, S; Courty, B; Delagnes, E; Delgado, C; Ernenwein, J-P; Fegan, S; Ferreira, O; Fesquet, M; Fontaine, G; Fouque, N; Henault, F; Gascón, D; Herranz, D; Hermel, R; Hoffmann, D; Houles, J; Karkar, S; Khelifi, B; Knödlseder, J; Martinez, G; Lacombe, K; Lamanna, G; LeFlour, T; Lopez-Coto, R; Louis, F; Mathieu, A; Moulin, E; Nayman, P; Nunio, F; Olive, J-F; Panazol, J-L; Petrucci, P-O; Punch, M; Prast, J; Ramon, P; Riallot, M; Ribó, M; Rosier-Lees, S; Sanuy, A; Siero, J; Tavernet, J-P; Tejedor, L A; Toussenel, F; Vasileiadis, G; Voisin, V; Waegebert, V; Zurbach, C


    In the framework of the next generation of Cherenkov telescopes, the Cherenkov Telescope Array (CTA), NectarCAM is a camera designed for the medium size telescopes covering the central energy range of 100 GeV to 30 TeV. NectarCAM will be finely pixelated (~ 1800 pixels for a 8 degree field of view, FoV) in order to image atmospheric Cherenkov showers by measuring the charge deposited within a few nanoseconds time-window. It will have additional features like the capacity to record the full waveform with GHz sampling for every pixel and to measure event times with nanosecond accuracy. An array of a few tens of medium size telescopes, equipped with NectarCAMs, will achieve up to a factor of ten improvement in sensitivity over existing instruments in the energy range of 100 GeV to 10 TeV. The camera is made of roughly 250 independent read-out modules, each composed of seven photo-multipliers, with their associated high voltage base and control, a read-out board and a multi-service backplane board. The read-out b...

  11. Modeled hydraulic redistribution in tree-grass, CAM-grass, and tree-CAM associations: the implications of crassulacean acid metabolism (CAM). (United States)

    Yu, Kailiang; Foster, Adrianna


    Past studies have largely focused on hydraulic redistribution (HR) in trees, shrubs, and grasses, and recognized its role in interspecies interactions. HR in plants that conduct crassulacean acid metabolism (CAM), however, remains poorly investigated, as does the effect of HR on transpiration in different vegetation associations (i.e., tree-grass, CAM-grass, and tree-CAM associations). We have developed a mechanistic model to investigate the net direction and magnitude of HR at the patch scale for tree-grass, CAM-grass, and tree-CAM associations at the growing season to yearly timescale. The modeling results show that deep-rooted CAM plants in CAM-grass associations could perform hydraulic lift at a higher rate than trees in tree-grass associations in a relatively wet environment, as explained by a significant increase in grass transpiration rate in the shallow soil layer, balancing a lower transpiration rate by CAM plants. By comparison, trees in tree-CAM associations may perform hydraulic descent at a higher rate than those in tree-grass associations in a dry environment. Model simulations also show that hydraulic lift increases the transpiration of shallow-rooted plants, while hydraulic descent increases that of deep-rooted plants. CAM plants transpire during the night and thus perform HR during the day. Based on these model simulations, we suggest that the ability of CAM plants to perform HR at a higher rate may have different effects on the surrounding plant community than those of plants with C3 or C4 photosynthetic pathways (i.e., diurnal transpiration).

  12. From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). (United States)

    Aurelio, Luigi; Scullino, Carmen V; Pitman, Melissa R; Sexton, Anna; Oliver, Victoria; Davies, Lorena; Rebello, Richard J; Furic, Luc; Creek, Darren J; Pitson, Stuart M; Flynn, Bernard L


    The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results using this pharmacological agent are complicated by several factors: poor SK1/2 selectivity, additional activity as an inducer of SK1-degradation, and off-target effects, including its recently identified capacity to inhibit dihydroceramide desaturase-1 (Des1). In this study, we have delineated the structure-activity relationship (SAR) for these different targets and correlated them to that required for anticancer activity and determined that Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. In the course of these efforts, a series of novel SK1, SK2, and Des1 inhibitors have been generated, including compounds with significantly greater anticancer activity.

  13. Inhibition of protein kinase CbetaII increases glucose uptake in 3T3-L1 adipocytes through elevated expression of glucose transporter 1 at the plasma membrane.

    NARCIS (Netherlands)

    Bosch, R.R.; Bazuine, M.; Wake, M.M.; Span, P.N.; Olthaar, A.J.; Schurmann, A.; Maassen, J.A.; Hermus, A.R.M.M.; Willems, P.H.G.M.; Sweep, C.G.J.


    The mechanism via which diacylglycerol-sensitive protein kinase Cs (PKCs) stimulate glucose transport in insulin-sensitive tissues is poorly defined. Phorbol esters, such as phorbol-12-myristate-13-acetate (PMA), are potent activators of conventional and novel PKCs. Addition of PMA increases the rat

  14. Input torque balancing using a cam-based centrifugal pendulum: design optimization and robustness (United States)

    Demeulenaere, B.; Spaepen, P.; De Schutter, J.


    In a companion paper (Input torque balancing using a cam-based centrifugal pendulum: design procedure and example, J. Sound Vib.), the cam-based centrifugal pendulum (CBCP) was introduced as a simple, cam-based, input torque balancing mechanism. The differential equation that governs the CBCP cam design was derived and a methodology for solving it was developed. Furthermore, in a design example, the CBCP was applied to balance the input torque of a high-speed cam-follower mechanism, driving the sley of a weaving loom. The present paper firstly shows how the design parameters for this particular design example can be optimized, so as to obtain a compact and technologically feasible mechanism. The formulation of the optimization problem is based on a parameterization of the CBCP rotor and coupler shape. Because of its nonconvex nature, the optimization problem is solved using a multi-start sequential quadratic programming (SQP) approach. A design chart, based on an exhaustive analysis, is introduced which (i) allows the designer to perform the design optimization in a quick and approximative way, and (ii) gives considerable insight into the behavior of the SQP-algorithm. Secondly, the CBCP is applied to an industrial case study, that is, a weaving loom. The robustness of the CBCP is illustrated by showing that input torque balancing solely the sley movement enhances the overall dynamic machine behavior, despite the presence of the non-balanced shed motion. A particular contribution of this part is the determination of the weaving loom regime behavior in the frequency domain, an approach which is believed to be novel in mechanism literature.

  15. Fit of CAD/CAM implant frameworks: a comprehensive review. (United States)

    Abduo, Jaafar


    Computer-aided design and computer-aided manufacturing (CAD/CAM) is a strongly emerging prosthesis fabrication method for implant dentistry. Currently, CAD/CAM allows the construction of implant frameworks from different materials. This review evaluates the literature pertaining to the precision fit of fixed implant frameworks fabricated by CAD/CAM. Following a comprehensive electronic search through PubMed (MEDLINE), 14 relevant articles were identified. The results indicate that the precision fit of CAD/CAM frameworks exceeded the fit of the 1-piece cast frameworks and laser-welded frameworks. A similar fit was observed for CAD/CAM frameworks and bonding of the framework body to prefabricated cylinders. The influence of CAD/CAM materials on the fit of a framework is minimal.

  16. Research in non-equalization machining method for spatial cam

    Institute of Scientific and Technical Information of China (English)

    Jun-hua CHEN; Yi-jie WU


    Many kinds of devices with cam have been widely used in various mechanical equipments.However,non-equalization machining for spatial cam trough remains to be a difficult problem.This paper focuses on the analysis of ruaning conditions and machining processes of spatial cam with oscillating follower.We point out the common errors in the biased distance cutting.By analyzing the motion of oscillating follower of spatial cam,we present a new 3D curve expansion model of spatial cam trough-outline.Based on this model.we have proposed a machining method for trochoidal milling with non-equalization diameter cutter.This new method has led to a creative and effective Way for non.equalization diameter machining for spatial cam with oscillating follower.

  17. Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II. Second-Generation Analogues with Enhanced Potency, Selectivity, and Pharmacodynamic Modulation in Vivo. (United States)

    Burch, Jason D; Barrett, Kathy; Chen, Yuan; DeVoss, Jason; Eigenbrot, Charles; Goldsmith, Richard; Ismaili, M Hicham A; Lau, Kevin; Lin, Zhonghua; Ortwine, Daniel F; Zarrin, Ali A; McEwan, Paul A; Barker, John J; Ellebrandt, Claire; Kordt, Daniel; Stein, Daniel B; Wang, Xiaolu; Chen, Yong; Hu, Baihua; Xu, Xiaofeng; Yuen, Po-Wai; Zhang, Yamin; Pei, Zhonghua


    The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We have previously disclosed a structure- and property-guided lead optimization effort which resulted in the discovery of a new series of tetrahydroindazole-containing selective ITK inhibitors. Herein we disclose further optimization of this series that resulted in further potency improvements, reduced off-target receptor binding liabilities, and reduced cytotoxicity. Specifically, we have identified a correlation between the basicity of solubilizing elements in the ITK inhibitors and off-target antiproliferative effects, which was exploited to reduce cytotoxicity while maintaining kinase selectivity. Optimized analogues were shown to reduce IL-2 and IL-13 production in vivo following oral or intraperitoneal dosing in mice.

  18. A panorama of dental CAD/CAM restorative systems. (United States)

    Liu, Perng-Ru


    In the last 2 decades, exciting new developments in dental materials and computer technology have led to the success of contemporary dental computer-aided design/computer-aided manufacturing (CAD/CAM) technology. Several highly sophisticated chairside and laboratory CAD/CAM systems have been introduced or are under development. This article provides an overview of the development of various CAD/CAM systems. Operational components, methodologies, and restorative materials used with common CAD/CAM systems are discussed. Research data and clinical studies are presented to substantiate the clinical performance of these systems.

  19. Panorama of dental CAD/CAM restorative systems. (United States)

    Liu, Perng-Ru; Essig, Milton E


    In the past two decades, exciting new developments in dental materials and computer technology have led to the success of contemporary dental computer-aided design/computer-aided manufacture (CAD/CAM) technology. Several highly sophisticated in-office and laboratory CAD/CAM systems have been introduced or are under development. This article provides an overview of the development of various CAD/CAM systems. Operational components, methodologies, and restorative materials used with common CAD/CAM systems are discussed. Research data and clinical studies are presented to substantiate the clinical performance of these systems.

  20. Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the hippocampus of chronic multiple-stressed rats

    Institute of Scientific and Technical Information of China (English)


    Background The effect of chronic stress on cognitive functions has been one of the hot topic in neuroscience. But there has been much controversy over its mechanism. Such single stressor applied in the past could not simulate complicated living circumstances that people confronted with. The aim of this study was to investigate the effects of chronic multiple-stress on learning and memory as well as on the levels of calcium/calmodulin-dependent protein kinase II (CaMKII), calmodulin (CaM) mRNA, and cAMP-response element binding protein (CREB) mRNA in the hippocampus of rats. Methods The rats were divided randomly into stressed and control groups. The stressed group was given chronic multiple-stress for 6 weeks to set up a chronic multiple-stressed model. The rats' performance of spatial learning and memory was tested using Morris Water Maze (MWM) and Y-maze. Meanwhile, the expressions of CaMKII, CaM mRNA and CREB mRNA of rats' hippocampus were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the width of synaptic cleft and the thickness of post-synaptic densities (PSD) were observed in the hippocampal CA3 region of rats by electron microscopy. Results After exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group (P<0.05, P<0.01). The width of synaptic cleft was smaller and the thickness of PSD was larger in the hippocampal CA3 region of the stressed group than in that of the control group (P<0.01). The CaMKII immunostaining of the stressed group was stronger than that of the control group in the stratum radiatum and oriens of the hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis indicated that the expression of CaMKII, CaM mRNA, and CREB mRNA in the hippocampus of the stressed group was higher than that of the control group (P<0.05, P<0.01). Conclusions The

  1. Enhanced casein kinase II activity during mouse embryogenesis. Identification of a 110-kDa phosphoprotein as the major phosphorylation product in mouse embryos and Krebs II mouse ascites tumor cells

    DEFF Research Database (Denmark)

    Schneider, H R; Reichert, G H; Issinger, O G


    , increased phosphorylation of a 110-kDa protein is observed. Treatment of the embryo extracts with heparin, a highly specific inhibitor of CKII activity, results in a drastic reduction of the 110-kDa protein phosphorylation indicating that the protein might be a CKII-specific substrate. Rapidly proliferating...... mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (cAMP- and cGMP-dependent protein kinases) only show a basal level of enzyme...

  2. Synthesis and evaluation of the antiproliferative activity of novel pyrrolo[1,2-a]quinoxaline derivatives, potential inhibitors of Akt kinase. Part II. (United States)

    Desplat, Vanessa; Moreau, Stephane; Gay, Aurore; Fabre, Solene Belisle; Thiolat, Denis; Massip, Stephane; Macky, Gregory; Godde, Frederic; Mossalayi, Djavad; Jarry, Christian; Guillon, Jean


    Attenuation of protein kinases by selective inhibitors is an extremely active field of activity in anticancer drug development. Therefore, Akt, a serine/threonine protein kinase, also known as protein kinase B (PKB), represents an attractive potential target for therapeutic intervention. Recent efforts in the development and biological evaluation of small molecule inhibitors of Akt have led to the identification of novel inhibitors with various heterocycle scaffolds. Based on previous results obtained on the antiproliferative activities of new pyrrolo[1,2-a]quinoxalines, a novel series was designed and synthesized from various substituted phenyl-1H-pyrrole-2-carboxylic acid alkyl esters via a multistep heterocyclization process. These new compounds were tested for their in vitro ability to inhibit the proliferation of the human leukemic cell lines K562, U937, and HL60, and the breast cancer cell line MCF7. The first biological evaluation of our new substituted pyrrolo[1,2-a]quinoxalines showed antiproliferative activity against the tested cell lines. From a general SAR point of view, these preliminary biological results highlight the importance of substitution at the C-4 position of the pyrroloquinoxaline scaffold by a benzylpiperidinyl fluorobenzimidazole group, and also the need for a functionalization on the pyrrole ring.

  3. The CamKKβ Inhibitor STO609 Causes Artefacts in Calcium Imaging and Selectively Inhibits BKCa in Mouse Carotid Body Type I Cells. (United States)

    Jurcsisn, Jennifer G; Pye, Richard L; Ali, Jon; Barr, Barbara L; Wyatt, Christopher N


    It has previously been reported that AMP-activated protein kinase (AMPK) may be critical for hypoxic chemotransduction in carotid body type I cells. This study sought to determine the importance of the regulatory upstream kinase of AMPK, CamKKβ, in the acute response to hypoxia in isolated mouse type I cells.Initial data indicated several previously unreported artefacts associated with using the CamKKβ inhibitor STO609 and Ca(2+) imaging techniques. Most importantly Fura-2 and X-Rhod1 imaging revealed that STO609 quenched emission fluorescence even in the absence of intracellular Ca(2+) ([Ca(2+)](I)). Furthermore, STO609 (100 μM) rapidly inhibited outward macroscopic currents and this inhibition was abolished in the presence of the selective BK(Ca) inhibitor paxilline.Taken together these data suggest that ST0609 should be used with caution during Ca(2+) imaging studies as it can directly interact with Ca(2+) binding dyes. The rapid inhibitory effect of STO609 on BK(Ca) was unexpected as the majority of studies using this compound required an incubation of approximately 10 min to inhibit the kinase. Furthermore, as AMPK activation inhibits BK(Ca), inhibiting AMPK's upstream kinases would, if anything, be predicted to have the opposite effect on BK(Ca). Future work will determine if the inhibition of BK(Ca) is via CamKKβ or via an off target action of STO609 on the channel itself.

  4. Subaru Prime Focus Camera -- Suprime-Cam --

    CERN Document Server

    Miyazaki, S; Sekiguchi, M; Okamura, S; Doi, M; Furusawa, H; Hamabe, M; Imi, K; Kimura, M; Nakata, F; Okada, N; Ouchi, M; Shimasaku, K; Yagi, M; Yasuda, N; Miyazaki, Satoshi; Komiyama, Yutaka; Sekiguchi, Maki; Okamura, Sadanori; Doi, Mamoru; Furusawa, Hisanori; Hamabe, Masaru; Imi, Katsumi; Kimura, Masahiki; Nakata, Fumiaki; Okada, Norio; Ouchi, Masami; Shimasaku, Kazuhiro; Yagi, Masafumi; Yasuda, Naoki


    We have built an 80 mega pixels (10240 X 8192) mosaic CCD camera, called Suprime-Cam, for the wide field prime focus of the 8.2 m Subaru telescope. Suprime-Cam covers a field of view 34 arcmin X 27 arcmin, a unique facility among the the 8 - 10 m class telescopes, with a resolution of 0.202 arcsec per pixel. The focal plane consists of ten high-resistivity 2kX4k CCDs developed by MIT Lincoln Laboratory and these are cooled by a large stirling cycle cooler. The CCD readout electronics are developed originally by our group (M-Front & Messia-III) and the system is designed scalable that allows multiple read-out of tens of CCDs. It takes 50 seconds to readout entire arrays. We have designed a filter exchange mechanism of jukebox type that can holds up to ten large filters (205 X 170 X 15 mm^3). The wide field corrector is basically a three-lens Wynne-type but has a new type of atmospheric dispersion corrector. The corrector provides flat focal plane and un-vignetted field of view of 30 arcmin in diameter. Ach...

  5. CAD/CAM: Practical and Persuasive in Canadian Schools (United States)

    Willms, Ed


    Chances are that many high school students would not know how to use drafting instruments, but some might want to gain competence in computer-assisted design (CAD) and possibly computer-assisted manufacturing (CAM). These students are often attracted to tech courses by the availability of CAD/CAM instructions, and many go on to impress employers…

  6. A systematic review of CAD/CAM fit restoration evaluations. (United States)

    Boitelle, P; Mawussi, B; Tapie, L; Fromentin, O


    The evolution and development of CAD/CAM systems have led to the production of prosthetic reconstructions by going beyond the use of traditional techniques. Precision adjustment of prosthetic elements is considered essential to ensure sustainable restoration and dental preparation. The purpose of this article was to summarise the current literature on the fitting quality of fixed prostheses obtained by CAD/CAM technology.

  7. Mechanics of post-cam engagement during simulated dynamic activity. (United States)

    Fitzpatrick, Clare K; Clary, Chadd W; Cyr, Adam J; Maletsky, Lorin P; Rullkoetter, Paul J


    Posterior-stabilized (PS) total knee arthroplasty (TKA) components employ a tibial post and femoral cam mechanism to guide anteroposterior knee motion in lieu of the posterior cruciate ligament. Some PS TKA patients report a clicking sensation when the post and cam engage, while severe wear and fracture of the post; we hypothesize that these complications are associated with excessive impact velocity at engagement. We evaluated the effect of implant design on engagement dynamics of the post-cam mechanism and resulting polyethylene stresses during dynamic activity. In vitro simulation of a knee bend activity was performed for four cadaveric specimens implanted with PS TKA components. Post-cam engagement velocity and flexion angle at initial contact were determined. The experimental data were used to validate computational predictions of PS mechanics using the same loading conditions. A lower limb model was subsequently utilized to compare engagement mechanics of eight TKA designs, relating differences between implants to geometric design features. Flexion angle and post-cam velocity at engagement demonstrated considerable ranges among designs (23°-89°, and 0.05-0.22 mm/°, respectively). Post-cam velocity was correlated (r = 0.89) with tibiofemoral condylar design features. Condylar geometry, in addition to post-cam geometry, played a significant role in minimizing engagement velocity and forces and stresses in the post. This analysis guides selection and design of PS implants that facilitate smooth post-cam engagement and reduce edge loading of the post.

  8. EpCAM : Structure and function in health and disease

    NARCIS (Netherlands)

    Schnell, Ulrike; Cirulli, Vincenzo; Giepmans, Ben N. G.


    Injection of tumor cells in mice more than 30 years ago resulted in the discovery of an epithelial antigen, later defined as a cell adhesion molecule (EpCAM). Although EpCAM has since evoked significant interest as a target in cancer therapy, mechanistic insights on the functions of this glycoprotei

  9. An antisense oligodeoxynucleotide targeted against the type II sub. beta. regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects

    Energy Technology Data Exchange (ETDEWEB)

    Tortora, G.; Clair, T.; Cho-Chung, Y.S. (National Institutes of Health, Bethesda, MD (USA))


    The type II{sub {beta}} regulatory subunit of cAMP-dependent protein kinase (RII{sub {beta}}) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this tissue, HL-60 human promyelocytic leukemia cells were exposed to RII{sub {beta}} antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII{sub {beta}} antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII{sub {beta}} protein. Exposure to RII{sub {beta}} sense, RI{sub {alpha}} and RII{sub {alpha}} antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII{sub {beta}} regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.

  10. UY Puppis A New Anomalous Z Cam Type Dwarf Nova

    CERN Document Server

    Stubbings, Rod


    The defining characteristic of Z Cam stars are standstills in their light curves. Some Z Cams exhibit atypical behaviour by going into outburst from a standstill. It has previously been suggested that UY Pup had been a Z Cam star, but it was ruled out due to its long-term light curve. However, in December 2015 UY Pup went into outburst and unexpectedly entered into a short standstill instead of returning to quiescence. Furthermore, UY Pup exhibited additional unusual behaviour with two outbursts detected during its standstill. After this standstill UY Pup made a brief excursion to a quiescence state and slowly rose to a longer and well-defined standstill, where it again went into another outburst. Through comparative analysis, researching and observational data of UY Pup it is evident and thus concluded that it is indeed a Z Cam star, in which renders it to be one of only four known anomalous Z Cam stars.

  11. Treatment Preferences for CAM in Children with Chronic Pain

    Directory of Open Access Journals (Sweden)

    Jennie C. I. Tsao


    Full Text Available CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls (mean age = 14.5 years ± 2.4; range = 8–18 years presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80% were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy, pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities.

  12. Treatment Preferences for CAM in children with chronic pain. (United States)

    Tsao, Jennie C I; Meldrum, Marcia; Kim, Su C; Jacob, Margaret C; Zeltzer, Lonnie K


    CAM therapies have become increasingly popular in pediatric populations. Yet, little is known about children's preferences for CAM. This study examined treatment preferences in chronic pediatric pain patients offered a choice of CAM therapies for their pain. Participants were 129 children (94 girls) (mean age = 14.5 years +/- 2.4; range = 8-18 years) presenting at a multidisciplinary, tertiary clinic specializing in pediatric chronic pain. Bivariate and multivariate analyses were used to examine the relationships between CAM treatment preferences and patient's sociodemographic and clinical characteristics, as well as their self-reported level of functioning. Over 60% of patients elected to try at least one CAM approach for pain. The most popular CAM therapies were biofeedback, yoga and hypnosis; the least popular were art therapy and energy healing, with craniosacral, acupuncture and massage being intermediate. Patients with a diagnosis of fibromyalgia (80%) were the most likely to try CAM versus those with other pain diagnoses. In multivariate analyses, pain duration emerged as a significant predictor of CAM preferences. For mind-based approaches (i.e. hypnosis, biofeedback and art therapy), pain duration and limitations in family activities were both significant predictors. When given a choice of CAM therapies, this sample of children with chronic pain, irrespective of pain diagnosis, preferred non-invasive approaches that enhanced relaxation and increased somatic control. Longer duration of pain and greater impairment in functioning, particularly during family activities increased the likelihood that such patients agreed to engage in CAM treatments, especially those that were categorized as mind-based modalities.

  13. Complementary and alternative medicine (CAM providers’ views of chronic low back pain patients’ expectations of CAM therapies: a qualitative study

    Directory of Open Access Journals (Sweden)

    Schafer Lisa M


    Full Text Available Abstract Background Some researchers think that patients with higher expectations for CAM therapies experience better outcomes and that enthusiastic providers can enhance treatment outcomes. This is in contrast to evidence suggesting conventional medical providers often reorient patient expectations to better match what providers believe to be realistic. However, there is a paucity of research on CAM providers’ views of their patients’ expectations regarding CAM therapy and the role of these expectations in patient outcomes. Methods To better understand how CAM providers view and respond to their patients’ expectations of a particular therapy, we conducted 32 semi-structured, qualitative interviews with acupuncturists, chiropractors, massage therapists and yoga instructors identified through convenience sampling. Interviews were recorded, transcribed and analyzed thematically using Atlas ti version 6.1. Results CAM providers reported that they attempt to ensure that their patients’ expectations are realistic. Providers indicated they manage their patients’ expectations in a number of domains— roles and responsibilities of providers and patients, treatment outcomes, timeframe for improvement, and treatment experience. Providers reported that patients’ expectations change over time and that they need to continually manage these expectations to enhance patient engagement and satisfaction with treatment. Conclusions Providers of four types of CAM therapies viewed patients’ expectations as an important component of their experiences with CAM therapy and indicated that they try to align patient expectations with reality. These findings suggest that CAM providers are similar in this respect to conventional medical providers.

  14. Effects of light intensity on the morphology and CAM photosynthesis of Vanilla planifolia Andrews

    Directory of Open Access Journals (Sweden)

    María Claudia Díez


    Full Text Available Vanilla planifolia is a neotropical orchid, whose fruits produce the natural vanilla, a fundamental ingredient for the food and cosmetic industry. Because of its importance in the world market, it is cultivated in many tropical countries and recently its cultivation has started in Colombia. This species requires shade for its development; however, the optimal of light conditions are unknown. This work evaluates the effect of different light intensities on CAM photosynthesis, physiology, morphology, and growth of this species. For this, vanilla seedlings were subjected to four treatments of relative illumination (RI (T1=8%, T2=17%, T3=31% and T4=67%. Most CO2 assimilation occurred along night in all treatments, which confirms that vanilla is a strong CAM species. Plants grown under high lighting (67% RI had almost half of the photosynthesis in treatments of intermediate lighting (17 and 31%, which is consistent with the lower nocturnal acid accumulation in that treatment. Likewise, the photochemical efficiency of photosystem II (Fv / Fm showed that in plants of the 67% RI occurred high radiation stress. On the other hand, vanilla plants reached greater length, leaf area, and total biomass when grown under intermediate radiation (17 and 31% RI. These results suggest that high radiation alters the functioning of vanilla plants, inhibiting photosynthesis and growth, and that highly shaded environments not significantly affected the CAM photosynthesis of vanilla; however, in the long-term this species showed higher photosynthesis and growth under intermediate levels of radiation

  15. Novel Diagnosis of Lyme Disease: Potential for CAM Intervention

    Directory of Open Access Journals (Sweden)

    Aristo Vojdani


    Full Text Available Lyme disease (LD is the most common tick-borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. Insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. The goal of this article is 4-fold: (i to detail LD infection and pathology, (ii to review prevalent diagnostic methods, emphasizing inherent problems, (iii to introduce the usage of in vivo induced antigen technology (IVIAT in clinical diagnostics and (iv to underscore the relevance of a novel comprehensive LD diagnostic approach to practitioners of Complementary and Alternative Medicine (CAM. Utilization of this analytical method will increase the accuracy of the diagnostic process and abridge the time to treatment, with antibiotics, herbal medicines and nutritional supplements, resulting in improved quality of care and disease prognosis.

  16. Immediate CAD/ CAM Custom Fabricated Dental Implants

    Directory of Open Access Journals (Sweden)

    Jafar Kolahi


    Full Text Available Introduction: There will almost always be gaps between cylin-drical or screw shaped prefabricated implant surface and funnel-shaped tooth socket when an implant is placed immediately after tooth extraction. Hence expensive and difficult bone grafting is re-quired. A custom fabricated implant will be a pragmatic solution for this limitation.The hypothesis: First step following extraction of a tooth is data capture or scanning via a 3D scan method e.g. coordinate measuring machine or non-contact laser scanners such as triangulation range finder. Second step is reconstruction or modeling via editable CAD (computer-aided design model, allowing us to add retentive holes and correction of implant angle. Third step is fabrication via CAM (computer aided manufacturing followed by plasma cleaning process. Fourth step is insertion of the CAD/CAM custom fabricated one-stage implant in the fresh tooth socket. Optimal time for this step is 24-48 hours after extraction. The custom fabricated implant should not load 3-4 months. Usage of chlorhexidine mouth-rinse or chewing gum twice daily for 2 weeks and, in some cases oral antibiotic is recommended. Evaluation of the hypothesis: Contemporary dental implant system faced with several clinical and anatomical limitations such is low sinuses or nerve bundles. Complex and expensive surgical procedures such as nerve repositioning and sinus lift are frequently required. With custom fabricated implant we can overcome several of these limitations because insertion of custom fabricated implant will perform before alveolar bone recession.

  17. Turnkey CAD/CAM systems' integration with IPAD systems (United States)

    Blauth, R. E.


    Today's commercially available turnkey CAD/CAM systems provide a highly interactive environment, and support many specialized application functions for the design/drafting/manufacturing process. This paper presents an overview of several aerospace companies which have successfully integrated turnkey CAD/CAM systems with their own company wide engineering and manufacturing systems. It also includes a vendor's view of the benefits as well as the disadvantages of such integration efforts. Specific emphasis is placed upon the selection of standards for representing geometric engineering data and for communicating such information between different CAD/CAM systems.

  18. Single unit CAD/CAM restorations: a literature review. (United States)

    Freedman, Michael; Quinn, Frank; O'Sullivan, Michael


    Computer-aided design/computer-aided manufacture (CAD/CAM) has been used in dentistry since 1987. Since then, many CAD/CAM systems have been described, which enable the production of chair-side single unit dental restorations. These restorations are of comparable quality to those made by conventional techniques and have some specific advantages, including rapid production, improved wear properties, decreased laboratory fee and improved cross infection control. This literature review investigates the evidence base for the use of single unit CAD/CAM restorations. Materials, marginal gap, aesthetics, post-operative sensitivity, cementation, cost-effectiveness and longevity are discussed.

  19. Camønoen: Mobilizing pilgrim trails along collaborative platforms

    DEFF Research Database (Denmark)

    Gyimóthy, Szilvia; Widtfeld Meged, Jane


    and citizens alike? The recently opened pilgrim trail, Camønoen represents an adapted collaborative business model and as such an appropriate case to study new coastal value creation processes. Camønoen is a 175 km long newly designed walking trail across the islands of Møn, Nyord and Bogø. The trail...... is augmented by a digital platform on which hikers may directly connect with local citizens and book experiences ranging from private dinners to bird-watching and berry-picking. The platform Camø is hosted by the regional museum, which neither charges for intermediation, nor is responsible for vetting...

  20. Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C.


    Williams, B.; Tsai, P.; Schrier, R W


    Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface recepto...

  1. Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II α (CaMKIIα) mRNAs by the RNA-binding Protein HuD. (United States)

    Sosanya, Natasha M; Cacheaux, Luisa P; Workman, Emily R; Niere, Farr; Perrone-Bizzozero, Nora I; Raab-Graham, Kimberly F


    The fate of a memory, whether stored or forgotten, is determined by the ability of an active or tagged synapse to undergo changes in synaptic efficacy requiring protein synthesis of plasticity-related proteins. A synapse can be tagged, but without the "capture" of plasticity-related proteins, it will not undergo long lasting forms of plasticity (synaptic tagging and capture hypothesis). What the "tag" is and how plasticity-related proteins are captured at tagged synapses are unknown. Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα) is critical in learning and memory and is synthesized locally in neuronal dendrites. The mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that increases CaMKIIα protein expression; however, the mechanism and site of dendritic expression are unknown. Herein, we show that mTOR activity mediates the branch-specific expression of CaMKIIα, favoring one secondary, daughter branch over the other in a single neuron. mTOR inhibition decreased the dendritic levels of CaMKIIα protein and mRNA by shortening its poly(A) tail. Overexpression of the RNA-stabilizing protein HuD increased CaMKIIα protein levels and preserved its selective expression in one daughter branch over the other when mTOR was inhibited. Unexpectedly, deleting the third RNA recognition motif of HuD, the domain that binds the poly(A) tail, eliminated the branch-specific expression of CaMKIIα when mTOR was active. These results provide a model for one molecular mechanism that may underlie the synaptic tagging and capture hypothesis where mTOR is the tag, preventing deadenylation of CaMKIIα mRNA, whereas HuD captures and promotes its expression in a branch-specific manner.

  2. Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II α (CaMKIIα) mRNAs by the RNA-binding Protein HuD* (United States)

    Sosanya, Natasha M.; Cacheaux, Luisa P.; Workman, Emily R.; Niere, Farr; Perrone-Bizzozero, Nora I.; Raab-Graham, Kimberly F.


    The fate of a memory, whether stored or forgotten, is determined by the ability of an active or tagged synapse to undergo changes in synaptic efficacy requiring protein synthesis of plasticity-related proteins. A synapse can be tagged, but without the “capture” of plasticity-related proteins, it will not undergo long lasting forms of plasticity (synaptic tagging and capture hypothesis). What the “tag” is and how plasticity-related proteins are captured at tagged synapses are unknown. Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) is critical in learning and memory and is synthesized locally in neuronal dendrites. The mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that increases CaMKIIα protein expression; however, the mechanism and site of dendritic expression are unknown. Herein, we show that mTOR activity mediates the branch-specific expression of CaMKIIα, favoring one secondary, daughter branch over the other in a single neuron. mTOR inhibition decreased the dendritic levels of CaMKIIα protein and mRNA by shortening its poly(A) tail. Overexpression of the RNA-stabilizing protein HuD increased CaMKIIα protein levels and preserved its selective expression in one daughter branch over the other when mTOR was inhibited. Unexpectedly, deleting the third RNA recognition motif of HuD, the domain that binds the poly(A) tail, eliminated the branch-specific expression of CaMKIIα when mTOR was active. These results provide a model for one molecular mechanism that may underlie the synaptic tagging and capture hypothesis where mTOR is the tag, preventing deadenylation of CaMKIIα mRNA, whereas HuD captures and promotes its expression in a branch-specific manner. PMID:25944900

  3. CAD/CAM approach to improving industry productivity gathers momentum (United States)

    Fulton, R. E.


    Recent results and planning for the NASA/industry Integrated Programs for Aerospace-Vehicle Design (IPAD) program for improving productivity with CAD/CAM methods are outlined. The industrial group work is being mainly done by Boeing, and progress has been made in defining the designer work environment, developing requirements and a preliminary design for a future CAD/CAM system, and developing CAD/CAM technology. The work environment was defined by conducting a detailed study of a reference design process, and key software elements for a CAD/CAM system have been defined, specifically for interactive design or experiment control processes. Further work is proceeding on executive, data management, geometry and graphics, and general utility software, and dynamic aspects of the programs being developed are outlined

  4. Resin-composite blocks for dental CAD/CAM applications. (United States)

    Ruse, N D; Sadoun, M J


    Advances in digital impression technology and manufacturing processes have led to a dramatic paradigm shift in dentistry and to the widespread use of computer-aided design/computer-aided manufacturing (CAD/CAM) in the fabrication of indirect dental restorations. Research and development in materials suitable for CAD/CAM applications are currently the most active field in dental materials. Two classes of materials are used in the production of CAD/CAM restorations: glass-ceramics/ceramics and resin composites. While glass-ceramics/ceramics have overall superior mechanical and esthetic properties, resin-composite materials may offer significant advantages related to their machinability and intra-oral reparability. This review summarizes recent developments in resin-composite materials for CAD/CAM applications, focusing on both commercial and experimental materials.

  5. Complementary and alternative (CAM) dietary therapies for cancer. (United States)

    Weitzman, Sheila


    Complementary and alternative (CAM) therapies include a wide spectrum of dietary practices, some of which are claimed to cure cancer. Observational studies have shown consistently that predominantly plant-based diets reduce the risk for some adult type cancers such as breast cancer and prostate cancer. These studies form the basis of the American Cancer Society (ACS) nutritional guidelines. Many CAM diets prescribe a similar low fat, high fiber, high fruit and vegetable type diet, but also add detoxification and many different supplements to the basic diet which is then claimed to cure cancer. The potential advantages and disadvantages of CAM diets are discussed. Many aspects can be potentially harmful, particularly to the child with cancer. Advantages include involvement of the child and family in decision-making and care. There is no evidence to support the claims that CAM dietary therapies cure cancer.

  6. Surgical hip dislocation for treatment of cam femoroacetabular impingement

    Directory of Open Access Journals (Sweden)

    Milind M Chaudhary


    Conclusion: Cam femoroacetabular Impingement causing pain and limitation of hip movements was treated by open osteochondroplasty after surgical hip dislocation. This reduced pain, improved hip motion and gave good to excellent results in the short term.

  7. Special Section: Complementary and Alternative Medicine (CAM): Time to Talk (United States)

    ... with your health care providers any complementary and alternative medicines you take or are thinking about starting. Photo: ... and older use some form of complementary and alternative medicine (CAM). But less than one-third who use ...

  8. Finding the Evidence in CAM: a Student's Perspective

    Directory of Open Access Journals (Sweden)

    Jeffrey Ghassemi


    Full Text Available This commentary offers a future health care provider's perspective on the role of complementary and alternative medicine (CAM in Western (namely, in US medical education and practice. As a student of both public health and medicine in the United States, Jeffrey Ghassemi is interested in CAM's contribution to improving medical practice and teaching. The commentary highlights the ambiguous definitions of CAM to Westerners despite the rising popularity of and expenditures for alternative modalities of care. It then argues for collaboration between alternative and established medical communities to ascertain the scientific merits of CAM. It concludes by calling for a new medical paradigm that embraces the philosophies of both communities to advance education and patient care.

  9. Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src.

    Directory of Open Access Journals (Sweden)

    Silviya R Stateva

    Full Text Available Src family non-receptor tyrosine kinases play a prominent role in multiple cellular processes, including: cell proliferation, differentiation, cell survival, stress response, and cell adhesion and migration, among others. And when deregulated by mutations, overexpression, and/or the arrival of faulty incoming signals, its hyperactivity contributes to the development of hematological and solid tumors. c-Src is a prototypical member of this family of kinases, which is highly regulated by a set of phosphorylation events. Other factor contributing to the regulation of Src activity appears to be mediated by the Ca2+ signal generated in cells by different effectors, where the Ca2+-receptor protein calmodulin (CaM plays a key role. In this report we demonstrate that CaM directly interacts with Src in both Ca2+-dependent and Ca2+-independent manners in vitro and in living cells, and that the CaM antagonist N-(6-aminohexyl-5-chloro-1-naphthalenesulfonamide (W-7 inhibits the activation of this kinase induced by the upstream activation of the epidermal growth factor receptor (EGFR, in human carcinoma epidermoide A431 cells, and by hydrogen peroxide-induced oxidative stress, in both A431 cells and human breast adenocarcinoma SK-BR-3 cells. Furthermore, we show that the Ca2+/CaM complex strongly activates the auto-phosphorylation and tyrosine kinase activity of c-Src toward exogenous substrates, but most relevantly and for the first time, we demonstrate that Ca2+-free CaM (apo-CaM exerts a far higher activatory action on Src auto-phosphorylation and kinase activity toward exogenous substrates than the one exerted by the Ca2+/CaM complex. This suggests that a transient increase in the cytosolic concentration of free Ca2+ is not an absolute requirement for CaM-mediated activation of Src in living cells, and that a direct regulation of Src by apo-CaM could be inferred.

  10. Availability Analysis of the Ventilation Stack CAM Interlock System

    CERN Document Server

    Young, J


    Ventilation Stack Continuous Air Monitor (CAM) Interlock System failure modes, failure frequencies, and system availability have been evaluated for the RPP. The evaluation concludes that CAM availability is as high as assumed in the safety analysis and that the current routine system surveillance is adequate to maintain this availability credited in the safety analysis, nor is such an arrangement predicted to significantly improve system availability.

  11. The pineapple genome and the evolution of CAM photosynthesis. (United States)

    Ming, Ray; VanBuren, Robert; Wai, Ching Man; Tang, Haibao; Schatz, Michael C; Bowers, John E; Lyons, Eric; Wang, Ming-Li; Chen, Jung; Biggers, Eric; Zhang, Jisen; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Zhang, Jian; Ye, Zhangyao; Miao, Chenyong; Lin, Zhicong; Wang, Hao; Zhou, Hongye; Yim, Won C; Priest, Henry D; Zheng, Chunfang; Woodhouse, Margaret; Edger, Patrick P; Guyot, Romain; Guo, Hao-Bo; Guo, Hong; Zheng, Guangyong; Singh, Ratnesh; Sharma, Anupma; Min, Xiangjia; Zheng, Yun; Lee, Hayan; Gurtowski, James; Sedlazeck, Fritz J; Harkess, Alex; McKain, Michael R; Liao, Zhenyang; Fang, Jingping; Liu, Juan; Zhang, Xiaodan; Zhang, Qing; Hu, Weichang; Qin, Yuan; Wang, Kai; Chen, Li-Yu; Shirley, Neil; Lin, Yann-Rong; Liu, Li-Yu; Hernandez, Alvaro G; Wright, Chris L; Bulone, Vincent; Tuskan, Gerald A; Heath, Katy; Zee, Francis; Moore, Paul H; Sunkar, Ramanjulu; Leebens-Mack, James H; Mockler, Todd; Bennetzen, Jeffrey L; Freeling, Michael; Sankoff, David; Paterson, Andrew H; Zhu, Xinguang; Yang, Xiaohan; Smith, J Andrew C; Cushman, John C; Paull, Robert E; Yu, Qingyi


    Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 and MD2 and a wild pineapple relative, Ananas bracteatus accession CB5. The pineapple genome has one fewer ancient whole-genome duplication event than sequenced grass genomes and a conserved karyotype with seven chromosomes from before the ρ duplication event. The pineapple lineage has transitioned from C3 photosynthesis to CAM, with CAM-related genes exhibiting a diel expression pattern in photosynthetic tissues. CAM pathway genes were enriched with cis-regulatory elements associated with the regulation of circadian clock genes, providing the first cis-regulatory link between CAM and circadian clock regulation. Pineapple CAM photosynthesis evolved by the reconfiguration of pathways in C3 plants, through the regulatory neofunctionalization of preexisting genes and not through the acquisition of neofunctionalized genes via whole-genome or tandem gene duplication.

  12. Aquatic CAM photosynthesis: a brief history of its discovery (United States)

    Keeley, Jon E.


    Aquatic CAM (Crassulacean Acid Metabolism) photosynthesis was discovered while investigating an unrelated biochemical pathway concerned with anaerobic metabolism. George Bowes was a significant contributor to this project early in its infancy. Not only did he provide me with some valuable perspectives on peer review rejections, but by working with his gas exchange system I was able to take our initial observations of diel fluctuations in malic acid to the next level, showing this aquatic plant exhibited dark CO2 uptake. CAM is universal in all aquatic species of the worldwide Lycophyta genus Isoetes and non-existent in terrestrial Isoetes. Outside of this genus aquatic CAM has a limited occurrence in three other families, including the Crassulaceae. This discovery led to fascinating adventures in the highlands of the Peruvian Andes in search of Stylites, a terrestrial relative of Isoetes. Stylites is a plant that is hermetically sealed from the atmosphere and obtains all of its carbon from terrestrial sources and recycles carbon through CAM. Considering the Mesozoic origin of Isoetes in shallow pools, coupled with the fact that aquatic Isoetes universally possess CAM, suggests the earliest evolution of CAM photosynthesis was most likely not in terrestrial plants.

  13. Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1 promoter and its regulation by Sp1

    Directory of Open Access Journals (Sweden)

    Botella Luisa M


    Full Text Available Abstract Background Activin receptor-like kinase 1 (ALK1 is a Transforming Growth Factor-β (TGF-β receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1 give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. Results We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210 was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. Conclusions Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into

  14. The Subaru Hyper Suprime-Cam Survey (United States)

    Strauss, Michael A.; Hyper Suprime-Cam Team


    High-latitude wide-field optical imaging surveys allow us to address scientific questions ranging from the properties of asteroids in the Solar System, to the structure of the Milky Way halo, to galaxy evolution, to the distribution of dark matter in the universe and the properties and evolution of dark energy. Hyper Suprime-Cam (HSC) is an imaging camera with a 1.77 deg2 field of view, mounted at the Prime Focus of the Subaru 8.2-m telescope operated by the National Astronomical Observatory of Japan on the summit of Maunakea in Hawaii. A consortium of astronomers from Japan, Taiwan and Princeton University is carrying out a three-layer, 300-night, multiband survey with this instrument. The Wide Layer will cover 1400 deg2 in five broad bands (grizy), to a 5 sigma point-source depth of r~26. The Deep Layer will cover 28 deg2 in four separate fields, going a magnitude deeper, and including narrow-band imaging to identify Lyman-alpha emitters at high redshift. The Ultradeep Layer will go a magnitude deeper still in two pointings (3.5 deg2), allowing studies of supernovae and other variable phenomenae.The survey started in 2014, and will continue through 2019. We have covered 240 deg2 of the Wide Layer in all five bands, and the median seeing in the i band is 0.60 arcseconds. In this introductory talk to the HSC special session, I will describe the quality of the data, plans for public data release, and touch upon some of the early science results, which range from the discovery of an ultrafaint dwarf galaxy in the Milky Way halo, to significant numbers of quasars and galaxies with redshifts between 5.7 and 7, to measurements of gravitational weak lensing around clusters.


    Directory of Open Access Journals (Sweden)

    Bernardo Nugroho Yahya


    Full Text Available The future industry is the one who can manage the information system. Today, communication technology and distributed system computerization already have the ability to implement system that able to exchange and share information between different users. Product Data Management (PDM is an up-to-date and excellent method on managing the exchange and share of information. PDM is able to integrate and manage data analyzing process and documentation of the related product component physically. By adjusting the CAD/CAM on certain condition, the PDM will function maximally by using the information based on STEP (Standard for the Exchange of Product Data model. This article will explain the relationship between PDM system and CAD/CAM on industry. Abstract in Bahasa Indonesia : Sistem informasi merupakan ujung tombak sebuah perusahaan yang unggul di masa depan. Komputerisasi dengan sistem yang terdistribusi dan teknologi komunikasi saat ini memiliki kemampuan untuk mengimplementasikan sistem yang dapat menukar dan men-share informasi antar user yang berbeda. Teknologi yang mendapat cukup perhatian luas dalam hal pertukaran dan sharing informasi ini adalah Product Data Management (PDM. PDM dapat mengintegrasikan dan mengatur proses pengolahan data dan dokumen teknik yang berhubungan dengan komponen fisik produk yang bersangkutan. PDM akan berfungsi maksimal apabila kesesuaian dengan CAD/CAM diatur sedemikian rupa, dihubungkan dengan informasi berbasiskan STEP (Standard for the Exchange of Product Data model. Artikel ini akan menjelaskan hubungan antara sistem PDM dengan CAD/CAM dalam industri. Kata kunci: PDM, Manajemen Data, CAD/CAM, STEP.

  16. CamBAfx: Workflow Design, Implementation and Application for Neuroimaging. (United States)

    Ooi, Cinly; Bullmore, Edward T; Wink, Alle-Meije; Sendur, Levent; Barnes, Anna; Achard, Sophie; Aspden, John; Abbott, Sanja; Yue, Shigang; Kitzbichler, Manfred; Meunier, David; Maxim, Voichita; Salvador, Raymond; Henty, Julian; Tait, Roger; Subramaniam, Naresh; Suckling, John


    CamBAfx is a workflow application designed for both researchers who use workflows to process data (consumers) and those who design them (designers). It provides a front-end (user interface) optimized for data processing designed in a way familiar to consumers. The back-end uses a pipeline model to represent workflows since this is a common and useful metaphor used by designers and is easy to manipulate compared to other representations like programming scripts. As an Eclipse Rich Client Platform application, CamBAfx's pipelines and functions can be bundled with the software or downloaded post-installation. The user interface contains all the workflow facilities expected by consumers. Using the Eclipse Extension Mechanism designers are encouraged to customize CamBAfx for their own pipelines. CamBAfx wraps a workflow facility around neuroinformatics software without modification. CamBAfx's design, licensing and Eclipse Branding Mechanism allow it to be used as the user interface for other software, facilitating exchange of innovative computational tools between originating labs.

  17. CamBAfx: workflow design, implementation and application for neuroimaging

    Directory of Open Access Journals (Sweden)

    Cinly Ooi


    Full Text Available CamBAfx is a workflow application designed for both researchers who use workflows to process data (consumers and those who design them (designers. It provides a front-end (user interface optimized for data processing designed in a way familiar to consumers. The back-end uses a pipeline model to represent workflows since this is a common and useful metaphor used by designers and is easy to manipulate compared to other representations like programming scripts. As an Eclipse Rich Client Platform application, CamBAfx's pipelines and functions can be bundled with the software or downloaded post-installation. The user interface contains all the workflow facilities expected by consumers. Using the Eclipse Extension Mechanism designers are encouraged to customize CamBAfx for their own pipelines. CamBAfx wraps a workflow facility around neuroinformatics software without modification. CamBAfx's design, licensing and Eclipse Branding Mechanism allow it to be used as the user interface for other software, facilitating exchange of innovative computational tools between originating labs.

  18. The Pleiotropic Role of L1CAM in Tumor Vasculature (United States)

    Angiolini, Francesca; Cavallaro, Ugo


    Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM), a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach. PMID:28134764

  19. Far-infrared radiation acutely increases nitric oxide production by increasing Ca{sup 2+} mobilization and Ca{sup 2+}/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung-Hyun; Lee, Sangmi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Cho, Du-Hyong [Department of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701 (Korea, Republic of); Park, Young Mi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Kang, Duk-Hee [Division of Nephrology, Department of Internal Medicine, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Jo, Inho, E-mail: [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of)


    Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser{sup 1179} phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser{sup 1179} phosphorylation. •FIR increases intracellular Ca{sup 2+} levels. •Thermo-sensitive TRPV Ca{sup 2+} channels are unlikely to be involved in the FIR-mediated eNOS-Ser{sup 1179} phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser{sup 1179}) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca{sup 2+} levels. Treatment with KN-93, a selective inhibitor of Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. This

  20. Are different generations of CAD/CAM milling machines capable to produce restorations with similar quality? (United States)

    Roperto, Renato; Assaf, Hussein; Soares-Porto, Thiago; Lang, Lisa; Teich, Sorin


    Background Different CAD/CAM machines’ generation may impact the restoration overall quality. The present study evaluated the marginal fit of CAD/CAM restorations manufactured with different generations of CEREC milling unit systems. Material and Methods Sixteen typodont teeth were divided into two groups (n=8) according to the machine’s generation assigned. These are control group (G1): Cerec AC with Bluecam/Cerec 3 milling unit and (G2): Cerec AC with Bluecam/MC XL Premium Package milling unit. Scanning of the preparation were performed and crowns were milled using the Vita Mark II blocks. Blocks were cemented using epoxy glue on the pulpal floor only and finger pressure applied for 1 min. Upon completion of the cementation step, misfits between the restoration and abutment were measured by microphotography and the silicone replica technique using light body silicon material on Mesial (M) and Distal (D) surfaces. Results Mean and SDs of marginal gaps in micrometers were: G1/M: 94.90 (±38.52), G1/D: 88.53 (±44.87), G2/M: 85.65 (±29.89), G2/D: 95.28 (±28.13). Two-way ANOVA indicated no significant differences among different groups (P>0.05); surface area (P>0.05) and the interaction (P>0.05). Overall, G2 had greater margin gaps than G1, however, without statistical difference (P>0.05). Conclusions Difference in milling unit generation did not significantly affect the marginal fit. Marginal gap means were in the range of the clinical acceptance levels for both generations of Cerec milling units, regardless the teeth site area. Key words:CAD/CAM, margin, ceramics. PMID:27703611

  1. On the nature of facultative and constitutive CAM: environmental and developmental control of CAM expression during early growth of Clusia, Kalanchöe, and Opuntia. (United States)

    Winter, Klaus; Garcia, Milton; Holtum, Joseph A M


    The capacity to induce crassulacean acid metabolism developmentally (constitutive CAM) and to up-regulate CAM expression in response to drought stress (facultative CAM) was studied in whole shoots of seven species by measuring net CO(2) gas exchange for up to 120 day-night cycles during early growth. In Clusia rosea, CAM was largely induced developmentally. Well-watered seedlings began their life cycle as C(3) plants and developed net dark CO(2) fixation indicative of CAM after the initiation of the fourth leaf pair following the cotyledons. Thereafter, CAM activity increased progressively and drought stress led to only small additional, reversible increases in dark CO(2) fixation. In contrast, CAM expression was overwhelmingly under environmental control in seedlings and mature plants of Clusia pratensis. C(3)-type CO(2) exchange was maintained under well-watered conditions, but upon drought stress, CO(2) exchange shifted, in a fully reversible manner, to a CAM-type pattern. Clusia minor showed CO(2) exchange reponses intermediate to those of C. rosea and C. pratensis. Clusia cretosa operated in the C(3) mode at all times. Notably, reversible stress-induced increases of dark CO(2) fixation were also observed during the developmental progression to pronounced CAM in young Kalanchoë daigremontiana and Kalanchoë pinnata, two species considered constitutive CAM species. Drought-induced up-regulation of CAM was even detected in young cladodes of a cactus, Opuntia ficus-indica, an archetypal constitutive CAM species. Evidently, the defining characteristics of constitutive and facultative CAM are shared, to variable degrees, by all CAM species.

  2. Principle and curve of planetary indexing cam mechanisms

    Institute of Scientific and Technical Information of China (English)

    LIU Ming-tao; ZHANG Ce; YANG Yu-hu


    A new type of planetary indexing cam mechanism called type IV is presented.The transmission principle of type IV is discussed.Based on the principle of formarion of conjugate tooth contour,the equations of the cam's pitch curve are derived.The continuity and symmetry of the cain's pitch curve are also analyzed.It can be concluded that:1) This type has no output institution so the output precision can be improved;2) The asymmetrical two-ring structure is used to-overcome dead point and its phase angle is equal to (π-2π/n) ;3) The continuous condition of the cam's pitch curve is that the average transmission ratio is -n in an intermittent motion period.

  3. GravityCam: Higher Resolution Visible Wide-Field Imaging

    CERN Document Server

    Mackay, Craig; Steele, Iain


    The limits to the angular resolution achievable with conventional ground-based telescopes are unchanged over 70 years. Atmospheric turbulence limits image quality to typically ~1 arcsec in practice. We have developed a new concept of ground-based imaging instrument called GravityCam capable of delivering significantly sharper images from the ground than is normally possible without adaptive optics. The acquisition of visible images at high speed without significant noise penalty has been made possible by advances in optical and near IR imaging technologies. Images are recorded at high speed and then aligned before combination and can yield a 3-5 fold improvement in image resolution. Very wide survey fields are possible with widefield telescope optics. We describe GravityCam and detail its application to accelerate greatly the rate of detection of Earth size planets by gravitational microlensing. GravityCam will also improve substantially the quality of weak shear studies of dark matter distribution in distant...

  4. Xi-CAM v1.2.3

    Energy Technology Data Exchange (ETDEWEB)


    Xi-CAM aims to provide a community driven platform for multimodal analysis in synchrotron science. The platform core provides a robust plugin infrastructure for extensibility, allowing continuing development to simply add further functionality. Current modules include tools for characterization with (GI)SAXS, Tomography, and XAS. This will continue to serve as a development base as algorithms for multimodal analysis develop. Seamless remote data access, visualization and analysis are key elements of Xi-CAM, and will become critical to synchrotron data infrastructure as expectations for future data volume and acquisition rates rise with continuously increasing throughputs. The highly interactive design elements of Xi-cam will similarly support a generation of users which depend on immediate data quality feedback during high-throughput or burst acquisition modes.

  5. MegaPipe: the MegaCam image stacking pipeline

    CERN Document Server

    Gwyn, Stephen D J


    This paper describes the MegaPipe image processing pipeline at the Canadian Astronomical Data Centre (CADC). The pipeline takes multiple images from the MegaCam mosaic camera on CFHT and combines them into a single output image. MegaPipe takes as input detrended MegaCam images and does a careful astrometric and photometric calibration on them. The calibrated images are then resampled and combined into image stacks. MegaPipe is run on PI data by request, data from large surveys (the CFHT Legacy Survey and the Next Generation Virgo Survey) and all non-proprietary MegaCam data in the CFHT archive. The stacked images and catalogs derived from these images are available through the CADC website. Currently, 1500 square degrees have been processed.

  6. Passivity of conventional and CAD/CAM fabricated implant frameworks. (United States)

    de Araújo, Gabriela Monteiro; de França, Danilo Gonzaga Bernardo; Silva Neto, João Paulo; Barbosa, Gustavo Augusto Seabra


    The objective of this research was to evaluate the passivity by measuring the passive fit and strain development of frameworks screwed on abutments, made by CAD/CAM technology, and to compare these parts with samples manufactured by conventional casting. Using CAD/CAM technology, four samples were made from zirconia (Zircad) and four samples were manufactured from cobalt-chrome (CoCrcad). The control groups were four specimens of cobalt-chrome, made by one-piece casting (CoCrci), with a total of 12 frameworks. To evaluate the passive fit, the vertical misfit at the abutment-framework interface was measured with scanning electron microscopy (250×) when only one screw was tightened. The mean strain in these frameworks was analyzed by photoelasticity test. A significant difference in the passive fit was observed between the control and sample groups. CoCrcad exhibited the best value of passive fit (48.76±13.45 µm) and CoCrci the worst (187.55±103.63 µm); Zircad presented an intermediate value (103.81±43.15 µm). When compared to the other groups, CoCrci showed the highest average stress around the implants (17.19±7.22 kPa). It was concluded that CAD/CAM-fabricated frameworks exhibited better passivity compared with conventionally fabricated frameworks. CAD/CAM-fabricated Co-Cr frameworks may exhibit better passive fit compared with CAD/CAM-fabricated zirconia frameworks. Even so, similar levels of stress were achieved for CAD/CAM-fabricated frameworks.

  7. CAD/CAM generated all-ceramic primary telescopic prostheses. (United States)

    Kurbad, A; Ganz, S; Kurbad, S


    Computer-aided design and manufacturing (CAD/CAM) systems have proven effective not only for the manufacture of crown and bridge frameworks, inlays, onlays and veneers, but also for the generation of all-ceramic primary telescopic prostheses in more than 10 years of use in dental technology. The new InLab 4.0 software generation makes it possible to design and mill primary telescopic prostheses with CAD/CAM technology. The computer-generated raw crowns for these restorations require very little manual adaptation. The secondary crowns are manufactured by electroforming and bonded onto the tertiary structure or framework.

  8. Impact of IPAD on CAD/CAM database university research (United States)

    Leach, L. M.; Wozny, M. J.


    IPAD program has provided direction, focus and software products which impacted on CAD/CAM data base research and follow-on research. The relationship of IPAD to the research projects which involve the storage of geometric data in common data ase facilities such as data base machines, the exchange of data between heterogeneous data bases, the development of IGES processors, the migration of lrge CAD/CAM data base management systems to noncompatible hosts, and the value of RIM as a research tool is described.

  9. CAD/CAM in the Brazilian aeronautical industry (United States)

    Lampi, L. H.; Embraer, S. A.

    Features, applications and progress in the usage of CAD/CAM since 1980 by an aircraft manufacturer in Brazil are described. The system comprises 34 graphics work stations dedicated to structural design, lofting, electrical cable routing, finite element modeling and quality control. Standardized work methods have been devised to enhance productivity. Programs have been defined for finite element stress analysis and generating wiring diagrams. The computerized design capabilities have increased productivity for hole boring accuracy through work on digitized controllers. Psychological testing has been initiated to identify users who can adapt more easily to CAD/CAM utilization.

  10. FlashCam: A fully digital camera for CTA telescopes

    CERN Document Server

    Pühlhofer, G; Biland, A; Florin, D; Föhr, C; Gadola, A; Hermann, G; Kalkuhl, C; Kasperek, J; Kihm, T; Koziol, J; Manalaysay, A; Marszalek, A; Rajda, P J; Schanz, T; Steiner, S; Straumann, U; Tenzer, C; Vogler, P; Vollhardt, A; Weitzel, Q; Winiarski, K; Zietara, K


    The future Cherenkov Telescope Array (CTA) will consist of several tens of telescopes of different mirror sizes. CTA will provide next generation sensitivity to very high energy photons from few tens of GeV to >100 TeV. Several focal plane instrumentation options are currently being evaluated inside the CTA consortium. In this paper, the current status of the FlashCam prototyping project is described. FlashCam is based on a fully digital camera readout concept and features a clean separation between photon detector plane and signal digitization/triggering electronics.

  11. Crystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases. (United States)

    Safo, Martin K; Musayev, Faik N; di Salvo, Martino L; Hunt, Sharyn; Claude, Jean-Baptiste; Schirch, Verne


    The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were determined in the unliganded and binary complexes with either MgATP or pyridoxal to 2.1-, 2.6-, and 3.2-A resolutions, respectively. The active site of ePL kinase 1 does not show significant conformational change upon binding of either pyridoxal or MgATP. Like sheep PL kinase, ePL kinase 1 exhibits a sequential random mechanism. Unlike sheep pyridoxal kinase, ePL kinase 1 may not tolerate wide variation in the size and chemical nature of the 4' substituent on the substrate. This is the result of differences in a key residue at position 59 on a loop (loop II) that partially forms the active site. Residue 59, which is His in ePL kinase 1, interacts with the formyl group at C-4' of pyridoxal and may also determine if residues from another loop (loop I) can fill the active site in the absence of the substrate. Both loop I and loop II are suggested to play significant roles in the functions of PL kinases.

  12. Performance of different polishing techniques for direct CAD/CAM ceramic restorations. (United States)

    Flury, Simon; Lussi, Adrian; Zimmerli, Brigitte


    This in vitro study evaluated the performance of three ceramic and two commonly used polishing methods on two CAD/CAM ceramics. Surface roughness and quality were compared. A glazed group (GLGR) of each ceramic material served as reference. One-hundred and twenty specimens of VITABLOCS Mark II (VITA) and 120 specimens of IPS Empress CAD (IPS) were roughened in a standardized manner. Twenty VITA and 20 IPS specimens were glazed (VITA Akzent Glaze/Empress Universal Glaze). Five polishing methods were investigated (n=20/group): 1) EVE Diacera W11DC-Set (EVE), 2) JOTA 9812-Set (JOTA), 3) OptraFine-System (OFI), 4) Sof-Lex 2382 discs (SOF) and 5) Brownie/Greenie/Occlubrush (BGO). Polishing quality was measured with a surface roughness meter (Ra and Rz values). The significance level was set at alpha=0.05. Kruskal Wallis tests and pairwise Wilcoxon rank sum tests with Bonferroni-Holm adjustment were used. Qualitative surface evaluation of representative specimens was done with SEM. On VITA ceramics, SOF produced lower Ra (psystems are still of interest to clinicians using CAD/CAM, as these methods are universally applicable and showed an increased durability compared to the investigated silicon polishers.

  13. Luting of CAD/CAM ceramic inlays: direct composite versus dual-cure luting cement. (United States)

    Kameyama, Atsushi; Bonroy, Kim; Elsen, Caroline; Lührs, Anne-Katrin; Suyama, Yuji; Peumans, Marleen; Van Meerbeek, Bart; De Munck, Jan


    The aim of this study was to investigate bonding effectiveness in direct restorations. A two-step self-etch adhesive and a light-cure resin composite was compared with luting with a conventional dual-cure resin cement and a two-step etch and rinse adhesive. Class-I box-type cavities were prepared. Identical ceramic inlays were designed and fabricated with a computer-aided design/computer-aided manufacturing (CAD/CAM) device. The inlays were seated with Clearfil SE Bond/Clearfil AP-X (Kuraray Medical) or ExciTE F DSC/Variolink II (Ivoclar Vivadent), each by two operators (five teeth per group). The inlays were stored in water for one week at 37°C, whereafter micro-tensile bond strength testing was conducted. The micro-tensile bond strength of the direct composite was significantly higher than that from conventional luting, and was independent of the operator (P<0.0001). Pre-testing failures were only observed with the conventional method. High-power light-curing of a direct composite may be a viable alternative to luting lithium disilicate glass-ceramic CAD/CAM restorations.

  14. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

    Directory of Open Access Journals (Sweden)

    Peter Rellos

    Full Text Available UNLABELLED: Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

  15. Beta2-containing nicotinic acetylcholine receptors mediate calcium/calmodulin-dependent protein kinase-II and synapsin I protein levels in the nucleus accumbens after nicotine withdrawal in mice. (United States)

    Jackson, Kia J; Imad Damaj, M


    Nicotinic acetylcholine receptors are calcium-permeable and the initial targets for nicotine. Studies suggest that calcium-dependent mechanisms mediate some behavioral responses to nicotine; however, the post-receptor calcium-dependent mechanisms associated with chronic nicotine and nicotine withdrawal remain unclear. The proteins calcium/calmodulin-dependent protein kinase II (CaMKII) and synapsin I are essential for neurotransmitter release and were shown to be involved in drug dependence. In the current study, using pharmacological techniques, we sought to (a) complement previously published behavioral findings from our lab indicating a role for calcium-dependent signaling in nicotine dependence and (b) expand on previously published acute biochemical and pharmacological findings indicating the relevance of calcium-dependent mechanisms in acute nicotine responses by evaluating the function of CaMKII and synapsin I after chronic nicotine and withdrawal in the nucleus accumbens, a brain region implicated in drug dependence. Male mice were chronically infused with nicotine for 14 days, and treated with the β2-selective antagonist dihydro-β-erythroidine (DHβE), or the α7 antagonist, methyllycaconitine citrate (MLA) 20min prior to dissection of the nucleus accumbens. Results show that phosphorylated and total CaMKII and synapsin I protein levels were significantly increased in the nucleus accumbens after chronic nicotine infusion, and reduced after treatment with DHβE, but not MLA. A spontaneous nicotine withdrawal assessment also revealed significant reductions in phosphorylated CaMKII and synapsin I levels 24h after cessation of nicotine treatment. Our findings suggest that post-receptor calcium-dependent mechanisms associated with nicotine withdrawal are mediated through β2-containing nicotinic receptors.

  16. Active Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII Regulates NMDA Receptor Mediated Postischemic Long-Term Potentiation (i-LTP by Promoting the Interaction between CaMKII and NMDA Receptors in Ischemia

    Directory of Open Access Journals (Sweden)

    Ning Wang


    Full Text Available Active calcium/calmodulin-dependent protein kinase II (CaMKII has been reported to take a critical role in the induction of long-term potentiation (LTP. Changes in CaMKII activity were detected in various ischemia models. It is tempting to know whether and how CaMKII takes a role in NMDA receptor (NMDAR-mediated postischemic long-term potentiation (NMDA i-LTP. Here, we monitored changes in NMDAR-mediated field excitatory postsynaptic potentials (NMDA fEPSPs at different time points following ischemia onset in vitro oxygen and glucose deprivation (OGD ischemia model. We found that 10 min OGD treatment induced significant i-LTP in NMDA fEPSPs, whereas shorter (3 min or longer (25 min OGD treatment failed to induce prominent NMDA i-LTP. CaMKII activity or CaMKII autophosphorylation displays a similar bifurcated trend at different time points following onset of ischemia both in vitro OGD or in vivo photothrombotic lesion (PT models, suggesting a correlation of increased CaMKII activity or CaMKII autophosphorylation with NMDA i-LTP. Disturbing the association between CaMKII and GluN2B subunit of NMDARs with short cell-permeable peptides Tat-GluN2B reversed NMDA i-LTP induced by OGD treatment. The results provide support to a notion that increased interaction between NMDAR and CaMKII following ischemia-induced increased CaMKII activity and autophosphorylation is essential for induction of NMDA i-LTP.

  17. CAM visual stimulation with conventional method of occlusion treatment in amblyopia: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Ali Reza Jafari


    Conclusion: Using of CAM visual stimulation along with conventional occlusion will further improve visual acuity and stereopsis in amblyopic children. These findings recommended the CAM visual stimulation as an accompanying and complementary method in amblyopia treatment.

  18. Special Section: Complementary and Alternative Medicine (CAM):Quiz on Complementary and Alternative Medicine (United States)

    ... Issues Special Section CAM Quiz on Complementary and Alternative Medicine Past Issues / Winter 2009 Table of Contents For ... for low back pain. True False Complementary and alternative medicine (CAM) includes: Meditation Chiropractic Use of natural products, ...

  19. Antioxidant, DNA interaction, VEGFR2 kinase, topoisomerase I and in vitro cytotoxic activities of heteroleptic copper(II) complexes of tetrazolo[1,5-a]pyrimidines and diimines. (United States)

    Haleel, A; Mahendiran, D; Veena, V; Sakthivel, N; Rahiman, A Kalilur


    A series of heteroleptic mononuclear copper(II) complexes of the type [Cu(L(1-3))(diimine)]ClO4 (1-6) containing three tetrazolo[1,5-a]pyrimidine core ligands, ethyl 5-methyl-7-(2-hydroxyphenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (HL(1)), ethyl 5-methyl-7-(4-diethylamino-2-hydroxyphenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (HL(2)) or ethyl 5-methyl-7-(2-hydroxy-4-nitrophenyl)-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (HL(3)), and two diimine coligands, 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) have been synthesized and characterized by spectral methods. The geometry of complexes have been determined with the help of electronic absorption and EPR splitting patterns, which suggest four coordinated square planar geometry around copper(II) ion. The lowering of HOMO-LUMO band gap value of complex 4 implies its higher biological activity compared to other complexes. Antioxidant studies revealed that the complexes possess considerable radical scavenging potency against DPPH. The binding studies of the complexes with calf thymus DNA (CT-DNA) revealed groove mode of binding, which was further supported by docking simulation. The complexes 3 and 4 strongly inhibit the topoisomerase I, and also strongly interact with VEGFR2 kinase receptor via π-π, σ-π and hydrogen bonding interaction. Gel electrophoresis experiments demonstrated the ability of the complexes to cleave plasmid DNA in the absence of activators. In vitro cytotoxic activities of the complexes were examined on three cancerous cell lines such as human lung (A549), cervical (HeLa) and colon (HCT-15), and two normal cells such as human embryonic kidney (HEK) and peripheral blood mononuclear cells (PBMCs). The live cell and fluorescent imaging of cancer cells were observed with acridine orange/ethidium bromide staining assay. All encouraging chemical and biological findings indicate that the complex 4 is a suitable candidate for drug target.

  20. Mitochondrial respiration in ME-CAM, PEPCK-CAM, and C₃ succulents: comparative operation of the cytochrome, alternative, and rotenone-resistant pathways. (United States)

    Peckmann, Klaus; von Willert, Dieter J; Martin, Craig E; Herppich, Werner B


    Mitochondria are important in the function and control of Crassulacean acid metabolism (CAM) during organic acid accumulation at night and acid decarboxylation in the day. In plants of the malic enzyme-(ME) type and the phosphoenolpyruvate carboxykinase- (PEPCK) type, mitochondria may exert their role in the control of the diurnal rhythm of malic and citric acids to a differential degree. In plants of both CAM types, the oxidative capacity of mitochondria, as well as the activity of CAM-linked mitochondrial enzymes, and of the alternative and the rotenone-resistant pathways of substrate oxidation were compared. Furthermore, a C₃ succulent was included, as well as both C₃ and CAM forms of Mesembryanthemum crystallinum during a salt-induced C₃-to-CAM shift. Mitochondria of PEPCK-type CAM plants exhibited a lower activity of malate oxidation, ratio of malate to succinate oxidation, and activity of mitochondrial NAD-ME. With the exception of Kalanchoë daigremontiana, leaf mitochondria of all other CAM species were highly sensitive to cyanide (80-100%), irrespective of the oxidant used. This indicates that the alternative oxidase is not of general importance in CAM. By contrast, rotenone-insensitive substrate oxidation was very high (50-90%) in all CAM species. This is the first comparison of the rotenone-insensitive pathway of respiration in plants with different CAM-types. The results of this study confirm that mitochondria are involved in the control of CAM to different degrees in the two CAM types, and they highlight the multiple roles of mitochondria in CAM.

  1. Effects of Complementary and Alternative Medicines (CAM) on the Metabolism and Transport of Anticancer Drugs


    Mooiman, K.D.


    The use of complementary and alternative medicines (CAM), such as herbs and dietary supplements, has become more popular among cancer patients. Cancer patients use these supplements for different reasons such as reduction of side effects and improvement of their quality of life. In general, the use of CAM is considered as safe. However, concomitant use of CAM and anticancer drugs could result in serious safety issues since CAM have the potential to cause pharmacokinetic interactions with conv...

  2. 21 CFR 872.3661 - Optical Impression Systems for CAD/CAM. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Optical Impression Systems for CAD/CAM. 872.3661... (CAD/CAM) is a device used to record the topographical characteristics of teeth, dental impressions, or... Design and Manufacturing (CAD/CAM) of Dental Restorations; Guidance for Industry and FDA.” For...

  3. The detection of EpCAM+ and EpCAM– circulating tumor cells

    NARCIS (Netherlands)

    Wit, de Sanne; Dalum, van Guus; Lenferink, Aufried; Tibbe, Arjan G.J.; Hilterman, T. Jeroen N.; Groen, Harry J.M.; Rijn, van Cees J.M.; Terstappen, Leon W.M.M.


    EpCAM expressing circulating tumor cells, detected by CellSearch, are predictive of short survival in several cancers and may serve as a liquid biopsy to guide therapy. Here we investigate the presence of EpCAM+ CTC detected by CellSearch and EpCAM– CTC discarded by CellSearch, after EpCAM based enr

  4. Schools (Students) Exchanging CAD/CAM Files over the Internet. (United States)

    Mahoney, Gary S.; Smallwood, James E.

    This document discusses how students and schools can benefit from exchanging computer-aided design/computer-aided manufacturing (CAD/CAM) files over the Internet, explains how files are exchanged, and examines the problem of selected hardware/software incompatibility. Key terms associated with information search services are defined, and several…

  5. Fabricating Complete Dentures with CAD/CAM and RP Technologies. (United States)

    Bilgin, Mehmet Selim; Erdem, Ali; Aglarci, Osman Sami; Dilber, Erhan


    Two techological approaches for fabricating dentures; computer-aided design and computer-aided manufacturing (CAD/CAM) and rapid prototyping (RP), are combined with the conventional techniques of impression and jaw relation recording to determine their feasibility and applicability. Maxillary and mandibular edentulous jaw models were produced using silicone molds. After obtaining a gypsum working model, acrylic bases were crafted, and occlusal rims for each model were fabricated with previously determined standard vertical and centric relationships. The maxillary and mandibular relationships were recorded with guides. The occlusal rims were then scanned with a digital scanner. The alignment of the maxillary and mandibular teeth was verified. The teeth in each arch were fabricated in one piece, or set, either by CAM or RP. Conventional waxing and flasking was then performed for both methods. These techniques obviate a practitioner's need for technicians during design and provide the patient with an opportunity to participate in esthetic design with the dentist. In addition, CAD/CAM and RP reduce chair time; however, the materials and techniques need further improvements. Both CAD/CAM and RP techniques seem promising for reducing chair time and allowing the patient to participate in esthetics design. Furthermore, the one-set aligned artificial tooth design may increase the acrylic's durability.

  6. Including CAD/CAM dentistry in a dental school curriculum. (United States)

    Browning, William D; Reifeis, Paul; Willis, Lisa; Kirkup, Michele L


    Shaping a clinical curriculum that is appropriate for novice dentists, is based on high-quality evidence of efficacy, yet reflects current practices is challenging. CAD/CAM units have been available to dentists since the late '80s. Recent improvements in the software, hardware and the clinical performance of available all-ceramic blocks have keyed a surge in interest. Based on a careful review of the systems available and, equally importantly, a review of the research regarding the longevity of reinforced glass ceramics, IUSD decided to add training on the use of the E4D CAD/CAM system to the curriculum. Students now receive lectures, preclinical hands-on training and clinical experience in fabricating all-ceramic restorations. At present any student who is interested in providing an all-ceramic restoration for his/her patient can do so using our CAD/CAM system. In a little less than one year our undergraduate dental students have provided 125 all-ceramic crowns to their patients. Clinical faculty have been impressed with the marginal fit and esthetics of the crowns. Finally, with students designing, milling, sintering and staining the restorations the CAD/CAM systems has reduced lab costs significantly.

  7. The pineapple genome and the evolution of CAM photosynthesis (United States)

    Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 ...

  8. Footage: Action Cam Shorts as Cartographic Captures of Time.

    NARCIS (Netherlands)

    Verhoeff, N.


    This short article reflects on short videos of action cam footage that are widely disseminated on online platforms. These first-person perspective shorts are compared to early cinema’s phantom rides in the use of point-of-view shots, and a dizzying effect of heightened mobility and versatility in ca

  9. Doing Performance Appraisal the Right Way: The CAM Process. (United States)

    Ramsgard, William C.


    Explains the CAM (Clarity, Awareness, Merit Recognition) process for performance reviews in which supervisors declare personal values, expectations, and operational methods; select employee skills for enhancement and define results; provide feedback, recognition and reinforcement; and distribute merit rewards and build deeper mutual commitments to…

  10. Phosphorylation of anchoring protein by calmodulin protein kinase associated to the sarcoplasmic reticulum of rabbit fast-twitch muscle. (United States)

    Damiani, E; Sacchetto, R; Margreth, A


    Regulatory phosphorylation of phospholamban and of SR Ca(2+)-ATPase SERCA2a isoform by endogenous CaM-K II in slow-twitch skeletal and cardiac sarcoplasmic reticulum (SR) is well documented, but much less is known of the exact functional role of CaM K II in fast-twitch muscle SR. Recently, it was shown that RNA splicing of brain-specific alpha CaM K II, gives rise to a truncated protein (alpha KAP), consisting mainly of the association domain, serving to anchor CaM K II to SR membrane in rat skeletal muscle [Bayer, K.-U., et al. (1998) EMBO J. 19, 5598-5605]. In the present study, we searched for the presence of alpha KAP in sucrose-density purified SR membrane fractions from representative fast-twitch and slow-twitch limb muscles, both of the rabbit and the rat, using immunoblot techniques and antibody directed against the association domain of alpha CaM K II. Putative alpha KAP was immunodetected as a 23-kDa electrophoretic component on SDS-PAGE of the isolated SR from fast-twitch but not from slow-twitch muscle, and was further identified as a specific substrate of endogenous CaM K II, in the rabbit. Immunodetected, (32)P-labeled, non-calmodulin binding protein, behaved as a single 23-kDa protein species under several electrophoretic conditions. The 23-kDa protein, with defined properties, was isolated as a complex with 60-kDa delta CaM K II isoform, by sucrose-density sedimentation analysis. Moreover, we show here that putative alphaKAP, in spite of its inability to bind CaM in ligand blot overlay, co-eluted with delta CaM K II from CaM-affinity columns. That raises the question of whether CaM K II-mediated phosphorylation of alpha KAP and triadin together might be involved in a molecular signaling pathway important for SR Ca(2+)-release in fast-twitch muscle SR.

  11. Purification and characterization of a Ca2+ -dependent/calmodulin-stimulated protein kinase from moss chloronema cells

    Indian Academy of Sciences (India)

    Jacinta S D’souza; Man Mohan Johri


    We have demonstrated the presence of a Ca2+-dependent/calmodulin-stimulated protein kinase (PK) in chloronema cells of the moss Funaria hygrometrica. The kinase, with a molecular mass of 70,000 daltons (PK70), was purified to homogeneity using ammonium sulphate fractionation, DEAE-cellulose chromatography, and calmodulin (CaM)-agarose affinity chromatography. The kinase activity was stimulated at a concentration of 50 M free Ca2+, and was further enhanced 3–5-fold with exogenously added 3–1000 nm moss calmodulin (CaM). Autophosphorylation was also stimulated with Ca2+ and CaM. Under in vitro conditions, PK70 phosphorylated preferentially lysine-rich substrates such as HIIIS and HVS. This PK shares epitopes with the maize Ca2+-dependent/calmodulin-stimulated PK (CCaMK) and also exhibits biochemical properties similar to the maize, lily, and tobacco CCaMK. We have characterized it as a moss CCaMK.

  12. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase


    Marialuisa Moccia; Qingsong Liu; Teresa Guida; Giorgia Federico; Annalisa Brescia; Zheng Zhao; Hwan Geun Choi; Xianming Deng; Li Tan; Jinhua Wang; Marc Billaud; Gray, Nathanael S.; Francesca Carlomagno; Massimo Santoro


    Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the 'DFG-out' inactive conformation of RET activation loop. They blocked RET-media...

  13. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I;


    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  14. Abnormal placental development and early embryonic lethality in EpCAM-null mice.

    Directory of Open Access Journals (Sweden)

    Keisuke Nagao

    Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

  15. The Unsuspecting CAM User: Cancer patients and the changing nature of holistic health

    Directory of Open Access Journals (Sweden)

    A M. Kabel


    Full Text Available The number of cancer patients using complementary and alternative medicine (CAM in the United States is growing, yet little is known about the meaning these activities have for users. Current literature supports the assumption that stigma surrounding CAM and holistic health practices are responsible for the reluctance of many cancer patients to self-identify as CAM users. This study explored the frequency of use, and familiarity with CAM among 25 female patients at a Midwestern oncology clinic. Findings suggest that patients need to be asked about CAM use multiple times and in multiple formats to gain an accurate assessment. Also, the assumptions about stigma may no longer be the reason patients are less than forthcoming about CAM use. The rise of integrative medicine and shifting boundaries of the holistic health movement may be equally, or in some cases, more responsible for the reluctance for CAM users to self-identify.

  16. Linoleic acid-induced expression of inducible nitric oxide synthase and cyclooxygenase II via p42/44 mitogen-activated protein kinase and nuclear factor-kappaB pathway in retinal pigment epithelial cells. (United States)

    Fang, I-Mo; Yang, Chang-Hao; Yang, Chung-May; Chen, Muh-Shy


    High linoleic acid (LA) intake is known to correlate with age-related macular degeneration (AMD), but the molecular mechanisms remain unclear. This study was conducted to investigate the effects of LA on expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase II (COX-2) and their associated signaling pathways in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were treated with different concentrations of LA. Expressions of iNOS and COX-2 were examined using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Concentrations of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in the culture medium were determined by enzyme-link immunosorbent assay (ELISA). Activation of p42/44, p38, JNK mitogen-activated protein kinase (MAPK) and nuclear factors (NF)-kappaB were evaluated by Western blot analysis and electrophoretic mobility shift assay (EMSA). We found that LA induced expression of iNOS and COX-2 in RPE cells at the mRNA and protein levels in a time-and dose-dependent manner. Upregulation of iNOS and COX-2 resulted in increased production of NO and PGE(2). Moreover, LA caused degradation of IkappaB and increased NF-kappaB DNA binding activity. Effects of LA-induced iNOS and COX-2 expression were inhibited by a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). LA activated p42/44, but not p38 or JNK MAPK. Inhibition of p42/44 activity by PD98059 significantly reduced LA-induced activation of NF-kappaB. Linoleic acid-induced expression of iNOS and COX-2 as well as PGE(2) and NO release in RPE cells were sequentially mediated through activation of p42/p44, MAPK, then NF-kappaB. These results may provide new insights into both mechanisms of LA action on RPE cells and pathogenesis of age-related macular degeneration.

  17. 1H-NMR study of diamagnetic cytochrome P450cam: assignment of heme resonances and substrate dependance of one cysteinate beta proton. (United States)

    Mouro, C; Bondon, A; Simonneaux, G; Jung, C


    The 1H-NMR study of diamagnetic cytochrome P450cam FeII-CO has been performed for the first time. Chemical shifts of the cysteinate fifth ligand protons and of several heme protons have been assigned through 1- and 2-dimensional spectra at 500 MHz. A substrate dependance has been observed for the resonance of the cysteinate proton detected in the high-field region.

  18. Code Red & Sir Cam 巡礼

    Institute of Scientific and Technical Information of China (English)


    @@ 发现针对IIS的"Code Red"蠕虫病毒美国IT业界团体Info rmation Technology A ssociation ofAmerica(ITAA)与安全产品开发商于美国当地时间7月20日发布了有关蠕虫"Code Red"的警告.目前受这种蠕虫破坏的面积正在迅速扩大.Code Red是利用美国微软的"Inte rnet InformationServer(IIS)"的缓冲器溢出这一安全漏洞进行感染的蠕虫.这一安全漏洞在6月被发现,该蠕虫可以感染那些没有使用补丁程序的个人电脑.攻击者除了控制被感染的服务器对WWW站点进行改写外,还会发动DoS(拒绝服务)攻击以及格式化硬盘等非法行为.

  19. Code Red & Sir Cam 巡礼

    Institute of Scientific and Technical Information of China (English)


    @@ 发现针对IIS的"Code Red"蠕虫病毒 美国IT业界团体Info rmation Technology A ssociation ofAmerica(ITAA)与安全产品开发商于美国当地时间7月20日发布了有关蠕虫"Code Red"的警告.目前受这种蠕虫破坏的面积正在迅速扩大.Code Red是利用美国微软的"Inte rnet InformationServer(IIS)"的缓冲器溢出这一安全漏洞进行感染的蠕虫.这一安全漏洞在6月被发现,该蠕虫可以感染那些没有使用补丁程序的个人电脑.攻击者除了控制被感染的服务器对WWW站点进行改写外,还会发动DoS(拒绝服务)攻击以及格式化硬盘等非法行为.

  20. Different CAD/CAM-processing routes for zirconia restorations: influence on fitting accuracy. (United States)

    Kohorst, Philipp; Junghanns, Janet; Dittmer, Marc P; Borchers, Lothar; Stiesch, Meike


    The aim of the present in vitro study was to evaluate the influence of different processing routes on the fitting accuracy of four-unit zirconia fixed dental prostheses (FDPs) fabricated by computer-aided design/computer-aided manufacturing (CAD/CAM). Three groups of zirconia frameworks with ten specimens each were fabricated. Frameworks of one group (CerconCAM) were produced by means of a laboratory CAM-only system. The other frameworks were made with different CAD/CAM systems; on the one hand by in-laboratory production (CerconCAD/CAM) and on the other hand by centralized production in a milling center (Compartis) after forwarding geometrical data. Frameworks were then veneered with the recommended ceramics, and marginal accuracy was determined using a replica technique. Horizontal marginal discrepancy, vertical marginal discrepancy, absolute marginal discrepancy, and marginal gap were evaluated. Statistical analyses were performed by one-way analysis of variance (ANOVA), with the level of significance chosen at 0.05. Mean horizontal discrepancies ranged between 22 μm (CerconCAM) and 58 μm (Compartis), vertical discrepancies ranged between 63 μm (CerconCAD/CAM) and 162 μm (CerconCAM), and absolute marginal discrepancies ranged between 94 μm (CerconCAD/CAM) and 181 μm (CerconCAM). The marginal gap varied between 72 μm (CerconCAD/CAM) and 112 μm (CerconCAM, Compartis). Statistical analysis revealed that, with all measurements, the marginal accuracy of the zirconia FDPs was significantly influenced by the processing route used (p CAD/CAM systems are more precise than the CAM-only system for the manufacture of four-unit FDPs.

  1. Divergent distribution of the sensor kinase CosS in non-thermophilic Campylobacter species and its functional incompatibility with the Campylobacter jejuni CosR (United States)

    Two-component signal transduction system is commonly composed of a sensor histidine kinase and a response regulator, modulating gene expression in response to environmental changes through a phosphorylation-dependent process. CosR is an OmpR-type response regulator essential for the viability of Cam...

  2. Tufting enteropathy with EpCAM mutation: case report

    Directory of Open Access Journals (Sweden)

    Karla Lais Pêgas


    Full Text Available Tufting enteropathy (TE, also known as intestinal epithelial dysplasia (IED, is a rare congenital enteropathy related to an earlyonset of severe intractable diarrhea due to specific abnormalities of the intestinal epithelium and mutations of the EpCAM gene. TE is characterized by clinical and histological heterogeneity, such as with low or without mononuclear cell infiltration of the lamina propria, and abnormalities of basement membrane. TE can be associated with malformations, other epithelial diseases, or to abnormal enterocytes development and/or differentiation. The authors report a case of a Brazilian child with TE associated with c.556-14A>G mutation in the EpCAM gene (NM_002354.2.

  3. CAM Modalities Can Stimulate Advances in Theoretical Biology

    Directory of Open Access Journals (Sweden)

    Alex Hankey


    Full Text Available Most complementary medicine is distinguished by not being supported by underlying theory accepted by Western science. However, for those who accept their validity, complementary and alternative medicine (CAM modalities offer clues to understanding physiology and medicine more deeply. Ayurveda and vibrational medicine are stimulating new approaches to biological regulation. The new biophysics can be integrated to yield a single consistent theory, which may well underly much of CAM—a true ‘physics of physick’. The resulting theory seems to be a new, fundamental theory of health and etiology. It suggests that many CAM approaches to health care are scientifically in advance of those based on current Western biology. Such theories may well constitute the next steps in our scientific understanding of biology itself. If successfully developed, these ideas could result in a major paradigm shift in both biology and medicine, which will benefit all interested parties—consumers, health professionals, scientists, institutions and governments.

  4. The faulty statistics of complementary alternative medicine (CAM). (United States)

    Pandolfi, Maurizio; Carreras, Giulia


    The authors illustrate the difficulties involved in obtaining a valid statistical significance in clinical studies especially when the prior probability of the hypothesis under scrutiny is low. Since the prior probability of a research hypothesis is directly related to its scientific plausibility, the commonly used frequentist statistics, which does not take into account this probability, is particularly unsuitable for studies exploring matters in various degree disconnected from science such as complementary alternative medicine (CAM) interventions. Any statistical significance obtained in this field should be considered with great caution and may be better applied to more plausible hypotheses (like placebo effect) than that examined - which usually is the specific efficacy of the intervention. Since achieving meaningful statistical significance is an essential step in the validation of medical interventions, CAM practices, producing only outcomes inherently resistant to statistical validation, appear not to belong to modern evidence-based medicine.

  5. Illness narratives in cancer: CAM and spiritual practices

    DEFF Research Database (Denmark)

    Ulrich, Anita; Evron, Lotte; Ostenfeld-Rosenthal, Ann


    Objectives: In this paper,we investigate Danish cancer patients’ narratives on spiritual beliefs and practices and the relationship these practices may have to complementary and alternative medicine (CAM). Design: Narrative inquiry is used to uncover how spiritual beliefs and practices may......, religious and spiritual issues were not extensively unfolded in participants’ illness narratives. However, these issues were significantly elaborated on in narratives by four female participants. Conclusion: We propose that for some cancer patients CAM may function, not only or primarily as a treatment...... for cancer related symptoms and side effects, but as a spiritual practice as well. For some individuals this may be true to an even higher extent than in established religious institutions....

  6. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael;


    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarchaea...... that a functional deoxyribonucleoside salvage pathway is not crucial for the archaeal cell....

  7. Integrated CAD/CAM: Problems, prognosis, and role of IPAD (United States)

    Nilson, E. N.


    Major technology problems impede the development and evolution of totally integrated interactive CAD/CAM systems. IPAD is playing an important role in the identification of these problems and is contributing significantly to their solution. It is the purpose of this presentation to examine some of these issues, look at the prognosis of obtaining effective solutions, and point up some of the past and expected contributions of IPAD to this technology.

  8. Lucrécio, Camões e os deuses

    Directory of Open Access Journals (Sweden)

    Milton Torres


    Full Text Available Este artigo trata do uso que Lucrécio e Camões fizeram dos deuses da mitologia clássica, por razões pertinentes às convenções da poesia épica e a despeito de sua descrença na existência dos mesmos, sugerindo que ambos constróem os deuses para depois desconstruí-los de forma cabal e definitiva.

  9. ChemCam analysis of Martian fine dust (United States)

    Lasue, Jeremie; Mangold, Nicolas; Cousin, Agnes; Meslin, Pierre-Yves; Wiens, Roger; Gasnault, Olivier; Rapin, William; Schroder, Susanne; Ollila, Ann; Fabre, Cécile; Berger, Gilles; Le Mouélic, Stéphane; Dehouck, Erwin; Forni, Olivier; Maurice, Sylvestre; Anderson, Ryan; Bridges, Nathan; Clark, Benton; Clegg, Samuel; d'Uston, Claude; Goetz, Walter; Johnson, Jeffrey R.; Lanza, Nina; Madsen, Morten; Melikechi, Noureddine; Newsom, Horton; Sautter, Violaine; Martin-Torres, Javier; Zorzano, Maria-Paz; MSL Science Team


    In this work, we examine the chemical composition of dust observed by the Chemistry Camera (ChemCam) instrument onboard the Mars Science Laboratory (MSL) rover at Gale Crater. The Laser Induced Breakdown Spectroscopy technique analyses samples without preparation, which allows detection of the elemental composition of surface deposits. Mars aeolian fine dust (soils encountered at Gale crater. The composition is also similar to the soils and fine dust measured by APXS for the elements common to both instruments. The minor elements quantified by ChemCam (Ba, Sr, Rb, Li, Mn, Cr) are within the range of soil surveys, but we see a higher concentration of Li than in other types of remotely characterized targets. Sulfur is possibly detected at the ChemCam limit of detection. Hydrogen is clearly identified, indicating that this fine dust is a contributor to the H content of the martian soils, as also detected by the SAM and CheMin instruments, and provides constraints as to which fraction of the Martian surface is hydrated and altered. In conclusion, the finest fraction of dust particles on the surface of Mars contains hydrated components mixed intimately within the fine aeolian dust fraction, suggesting that this dust likely originates from mechanical weathering of altered grains.

  10. Comparison Between GAMIL, and CAM2 on Interannual Variability Simulation

    Institute of Scientific and Technical Information of China (English)


    Recently, a new atmospheric general circulation model (GAMIL: Grid-point Atmospheric Model of IAP LASG) has been developed at the Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences (CAS), which is based on the Community Atmospheric Model Version 2 (CAM2) of the National Center for Atmospheric Research (NCAR). Since the two models have the same physical processes but different dynamical cores, the interannual variability simulation performances of the two models are compared. The ensemble approach is used to reduce model internal variability.In general, the simulation performances of the two models are similar. Both models have good performance in simulating total space-time variability and the Southern Oscillation Index. GAMIL performs better in the Eastern Asian winter circulation simulation than CAM2, and the model internal variability of GAMIL has a better response to external forcing than that of CAM2. These indicate that the improvement of the dynamic core is very important. It is also verified that there is less predictability in the middle and high latitudes than in the low latitudes.

  11. Optical spectroscopy of RU Cam, a pulsating carbon star

    CERN Document Server

    Kipper, Tonu


    We analysed the high resolution spectra of a RU Cam, classified as W Vir type star. The atmospheric parameters of RU Cam were estimated Teff=5250K and log g=1.0. The hydrogen deficiency of RU Cam was not confirmed. The iron abundance, [Fe/H]=-0.37, is close to the solar one. Abundances of most other elements are also close to normal. We found considerable excesses of carbon and nitrogen: [C/Fe]=+0.98, [N/Fe]=+0.60. The carbon to oxygen ratio is C/O$\\ge$1. The carbon isotopic abundance ratio is equal to C^12/C^13=4.5. For sodium a moderate overabundance Na/Fe=+0.55 was obtained. For two moments of observations we found close heliocentric velocity values, Vr=-21.7+/-0.8 and -23.1+/-1.0 km/s. Both spectra contain a peculiar feature - an emission component of NaI doublet which location agrees with the radial velocity from the bulk of metallic lines. For our two observing moments we found no dependence of radial velocities on the formation depth or on excitation energy for metallic lines.

  12. Product Recommendation System Based on Personal Preference Model Using CAM (United States)

    Murakami, Tomoko; Yoshioka, Nobukazu; Orihara, Ryohei; Furukawa, Koichi

    Product recommendation system is realized by applying business rules acquired by data maining techniques. Business rules such as demographical patterns of purchase, are able to cover the groups of users that have a tendency to purchase products, but it is difficult to recommend products adaptive to various personal preferences only by utilizing them. In addition to that, it is very costly to gather the large volume of high quality survey data, which is necessary for good recommendation based on personal preference model. A method collecting kansei information automatically without questionnaire survey is required. The constructing personal preference model from less favor data is also necessary, since it is costly for the user to input favor data. In this paper, we propose product recommendation system based on kansei information extracted by text mining and user's preference model constructed by Category-guided Adaptive Modeling, CAM for short. CAM is a feature construction method that can generate new features constructing the space where same labeled examples are close and different labeled examples are far away from some labeled examples. It is possible to construct personal preference model by CAM despite less information of likes and dislikes categories. In the system, retrieval agent gathers the products' specification and user agent manages preference model, user's likes and dislikes. Kansei information of the products is gained by applying text mining technique to the reputation documents about the products on the web site. We carry out some experimental studies to make sure that prefrence model obtained by our method performs effectively.

  13. The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice. (United States)

    Muraille, E; Dassesse, D; Vanderwinden, J M; Cremer, H; Rogister, B; Erneux, C; Schiffmann, S N


    The germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their effects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identified Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2, SHIP2, has the potential to regulate neuronal development. Using in situ hybridization technique with multiple synthetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic stages and subventricular zones at latter stages of brain and spinal cord and in the sympathetic chain. No significant expression was seen in differentiated fields. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphery, large expression was detected in muscle and kidney and moderate expression in thyroid, pituitary gland, digestive system and bone. In the adult brain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior subventricular zone, the rostral migratory stream and the olfactory tubercle. SHIP2 was also detected in the choroid plexuses and the granular layer of the cerebellum. The specificity of SHIP2 expression in neural stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA signal in neural cell adhesion molecule (N-CAM)-deficient mice, which present an accumulation of progenitor cells in the anterior subventricular zone and the rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by western blotting in proliferating neurospheres in culture and its downregulation in non-proliferating differentiated neurospheres. In conclusion, the close correlation between

  14. An open CAM system for dentistry on the basis of China-made 5-axis simultaneous contouring CNC machine tool and industrial CAM software. (United States)

    Lu, Li; Liu, Shusheng; Shi, Shenggen; Yang, Jianzhong


    China-made 5-axis simultaneous contouring CNC machine tool and domestically developed industrial computer-aided manufacture (CAM) technology were used for full crown fabrication and measurement of crown accuracy, with an attempt to establish an open CAM system for dental processing and to promote the introduction of domestic dental computer-aided design (CAD)/CAM system. Commercially available scanning equipment was used to make a basic digital tooth model after preparation of crown, and CAD software that comes with the scanning device was employed to design the crown by using domestic industrial CAM software to process the crown data in order to generate a solid model for machining purpose, and then China-made 5-axis simultaneous contouring CNC machine tool was used to complete machining of the whole crown and the internal accuracy of the crown internal was measured by using 3D-MicroCT. The results showed that China-made 5-axis simultaneous contouring CNC machine tool in combination with domestic industrial CAM technology can be used for crown making and the crown was well positioned in die. The internal accuracy was successfully measured by using 3D-MicroCT. It is concluded that an open CAM system for dentistry on the basis of China-made 5-axis simultaneous contouring CNC machine tool and domestic industrial CAM software has been established, and development of the system will promote the introduction of domestically-produced dental CAD/CAM system.

  15. EpCAM modulates NF-κB signaling and interleukin-8 expression in breast cancer. (United States)

    Sankpal, Narendra V; Fleming, Timothy P; Gillanders, William E


    The epithelial cell adhesion molecule (EpCAM) is a 40-kD type I transmembrane protein that is overexpressed in human epithelial cancers and is currently the target of molecular therapy based on its overexpression at the cell surface. Recently, we and others have shown a role for EpCAM in cell signaling and carcinogenesis, and EpCAM expression seems to promote breast cancer invasion. Interleukin-8 (IL-8/CXCL-8) is an inflammatory cytokine that has recently been shown to modulate breast cancer invasion and angiogenesis. In preliminary experiments, we identified a correlation between EpCAM and IL-8 expression in primary human breast cancers. Specific ablation of EpCAM in breast cancer cell lines results in decreased IL-8 expression, and IL-8 contributes to EpCAM-dependent breast cancer invasion. Specific ablation of EpCAM is also associated with decreased NF-κB transcription factor activity, decreased phosphorylation of the NF-κB family member RELA, and increased IκBα protein expression. EpCAM modulates IL-8 expression at baseline, and following IL-1β stimulation, which is known to be a potent inducer of NF-κB in breast cancer. In functional rescue experiments, specific ablation of RELA or forced expression of the NF-κB inhibitor protein IκBα prevented EpCAM-dependent rescue of IL-8 promoter activity. These studies show for the first time that EpCAM can modulate NF-κB transcription factor activity and IL-8 expression in breast cancer and confirm the role of EpCAM signaling in modulating breast cancer invasion. Further study is required to define the molecular mechanism(s) of EpCAM signaling in breast cancer and to direct the rational development of molecular therapies targeting EpCAM.

  16. Evaluating rare amino acid substitutions (RGC_CAMs in a yeast model clade.

    Directory of Open Access Journals (Sweden)

    Kenneth Polzin

    Full Text Available When inferring phylogenetic relationships, not all sites in a sequence alignment are equally informative. One recently proposed approach that takes advantage of this inequality relies on sites that contain amino acids whose replacement requires multiple substitutions. Identifying these so-called RGC_CAM substitutions (after Rare Genomic Changes as Conserved Amino acids-Multiple substitutions requires that, first, at any given site in the amino acid sequence alignment, there must be a minimum of two different amino acids; second, each amino acid must be present in at least two taxa; and third, the amino acids must require a minimum of two nucleotide substitutions to replace each other. Although theory suggests that RGC_CAM substitutions are expected to be rare and less likely to be homoplastic, the informativeness of RGC_CAM substitutions has not been extensively evaluated in biological data sets. We investigated the quality of RGC_CAM substitutions by examining their degree of homoplasy and internode certainty in nearly 2.7 million aligned amino acid sites from 5,261 proteins from five species belonging to the yeast Saccharomyces sensu stricto clade whose phylogeny is well-established. We identified 2,647 sites containing RGC_CAM substitutions, a number that contrasts sharply with the 100,887 sites containing RGC_non-CAM substitutions (i.e., changes between amino acids that require only a single nucleotide substitution. We found that RGC_CAM substitutions had significantly lower homoplasy than RGC_non-CAM ones; specifically RGC_CAM substitutions showed a per-site average homoplasy index of 0.100, whereas RGC_non-CAM substitutions had a homoplasy index of 0.215. Internode certainty values were also higher for sites containing RGC_CAM substitutions than for RGC_non-CAM ones. These results suggest that RGC_CAM substitutions possess a strong phylogenetic signal and are useful markers for phylogenetic inference despite their rarity.

  17. Pattern and predictors of complementary and alternative medicine (CAM) use among pediatric patients with epilepsy. (United States)

    Doering, Jan H; Reuner, Gitta; Kadish, Navah E; Pietz, Joachim; Schubert-Bast, Susanne


    Parents of pediatric patients with chronic conditions such as epilepsy increasingly opt for complementary and alternative medicine (CAM). However, data on the pattern and reasons of CAM use in childhood epilepsy are scarce. The objectives of this study were as follows: first, to characterize CAM use among pediatric patients with epilepsy by assessing its spectrum, prevalence, costs, and frequency of use; second, to evaluate the influence of CAM use on compliance and satisfaction with conventional care as well as to explore parent-child neurologist communication concerning CAM; and third, to investigate predictors of CAM use. A postal survey was administered to all parents of pediatric outpatients with epilepsy aged 6 to 12, who have received treatment at the neuropediatric outpatient clinic of the University Children's Hospital Heidelberg between 2007 and 2009. One hundred thirty-two of the 297 distributed questionnaires were suitable for inclusion in statistical analysis (44.7%). Forty-nine participants indicated that their children used CAM during the previous year (37.1%). Thirty different types of CAM were used, with homeopathy (55.1%), osteopathy (24.5%), and kinesiology (16.3%) being the most commonly named. A mean of 86€ (0€-500€) and 3h (1 h-30 h) per month was committed to CAM treatment. Only 53% of the users informed their child neurologist of the additional CAM treatment, while 85.6% of all parents wished to discuss CAM options with their child neurologist. Seventy-five percent of users considered the CAM treatment effective. Among the participants most likely to seek CAM treatment are parents whose children show a long duration of epileptic symptoms, parents who make use of CAM treatment themselves, and parents who value a holistic and natural treatment approach. A substantial portion of pediatric patients with epilepsy receive CAM treatment. The high prevalence of use and significant level of financial and time resources spent on CAM indicate the

  18. Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain

    DEFF Research Database (Denmark)

    Naik, M U; Benedikz, Eirikur; Hernandez, I


    Protein kinase C (PKC) is a multigene family of at least ten isoforms, nine of which are expressed in brain (alpha, betaI, betaII, gamma, delta, straightepsilon, eta, zeta, iota/lambda). Our previous studies have shown that many of these PKCs participate in synaptic plasticity in the CA1 region o...

  19. Chemistry of diagenetic features analyzed by ChemCam at Pahrump Hills, Gale crater, Mars (United States)

    Nachon, Marion; Mangold, Nicolas; Forni, Olivier; Kah, Linda C.; Cousin, Agnes; Wiens, Roger C.; Anderson, Ryan; Blaney, Diana L.; Blank, Jen G.; Calef, Fred J.; Clegg, Samuel M.; Fabre, Cecile; Fisk, Martin R.; Gasnault, Olivier; Grotzinger, John P.; Kronyak, Rachel; Lanza, Nina L.; Lasue, Jeremie; Le Deit, Laetitia; Le Mouelic, Stephane; Maurice, Sylvestre; Meslin, Pierre-Yves; Oehler, D. Z.; Payre, Valerie; Rapin, William; Schroder, Susanne; Stack, Katherine M.; Sumner, Dawn


    The Curiosity rover's campaign at Pahrump Hills provides the first analyses of lower Mount Sharp strata. Here we report ChemCam elemental composition of a diverse assemblage of post-depositional features embedded in, or cross-cutting, the host rock. ChemCam results demonstrate their compositional diversity, especially compared to the surrounding host rock: (i) Dendritic aggregates and relief enhanced features, characterized by a magnesium enhancement and sulfur detection, and interpreted as Mg-sulfates; (ii) A localized observation that displays iron enrichment associated with sulfur, interpreted as Fe-sulfate; (iii) Dark raised ridges with varying Mg- and Ca-enriched compositions compared to host rock; (iv) Several dark-toned veins with calcium enhancement associated with fluorine detection, interpreted as fluorite veins. (v) Light-toned veins with enhanced calcium associated with sulfur detection, and interpreted as Ca-sulfates. The diversity of the Pahrump Hills diagenetic assemblage suggests a complex post-depositional history for fine-grained sediments for which the origin has been interpreted as fluvial and lacustrine. Assessment of the spatial and relative temporal distribution of these features shows that the Mg-sulfate features are predominant in the lower part of the section, suggesting local modification of the sediments by early diagenetic fluids. In contrast, light-toned Ca-sulfate veins occur in the whole section and cross-cut all other features. A relatively late stage shift in geochemical conditions could explain this observation. The Pahrump Hills diagenetic features have no equivalent compared to targets analyzed in other locations at Gale crater. Only the light-toned Ca-sulfate veins are present elsewhere, along Curiosity's path, suggesting they formed through a common late-stage process that occurred at over a broad area.

  20. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A;


    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  1. A new calmodulin-binding motif for inositol 1,4,5-trisphosphate 3-kinase regulation. (United States)

    Franco-Echevarría, Elsa; Baños-Sanz, Jose I; Monterroso, Begoña; Round, Adam; Sanz-Aparicio, Julia; González, Beatriz


    IP3-3K [Ins(1,4,5)P3 3-kinase] is a key enzyme that catalyses the synthesis of Ins(1,3,4,5)P4, using Ins(1,4,5)P3 and ATP as substrates. Both inositides, substrate and product, present crucial roles in the cell. Ins(1,4,5)P3 is a key point in Ca2+ metabolism that promotes Ca2+ release from intracellular stores and together with Ins(1,3,4,5)P4 regulates Ca2+ homoeostasis. In addition, Ins(1,3,4,5)P4 is involved in immune cell development. It has been proved that Ca2+/CaM (calmodulin) regulates the activity of IP3-3K, via direct interaction between both enzymes. Although we have extensive structural knowledge of the kinase domains of the three IP3-3K isoforms, no structural information is available about the interaction between IP3-3K and Ca2+/CaM. In the present paper we describe the crystal structure of the complex between human Ca2+/CaM and the CaM-binding region of human IP3-3K isoform A (residues 158-183) and propose a model for a complex including the kinase domain. The structure obtained allowed us to identify all of the key residues involved in the interaction, which have been evaluated by site-directed mutagenesis, pull-down and fluorescence anisotropy experiments. The results allowed the identification of a new CaM-binding motif, expanding our knowledge about how CaM interacts with its partners.

  2. Understanding dental CAD/CAM for restorations--the digital workflow from a mechanical engineering viewpoint. (United States)

    Tapie, L; Lebon, N; Mawussi, B; Fron Chabouis, H; Duret, F; Attal, J-P


    As digital technology infiltrates every area of daily life, including the field of medicine, so it is increasingly being introduced into dental practice. Apart from chairside practice, computer-aided design/computer-aided manufacturing (CAD/CAM) solutions are available for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental solutions can be considered a chain of digital devices and software for the almost automatic design and creation of dental restorations. However, dentists who want to use the technology often do not have the time or knowledge to understand it. A basic knowledge of the CAD/CAM digital workflow for dental restorations can help dentists to grasp the technology and purchase a CAM/CAM system that meets the needs of their office. This article provides a computer-science and mechanical-engineering approach to the CAD/CAM digital workflow to help dentists understand the technology.

  3. Comparison of phosphorylation of ribosomal proteins from HeLa and Krebs II ascites-tumour cells by cyclic AMP-dependent and cyclic GMP-dependent protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Beier, H; Speichermann, N


    identified by two-dimensional gel electrophoresis. Almost identical results were obtained when ribosomal subunits from HeLa or ascites-tumour cells were used. About 50-60% of the total radioactive phosphate incorporated into small-subunit ribosomal proteins by either kinase was associated with protein S6...

  4. Effects of Taohong Siwu Decoction Ⅱ in the Chick Chorioallantoic Membrane (CAM) Assay and on B16 Melanoma in Mice and Endothelial Cells ECV304 Proliferation

    Institute of Scientific and Technical Information of China (English)


    Objective: To investigate the anti-angiogenesis action of Taohong Siwu Decoction Ⅱ (THSWD Ⅱ). Methods:The chick chorioallantoic membrane (CAM) assay was adopted to study the anti-angiogenesis action of THSWD Ⅱ; the MTT test was used to investigate its effect on proliferation of the human umbilical vein endothelial cells ECV304; and the immunohistochemical method was used to observe the effect of THSWD Ⅱ on the expression of kinase insert domain containing receptor/fetal liver kinase 1 (KDR/Flk-1) and the microvessel density (MVD) of B 16 melanoma in mice. Results: After treatment with THSWD Ⅱ, the blood vessel index of CAM and the absorbency of ECV304 in the THSWD Ⅱ lmg/ml group and the 2mg/ml group decreased significantly (P<0.01); the weight, the expression of KDR/Flk-1 and the MVD of B16 melanoma in mice reduced significantly in the THSWD Ⅱ 5g/kg group, the 10g/kg group and the TSHSWD10g/kg plus cyclophosphamide group (P<0.01). Conclusion: THSWD Ⅱ has the actions of anti-angiogenesis, and inhibiting the proliferation of ECV304 cells and the growth of B16 melanoma. The clinical anti-tumour mechanism is considered to be related possibly to its anti-angiogenesis action by inhibiting the expression of KDR/FIK- 1.

  5. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei (United States)

    Li, H.; Roux, S. J.


    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  6. Measurement of J-integral in CAD/CAM dental ceramics and composite resin by digital image correlation. (United States)

    Jiang, Yanxia; Akkus, Anna; Roperto, Renato; Akkus, Ozan; Li, Bo; Lang, Lisa; Teich, Sorin


    Ceramic and composite resin blocks for CAD/CAM machining of dental restorations are becoming more common. The sample sizes affordable by these blocks are smaller than ideal for stress intensity factor (SIF) based tests. The J-integral measurement calls for full field strain measurement, making it challenging to conduct. Accordingly, the J-integral values of dental restoration materials used in CAD/CAM restorations have not been reported to date. Digital image correlation (DIC) provides full field strain maps, making it possible to calculate the J-integral value. The aim of this study was to measure the J-integral value for CAD/CAM restorative materials. Four types of materials (sintered IPS E-MAX CAD, non-sintered IPS E-MAX CAD, Vita Mark II and Paradigm MZ100) were used to prepare beam samples for three-point bending tests. J-integrals were calculated for different integral path size and locations with respect to the crack tip. J-integral at path 1 for each material was 1.26±0.31×10(-4)MPam for MZ 100, 0.59±0.28×10(-4)MPam for sintered E-MAX, 0.19±0.07×10(-4)MPam for VM II, and 0.21±0.05×10(-4)MPam for non-sintered E-MAX. There were no significant differences between different integral path size, except for the non-sintered E-MAX group. J-integral paths of non-sintered E-MAX located within 42% of the height of the sample provided consistent values whereas outside this range resulted in lower J-integral values. Moreover, no significant difference was found among different integral path locations. The critical SIF was calculated from J-integral (KJ) along with geometry derived SIF values (KI). KI values were comparable with KJ and geometry based SIF values obtained from literature. Therefore, DIC derived J-integral is a reliable way to assess the fracture toughness of small sized specimens for dental CAD/CAM restorative materials; however, with caution applied to the selection of J-integral path.

  7. Effects of EpCAM overexpression on human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Krobitsch Sylvia


    Full Text Available Abstract Background Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients. Methods In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed. Results For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578TEpCAM and MDA-MB-231EpCAM indicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231EpCAM but not Hs578TEpCAM cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression. Conclusions These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.

  8. CamOn: A Real-Time Autonomous Camera Control System

    DEFF Research Database (Denmark)

    Burelli, Paolo; Jhala, Arnav Harish


    contributes to the potential field that is used to determine po- sition and movement of the camera. Composition constraints for the camera are modelled as potential fields for controlling the view target of the camera. CamOn combines the compositional benefits of constraint- based camera systems, and improves......This demonstration presents CamOn, an autonomous cam- era control system for real-time 3D games. CamOn employs multiple Artificial Potential Fields (APFs), a robot motion planning technique, to control both the location and orienta- tion of the camera. Scene geometry from the 3D environment...


    Institute of Scientific and Technical Information of China (English)


    Based on probability and statistic, a design method of precision cam profile concerning the influence of random processing errors is advanced. Combining the design with the process, which can be used to predict that cam profiles will be successfully processed or not in the design stage, design of the cam can be done by balancing the economization and reliability. In addition, an fuzzy deduction method based on Bayers formula is advanced to estimate processing reasonable of the designed precision cam profile, and it take few samples.

  10. Initiating a Reiki or CAM program in a healthcare organization--developing a business plan. (United States)

    Vitale, Anne


    Complementary and alternative medicine (CAM) services, such as Reiki, continue to be offered to consumers in many hospitals and other health care organizations. There is growing interest among nurses, doctors, and other health care providers for the integration of CAM therapies into traditional settings. Health care organizations are responding to this need but may not know how to start CAM programs. Starting a Reiki program in a health care setting must be envisioned in a business model approach. This article introduces nurses and other health care providers to the basic concepts of business plan development and important steps to follow when starting a Reiki or CAM program.

  11. The use of CAM by women suffering from nausea and vomiting during pregnancy

    Directory of Open Access Journals (Sweden)

    Smith Michael


    Full Text Available Abstract Background Nausea and vomiting during pregnancy (NVP affects two-thirds of pregnant women to varying degrees and over the years many modalities have been used to try to alleviate this often debilitating condition. There is a paucity of information in the literature about the use or efficacy of complementary and alternative medicine (CAM for the treatment of this condition that affects so many women. Our primary objective was to examine the prevalence of CAM usage by women suffering from NVP. Our secondary objective was to ascertain if women had any supervision in the use of these treatments. Methods Women who called The Motherisk NVP helpline, were asked after the counseling session to complete a questionnaire, which included demographic data as well as information about their CAM use. Results Seventy women completed the questionnaire. 61% reported using CAM therapies, of which the three most popular were: ginger, vitamin B6 and acupressure. 21% of those who reported using CAM, had consulted CAM practitioners, 8% their physicians or pharmacists and 71% discussed the usage with family, friends and other allied health professionals. Women who did not use CAM stated they would probably use these modalities if there was more information about the safety in pregnancy. Conclusion Pregnant women with NVP are mirroring the trend in the general population of the use of CAM. They are also using CAM therapies with little supervision from practitioners experienced in the use of these modalities.

  12. Using bacteria to determine protein kinase specificity and predict target substrates.

    Directory of Open Access Journals (Sweden)

    Michael F Chou

    Full Text Available The identification of protein kinase targets remains a significant bottleneck for our understanding of signal transduction in normal and diseased cellular states. Kinases recognize their substrates in part through sequence motifs on substrate proteins, which, to date, have most effectively been elucidated using combinatorial peptide library approaches. Here, we present and demonstrate the ProPeL method for easy and accurate discovery of kinase specificity motifs through the use of native bacterial proteomes that serve as in vivo libraries for thousands of simultaneous phosphorylation reactions. Using recombinant kinases expressed in E. coli followed by mass spectrometry, the approach accurately recapitulated the well-established motif preferences of human basophilic (Protein Kinase A and acidophilic (Casein Kinase II kinases. These motifs, derived for PKA and CK II using only bacterial sequence data, were then further validated by utilizing them in conjunction with the scan-x software program to computationally predict known human phosphorylation sites with high confidence.

  13. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Boura, Evzen, E-mail:; Nencka, Radim, E-mail:


    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.

  14. Avaliação da resistência à fratura de coroas CAD-CAM sobre pilares sólidos


    Stona, Deborah


    O objetivo do estudo foi avaliar a resistência à fratura de coroas cerâmicas utilizando o sistema CAD-CAM Cerec sobre pilares sólidos. Sessenta réplicas de implante synocta RN e pilar sólido foram incluídos em resina acrílica autopolimerizável, sendo divididas aleatoriamente (n=20 por grupo). Três tipos de cerâmicas foram utilizadas: Mark II (feldspática), IPS Empress CAD (leucita) e IPS e. max CAD (dissilicato de lítio). As coroas foram confeccionadas através do sistema CAD-CAM utilizando o ...

  15. CAD/CAM and scientific data management at Dassault (United States)

    Bohn, P.


    The history of CAD/CAM and scientific data management at Dassault are presented. Emphasis is put on the targets of the now commercially available software CATIA. The links with scientific computations such as aerodynamics and structural analysis are presented. Comments are made on the principles followed within the company. The consequences of the approximative nature of scientific data are examined. Consequence of the new history function is mainly its protection against copy or alteration. Future plans at Dassault for scientific data appear to be in opposite directions compared to some general tendencies.

  16. Applying DER-CAM for IIT Microgrid Explansion Planning

    Energy Technology Data Exchange (ETDEWEB)

    Shahidehpour, Mohammad [Illinois Inst. of Technology, Chicago, IL (United States); Li, Zuyi [Illinois Inst. of Technology, Chicago, IL (United States); Wang, Jianhui [Argonne National Lab. (ANL), Argonne, IL (United States); Chen, Chen [Argonne National Lab. (ANL), Argonne, IL (United States)


    The Distributed Energy Resources Customer Adoption Model (DER-CAM) is an economic and environmental model of customer DER adoption. This model has been in development at the Lawrence Berkeley National Laboratory since 2000. The objective of the model is to find optimal DER investments while minimizing total energy costs or carbon dioxide (CO2) emissions, or achieving a weighted objective that simultaneously considers both criteria. The Illinois Institute of Technology (IIT) Microgrid project started in August 2008, and the majority of the project was completed in May 2013. IIT Microgrid, funded mostly by a grant from the U.S. Department of Energy as well as State and philanthropic contributions, empowers the campus consumers with the objective of establishing a smart microgrid that is highly reliable, economically viable, environmentally friendly, fuel-efficient, and resilient in extreme circumstances with a self-healing capability. In this project, we apply DER-CAM to study the expansion planning of the IIT Microgrid. First, the load data, environmental data, utility data, and technology data for the IIT Microgrid are gathered and organized to follow the DER-CAM input requirements. Then, DERCAM is applied to study the expansion planning of the IIT Microgrid for different cases, where different objectives in DER-CAM and different utility conditions are tested. Case 1 considers the objective of minimizing energy costs with fixed utility rates and 100% electric utility availability. Case 2 considers the objective of minimizing energy costs with real-time utility rates and 4 emergency weeks when the IIT Microgrid does not have access to the electric utility grid and has to operate in island mode. In Case 3, the utility rates are restored to fixed values and 100% electric utility availability is assumed, but a weighted multi-objective (Obj: a × costs + b × CO2 emissions, where a and b are weights for cost minimization and CO2 emissions minimization) is utilized to

  17. Relevant Applications of Tools in UG NX CAM Module

    Directory of Open Access Journals (Sweden)

    Zhang En Guang


    Full Text Available In this paper, the methods to establish the custom magazine have been proposed while the UG NX CAM module is employed to conduct the CNC milling programming. At the same time, how to set the parameters of the cutting tool has been also analyzed; in the creation of tools, the use of shank and holder as well as the use of handle check functions in NC machining has been introduced; meanwhile, the secondary rough machining of corner and the application of clean-cut features have been discussed.

  18. CAD/CAM from the graphic-design perspective

    Energy Technology Data Exchange (ETDEWEB)

    Marcus, A.


    CAD/CAM systems have evolved elaborate human-computer interfaces in order to facilitate the creation of highly detailed and specialized schematic diagrams and texts. Although these systems have powerful capacities in terms of graphics editing, data manipulation, and data storage, insufficient attention has been given to making the online interface (together with supporting documentation) user-friendly, i.e., understandable, memorable, and appealing to the general user. Graphic-design considerations in particular have been routinely overlooked. Graphic design concerns typography, symbol design, color, spatial layout, and temporal sequencing. Graphic design can assist computer science by providing insight and expertise in designing effective communication between human being and machine.

  19. Experimental and analytical investigation of finger-follower cam systems (United States)

    Hsu, Wensyang

    A predictive dynamic model to compute the motions of components in cam systems, along with the experimental work to verify the model are described. The major components in finger-follower cam systems include the cam, the follower, the hydraulic lash adjuster, and the valve spring, equipped sometimes with a helical valve spring cup damper. In order to fully describe the dynamics of such a system, a lumped/distributed parameter model for the finger-follower cam system with a moving follower pivot is proposed. The valve spring is modeled as a distributed parameter element, and the adjuster is modeled as a stiff spring with viscous damping. The coulomb friction combined with viscous damping between sliding surfaces are also considered. The model predicts toss between the adjuster and the follower at 2535 rpm, and experiment indicates toss starting at 2520 rpm. It is found by simulation that designing hydraulic lash adjuster to be as rigid as possible is essential to successful high speed operation of finger-follower valve trains because a 50 percent decrease in the compliance of the adjuster could increase the maximum camshaft operating speed 150 rpm. Total elimination of the hydraulic lash adjuster is not always feasible because hydraulic lash adjusters can eliminate the clearance between components and do not need to be mechanically, manually adjusted. In order to provide a more stable and precise description on the dynamic response of the adjuster, a two-mode dynamic model for the adjuster is proposed by considering the oil compressibility in the oil chamber, as well as the oil leakage through the annular gap. Furthermore, the effect due to the oil flow from the central orifice to the oil chamber is also studied analytically and experimentally. The inertia effects of the helical valve spring can be suppressed by a cup damper. Damping between the damper and spring wire is found to depend only weakly on relative sliding velocity. The current formula in computing

  20. Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence. (United States)

    Han, Ying-Hao; Kim, Hyun-Sun; Kim, Jin-Man; Kim, Sang-Keun; Yu, Dae-Yeul; Moon, Eun-Yi


    Reactive oxygen species (ROS) were generated in all oxygen-utilizing organisms. Peroxiredoxin II (Prx II) as one of antioxidant enzymes may play a protective role against the oxidative damage caused by ROS. In order to define the role of Prx II in organismal aging, we evaluated cellular senescence in Prx II(-/-) mouse embryonic fibroblast (MEF). As compared to wild type MEF, cellular senescence was accelerated in Prx II(-/-) MEF. Senescence-associated (SA)-beta-galactosidase (Gal)-positive cell formation was about 30% higher in Prx II(-/-) MEF. N-Acetyl-l-cysteine (NAC) treatment attenuated SA-beta-Gal-positive cell formation. Prx II(-/-) MEF exhibited the higher G2/M (41%) and lower S (1.6%) phase cells as compared to 24% and 7.3% [corrected] in wild type MEF, respectively. A high increase in the p16 and a slight increase in the p21 and p53 levels were detected in PrxII(-/-) MEF cells. The cellular senescence of Prx II(-/-) MEF was correlated with the organismal aging of Prx II(-/-) mouse skin. While extracellular signal-regulated kinase (ERK) and p38 activation was detected in Prx II(-/-) MEF, ERK and c-Jun N-terminal kinase (JNK) activation was detected in Prx II(-/-) skin. These results suggest that Prx II may function as an enzymatic antioxidant to prevent cellular senescence and skin aging.

  1. Studying Kinetochore Kinases

    NARCIS (Netherlands)

    Saurin, Adrian T; Kops, Geert J P L


    Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics

  2. Pkh-kinases control eisosome assembly and organization


    Walther, TC; Aguilar, PS; Fröhlich, F.; Chu, F.; Moreira, K.; Burlingame, Al; WALTER, P.


    Eisosomes help sequester a subgroup of plasma membrane proteins into discrete membrane domains that colocalize with sites of endocytosis. Here we show that the major eisosome component Pil1 in vivo is a target of the long-chain base (LCB, the biosynthetic precursors to sphingolipids)-signaling pathway mediated by the Pkh-kinases. Eisosomes disassemble if Pil1 is hyperphosphorylated (i) upon overexpression of Pkh-kinases, (ii) upon reducing LCB concentrations by inhibiting serine-palmitoyl tra...

  3. Status of the CAMS-BeNeLux network (United States)

    Roggemans, P.; Johannink, C.; Breukers, M.


    An overview is being given of the further expansion of the CAMS@BeNeLux network since previous IMC, July 2015 until May 2016. The weather proved less favorable than in the year before, but thanks to a number of new cameras and extra observing stations, the overall performance of the network remained at the same level in spite of the often poor weather circumstances. This paper compares the Kappa-Cygnids performance of 2015 with the analyses made for the 2014 data, following the same methodology. In 2015 the Kappa Cygnids were remarkable absent which confirms the periodic nature of the abundant Kappa-Cygnids display in 2014. The CAMS@BeNeLux network was the first to draw attention to enhanced activity of the newly discovered Chi Cygnids meteor shower with 5 accurate orbits in the night of 14-15 September 2015. A search through a selection of all orbits of September 2015 yield 71 possible Chi Cygnid orbits of which 18 were selected to calculate the average orbital elements.

  4. CamShift Tracking Method Based on Target Decomposition

    Directory of Open Access Journals (Sweden)

    Chunbo Xiu


    Full Text Available In order to avoid the inaccurate location or the failure tracking caused by the occlusion or the pose variation, a novel tracking method is proposed based on CamShift algorithm by decomposing the target into multiple subtargets for location separately. Distance correlation matrices are constructed by the subtarget sets in the template image and the scene image to evaluate the correctness of the location results. The error locations of the subtargets can be corrected by resolving the optimization function constructed according to the relative positions among the subtargets. The directions and sizes of the correctly located subtargets with CamShift algorithm are updated to reduce the disturbance of the background in the tracking progress. Simulation results show that the method can perform the location and tracking of the target and has better adaptability to the scaling, translation, rotation, and occlusion. Furthermore, the computational cost of the method increases slightly, and its average tracking computational time of the single frame is less than 25 ms, which can meet the real-time requirement of the TV tracking system.

  5. Preparation and Preliminary Application of MAdCAM-1 Polyclonal Antibody in Dairy Cows with Subclinical Mastitis. (United States)

    Xu, Chuang; Chen, Yuanyuan; Chang, Qiaocheng; Xia, Cheng; Yang, Wei; Zhang, Hongyou


    MAdCAM-1 plays an important role in mediating immune response and inflammation. This study aimed to express and purify a fusion protein of MAdCAM-1 in prokaryotic cells and to prepare rat anti-bovine MAdCAM-1 polyclonal antibodies. Prokaryotic expression vector pGEX-4T-1-MAdCAM-1 and pET-28a-MAdCAM-1 were constructed, respectively. The above plasmids were transformed into BL21 Escherichia coli strain. These recombinant strains were induced by IPTG and identified by Western blot analysis and SDS-PAGE. Wistar rats were immunized with recombinant protein (pET-28a-MAdCAM-1) emulsified with Freund's adjuvant, and antibody titers were measured by indirect ELISA. Antibody titers reached the highest value (1:128,000) after the third immunization. Western blot showed that rat anti-bovine MAdCAM-1 polyclonal antibody can not only recognize recombinant MAdCAM-1 protein expressed in E. coli but also recognizes natural MAdCAM-1 protein extracted from bovine tissues. However, commercial anti-mouse MAdCAM-1 monoclonal antibodies did not recognize the recombinant MAdCAM-1 protein or natural protein, which indicated no cross-reactivity between bovine MAdCAM-1 and mouse MAdCAM-1. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis showed that MAdCAM-1 expression was limited in mammary lymphoid nodes of subclinical mastitis in dairy cows. We speculate that MAdCAM-1 expression is inconsistent in different periods of the dairy cows. The successful preparation of rat anti-bovine MAdCAM-1 polyclonal antibody and its preliminary application in dairy cows provide the foundation for further study of the mechanism of anti-inflammation of MAdCAM-1 in dairy cows with subclinical mastitis.

  6. A Prospective, Multicenter Study of Complementary/Alternative Medicine (CAM) Utilization During Definitive Radiation for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moran, Meena S., E-mail: [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Therapy, William W. Backus Hospital, Norwich, Connecticut (United States); Ma Shuangge [Department of Epidemiology and Public Health, Yale University, New Haven, Connecticut (United States); Jagsi, Reshma [University of Michigan, Department of Radiation Oncology, Ann Arbor, MI (United States); Yang, Tzu-I Jonathan [Yale University School of Medicine, New Haven, Connecticut (United States); Higgins, Susan A. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Therapy, Shoreline Medical Center, Guilford, Connecticut (United States); Weidhaas, Joanne B. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Wilson, Lynn D. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Therapy, Lawrence and Memorial Hospital, New London, Connecticut (United States); Lloyd, Shane [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Peschel, Richard [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Therapy, Lawrence and Memorial Hospital, New London, Connecticut (United States); Gaudreau, Bryant [Department of Radiation Therapy, William W. Backus Hospital, Norwich, Connecticut (United States); Rockwell, Sara [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States)


    Purpose: Although complementary and alternative medicine (CAM) utilization in breast cancer patients is reported to be high, there are few data on CAM practices in breast patients specifically during radiation. This prospective, multi-institutional study was conducted to define CAM utilization in breast cancer during definitive radiation. Materials/Methods: A validated CAM instrument with a self-skin assessment was administered to 360 Stage 0-III breast cancer patients from 5 centers during the last week of radiation. All data were analyzed to detect significant differences between users/nonusers. Results: CAM usage was reported in 54% of the study cohort (n=194/360). Of CAM users, 71% reported activity-based CAM (eg, Reiki, meditation), 26% topical CAM, and 45% oral CAM. Only 16% received advice/counseling from naturopathic/homeopathic/medical professionals before initiating CAM. CAM use significantly correlated with higher education level (P<.001), inversely correlated with concomitant hormone/radiation therapy use (P=.010), with a trend toward greater use in younger patients (P=.066). On multivariate analysis, level of education (OR: 6.821, 95% CI: 2.307-20.168, P<.001) and hormones/radiation therapy (OR: 0.573, 95% CI: 0.347-0.949, P=.031) independently predicted for CAM use. Significantly lower skin toxicity scores were reported in CAM users vs nonusers, respectively (mild: 34% vs 25%, severe: 17% vs 29%, P=.017). Conclusion: This is the first prospective study to assess CAM practices in breast patients during radiation, with definition of these practices as the first step for future investigation of CAM/radiation interactions. These results should alert radiation oncologists that a large percentage of breast cancer patients use CAM during radiation without disclosure or consideration for potential interactions, and should encourage increased awareness, communication, and documentation of CAM practices in patients undergoing radiation treatment for breast

  7. The ExoMars PanCam Instrument (United States)

    Griffiths, Andrew; Coates, Andrew; Muller, Jan-Peter; Jaumann, Ralf; Josset, Jean-Luc; Paar, Gerhard; Barnes, David


    The ExoMars mission has evolved into a joint European-US mission to deliver a trace gas orbiter and a pair of rovers to Mars in 2016 and 2018 respectively. The European rover will carry the Pasteur exobiology payload including the 1.56 kg Panoramic Camera. PanCam will provide multispectral stereo images with 34 deg horizontal field-of-view (580 microrad/pixel) Wide-Angle Cameras (WAC) and (83 microrad/pixel) colour monoscopic "zoom" images with 5 deg horizontal field-of-view High Resolution Camera (HRC). The stereo Wide Angle Cameras (WAC) are based on Beagle 2 Stereo Camera System heritage [1]. Integrated with the WACs and HRC into the PanCam optical bench (which helps the instrument meet its planetary protection requirements) is the PanCam interface unit (PIU); which provides image storage, a Spacewire interface to the rover and DC-DC power conversion. The Panoramic Camera instrument is designed to fulfil the digital terrain mapping requirements of the mission [2] as well as providing multispectral geological imaging, colour and stereo panoramic images and solar images for water vapour abundance and dust optical depth measurements. The High Resolution Camera (HRC) can be used for high resolution imaging of interesting targets detected in the WAC panoramas and of inaccessible locations on crater or valley walls. Additionally HRC will be used to observe retrieved subsurface samples before ingestion into the rest of the Pasteur payload. In short, PanCam provides the overview and context for the ExoMars experiment locations, required to enable the exobiology aims of the mission. In addition to these baseline capabilities further enhancements are possible to PanCam to enhance it's effectiveness for astrobiology and planetary exploration: 1. Rover Inspection Mirror (RIM) 2. Organics Detection by Fluorescence Excitation (ODFE) LEDs [3-6] 3. UVIS broadband UV Flux and Opacity Determination (UVFOD) photodiode This paper will discuss the scientific objectives and resource

  8. 基于逆向工程技术圆柱凸轮机构的CAD/CAM%CAD/CAM of cylindrical cam mechanism based on re-verse engineering technology

    Institute of Scientific and Technical Information of China (English)

    蒋萌; 葛正浩; 屈毅; 李艳妮


    The papeer presents a new process and method of revere design and manufacturing of the cylindrical cam mechanism.By applying the Coordinate Measuring Machine (CMM) and the PRO/E software as the platform to carry out aided design, by taking Microsoft Visual C + + 6.0 as the development tool, and based on Windows platform, the cylindrical cam mechanism dealgn and manufacturing software is generated, allowing the design of cycle map and cam profile, checking the pressure angle and curvature radius rapidly, almulating the motion of cam. And the NC machining codes which can be directly used for numerical control machine were generated, achieviug the integration of design and manufacture of cylindrical cam mechanism. This CAD/CAM system can not only be applied in the reverse design of cylindrical cam mechanism, but alao used to achieve the forward de-sign of cylindrical ,cam mechanism quickly and easily. Finally, by taking reverse, design and manufacture of the cylindrical indexing cam as an example, the reverse design and manufacturing process and method of cylindrical cam mechanism based on reverse engineering technology has been explained in detail.%介绍了圆柱凸轮机构逆向设计与制造的流程和方法.利用三坐标测量机和Pro/E软件为平台实现辅助设计,以Microsolft Visual C++6.0为开发工具,基于Windows平台编制了圆柱凸轮机构设计与制造软件,实现了圆柱凸轮机构的循环图和轮廓设计,并可进行压力角及曲率半径的快速校核和凸轮的运动仿真,生成了直接用于数控机床的刀具NC加工代码,实现了圆柱凸轮机构设计制造一体化.此CAD/CAM系统不仅可用于圆柱凸轮机构的反求设计,亦可简单快捷地实现圆柱凸轮机构的正向设计.文中以圆柱分度凸轮的反求与制造为例详细说明了基于逆向工程技术圆柱凸轮机构的设计与制造方法和流程.

  9. Some Aspects on Technological Design of a Cam Type Workpiece Using CATIA Software

    Directory of Open Access Journals (Sweden)

    Calin-Octavian Miclosina


    Full Text Available The paper presents the geometrical models of cam and of semi-finished piece, obtained with CATIA software. Two cam technological routes are shown and the optimal route is chosen. From the technological route, rough milling operation is simulated with CATIA software. By using different milling parameters, various machining time values are obtained.

  10. Numerical verification of similar Cam-clay model based on generalized potential theory

    Institute of Scientific and Technical Information of China (English)

    钟志辉; 杨光华; 傅旭东; 温勇; 张玉成


    From the mathematical principles, the generalized potential theory can be employed to create constitutive model of geomaterial directly. The similar Cam-clay model, which is created based on the generalized potential theory, has less assumptions, clearer mathematical basis, and better computational accuracy. Theoretically, it is more scientific than the traditional Cam-clay models. The particle flow code PFC3D was used to make numerical tests to verify the rationality and practicality of the similar Cam-clay model. The verification process was as follows: 1) creating the soil sample for numerical test in PFC3D, and then simulating the conventional triaxial compression test, isotropic compression test, and isotropic unloading test by PFC3D; 2) determining the parameters of the similar Cam-clay model from the results of above tests; 3) predicting the sample’s behavior in triaxial tests under different stress paths by the similar Cam-clay model, and comparing the predicting results with predictions by the Cam-clay model and the modified Cam-clay model. The analysis results show that the similar Cam-clay model has relatively high prediction accuracy, as well as good practical value.

  11. Use of Complementary and Alternative Medicine (CAM) Treatments by Parents of Children with Autism Spectrum Disorders (United States)

    Christon, Lillian M.; Mackintosh, Virginia H.; Myers, Barbara J.


    Parents of children with autism spectrum disorders (ASDs) may elect to use complementary and alternative medicine (CAM) treatments with their children in place of, or in addition to, conventional treatments. CAM treatments are controversial and understudied and, for most, the efficacy has not been established. The current study (n = 248) examined…

  12. Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

    NARCIS (Netherlands)

    van der Gun, B. T. F.; Huisman, C.; Stolzenburg, S.; Kazemier, H. G.; Ruiters, M. H. J.; Blancafort, P.; Rots, M. G.


    Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear. Methods: Cell survival of ovar

  13. A Methodological Framework for Evaluating the Evidence for Complementary and Alternative Medicine (CAM) for Cancer

    DEFF Research Database (Denmark)

    Zachariae, Robert; Johannessen, Helle


    In spite of lacking evidence for effects on cancer progression itself, an increasing number of cancer patients use various types of complementary and alternative medicine (CAM). There is disagreement between CAM practitioners, researchers and clinical oncologists, as to how evidence concerning...

  14. A new radiological index for assessing asphericity of the femoral head in cam impingement

    DEFF Research Database (Denmark)

    Gosvig, K K; Jacobsen, S; Palm, H;


    Femoroacetabular cam impingement is thought to be a cause of premature osteoarthritis of the hip. The presence of cam malformation was determined in 2803 standardised anteroposterior (AP) pelvic radiographs from the Copenhagen Osteoarthritis Study by measuring the alpha (alpha) angle and the tria...

  15. Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer

    NARCIS (Netherlands)

    van der Gun, B. T. F.; de Groote, M. L.; Kazemier, H. G.; Arendzen, A. J.; Terpstra, P.; Ruiters, M. H. J.; McLaughlin, P. M. J.; Rots, M. G.


    BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma. METHODS: Expression of EpCAM and DNA m

  16. 基于CamShift的手势跟踪算法的定点实现%Fixed-Point Implementation of Gesture Tracking Algorithm Based on CamShift

    Institute of Scientific and Technical Information of China (English)



    在OpenCV 1.0中CamShift浮点算法的基础上,对算法进行定点实现。介绍CamShift算法的基本原理,详细阐述对CamShift浮点程序定点化的方案、流程和具体方法。定点化结果表明,定点化后程序与原浮点程序偏差较小。满足跟踪性能的要求.可用于下一步的硬件实现。%Describes the fixed-point implementation of CamShift algorithm based on OpenCV 1.0. Intro- duces the basic principles of the CamShift algorithm, and elaborates the float-point to fixed- point program and flow of CamShift algorithm. The result of experimentation shows that the de- viation between the float-point and fixed-point is small, can meet the requirement of tracking application, and can be used to the hardware implementation of next step.

  17. Aplikace CAD/CAM softwaru FeatureCAM při obrábění


    Foltán, Petr


    Diplomová práce obsahuje vypracovaný postup výroby části kokily pro gravitační lití pístů s využitím softwaru FeatureCAM. Zabývá se výběrem vhodného strojního a nástrojového vybavení, určením řezných podmínek a řešením výběru optimálních strategií obrábění v softwaru FeatureCAM. Celý proces obrábění je ověřen grafickou simulací a je doplněn výkresovou dokumentací součásti. The diploma thesis contains the manufacturing process of ingot mold part for pistons manufactured by gravity casting u...

  18. Phosphorylation of the mRNA cap binding protein and eIF-4A by different protein kinases

    Energy Technology Data Exchange (ETDEWEB)

    Hagedorn, C.H.


    These studies were done to determine the identity of a protein kinase that phosphorylates the mRNA cap binding protein (CBP). Two chromatographic steps (dye and ligand and ion exchange HPLC) produced a 500x purification of an enzyme activity in rabbit reticulocytes that phosphorylated CBP at serine residues. Isoelectric focusing analysis of kinase treated CBP demonstrated 5 isoelectric species of which the 2 most anodic species were phosphorylated (contained /sup 32/P). This kinase activity phosphorylated CBP when it was isolated or in the eIF-4F complex. Purified protein kinase C, cAMP or cGMP dependent protein kinase, casein kinase I or II, myosin light chain kinase or insulin receptor kinase did not significantly phosphorylate isolated CBP or CBP in the eIF-4F complex. However, cAMP and cGMP dependent protein kinases and casein kinase II phosphorylated eIF-4A but did not phosphorylate the 46 kDa component of eIF-4F. cAMP dependent protein kinase phosphorylated a approx. 220 kDa protein doublet in eIF-4F preparations. These studies indicate that CBP kinase activity probably represents a previously unidentified protein kinase. In addition, eIF-4A appears to be phosphorylated by several protein kinases whereas the 46 kDa component of the eIF-4F complex was not.

  19. Calcium/calmodulin-dependent protein kinase Ⅱ signaling system in cardiovascular diseases%钙/钙调蛋白激酶Ⅱ信号系统与心血管疾病

    Institute of Scientific and Technical Information of China (English)



    CaMKⅡ是钙/钙调蛋白激酶(Ca2 +/calmodulin-dependent protein kinase,CaMK)成员之一.心脏中的CaMK包括Ⅰ,Ⅱ和Ⅳ三种类型,CaMKⅡ含量最多.CaMKⅡ单体由氨基端的催化域、中间部分的调节域和羧基端的结合域组成.钙调蛋白(calmodulin,CaM)与Ca2+结合后被激活,结合于CaMKⅡ调节域中的CaM结合区激活CaMKⅡ.CaMKⅡ富集于T管并靠近L-Ca2通道,也存在于肌浆网和细胞核中.激活的CaMKⅡ通过多种途径调节细胞内Ca2+平衡,广泛参与心血管系统生理活动及病理变化的信号转导过程,与多种心血管系统疾病密切相关.目前研究认为,CaMKⅡ信号系统在心律失常、心肌肥厚、心力衰竭、缺血性心脏病和扩张性心肌病的发生和发展中起着重要作用.%Ca2+/calmodulin-dependent protein kinase II ( CaMKII ) is one of the members of calcium/calmodulin protein kinases ( CaMKs). There are 3 types of CaMKs ( I , II , and IV ) in the heart, while CaMKII is the most abundant one. CaMK II monomer is composed of catalytic domain in the N-terminal, combining domain in the C-terminal and adjust domain in the middle. When CaM is activated by Ca2 + , Ca2+/CaM combines with the adjust domain, and further activates CaMK II. CaMK II is rich in T tube, close to L-Ca2 + channel, and also exists in sacoplasmic reticulum ( SR) and nucleus. CaMK II can adjust the balance of Ca 2+ in cells through various pathways, and then regulate a variety of physiological and pathological signaling transductions in the cardiovascular system. Therefore it is closely related to the cardiovascular system disease. Recent studies have suggested that CaMK II plays an important role in the occurrence and development of arrhythmia, cardiac hypertrophy, heart failure, ischemic heart diseases, and dilated cardiomyopathy.

  20. Introduction to exploring opportunities for advancing collaborative adaptive management (CAM: integrating experience and practice

    Directory of Open Access Journals (Sweden)

    David L. Galat


    Full Text Available This Special Feature of Ecology and Society seeks to communicate a practitioner’s perspective on the application of collaborative adaptive management (CAM to contemporary natural resource management problems. One goal is to create an ongoing mechanism for dialogue that can connect practitioners, researchers, and policy makers. The core 15 papers are grouped into 3 categories that: (1 describe lessons learned through the practice of applying CAM principles to a specific project or generalizing principles from outcomes of a specific project; (2 summarize lessons learned from the author’s extensive CAM experiences; and (3 seek to be instructive of one or more CAM principles through a survey, evaluation, or comparison of multiple projects. Follow-up questions were submitted by authors to the online discussion section of Ecology and Society to stimulate interactive communication among readers and authors about their papers and CAM in general.

  1. Optimal Design of a Cam Mechanism with Translating Flat-Face Follower using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    I. Tsiafis


    Full Text Available The optimum design of a cam mechanism is a time consuming task, due to the numerous alternatives considerations. In the present work, the problem of design parameters optimization of a cam mechanism with translating flat - face follower is investigated from a multi - objective point of view. The design parameters, just like the cam base circle radius, the follower face width and the follower offset can be determined considering as the optimization criteria minimization of the cam size, of the input torque and of the contact stress. During the optimization procedure, a number of constraints regarding the pressure angle, the contact stress, etcare taken into account. The optimization approach, based on genetic algorithm, is applied to find the optimal solutions with respect to the a fore - mentioned objective function and to Ensure the kinematic requirements. Finally, the dynamic behavior of the designed cam mechanism is investigated considering the frictional forces.

  2. Analysis of 3D curve expansion of conical cam with oscillating tapered roller follower

    Institute of Scientific and Technical Information of China (English)


    This paper focuses on the analysis of running conditions and machining processes of conical cam with oscillating follower. We point out the common errors existing in the design and machining of the widely used plane expansion method of conical cam trough-out line. We show that the motion can be divided into two parts, i.e. the oscillating motion of oscillating bar and the rotary motion of oscillating bar relative to the conical cam. By increasing the rotary motion of oscillating bar, the motion path of tapered roller on oscillating bar (i.e. contour surface of conical cam) can be expanded on the cylinder. Based on these analyses,we present a creative and effective designing and machining method for 3D curve expansion of conical cam with oscillating follower.

  3. Survey of UK dentists regarding the use of CAD/CAM technology. (United States)

    Tran, D; Nesbit, M; Petridis, H


    Statement of the problem Digital workflows (CAD/CAM) have been introduced in dentistry during recent years. No published information exists on dentists' use and reporting of this technology.Purpose The purpose of this survey was to identify the infiltration of CAD/CAM technology in UK dental practices and to investigate the relationship of various demographic factors to the answers regarding use or non-use of this technology.Materials and methods One thousand and thirty-one online surveys were sent to a sample of UK dentists composing of both users and non-users of CAD/CAM. It aimed to reveal information regarding type of usage, materials, perceived benefits, barriers to access, and disadvantages of CAD/CAM dentistry. Statistical analysis was undertaken to test the influence of various demographic variables such as country of work, dentist experience, level of training and type of work (NHS or private).Results The number of completed responses totalled 385. Most of the respondents did not use any part of a digital workflow, and the main barriers to CAD/CAM use were initial costs and a lack of perceived benefit over conventional methods. Dentists delivering mostly private work were most likely to have adopted CAD/CAM technology (P CAD/CAM usage (P CAD/CAM had a big role to play in the future.Conclusion Most of the respondents did not use any part of a digital workflow. However, the majority of surveyed dentists were interested in incorporating CAD/CAM into their workflow, while most believed that it will have a big role in the future. There are still some concerns from dentists about the quality of chairside CAD/CAM restorations while the costs are still in the main hugely prohibitive (especially for NHS dentistry).

  4. CAM use in pediatric neurology: an exploration of concurrent use with conventional medicine.

    Directory of Open Access Journals (Sweden)

    Elaine Galicia-Connolly

    Full Text Available BACKGROUND: Previous studies have found that up to 60% of children with neurologic conditions have tried complementary and alternative medicine (CAM. OBJECTIVE: To assess the use of CAM among patients presenting to neurology clinics at two academic centers in Canada. METHODS: A survey instrument was developed to inquire about use of CAM products and therapies, including reasons for use, perceived helpfulness, and concurrent use with conventional medicine, and administered to patients or their parents/guardians at the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO in Ottawa. RESULTS: Overall CAM use at the Stollery was 78%, compared to 48% at CHEO. The most common CAM products used were multi-vitamins (84%, vitamin C (37%, homeopathic remedies (24%, and fish oil/omega 3 s (22%. The most common CAM practices used were massage (47%, chiropractic (37%, faith healing (18%, aromatherapy (16%, homeopathy (16%, and relaxation (16%. Many patients used CAM products at the same time as conventional medicine but just over half (57% discussed this concurrent use with their physician. CONCLUSION: CAM use is common in pediatric neurology patients and most respondents felt that it was helpful, with few or no harms associated. However, this use is often undisclosed, increasing possibility of interactions with conventional drugs. We urge clinicians to inquire about CAM use during routine history taking at every patient visit. Parents would clearly like more information about CAM from their specialty clinics; such information would be easier to share if more primary data were available about the safety and effectiveness of commonly used therapies.

  5. Prevalence and Predictors of Complementary and Alternative Medicine (CAM) Use among Ivy League College Students: Implications for Student Health Services (United States)

    Versnik Nowak, Amy L.; DeGise, Joe; Daugherty, Amanda; O'Keefe, Richard; Seward, Samuel, Jr.; Setty, Suma; Tang, Fanny


    Objective: Determine prevalence and types of complementary and alternative medicine (CAM) therapies used and test the significance of demographics and social cognitive constructs as predictors of CAM use in a college sample. Secondary purpose was to guide the integration of CAM therapies into college health services. Participants: Random,…

  6. EpCAM-selective elimination of carcinoma cells by a novel MAP-based cytolytic fusion protein

    NARCIS (Netherlands)

    Hristodorov, Dmitrij; Amoury, Manal; Mladenov, Radoslav; Niesen, Judith; Arens, Katharina; Berges, Nina; Hein, Lea; di Fiore, Stefano; Pham, Anh-Tuan; Huhn, Michael; Helfrich, Wijnand; Fischer, Rainer; Thepen, Theo; Barth, Stefan


    In normal epithelia, the epithelial cell adhesion molecule (EpCAM) expression is relatively low and only present at the basolateral cell surface. In contrast, EpCAM is aberrantly overexpressed in various human carcinomas. Therefore, EpCAM is considered to be a highly promising target for antibody-ba

  7. Social and Cultural Factors Affecting Complementary and Alternative Medicine (CAM Use during Menopause in Sydney and Bologna

    Directory of Open Access Journals (Sweden)

    Corinne van der Sluijs


    Full Text Available Background. Previous surveys found CAM use during menopause to be popular. This paper compares the results from two surveys (Sydney and Bologna to examine factors that determine the extent and pattern of CAM use to alleviate menopausal symptoms. Methods. Women, aged 45–65 years, who were symptomatic when transitioning through menopause or asymptomatic but taking menopause-specific treatments, were recruited in Sydney (n=1,296 and Bologna (n=1,106 to complete the same voluntary, anonymous, and self-administered questionnaire. The results were reanalysed using stratified analyses to determine similarities and differences. Results. Demographics of the two cohorts differed significantly. CAM was more popular in Sydney. The most significant determinants of CAM use were the use of CAM for other conditions besides menopause and the severity of vasomotor symptoms. Occupational status was a determinant of CAM use amongst Bologna respondents only. In order to relieve symptoms, Australian and Italian women used different CAM modalities whose effectiveness was generally perceived as good. Conclusion. CAM use is popular amongst menopausal women from Sydney and Bologna. Differences in the patterns of CAM use seem to depend on CAM availability and on the educational level and professional status of users. The complex interaction between market, social, and cultural factors of CAM use seems to be more influential on women’s choice of CAM than the available evidence of their effectiveness.

  8. Independent fluctuations of malate and citrate in the CAM species Clusia hilariana Schltdl. under low light and high light in relation to photoprotection. (United States)

    Miszalski, Zbigniew; Kornas, Andrzej; Rozpądek, Piotr; Fischer-Schliebs, Elke; Lüttge, Ulrich


    Clusia hilariana Schltdl. is described in literature as an obligate Crassulacean acid metabolism (CAM) species. In the present study we assessed the effect of irradiance with low light (LL, 200μmolm(-2)s(-1)) and high light (HL, 650-740μmolm(-2)s(-1)), on the interdependency of citrate and malate diurnal fluctuations. In plants grown at HL CAM-type oscillations of concentration of citrate and malate were obvious. However, at LL daily courses of both acids do not seem to indicate efficient utilization of these compounds as CO2 and NADPH sources. One week after transferring plants from LL to HL decarboxylation of malate was accelerated. Thus, in the CAM plant C. hilariana two independent rhythms of accumulation and decarboxylation of malate and citrate take place, which appear to be related to photosynthesis and respiration, respectively. Non photochemical quenching (NPQ) of photosystem II, especially well expressed during the evening hours was enhanced. Exposure to HL for 7 d activated oxidative stress protection mechanisms such as the interconversion of violaxanthin (V), antheraxanthin (A) and zeaxanthin (Z) (epoxydation/de-epoxydation) measured as epoxydation state (EPS). This was accompanied by a slight increase in the total amount of these pigments. However, all these changes were not observed in plants exposed to HL for only 2 d. Besides violaxanthin cycle components also lutein, which shows a small, but not significant increase, may be involved in dissipating excess light energy in C. hilariana.

  9. Evidence of Drought Stress Memory in the Facultative CAM, Aptenia cordifolia: Possible Role of Phytohormones.

    Directory of Open Access Journals (Sweden)

    Eva Fleta-Soriano

    Full Text Available Although plant responses to drought stress have been studied in detail in several plant species, including CAM plants, the occurrence of stress memory and possible mechanisms for its regulation are still very poorly understood. In an attempt to better understand the occurrence and possible mechanisms of regulation of stress memory in plants, we measured the concentrations of phytohormones in Aptenia cordifolia exposed to reiterated drought, together with various stress indicators, including leaf water contents, photosynthesis and mechanisms of photo- and antioxidant protection. Results showed that plants exposed to drought stress responded differently if previously challenged with a first drought. Gibberellin levels decreased upon exposure to the first drought and remained lower in double-stressed plants compared with those exposed to stress for the first time. In contrast, abscisic acid levels were higher in double- than single-stressed plants. This occurred in parallel with alterations in hydroperoxide levels, but not with malondialdehyde levels, thus suggesting an increased oxidation state that did not result in oxidative damage in double-stressed plants. It is concluded that (i drought stress memory occurs in double-stressed A. cordifolia plants, (ii both gibberellins and abscisic acid may play a role in plant response to repeated periods of drought, and (iii changes in abscisic acid levels in double-stressed plants may have a positive effect by modulating changes in the cellular redox state with a role in signalling, rather than cause oxidative damage to the cell.

  10. Evidence of Drought Stress Memory in the Facultative CAM, Aptenia cordifolia: Possible Role of Phytohormones. (United States)

    Fleta-Soriano, Eva; Pintó-Marijuan, Marta; Munné-Bosch, Sergi


    Although plant responses to drought stress have been studied in detail in several plant species, including CAM plants, the occurrence of stress memory and possible mechanisms for its regulation are still very poorly understood. In an attempt to better understand the occurrence and possible mechanisms of regulation of stress memory in plants, we measured the concentrations of phytohormones in Aptenia cordifolia exposed to reiterated drought, together with various stress indicators, including leaf water contents, photosynthesis and mechanisms of photo- and antioxidant protection. Results showed that plants exposed to drought stress responded differently if previously challenged with a first drought. Gibberellin levels decreased upon exposure to the first drought and remained lower in double-stressed plants compared with those exposed to stress for the first time. In contrast, abscisic acid levels were higher in double- than single-stressed plants. This occurred in parallel with alterations in hydroperoxide levels, but not with malondialdehyde levels, thus suggesting an increased oxidation state that did not result in oxidative damage in double-stressed plants. It is concluded that (i) drought stress memory occurs in double-stressed A. cordifolia plants, (ii) both gibberellins and abscisic acid may play a role in plant response to repeated periods of drought, and (iii) changes in abscisic acid levels in double-stressed plants may have a positive effect by modulating changes in the cellular redox state with a role in signalling, rather than cause oxidative damage to the cell.

  11. Using CAD/CAM to improve productivity - The IPAD approach (United States)

    Fulton, R. E.


    Progress in designing and implementing CAD/CAM systems as a result of the NASA Integrated Programs for Aerospace-Vehicle Design is discussed. Essential software packages have been identified as executive, data management, general user, and geometry and graphics software. Data communication, as a means to integrate data over a network of computers of different vendors, provides data management with the capability of meeting design and manufacturing requirements of the vendors. Geometry software is dependent on developmental success with solid geometry software, which is necessary for continual measurements of, for example, a block of metal while it is being machined. Applications in the aerospace industry, such as for design, analysis, tooling, testing, quality control, etc., are outlined.

  12. Chemical composition of umbu (Spondias tuberosa Arr. Cam seeds

    Directory of Open Access Journals (Sweden)

    Soraia Vilela Borges


    Full Text Available The umbu tree (Spondias tuberosa Arr. Cam is an important fruit tree the economy of the semi-arid northeastern region of Brazil. With the objective of finding use for the seeds, physical and chemical characterizations of the seeds from 2 cultivars in 2 maturation stages were carried out and their fatty acid and mineral profiles determined. The results showed no differences between the seeds analyzed. The yield was about 10% and the dimensions as follows: length from 1.48 to 2.11 cm and width from 0.76 to 1.16 cm. The average lipid content was 55% of which 69% was unsaturated and the average protein content was 24%. The seeds were a good source of the following minerals: P, K, Mg, Fe and Cu. The overall results indicated that the oil or the seeds could be used for food stuffs if no toxic agents were found.

  13. Photon counting phosphorescence lifetime imaging with TimepixCam (United States)

    Hirvonen, Liisa M.; Fisher-Levine, Merlin; Suhling, Klaus; Nomerotski, Andrei


    TimepixCam is a novel fast optical imager based on an optimized silicon pixel sensor with a thin entrance window and read out by a Timepix Application Specific Integrated Circuit. The 256 × 256 pixel sensor has a time resolution of 15 ns at a sustained frame rate of 10 Hz. We used this sensor in combination with an image intensifier for wide-field time-correlated single photon counting imaging. We have characterised the photon detection capabilities of this detector system and employed it on a wide-field epifluorescence microscope to map phosphorescence decays of various iridium complexes with lifetimes of about 1 μs in 200 μm diameter polystyrene beads.

  14. Innovative Design of Cam-Controlled Planetary Gear Trains

    Directory of Open Access Journals (Sweden)

    Wen-Hsiang Hsieh


    Full Text Available The objective of this paper is to perform the innovation design for the new structures of cam-controlled planetary gear trains (CCPGTs, based on the creative mechanism design methodology. Firstly, the design requirements and design constraints are summarized according to the kinematics characteristics of existing CCPGTs. Then, the (4, 5 and (5, 7 graphs are generated by the theory of number synthesis. After that, the atlas of feasible specialized graphs is obtained. Finally, the atlas of new designs is obtained through the particularization process. In addition, an illustrated example is given, and the feasibility of the design is verified by computer simulation using ADAMS software. The result indicates that new design can produce a more wide range of non-uniform motion than the existing design. Therefore, they are better alternatives for driving a variable speed input mechanism.

  15. Lacie phase 1 Classification and Mensuration Subsystem (CAMS) rework experiment (United States)

    Chhikara, R. S.; Hsu, E. M.; Liszcz, C. J.


    An experiment was designed to test the ability of the Classification and Mensuration Subsystem rework operations to improve wheat proportion estimates for segments that had been processed previously. Sites selected for the experiment included three in Kansas and three in Texas, with the remaining five distributed in Montana and North and South Dakota. The acquisition dates were selected to be representative of imagery available in actual operations. No more than one acquisition per biophase were used, and biophases were determined by actual crop calendars. All sites were worked by each of four Analyst-Interpreter/Data Processing Analyst Teams who reviewed the initial processing of each segment and accepted or reworked it for an estimate of the proportion of small grains in the segment. Classification results, acquisitions and classification errors and performance results between CAMS regular and ITS rework are tabulated.

  16. Building a Sectional Aerosol Model in CAM5 (United States)

    Yu, P.; Toon, O. B.


    Aerosols are widely distributed around the globe. In the current study I use a sectional aerosol microphysics model (CARMA) coupled with the NCAR global climate model, CAM5, to simulate the spatial-temporal distribution of various types of aerosols including organics, black carbon, sulfate, sea salt and dust. Organics and black carbon surface concentrations are simulated within ~50% over the U.S, and Europe compared with observations; the amount of modeled sulfate and organics are equal in UTLS region as observed by the Pre-AVE field campaign; aerosol extinction in the UTLS observed by SAGEII can be explained by secondary organic aerosols combined with sulfate aerosol. For treating secondary organic aerosols, the volatility-basis-set method improves the budget at surface level relative to the traditional two-product partitioning method; black carbon global budget is largely improved especially in high latitudes by introducing new emission database.

  17. Hydrogen detection with ChemCam at Gale crater (United States)

    Schröder, S.; Meslin, P.-Y.; Gasnault, O.; Maurice, S.; Cousin, A.; Wiens, R. C.; Rapin, W.; Dyar, M. D.; Mangold, N.; Forni, O.; Nachon, M.; Clegg, S.; Johnson, J. R.; Lasue, J.; Le Mouélic, S.; Ollila, A.; Pinet, P.; Sautter, V.; Vaniman, D.


    One of the main advantages of ChemCam's LIBS (Laser-Induced Breakdown Spectroscopy) instrument onboard the Curiosity rover is its potential to detect light elements such as hydrogen at fine scales, which has never been achieved on Mars. Hydrogen lines are detected in most of the data obtained within the first 320 sols of the mission at Gale crater, Mars. This work is a description of the hydrogen signal and its variability in the ChemCam LIBS spectra; it discusses the challenges of qualitative and quantitative analysis. Data acquisition and processing steps are investigated and optimized for the detection of hydrogen on Mars. Subtraction of an appropriate dark spectrum and the deconvolution of the superimposed emission of carbon from the low-pressure CO2-dominated atmosphere are particularly important. Because the intensities of hydrogen are also affected by matrix effects, the hydrogen signal was investigated within groups of targets sharing common chemical features and similar matrices. The different groups cover a variety of rock and soil compositions encountered along the traverse (calcium sulfate veins, mafic soils, felsic, Mg-rich and Fe-rich rocks) including data from both drill holes and their tailings. Almost all these targets were found to be hydrated to variable extents. Soils have systematically higher hydrogen signals than rocks and pebbles, probably as a result of their alteration. The results from rocks suggest that various alteration processes leading to their hydration have taken place, which is consistent with the fluvial lacustrine context, the diagenetic features, and the mineralogy observed by Curiosity in Yellowknife Bay.

  18. Enterococcus faecalis phosphomevalonate kinase. (United States)

    Doun, Stephanie S; Burgner, John W; Briggs, Scott D; Rodwell, Victor W


    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. E. faecalis genomic DNA and the polymerase chain reaction were used to clone DNA thought to encode phosphomevalonate kinase into pET28b(+). Double-stranded DNA sequencing verified the sequence of the recombinant gene. The encoded N-terminal hexahistidine-tagged protein was expressed in Escherichia coli with induction by isopropylthiogalactoside and purified by Ni(++) affinity chromatography, yield 20 mg protein per liter. Analysis of the purified protein by MALDI-TOF mass spectrometry established it as E. faecalis phosphomevalonate kinase. Analytical ultracentrifugation revealed that the kinase exists in solution primarily as a dimer. Assay for phosphomevalonate kinase activity used pyruvate kinase and lactate dehydrogenase to couple the formation of ADP to the oxidation of NADH. Optimal activity occurred at pH 8.0 and at 37 degrees C. The activation energy was approximately 5.6 kcal/mol. Activity with Mn(++), the preferred cation, was optimal at about 4 mM. Relative rates using different phosphoryl donors were 100 (ATP), 3.6 (GTP), 1.6 (TTP), and 0.4 (CTP). K(m) values were 0.17 mM for ATP and 0.19 mM for (R,S)-5-phosphomevalonate. The specific activity of the purified enzyme was 3.9 micromol substrate converted per minute per milligram protein. Applications to an immobilized enzyme bioreactor and to drug screening and design are discussed.

  19. Inhibitors of p21-activated kinases (PAKs). (United States)

    Rudolph, Joachim; Crawford, James J; Hoeflich, Klaus P; Wang, Weiru


    The p21-activated kinase (PAK) family of serine/threonine protein kinases plays important roles in cytoskeletal organization, cellular morphogenesis, and survival, and members of this family have been implicated in many diseases including cancer, infectious diseases, and neurological disorders. Owing to their large and flexible ATP binding cleft, PAKs, particularly group I PAKs (PAK1, -2, and -3), are difficult to drug; hence, few PAK inhibitors with satisfactory kinase selectivity and druglike properties have been reported to date. Examples are a recently discovered group II PAK (PAK4, -5, -6) selective inhibitor series based on a benzimidazole core, a group I PAK selective series based on a pyrido[2,3-d]pyrimidine-7-one core, and an allosteric dibenzodiazepine PAK1 inhibitor series. Only one compound, an aminopyrazole based pan-PAK inhibitor, entered clinical trials but did not progress beyond phase I trials. Clinical proof of concept for pan-group I, pan-group II, or PAK isoform selective inhibition has yet to be demonstrated.

  20. An 8-year evaluation of sintered ceramic and glass ceramic inlays processed by the Cerec CAD/CAM system

    DEFF Research Database (Denmark)

    Pallesen, U.; Dijken van, J.W.V.


    The purpose of this study was to evaluate Cerec CAD/CAM inlays processed of two industrially made machinable ceramics during an 8-yr follow-up period. Each of 16 patients received two similar ceramic inlays. Half the number of the inlays were made of a feldspathic (Vita Mark II) and the other...... of a glass ceramic (Dicor MGC) block. The inlays were luted with a dual resin composite and evaluated clinically using modified USPHS criteria at baseline, 8 months, 2, 3, 5, 6 and 8 yr, and indirectly using models. At baseline, 84% of the inlays were estimated as optimal and 16% as acceptable. Postoperative...... sensitivity was reported by one patient for 8 months. Of the 32 inlays evaluated during the 8 yr, 3 failed due to fracture of the material. No secondary caries was found adjacent to the inlays. No significant differences in the clinical performance were found between inlays made of the two ceramics. It can...

  1. Effects of tributylborane-activated adhesive and two silane agents on bonding computer-aided design and manufacturing (CAD/CAM) resin composite. (United States)

    Shinohara, Ayano; Taira, Yohsuke; Sawase, Takashi


    The present study was conducted to evaluate the effects of an experimental adhesive agent [methyl methacrylate-tributylborane liquid (MT)] and two adhesive agents containing silane on the bonding between a resin composite block of a computer-aided design and manufacturing (CAD/CAM) system and a light-curing resin composite veneering material. The surfaces of CAD/CAM resin composite specimens were ground with silicon-carbide paper, treated with phosphoric acid, and then primed with either one of the two silane agents [Scotchbond Universal Adhesive (SC) and GC Ceramic Primer II (GC)], no adhesive control (Cont), or one of three combinations (MT/SC, MT/GC, and MT/Cont). A light-curing resin composite was veneered on the primed CAD/CAM resin composite surface. The veneered specimens were subjected to thermocycling between 4 and 60 °C for 10,000 cycles, and the shear bond strengths were determined. All data were analyzed using analysis of variance and a post hoc Tukey-Kramer HSD test (α = 0.05, n = 8). MT/SC (38.7 MPa) exhibited the highest mean bond strengths, followed by MT/GC (30.4 MPa), SC (27.9 MPa), and MT/Cont (25.7 MPa), while Cont (12.9 MPa) and GC (12.3 MPa) resulted in the lowest bond strengths. The use of MT in conjunction with a silane agent significantly improved the bond strength. Surface treatment with appropriate adhesive agents was confirmed as a prerequisite for veneering CAD/CAM resin composite restorations.

  2. NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms. (United States)

    Love, Nick R; Pollak, Nadine; Dölle, Christian; Niere, Marc; Chen, Yaoyao; Oliveri, Paola; Amaya, Enrique; Patel, Sandip; Ziegler, Mathias


    Nicotinamide adenine dinucleotide phosphate (NADP) is a critical cofactor during metabolism, calcium signaling, and oxidative defense, yet how animals regulate their NADP pools in vivo and how NADP-synthesizing enzymes are regulated have long remained unknown. Here we show that expression of Nadk, an NAD(+) kinase-encoding gene, governs NADP biosynthesis in vivo and is essential for development in Xenopus frog embryos. Unexpectedly, we found that embryonic Nadk expression is dynamic, showing cell type-specific up-regulation during both frog and sea urchin embryogenesis. We analyzed the NAD kinases (NADKs) of a variety of deuterostome animals, finding two conserved internal domains forming a catalytic core but a highly divergent N terminus. One type of N terminus (found in basal species such as the sea urchin) mediates direct catalytic activation of NADK by Ca(2+)/calmodulin (CaM), whereas the other (typical for vertebrates) is phosphorylated by a CaM kinase-dependent mechanism. This work indicates that animal NADKs govern NADP biosynthesis in vivo and are regulated by evolutionarily divergent and conserved CaM-dependent mechanisms.

  3. Comparative evaluation of RetCam vs. gonioscopy images in congenital glaucoma

    Directory of Open Access Journals (Sweden)

    Raj V Azad


    Full Text Available Purpose: To compare clarity, exposure and quality of anterior chamber angle visualization in congenital glaucoma patients, using RetCam and indirect gonioscopy images. Design: Cross-sectional study Participants. Congenital glaucoma patients over age of 5 years. Materials and Methods: A prospective consecutive pilot study was done in congenital glaucoma patients who were older than 5 years. Methods used are indirect gonioscopy and RetCam imaging. Clarity of the image, extent of angle visible and details of angle structures seen were graded for both methods, on digitally recorded images, in each eye, by two masked observers. Outcome Measures: Image clarity, interobserver agreement. Results: 40 eyes of 25 congenital glaucoma patients were studied. RetCam image had excellent clarity in 77.5% of patients versus 47.5% by gonioscopy. The extent of angle seen was similar by both methods. Agreement between RetCam and gonioscopy images regarding details of angle structures was 72.50% by observer 1 and 65.00% by observer 2. Conclusions: There was good agreement between RetCam and indirect gonioscopy images in detecting angle structures of congenital glaucoma patients. However, RetCam provided greater clarity, with better quality, and higher magnification images. RetCam can be a useful alternative to gonioscopy in infants and small children without the need for general anesthesia.

  4. Design of Cylindrical Cam with Oscillating Follower Based on 3D Expansion of Planar Profile Model

    Institute of Scientific and Technical Information of China (English)

    CHEN Junhua; LIN Zuan; WU Yijie


    Cylindrical cam with oscillating follower is widely applicable and used in many mechanical devices and machines. However, a common error exists in the methods of designing planar profile for oscillating follower cylinder cam. In this study, we propose a new hypothesis to solve this design problem with the inclusion of deviation angle. On the basis of this new concept, equations for planar profile expansion and methods of calculating pressure angle are deduced by applying 3D expansion formula of the follower's motion orbit. When the pressure angle is less than allowable value, the minimum base radius can be determined by using MATLAB software. Accordingly, the planar profile of oscillating follower cylinder cam is generated by CAD software. This new method is practical and can be easily adopted for the design of oscillating follower cylindrical cam with desirable accuracy. We applied the method in the design of cylindrical cam for paper feeding mechanism used in high-speed printers. We calculated the planar profile and used it to direct the NC machine for the manufacture of the groove of cylindrical cam. The improved cylindrical cam met all of the requirements of speed and accuracy demanded by high-speed printers. Therefore, our new method has been validated by practical application.

  5. The CAM Education Program of the National Center for Complementary and Alternative Medicine: an overview. (United States)

    Pearson, Nancy J; Chesney, Margaret A


    The authors provide a historical context and overview of the experience of education projects at 14 health professions schools in the United States and the American Medical Students Association that were funded by the National Center for Complementary and Alternative Medicine at the National Institutes of Health in cohorts of five per year in 2000, 2001, and 2002-2003. These 15 projects were designed to incorporate CAM information into the curricula of conventional health professions schools. A longer-term goal was to accelerate the integration of CAM and conventional medicine. The overall program started in 2000 at a time when discussions about the definition, goals, and value of integrative medicine were already well underway. The efforts specific to each project, as well as the shared challenges, accomplishments, and collaborative efforts of all 15 projects, can provide guidance for the education of conventional health care providers about CAM in an integrative medicine environment. Challenging issues that must be faced include (1) the need to develop successful strategies to incorporate information about CAM into already dense health professions school curricula, (2) the need for conventional health professionals to have authoritative resources to provide their patients information about risks and benefits of CAM practices, and (3) the need to identify appropriate roles for CAM practitioners in educating conventional health professionals about CAM therapies. The authors discuss these issues and others and present some recommendations.

  6. Modeling analysis of the benefits of Crassulacean acid metabolism (CAM) for sustainable agriculture in arid regions (United States)

    Bartlett, M. S.; Vico, G.; Porporato, A. M.


    In view of the pressing needs to sustainably manage water and soil resources, especially in arid and semi-arid regions, here we propose a new carbon assimilation model that couples a simple yet mechanistic description of Crassulacean acid metabolism (CAM) photosynthesis to the soil-plant-atmosphere continuum. The model captures the full coupling of the CAM photosynthetic pathway with fluctuations in environmental conditions (cycles of light availability and air humidity, changes in soil moisture as driven by plant transpiration and rainfall occurrence). As such, the model is capable of reproducing the different phases of CAM, including daytime stomatal closure and photosynthesis from malic acid, afternoon stomatal opening for direct carbon assimilation, and nighttime stomatal opening for CO2 uptake and malic acid synthesis. Thanks to its versatility, our model allows us to relate CAM productivity, for both obligate and facultative CAM plants, to various soil moisture conditions including hydroclimatic scenarios of rainfall frequency and intensity as well as different night-time conditions of temperature, wind speed, and humidity. Our analyses show the potential productive benefits of CAM cultivation in dryland environments as feedstock and possible biofuel source, in terms of sustainable water use and economic benefits. In particular, the model is used to explore conditions where CAM plant resiliency to water stress makes these plants a more sustainable alternative to C3 and C4 species for potential deficit irrigation.


    Directory of Open Access Journals (Sweden)

    Panda Roshni


    Full Text Available Endometriosis is a gynaecological disease with a complex etiology. It is associated with severe pelvic pain, sub fertility and reduced quality of life. Endometriosis has a multifactorial etiology and therefore its management is also multidimensional. The main targets of therapy are controlling of the pain symptoms and increasing fertility where it is desired. Hormonal and surgical therapies are the two major treatment modalities available currently. But they are not without their side effects. Therefore many women explore Complementary and Alternative Medicine (CAM forms of treatment for symptomatic relief from pain. These CAM therapies have been used as an adjuvant to conventional therapy or as an independent form of treatment. CAM therapies are purported to have lesser side effects as compared to conventional medical formulations. Ancient Chinese and Indian medicine system have laid the foundation of several of the prevalent Cam practices. The following CAM practices have been discussed in the article-Acupuncture, Herbal therapy, Meditation and Hypnotherapy, Yoga, Exercise, Dietary therapy Aromatherapy and Massage, Reiki, Magnet therapy and Chiropractice. Randomized Clinical Trials (RCT have been conducted for some of the CAM therapies in Endometriosis and Acupuncture and Herbal and Dietary therapies have been found to have some positive effect on the patients. The efficacy of CAM therapies still needs substantial evidence to be integrated into general healthcare practices.

  8. CAM therapies among primary care patients using opioid therapy for chronic pain

    Directory of Open Access Journals (Sweden)

    Mundt Marlon P


    Full Text Available Abstract Background Complementary and alternative medicine (CAM is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. Method A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. Results Patients were treated for a variety of pain problems including low back pain (38.4%, headaches (9.9%, and knee pain (6.5%; the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248, chiropractic treatment (17.8%, n = 162, acupuncture (7.6%, n = 69, yoga (6.1%, n = 55, herbs and supplements (6.8%, n = 62, and prolotherapy (5.9%, n = 54. CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8% and prolotherapy (87.7%, whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. Conclusion This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.

  9. Regulated intramembrane proteolysis and degradation of murine epithelial cell adhesion molecule mEpCAM.

    Directory of Open Access Journals (Sweden)

    Matthias Hachmeister

    Full Text Available Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein, which is highly and frequently expressed in carcinomas and (cancer-stem cells, and which plays an important role in the regulation of stem cell pluripotency. We show here that murine EpCAM (mEpCAM is subject to regulated intramembrane proteolysis in various cells including embryonic stem cells and teratocarcinomas. As shown with ectopically expressed EpCAM variants, cleavages occur at α-, β-, γ-, and ε-sites to generate soluble ectodomains, soluble Aβ-like-, and intracellular fragments termed mEpEX, mEp-β, and mEpICD, respectively. Proteolytic sites in the extracellular part of mEpCAM were mapped using mass spectrometry and represent cleavages at the α- and β-sites by metalloproteases and the b-secretase BACE1, respectively. Resulting C-terminal fragments (CTF are further processed to soluble Aβ-like fragments mEp-β and cytoplasmic mEpICD variants by the g-secretase complex. Noteworthy, cytoplasmic mEpICD fragments were subject to efficient degradation in a proteasome-dependent manner. In addition the γ-secretase complex dependent cleavage of EpCAM CTF liberates different EpICDs with different stabilities towards proteasomal degradation. Generation of CTF and EpICD fragments and the degradation of hEpICD via the proteasome were similarly demonstrated for the human EpCAM ortholog. Additional EpCAM orthologs have been unequivocally identified in silico in 52 species. Sequence comparisons across species disclosed highest homology of BACE1 cleavage sites and in presenilin-dependent γ-cleavage sites, whereas strongest heterogeneity was observed in metalloprotease cleavage sites. In summary, EpCAM is a highly conserved protein present in fishes, amphibians, reptiles, birds, marsupials, and placental mammals, and is subject to shedding, γ-secretase-dependent regulated intramembrane proteolysis, and proteasome-mediated degradation.

  10. Update on Aurora Kinase Targeted Therapeutics in Oncology (United States)

    Green, Myke R.; Woolery, Joseph E.


    Introduction Mammalian cells contain three distinct serine/threonine protein kinases with highly conserved catalytic domains, including aurora A and B kinases that are essential regulators of mitotic entry and progression. Overexpression of aurora A and/or B kinase is associated with high proliferation rates and poor prognosis, making them ideal targets for anti-cancer therapy. Disruption of mitotic machinery is a proven anti-cancer strategy employed by multiple chemotherapeutic agents. Numerous small molecule inhibitors of the aurora kinases have been discovered and tested in vivo and in vitro, with a few currently in phase II testing. Areas covered This review provides the reader with updated results from both preclinical and human studies for each of the aurora kinase inhibitors (AKI) that are currently being investigated. The paper also covers in detail the late breaking and phase I data presented for AKIs thereby allowing the reader to compare and contrast individual and classrelated effects of AKIs. Expert opinion While the successful development and approval of an AKI for anti-cancer therapy remains unresolved, pre-clinical identification of resistant mechanisms would help design better early phase clinical trials where relevant combinations may be evaluated prior to phase II testing. The authors believe that aurora kinases are important anti-cancer targets that operate in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by providing a unique, targeted and complimentary anti-cancer mechanism, expand the available armamentarium against cancer. PMID:21556291

  11. Multiple host kinases contribute to Akt activation during Salmonella infection. (United States)

    Roppenser, Bernhard; Kwon, Hyunwoo; Canadien, Veronica; Xu, Risheng; Devreotes, Peter N; Grinstein, Sergio; Brumell, John H


    SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4) P2/PI(3-5) P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4) P2/PI(3-5) P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  12. Multiple host kinases contribute to Akt activation during Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Bernhard Roppenser

    Full Text Available SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4 P2/PI(3-5 P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4 P2/PI(3-5 P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  13. Plant phosphatidylinositol 3-kinase

    NARCIS (Netherlands)

    Lee, Y.; Munnik, T.; Munnik, T.


    Phosphatidylinositol 3-kinase (PI3K) phosphorylates the D-3 position of phosphoinositides. In Arabidopsis, only one PI3K exists, which belongs to the class-III PI3K subfamily which makes phosphatidylinositol 3-phosphate (PtdIns3P). The single AtPI3K gene is essential for survival, since loss of its

  14. Spatial data software integration - Merging CAD/CAM/mapping with GIS and image processing (United States)

    Logan, Thomas L.; Bryant, Nevin A.


    The integration of CAD/CAM/mapping with image processing using geographic information systems (GISs) as the interface is examined. Particular emphasis is given to the development of software interfaces between JPL's Video Image Communication and Retrieval (VICAR)/Imaged Based Information System (IBIS) raster-based GIS and the CAD/CAM/mapping system. The design and functions of the VICAR and IBIS are described. Vector data capture and editing are studied. Various software programs for interfacing between the VICAR/IBIS and CAD/CAM/mapping are presented and analyzed.

  15. Aesthetic treatment option for completely edentulous patients using CAD/CAM technology. (United States)

    Kleinman, Alejandro; Avendano, Sergio; Leyva, Francisco


    In recent years, advancements have been made in CAD/CAM technology that have allowed for the development of different treatments regarding the rehabilitation of patients with natural dentition, as well as patients with dental implants. Contemporary systems can also allow prosthetic rehabilitation for partially and completely edentulous patients. This article describes a restorative alternative to fixed implant-supported reconstruction of completely edentulous patients, utilizing a CAD/CAM-generated framework and CAD/CAM-generated all-ceramic cement-retained crowns. In addition to delivering an optimally aesthetic restoration, this design permits a precise and passive prosthetic fit.

  16. Digital data management for CAD/CAM technology. An update of current systems. (United States)

    Andreiotelli, M; Kamposiora, P; Papavasiliou, G


    Abstract - Computer-aided design/computer-aided manufacturing (CAD/CAM) technology continues to rapidly evolve in the dental community. This review article provides an overview of the operational components and methodologies used with some of the CAD/CAM systems. Future trends are also discussed. While these systems show great promise, the quality of performance varies among systems. No single system currently acquires data directly in the oral cavity and produces restorations using all materials available. Further refinements of these CAD/CAM technologies may increase their capabilities, but further special training will be required for effective use.

  17. Conservative restorative treatment using a single-visit, all-ceramic CAD/CAM system. (United States)

    Benk, Joel


    Computer-aided design/computer-aided manufacturing (CAD/CAM) continues to radically change the way in which the dental team plans, prepares, and fabricates a patient's restoration. This advancing technology offers the clinician the ability to scan the patient's failing dentition and then designs a long-lasting, reliable restoration based on this data. CAD/CAM systems also permit efficient, single-visit placement of the restoration while preserving much of the natural tooth structure. This article discusses how a chairside CAD/CAM system can be used to provide such a restoration in the posterior region in a single-visit.

  18. Aesthetic quadrant dentistry using a chairside CAD/CAM system: a case presentation. (United States)

    Klim, James


    There are numerous CAD/CAM technologies available today for the production of highly aesthetic restorations with strength and precision. Laboratory-based CAD/CAM systems typically require the patient to receive a provisional restoration and then return to the dental office for a second visit for placement of the definitive restoration upon receipt from the laboratory. Chairside systems, as described in the following case presentation, allow excellent benefits to be achieved in one patient visit. Thus, this case presentation describes the sequences associated with single-visit, in-office CAD/CAM quadrant dentistry.

  19. Comparative fracture strength analysis of Lava and Digident CAD/CAM zirconia ceramic crowns


    Kwon, Taek-Ka; Pak, Hyun-Soon; Yang, Jae-Ho; Han, Jung-Suk; Lee, Jai-Bong; Kim, Sung-Hun; Yeo, In-Sung


    PURPOSE All-ceramic crowns are subject to fracture during function. To minimize this common clinical complication, zirconium oxide has been used as the framework for all-ceramic crowns. The aim of this study was to compare the fracture strengths of two computer-aided design/computer-aided manufacturing (CAD/CAM) zirconia crown systems: Lava and Digident. MATERIALS AND METHODS Twenty Lava CAD/CAM zirconia crowns and twenty Digident CAD/CAM zirconia crowns were fabricated. A metal die was also ...

  20. Computer-assisted myelography (CAM) in the diagnosis of cervical disk disease. Correlation with surgical findings

    Energy Technology Data Exchange (ETDEWEB)

    Kotwica, Z.; Kasprzak, P. (Medical Univ. of Lodz, Dept. of Neurosurgery (Poland)); Chmielowski, M. (Medical Univ. of Lodz, School of Medicine, Dept. of Medical Imaging (Poland))

    A comparison was made between results obtained from preoperative computer-assisted myelography (CAM), on the one hand, and surgical findings, on the other, for 45 patients with suspicion of cervical disk disease. Full and correct diagnosis, subsequently confirmed by surgery, was enabled by CAM in 98% of all cases. Only one case was left in which preoperative diagnosis had been extraspinal tumour, while surgery revealed prolapse of the nucleus pulposus, the latter lying exposed on the anterior wall of the dural sac. The authors feel CAM to be sufficient for planning of surgical treatment for cervical disk desease, with other neuroradiological investigations, myelography or magnetic resonance tomography usually not being necessary. (orig.).

  1. CAM operated tool for proximate or remote holding of an object

    Energy Technology Data Exchange (ETDEWEB)

    Schrum, P.B.; Gajdzik, G.P. Jr.


    A tool for releasably holding an object includes a receptacle having an outer sleeve and a rotatable inner sleeve. The inner sleeve is coaxially positioned within the outer sleeve and includes a locking member. An insert which is adapted to be operably associated with the receptacle includes a cam. The cam includes a guide and a slot so that when the cam is inserted into the inner sleeve, the guide aligns the locking member with the slot allowing the locking member to engage the slot thereby holding the receptacle and the insert together.

  2. Strength of CAD/CAM-generated esthetic ceramic molar implant crowns


    D. Wolf; Bindl, A; Schmidlin, P.R; Lüthy, H; Mörmann, W H


    PURPOSE: One-visit in-office CAD/CAM fabrication of esthetic ceramic crowns as a superstructure for posterior implants is quite new. The aim of the study was to evaluate the strength of esthetic ceramic CAD/CAM crowns with varied occlusal thickness and seated with adhesive and nonadhesive cements on titanium and zirconia abutments. MATERIALS AND METHODS: Esthetic ceramic CAD/CAM-generated molar crowns (n = 15 per group) with occlusal thicknesses of 0.5 mm and 1.5 mm were seated on titanium (1...

  3. Electronic cam motion generation with special reference to constrained velocity, acceleration, and jerk. (United States)

    Liao, Chung-Shu; Jeng, Shyr-Long; Chieng, Wei-Hua


    Electronic cam motion involves velocity tracking control of the master motor and trajectory generation of the slave motor. Special concerns such as the limits of the velocity, acceleration, and jerk are beyond the considerations in the conventional electronic cam motion control. This study proposes the curve-fitting of a Lagrange polynomial to the cam profile, based on trajectory optimization by cubic B-spline interpolation. The proposed algorithms may yield a higher tracking precision than the conventional master-slaves control method does, providing an optimization problem is concerned. The optimization problem contains three dynamic constraints including velocity, acceleration, and jerk of the motor system.

  4. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  5. Evaluation of Shipbuilding CAD/CAM/CIM Systems - Phase II (Requirements for Future Systems) (United States)


    Odense Steel Shipyard SENER Ingenieria y Sistemas Peter Marks and Kathleen Riles, Authors of Aligning Technology Torben Andersen, Executive Vice...Sener Ingenieria y Sistemas - FORAN 3 • Intergraph-ISDP ● Black and Veatch - POWRTRAK. The information gleaned from these visits was immense. Perhaps

  6. IFEMS, an Interactive Finite Element Modeling System Using a CAD/CAM System (United States)

    Mckellip, S.; Schuman, T.; Lauer, S.


    A method of coupling a CAD/CAM system with a general purpose finite element mesh generator is described. The three computer programs which make up the interactive finite element graphics system are discussed.

  7. Development of CAD/CAM System for Cross Section’s Changing Hole Electrical Discharge Machining (United States)

    Ishida, Tohru; Ishiguro, Eiki; Kita, Masahiko; Nakamoto, Keiichi; Takeuchi, Yoshimi

    This study deals with the development of a new CAD/CAM system for fabricating holes whose cross sections change variously. The cross sections of machined holes are generally constant. The limitations in the shapes of holes that can be machined make obstacles in the design stage of industrial products. A new device that utilizes electrical discharge machining has been developed that can create holes with various cross sections to solve this problem. However, it has been impossible to put the device into practical use since there has been no software that has enabled the designed shapes to be easily machined. Therefore, we aimed at developing a new CAD/CAM system for machining the beforehand designed holes with changing cross sections by using the device. As the first step in developing the CAD/CAM system, the post processor in the CAM system is formulated in this paper.

  8. A Unique Opportunity for an Intercultural Discussion on CAM and Liver Disease

    Directory of Open Access Journals (Sweden)

    Francesco Marotta


    Full Text Available The meeting of the APASL, Asian Pacific Association for the Study of the Liver, was held in December 2004, in New Delhi, India. The meeting was held under the patronage of the APASL Committee and Board of Presidents of the National Liver Association and in conjunction with the annual conference of the Indian Association for the Study of Liver (INASL. The congress was designed to have a core meeting with three parallel sessions running throughout, dedicated research workshops and intensive breakfast sessions. This report concentrates on the two sessions devoted to complementary and alternative medicine (CAM and shows the latest research in CAM for liver disease and the concerns of doctors about integrating CAM with more traditional treatments. With researchers and practitioners gathering from all over the world, it was a unique opportunity for an intercultural discussion on CAM and liver disease.

  9. Commissioning and First Observations with Wide FastCam at the Telescopio Carlos S\\'anchez

    CERN Document Server

    Velasco, Sergio; Oscoz, Alejandro; López, Roberto L; Puga, Marta; Murga, Gaizka; Pérez-Garrido, Antonio; Pallé, Enric; Ricci, Davide; Ayuso, Ismael; Hernández-Sánchez, Mónica; Truant, Nicola


    The FastCam instrument platform, jointly developed by the IAC and the UPCT, allows, in real-time, acquisition, selection and storage of images with a resolution that reaches the diffraction limit of medium-sized telescopes. FastCam incorporates a specially designed software package to analyse series of tens of thousands of images in parallel with the data acquisition at the telescope. Wide FastCam is a new instrument that, using the same software for data acquisition, does not look for lucky imaging but fast observations in a much larger field of view. Here we describe the commissioning process and first observations with Wide FastCam at the Telescopio Carlos S\\'anchez (TCS) in the Observatorio del Teide.

  10. O-Cam: a new paradigm for investigating the effects of ostracism. (United States)

    Goodacre, Rani; Zadro, Lisa


    A new ostracism paradigm-O-Cam-was designed to combine the best qualities of both social ostracism (i.e., face-to-face interaction between the target and sources of ostracism) and cyber ostracism (i.e., confederate-free, highly controlled designs) paradigms. O-Cam consists of a simulated Web conference during which participants are either ostracized or included by 2 other participants whose actions, unbeknownst to the participants, are actually pretaped. The findings of preliminary studies indicate that O-Cam provides a powerful ostracism experience that yields psychological and behavioral responses that are consistent with those in other ostracism paradigms (e.g., Cyberball; Williams, 2007). Moreover, unlike in many previous ostracism paradigms, O-Cam provides researchers with the flexibility to manipulate the physical appearance and the verbal/nonbehavior of the sources of ostracism without the need for confederates.

  11. SuperCam Remote Sensing on the Mars 2020 Rover: Science Goals and Overview (United States)

    Wiens, R. C.; Maurice, S.; Rull, F.; SuperCam Team


    The Mars 2020 Science Definition Team (SDT) report emphasized the importance of fine-scale measurements, suggesting that the numerous pin-point observations made at remote distances by ChemCam was a very desirable capability.

  12. Involvement of Ca2+/CaM in the signal transduction of acetylcholine regulating stomatal movement

    Institute of Scientific and Technical Information of China (English)


    It has been known that the neurotransmitter acetylcholine (ACh) also exists in plants and is able to regulate the movement of stomata. In another aspect, Ca2+/CaM as the second messengers have a critical role of signal transduction in stomatal guard-cell. Here we showed that Ca2+/CaM were also involved in theACh regulated stomatal movement. In the medium containing Ca2+, the Ca2+ channel blockers (NIF and Ver) and CaM inhibitors (TFP and W7) could neutralize the ACh induced stomatal opening, however, they are ineffective in the medium containing K+. Those results indicated that Ca2+/CaM were involved in the signal transduction pathway of ACh regulating stomatal movement.

  13. CAD/CAM/CAI Application for High-Precision Machining of Internal Combustion Engine Pistons

    Directory of Open Access Journals (Sweden)

    V. V. Postnov


    Full Text Available CAD/CAM/CAI application solutions for internal combustion engine pistons machining was analyzed. Low-volume technology of internal combustion engine pistons production was proposed. Fixture for CNC turning center was designed.

  14. Study on glass infiltrated alumina(GIA) ceramic for CAD/CAM

    Institute of Scientific and Technical Information of China (English)

    LI Mingzhe; LI Hong; WANG Wei; Zhao Yunfeng


    @@ With the rapid development of computer technique , Computer aided design(CAD) and computer aided manufacturing(CAM) or computer integrated manufacturing(CIM) has became an alternative to the conventional technique for producingdental restorations.

  15. Complementary and alternative medicine (CAM) following traumatic brain injury (TBI): Opportunities and challenges. (United States)

    Hernández, Theresa D; Brenner, Lisa A; Walter, Kristen H; Bormann, Jill E; Johansson, Birgitta


    Traumatic brain injury (TBI) is highly prevalent and occurs in a variety of populations. Because of the complexity of its sequelae, treatment strategies pose a challenge. Given this complexity, TBI provides a unique target of opportunity for complementary and alternative medicine (CAM) treatments. The present review describes and discusses current opportunitites and challenges associated with CAM research and clinical applications in civilian, veteran and military service populations. In addition to a brief overview of CAM, the translational capacity from basic to clinical research to clinical practice will be described. Finally, a systematic approach to developing an adoptable evidence base, with proof of effectiveness based on the literature will be discussed. Inherent in this discussion will be the methodological and ethical challenges associated with CAM research in those with TBI and associated comorbidities, specifically in terms of how these challenges relate to practice and policy issues, implementation and dissemination. This article is part of a Special Issue entitled SI:Brain injury and recovery.

  16. An automated qualification framework for the MeerKAT CAM (Control-And-Monitoring) (United States)

    van den Heever, Lize; Marais, Neilen; Slabber, Martin


    This paper introduces and discusses the design of an Automated Qualification Framework (AQF) that was developed to automate as much as possible of the formal Qualification Testing of the Control And Monitoring (CAM) subsystem of the 64 dish MeerKAT radio telescope currently under construction in the Karoo region of South Africa. The AQF allows each Integrated CAM Test to reference the MeerKAT CAM requirement and associated verification requirement it covers and automatically produces the Qualification Test Procedure and Qualification Test Report from the test steps and evaluation steps annotated in the Integrated CAM Tests. The MeerKAT System Engineers are extremely happy with the AQF results, but mostly by the approach and process it enforces.

  17. Health psychology as a context for massage therapy: a conceptual model with CAM as mediator. (United States)

    Hymel, Glenn M; Rich, Grant J


    Health psychology represents a context within which massage therapy research, education, and practice can be positioned for the mutual benefit of both. Furthermore, complementary and alternative medicine (CAM) more often than not plays a mediating role in relating massage therapy to health psychology. On occasion, though, the linkage between health psychology and massage therapy can be quite direct without the mediating influence of CAM. This paper, accordingly, advances a conceptual model via both flowchart and Venn diagram displays for viewing the health psychology context for massage therapy with the possibility of CAM as a mediating factor. Attention is also given to the broad range of issues constituting contemporary health psychology as well as its correspondence to an equally diverse array of client populations and health conditions addressed in massage therapy research. Future directions in the areas of health psychology, CAM, and massage therapy are proposed with a view toward a mutual and reciprocal benefit accruing to these behavioral and health science arenas.

  18. Cooverexpression of EpCAM and c-myc genes in malignant breast tumours

    Indian Academy of Sciences (India)



    The overexpression of epithelial cell adhesion molecule (EpCAM), a proto-oncogene, affects progression, treatment, and diagnosis of many adenocarcinomas. C-myc has been shown to be a downstream target of EpCAM and is also one of the most important proto-oncogenes routinely overexpressed in breast cancer. However, cooverexpression of EpCAM and c-mycgenes has not been investigated in breast cancer tissues, particularly in Iranian population. The aim of this study was to assess the expression of EpCAM and c-myc genes in malignant breast cancer tissues using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) followed by analyses of the association between the outcomes. In this study, 122 fresh tissues, including 104 malignant and 18 benign samples, were disrupted by mortar and pestle, and then the RNA was isolated from the samples and converted to cDNA. The relative expression levels of EpCAM and c-myc genes were measured by2−ΔΔCt method using RT-qPCR. EpCAM protein level was also assessed in 66 cases using Western blot technique. UsingRT-qPCR method, our results showed that EpCAM was overexpressed in 48% of malignant and 11.1% of benign samples. Evaluating EpCAM protein overexpression in a portion of samples depicted the fully concordance rate between Western blot and RT-qPCR techniques. C-myc expression was first evaluated by RT-qPCR method, showing the overexpression rate of 39%and 28% in malignant and benign samples, respectively. These data were also quite concordant with the clinically available immunohistochemistry reports of the same samples studied in this study. Importantly, overexpression of EpCAM and c-myc was significantly associated and showed an agreement of 57.3%. This study demonstrated the cooverexpression of EpCAM and c-myc in breast tumours collected from breast cancer patients of the Iranian population. EpCAM and c-myc positive cases were significantly associated with reduced and enhanced risk of ER/PR positivity

  19. Genome sequence of a new Streptomyces coelicolor generalized transducing bacteriophage, ΦCAM. (United States)

    Monson, Rita; Salmond, George P C


    Streptomyces coelicolor is a model system for the study of Streptomyces, a genus of bacteria responsible for the production of many clinically important antibiotics. Here we report the genome sequence of ΦCAM, a new S. coelicolor generalized transducing bacteriophage, isolated from a soil sample originating from Lincolnshire, United Kingdom. Many open reading frames within ΦCAM shared high levels of similarity to a prophage from Salinispora tropica and a putative prophage in Streptomyces sp. strain C.

  20. CAM within a field force of countervailing powers: The case of Portugal. (United States)

    Almeida, Joana; Gabe, Jonathan


    This paper examines the extent to which the position of the medical profession and the state towards complementary and alternative medicine (CAM) practitioners has changed since the late 1990s, taking Portugal as a case study. Using Light's concept of countervailing powers, we consider the alliances, interests, rhetoric and degrees of control between these three actors over time, focussing particularly on the extent to which CAM practitioners have acted as a countervailing force in their relationship with the medical profession and the state. It also brings to the fore the position of supra-state agencies concerning CAM regulation. A critical discourse analysis was conducted on data derived from a systematic search of information dating from the late 1990s up to 2015. Our analysis suggests that CAM has emerged as an active player and a countervailing power in that it has had significant influence on the process of state policy-making. The medical profession, in turn, has moved from rejecting to 'incorporating' CAM, while the state has acted as a 'broker', trying to accommodate the demands and preferences of both actors while simultaneously demonstrating its power and autonomy in shaping health policy. In sum, the history of countermoves of CAM, the medical profession and the state in recasting power relations regarding CAM regulation in Portugal has highlighted the explanatory value of Light's countervailing power theory and the need to move away from a professional dominance and corporatist approach, in which CAM has simply been seen as subjugated to the power of the medical profession and the state.

  1. Cognitive interviews guide design of a new CAM patient expectations questionnaire


    Sherman, Karen J.; Eaves, Emery R; Ritenbaugh, Cheryl; Hsu, Clarissa; Cherkin, Daniel C; Turner, Judith A


    Background No consistent relationship exists between pre-treatment expectations and therapeutic benefit from various complementary and alternative medicine (CAM) therapies in clinical trials. However, many different expectancy measures have been used in those studies, with no validated questionnaires clearly focused on CAM and pain. We undertook cognitive interviews as part of a process to develop and validate such a questionnaire. Methods We reviewed questions about expectations of benefits ...

  2. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko


    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  3. CanariCam/GTC observations of (99942) Apophis

    CERN Document Server

    Licandro, J; Alvarez, C; Alí-Lagoa, V; Delbò, M


    The potentially hazardous asteroid (PHA) (99942) Apophis is one of the most remarkable near-Earth asteroids (NEA) in terms of impact hazard. A good determination of its surface thermal inertia is very important in order to evaluate the Yarkovsky effect on its orbital evolution. We present thermal infrared observations obtained on January 29, 2013, with CanariCam mid-infrared camera/spectrograph attached to the Gran Telescopio CANARIAS (GTC, Roque de los Muchachos Observatory, La Palma, Spain) using the Si2-8.7, Si6-12.5, and Q1-17.65 filters with the aim of deriving Apophis' diameter ($D$), geometric albedo ($p_V$), and thermal inertia ($\\Gamma$). We performed a detailed thermophysical model analysis of the GTC data combined with previously published thermal data obtained using Herschel Space Observatory PACS instrument at 70, 100, and 160 $\\mu$m.The thermophysical model fit of the data favors low surface roughness solutions (within a range of roughness slope angles $rms$ between 0.1 and 0.5), and constrains ...

  4. The Systemic Theory of Living Systems and Relevance to CAM

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    José A. Olalde Rangel


    Full Text Available The Systemic Theory of Living Systems is being published in several parts in eCAM. The theory is axiomatic. It originates from the phenomenological idea that physiological health is based on three factors: integrity of its structure or organization, O, functional organic energy reserve, E, and level of active biological intelligence, I. From the theory is derived a treatment strategy called Systemic Medicine (SM. This is based on identifying and prescribing phytomedicines and/or other medications that strengthen each factor. Energy-stimulating phytomedicines increase available energy and decrease total entropy of an open biological system by providing negative entropy. The same occurs with phytomedicines that act as biological intelligence modulators. They should be used as the first line of treatment in all ailments, since all pathologies, by definition, imply a higher than normal organic entropy. SM postulates that the state of health, H, of an individual, is effectively equal to the product of the strength of each factor H = O × E × I. SM observes that when all three factors are brought back to ideal levels, patients' conditions begin the recovery to normal health.

  5. SuprimeCam Observation of Sporadic Meteors during Perseids 2004

    CERN Document Server

    Iye, M; Yanagisawa, M; Ebizuka, N; Ohnishi, K; Hirose, C; Asami, N; Komiyama, Yu; Furusawa, H


    We report the serendipitous findings of 13 faint meteors and 44 artificial space objects by Subaru SuprimeCam imaging observations during 11-16 August 2004. The meteors, at about 100km altitude, and artificial satellites/debris in orbit, at 500km altitude or higher, were clearly discriminated by their apparent defocused image sizes. CCD photometry of the 13 meteors, including 1 Perseid, 1 Aquarid, and 11 sporadic meteors, was performed. We defined a peak video-rate magnitude by comparing the integrated photon counts from the brightest portion of the track traversed within 33ms to those from a 0-mag star during the same time duration. This definition gives magnitudes in the range 4.0< V_{vr} <6.4 and 4.1< I_{vr}<5.9 for these 13 meteors. The corresponding magnitude for virtual naked-eye observers could be somewhat fainter especially for the V-band observation, in which the [OI] 5577 line lasting about 1 sec as an afterglow could contribute to the integrated flux of the present 5-10 min CCD exposure...

  6. Enterococcus faecalis phosphomevalonate kinase


    Doun, Stephanie S.; Burgner, John W.; Briggs, Scott D.; Rodwell, Victor W.


    The six enzymes of the mevalonate pathway of isopentenyl diphosphate biosynthesis represent potential for addressing a pressing human health concern, the development of antibiotics against resistant strains of the Gram-positive streptococci. We previously characterized the first four of the mevalonate pathway enzymes of Enterococcus faecalis, and here characterize the fifth, phosphomevalonate kinase (E.C. E. faecalis genomic DNA and the polymerase chain reaction were used to clone D...

  7. Oncoprotein protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Karin, Michael (San Diego, CA); Hibi, Masahiko (San Diego, CA); Lin, Anning (La Jolla, CA); Davis, Roger (Princeton, MA); Derijard, Benoit (Shrewsbury, MA)


    An isolated polypeptide (JNK) characterized by having a molecular weight of 46kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  8. Understanding dental CAD/CAM for restorations--accuracy from a mechanical engineering viewpoint. (United States)

    Tapie, Laurent; Lebon, Nicolas; Mawussi, Bernardin; Fron-Chabouis, Hélène; Duret, Francois; Attal, Jean-Pierre


    As is the case in the field of medicine, as well as in most areas of daily life, digital technology is increasingly being introduced into dental practice. Computer-aided design/ computer-aided manufacturing (CAD/CAM) solutions are available not only for chairside practice but also for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental practice can be considered as the handling of devices and software processing for the almost automatic design and creation of dental restorations. However, dentists who want to use dental CAD/CAM systems often do not have enough information to understand the variations offered by such technology practice. Knowledge of the random and systematic errors in accuracy with CAD/CAM systems can help to achieve successful restorations with this technology, and help with the purchasing of a CAD/CAM system that meets the clinical needs of restoration. This article provides a mechanical engineering viewpoint of the accuracy of CAD/ CAM systems, to help dentists understand the impact of this technology on restoration accuracy.

  9. Complementing a Rural Pharmacy Course with CAM: Reflections from a Decade of Experience

    Directory of Open Access Journals (Sweden)

    Maree Simpson


    Full Text Available Substantial complementary medicines (CAM use is reported worldwide. Australian consumers use CAM for health maintenance, minor self-limiting disease states, and also for chronic conditions. The increasing use of CAM has required pharmacists to become increasingly more knowledgeable about CAM and the ethics of CAM recommendation. When the first Australian non-metropolitan pharmacy program was started at Charles Sturt University, in 1997, it was decided to incorporate two innovative courses to assist rurally educated students to engage with health consumers who expect pharmacists to be able to assist them with CAM. This discussion traces and reflects on the development, implementation and current situation of the Complementary Medicines for Pharmacy course. Over time, this course has evolved from a final year elective with a focus on familiarization to a mandated course with a phytomedicine focus to an integrated topic in final year with a focus on evidence, quality of evidence and professional decision-making demonstrated in a reflective professional portfolio. Of potentially greater importance, however, has been the introduction of complementary medicines as a topic in every year of the course with the goal of facilitating effective professional engagement with health consumers.

  10. Mutation in the sixth immunoglobulin domain of L1CAM is associated with migrational brain anomalies (United States)

    Shieh, Christine; Moser, Franklin; Graham, John M.; Watiker, Valerie


    Objective: To describe the phenotype of a patient with classical features of X-linked L1 syndrome associated with novel brain malformations. Methods: Diagnostic analysis included physical and dysmorphology examinations, MRI of the brain, and exome sequencing of the family trio. Results: We report a 2.5-year-old boy with developmental delay, dysmorphic facies, and adducted thumbs. MRI of the brain showed a truncated corpus callosum and periventricular heterotopias associated with polymicrogyria (PMG). Variant segregation analysis with exome sequencing discovered a novel maternally derived hemizygous variant in exon 14 of the L1CAM gene (c.1759 G>C; p.G587R). Conclusions: This novel L1CAM mutation was located in the protein's sixth immunoglobin domain and involved glycine-587, a key residue in the structure of L1CAM because of its interactions with lysine-606, which indicates that any mutation at this site would likely affect the secondary structure and function of the protein. The replacement of the small nonpolar glycine residue with a large basic arginine would have an even more dramatic result. The presentation of periventricular nodular heterotopias with overlying PMG is very uncommon, and its association with L1CAM may provide insight into other similar cases. Furthermore, this presentation indicates the important role that L1CAM plays in neuronal migration and brain development and extends the phenotype associated with L1CAM-associated disorders. PMID:27066571

  11. Analysis of gene sequences indicates that quantity not quality of chloroplast small HSPs improves thermotolerance in C4 and CAM plants. (United States)

    Shakeel, Samina N; Ul Haq, Noor; Heckathorn, Scott; Luthe, D S


    Chloroplast-localized small heat-shock proteins (Cp-sHSP) protect Photosystem II and thylakoid membranes during heat and other stresses, and Cp-sHSP production levels are related to plant thermotolerance. However, to date, a paucity of Cp-sHSP sequences from C4 or CAM species, or from other extremely heat-tolerant species, has precluded an examination to determine if Cp-sHSP genes or proteins might differ among plants with photosynthetic pathways or between heat-sensitive and heat-tolerant species. To investigate this, we isolated and characterized novel Cp-sHSP genes in four plant species: two moderately heat-tolerant C4 species, Spartina alterniflora (monocot) and Amaranthus retroflexus (eudicot), and two very heat-tolerant CAM species, Agave americana (monocot) and Ferocactus wislizenii (eudicot) (respective genes: SasHSP27.12, ArsHSP26.43, AasHSP26.85 and FwsHSP27.52) by PCR-based genome walking and cDNA RACE. Analysis of these Cp-sHSPs has confirmed the presence of conserved domains common to previously examined species. As expected, the transit peptide was found to be the most variable part of these proteins. Promoter analysis of these genes revealed differences in CAM versus C3 and C4 species that were independent of a general difference between monocots and eudicots observed for the entire protein. Heat-induced gene and protein expression indicated that Cp-sHSP protein levels were correlated with thermotolerance of photosynthetic electron transport, and that in most cases protein and transcript levels were correlated. Thus, available evidence indicates little variation in the amino acid sequence of Cp-sHSP mature proteins between heat-sensitive and -tolerant species, but that variation in Cp-sHSP protein production is related to heat tolerance or photosynthetic pathway (CAM vs. C3 and C4) and is driven by promoter differences. Key message We isolated and characterized four novel Cp-sHSP genes with promoters from wild plants, analysis has shown qualitative

  12. Overexpression of Fyn tyrosine kinase causes abnormal development of primary sensory neurons in Xenopus laevis embryos. (United States)

    Saito, R; Fujita, N; Nagata, S


    The expression and function of the Src family protein tyrosine kinase Fyn in Xenopus laevis embryos have been examined. In situ hybridization analysis demonstrated nervous system-specific expression of Fyn mRNA in tail-bud embryos. However, a class of primary sensory neurons; that is, Rohon-Beard (RB) neurons, which is positive for immunoglobulin superfamily cell adhesion molecules (CAM), neural cell adhesion molecule (N-CAM) and contactin, is devoid of Fyn expression. Injection of Fyn mRNA into one of the blastomeres at the 2-cell stage led to overexpression of Fyn in the injected half of the tail-bud embryos. Immunolabeling of the embryos with anti-HNK-1 antibody revealed that the peripheral axons of RB neurons were partially misguided and bound to each other to form abnormal subcutaneous fascicles. Similar abnormality was induced by injection of the Fyn overexpression vector. The incidence of abnormality appeared dose-dependent, being 68-92% of the injected embryos at 50-400 pg of mRNA. Co-injection of the contactin antisense vector depleted contactin mRNA accumulation without affecting Fyn overexpression and reduced the incidence of the abnormal RB-cell phenotype. However, the N-CAM antisense was ineffective in reducing this abnormality. These results suggest that Fyn can modify signals regulating axonal guidance or fasciculation in the developing X. laevis nervous system and that contactin may affect this action of Fyn.

  13. Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment. (United States)

    Filomeni, Giuseppe; Cardaci, Simone; Da Costa Ferreira, Ana Maria; Rotilio, Giuseppe; Ciriolo, Maria Rosa


    We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N']copper(II), named [Cu(isaepy)(2)], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38(MAPK) (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38(MAPK) and p53. Similarly, reverse genetics of p38(MAPK) yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38(MAPK)/p53. Fuel supplies counteracted [Cu(isaepy)(2)]-induced apoptosis and AMPK/p38(MAPK)/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)(2)] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38(MAPK)/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)(2)] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)(2)] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment.

  14. Optimized fluorescence diagnosis of tumors by comparing five-ALA-induced xenofluorescence and autofluorescence intensities of a murine tumor/nontumor tissue system cultivated on the CAM (United States)

    Stroebele, Simone; Dressler, Cathrin; Ismail, M. Samy; Daskalaki, Anita; Philipp, Carsten M.; Berlien, Hans-Peter; Weitzel, H.; Liebsch, M.; Spielmann, H.


    The in vivo model of the chorioallantoic membrane of fertilized chicken embryos (CAM) was employed for studying the fluorescence characteristics of tumor tissue in comparison with non tumorous tissue. Tumors were grown from the murine fibrosarcoma cell line SSK II and murine 3T3 fibroblasts (clone A31) were used for cultivating non tumorous tissue. Autofluorescence and xenofluorescence intensities induced by 5-aminolaevulinic acid (5-ALA) were compared. Exogenous administration of 5-ALA, an early precursor in haem synthesis, induces accumulation of endogenous photoactive porphyrins, in particular protoporphyrin IX (PpIX). Fluorescence investigations were performed after 3-4d of incubation, when the tissues had reached macroscopically three dimensional stages of growth. Fluorescences were excited with a HBO-X 100 W lamp (Carl Zeiss) at a wavelength (lambda) equals 405 plus or minus 5 nm. Emissions were detected in the spectral range above 630 nm and visualized by real time digital image processing (Argus 10, HAMAMATSU) using an ICCD camera (HAMAMATSU). After administration of 0.4 mmolar 5-ALA solution to the CAM inoculated tissues the SSK II tumors exhibited higher fluorescence intensities than the 3T3 non tumorous tissues. Autofluorescence intensities of both types of tissues were not distinguishable. Furthermore, the effects of several biochemicals on the xenofluorescence intensities of the fibrosarcoma and fibroblast tissues were investigated.

  15. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)


    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  16. Diacylglycerol Kinase Inhibition and Vascular Function. (United States)

    Choi, Hyehun; Allahdadi, Kyan J; Tostes, Rita C A; Webb, R Clinton


    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structural features. These diverse isoforms of DGK are considered to activate distinct cellular functions according to extracellular stimuli. Each DGK isoform is thought to play various roles inside the cell, depending on its subcellular localization (nuclear, ER, Golgi complex or cytoplasm). In vascular smooth muscle, vasoconstrictors such as angiotensin II, endothelin-1 and norepinephrine stimulate contraction by increasing inositol trisphosphate (IP(3)), calcium, DG and PKC activity. Inhibition of DGK could increase DG availability and decrease PA levels, as well as alter intracellular responses, including calcium-mediated and PKC-mediated vascular contraction. The purpose of this review is to demonstrate a role of DGK in vascular function. Selective inhibition of DGK isoforms may represent a novel therapeutic approach in vascular dysfunction.

  17. Comparative evaluation of feldespatic crowns fitness made from additional silicon impression and gypsum cast by CAD/CAM

    Directory of Open Access Journals (Sweden)

    Faramarz Zakavi


    Full Text Available Background and Aims: Marginal fit is one of the key factors in the success of fixed restoration. The aim of this study was to evaluate the fitness of feldespatic crowns made from additional silicon impression and gypsum cast by CAD/CAM.   Materials and Methods: 10 intact extracted upper premolar teeth were used for this experimental study. After preparation of the mounted teeth with radial shoulder finish line, 2 Vita Mark II feldespatic CAD/CAM machined crowns were fabricated for each tooth (one from scanning the additional silicone impression of the prepared tooth and the other one from the plaster model. Marginal gap of each crown was measured using SEM in two points on the mesial and 2 points on the buccal surface. Data were analyzed using Paired t-test with SPSS version 17 software (P<0.05.   Results: The mean of marginal gaps in crowns fabricated from additional silicone and model plaster were (155.13±37.11 and (130.18±12.35, respectively. However, no significant difference emerged between marginal gaps of the two methods (P=0.055. Also, the mean of marginal gaps in crowns fabricated from additional silicone and model plaster was higher in mesial (157.82±44.41 compared to buccal (127.50±24.26 region (P=0.003.   Conclusion: Marginal fit was not significantly differen ce between crown s made of the plaster casts and silicone molds and both methods showed the same results .

  18. EpCAM Aptamer-siRNA Chimera Targets and Regress Epithelial Cancer.

    Directory of Open Access Journals (Sweden)

    Nithya Subramanian

    Full Text Available Epithelial cell adhesion molecule (EpCAM, a cancer stem cell (CSC marker is over expressed in epithelial cancers and in retinoblastoma (RB. We fabricated an EpCAM targeting aptamer-siRNA chimera and investigated its anti-tumor property and EpCAM intracellular domain (EpICD mediated signaling in epithelial cancer. The anti-tumor efficacy of EpCAM aptamer-siEpCAM chimera (EpApt-siEp was evaluated by qPCR, northern and Western blotting in WERI-Rb1- RB cell line, primary RB tumor cells and in MCF7- breast cancer cell line. Anti-tumor activity of EpApt-siEp was studied in vivo using epithelial cancer (MCF7 mice xenograft model. The mechanism and pathways involved in the anti-tumor activity was further studied using protein arrays and qPCR. EpApt-siEp chimera was processed in vitro by dicer enzyme. Treatment of the WERI-Rb1 and MCF7 cells with EpApt-siEp revealed statistically significant down regulation of EpCAM expression (P<0.005 and concomitant reduction in cellular proliferation. In primary RB cells cultured from RB tumors, EpApt-siEp silenced EpCAM, significantly inhibited (P<0.01 cell proliferation and induced cytotoxicity. Knockdown of EpICD expressed in RB primary tumors led to repression of pluripotency markers, SOX2, OCT4, NANOG, and CD133. In vivo studies showed complete tumor growth regression without any toxicity in animals (P<0.001 and tumor tissues showed significant downregulation (P<0.05 of EpCAM, MRP1, ABCG2, stathmin, survivin and upregulation of ATM (P<0.05 leading to apoptosis by intrinsic pathway with minor alteration in cytokines. Our results revealed that EpApt-siEp potentially eradicated EpCAM positive cancer cells through CSC marker suppression and apoptosis, while sparing normal EpCAM negative adjacent cells.

  19. Kinase inhibitors: a new class of antirheumatic drugs

    Directory of Open Access Journals (Sweden)

    Kyttaris VC


    Full Text Available Vasileios C KyttarisDivision of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USAAbstract: The outlook for patients with rheumatoid arthritis has improved significantly over the last three decades with the use of disease-modifying antirheumatic drugs. However, despite the use of methotrexate, cytokine inhibitors, and molecules targeting T and B cells, a percentage of patients do not respond or lose their response over time. The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. In the past decade, small molecules targeting several kinases, such as p38 MAPK, Syk, and JAK have been developed. Several p38 MAPK inhibitors proved ineffective in treating rheumatoid arthritis. The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. Tofacitinib, a JAK1/3 inhibitor, was shown to be efficacious in two Phase III trials, while VX-509, a JAK3 inhibitor, showed promising results in a Phase II trial. Fostamatinib and tofacitinib were associated with increased rates of infection, elevation of liver enzymes, and neutropenia. Moreover, fostamatinib caused elevations of blood pressure and diarrhea, while tofacitinib was associated with an increase in creatinine and elevation of lipid levels.Keywords: rheumatoid arthritis, kinase inhibitors, mitogen-activated phosphokinase p38, spleen tyrosine kinase, Janus kinases

  20. Advances in computer-aided engineering: CAD/CAM-research at Delft University of Technology. Report of the VF-project CAD/CAM 1989-1994

    NARCIS (Netherlands)


    This book contains a collection of articles describing on-going CAD/CAM-research at several engineering faculties at Delft University of Technology. Two main themes covered in this book are 'Conceptual design of complex products' and 'Product modelling and product data exchange'.

  1. Fission yeast Cdk7 controls gene expression through both its CAK and C-terminal domain kinase activities. (United States)

    Devos, Maxime; Mommaerts, Elise; Migeot, Valerie; van Bakel, Harm; Hermand, Damien


    Cyclin-dependent kinase (Cdk) activation and RNA polymerase II transcription are linked by the Cdk7 kinase, which phosphorylates Cdks as a trimeric Cdk-activating kinase (CAK) complex, and serine 5 within the polymerase II (Pol II) C-terminal domain (CTD) as transcription factor TFIIH-bound CAK. However, the physiological importance of integrating these processes is not understood. Besides the Cdk7 ortholog Mcs6, fission yeast possesses a second CAK, Csk1. The two enzymes have been proposed to act redundantly to activate Cdc2. Using an improved analogue-sensitive Mcs6-as kinase, we show that Csk1 is not a relevant CAK for Cdc2. Further analyses revealed that Csk1 lacks a 20-amino-acid sequence required for its budding yeast counterpart, Cak1, to bind Cdc2. Transcriptome profiling of the Mcs6-as mutant in the presence or absence of the budding yeast Cak1 kinase, in order to uncouple the CTD kinase and CAK activities of Mcs6, revealed an unanticipated role of the CAK branch in the transcriptional control of the cluster of genes implicated in ribosome biogenesis and cell growth. The analysis of a Cdc2 CAK site mutant confirmed these data. Our data show that the Cdk7 kinase modulates transcription through its well-described RNA Pol II CTD kinase activity and also through the Cdc2-activating kinase activity.

  2. Additive CAD/CAM process for dental prostheses. (United States)

    Silva, Nelson R F A; Witek, Lukasz; Coelho, Paulo G; Thompson, Van P; Rekow, Elizabeth D; Smay, Jim


    This article describes the evolution of a computer-aided design/computer-aided manufacturing (CAD/CAM) process where ceramic paste is deposited in a layer-by-layer sequence using a computer numerical control machine to build up core and fixed partial denture (FPD) structures (robocasting). Al(2)O(3) (alumina) or ZrO(2) (Y-TZP) are blended into a 0.8% aqueous solution of ammonium polyacrylate in a ratio of approximately 1:1 solid:liquid. A viscosifying agent, hydroxypropyl methylcellulose, is added to a concentration of 1% in the liquid phase, and then a counter polyelectrolyte is added to gel the slurry. There are two methods for robocasting crown structures (cores or FPD framework). One is for the core to be printed using zirconia ink without support materials, in which the stereolithography (STL) file is inverted (occlusal surface resting on a flat substrate) and built. The second method uses a fugitive material composed of carbon black codeposited with the ceramic material. During the sintering process, the carbon black is removed. There are two key challenges to successful printing of ceramic crowns by the robocasting technique. First is the development of suitable materials for printing, and second is the design of printing patterns for assembly of the complex geometry required for a dental restoration. Robocasting has room for improvement. Current development involves enhancing the automation of nozzle alignment for accurate support material deposition and better fidelity of the occlusal surface. An accompanying effort involves calculation of optimal support structures to yield the best geometric results and minimal material usage.

  3. From Artisanal to CAD-CAM Blocks: State of the Art of Indirect Composites. (United States)

    Mainjot, A K; Dupont, N M; Oudkerk, J C; Dewael, T Y; Sadoun, M J


    Indirect composites have been undergoing an impressive evolution over the last few years. Specifically, recent developments in computer-aided design-computer-aided manufacturing (CAD-CAM) blocks have been associated with new polymerization modes, innovative microstructures, and different compositions. All these recent breakthroughs have introduced important gaps among the properties of the different materials. This critical state-of-the-art review analyzes the strengths and weaknesses of the different varieties of CAD-CAM composite materials, especially as compared with direct and artisanal indirect composites. Indeed, new polymerization modes used for CAD-CAM blocks-especially high temperature (HT) and, most of all, high temperature-high pressure (HT-HP)-are shown to significantly increase the degree of conversion in comparison with light-cured composites. Industrial processes also allow for the augmentation of the filler content and for the realization of more homogeneous structures with fewer flaws. In addition, due to their increased degree of conversion and their different monomer composition, some CAD-CAM blocks are more advantageous in terms of toxicity and monomer release. Finally, materials with a polymer-infiltrated ceramic network (PICN) microstructure exhibit higher flexural strength and a more favorable elasticity modulus than materials with a dispersed filler microstructure. Consequently, some high-performance composite CAD-CAM blocks-particularly experimental PICNs-can now rival glass-ceramics, such as lithium-disilicate glass-ceramics, for use as bonded partial restorations and crowns on natural teeth and implants. Being able to be manufactured in very low thicknesses, they offer the possibility of developing innovative minimally invasive treatment strategies, such as "no prep" treatment of worn dentition. Current issues are related to the study of bonding and wear properties of the different varieties of CAD-CAM composites. There is also a crucial

  4. Information management and complementary alternative medicine: the anatomy of information about CAMs through PubMed. (United States)

    Corrao, Salvatore; Argano, Christiano; Colomba, Daniela; Ippolito, Calogero; Gargano, Vincenzo; Arcoraci, Vincenzo; Licata, Giuseppe


    In recent years, there has been a growing interest about complementary and alternative medicine (CAM), and the use of CAM interventions has become more common among people. For these reasons, health professionals must be able to effectively manage information in this field of knowledge according to an evidence-based point of view. This study assessed the anatomy of the available information about CAMs using PubMed, to give practical instructions to manage information in this field. We also analyzed the anatomy of information according to each alternative medicine branch, narrow and broad search methods, subset filters for indexed-for-Medline and non-indexed citations, and different publication types including randomized controlled trials (RCTs) and meta-analyses. Our results demonstrated that the use of CAMs subset (supplied by PubMed search engine) leads to a great number of citations determining an information overload. Our data reveal that it would be more useful to search for the CAM separately, identifying specific items and study design. Moreover, we found the largest number of randomized clinical trials and meta-analyses related to herbal medicine and acupuncture, neither RCTs nor meta-analyses were available for bach and flower remedies, auriculoacupuncture, iridology, and pranotherapy. For the first time, our study gives a comprehensive view of the anatomy of information regarding CAMs and each branch of them. We suggest a methodological approach to face with searching information about this emerging issue from an evidence-based point of view. Finally, our data pointed out some "grey zones" since neither RCTs nor meta-analyses were available for some CAMs.

  5. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana. (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice


    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate.

  6. Localisation of Protein Kinase C in Apoptosis and Neurite Outgrowth


    Schultz, Anna


    Protein kinase C (PKC) is a family of serine/threonine kinases, which are subgrouped into classical (a, bI, bII, g), novel (d, e, h, q) and atypical (z, i/l) isoforms. One major aim of this thesis work was to investigate if altered levels of PKC isoforms influence the apoptotic responses of malignant cell-lines. We show that overexpression of PKCd or PKCq renders SK-N-BE(2) neuroblastoma cells sensitive to apoptosis induced by phorbol esters or C2-ceramide. Moreover, overexpression of PKCa, P...

  7. The role of complementary and alternative medicine (CAM in Germany – A focus group study of GPs

    Directory of Open Access Journals (Sweden)

    Rosemann Thomas


    Full Text Available Abstract Background There has been a marked increase in the use of complementary and alternative medicine (CAM in recent years worldwide. In Germany, apart from 'Heilpraktiker' (= state-licensed, non-medical CAM practitioners, some general practitioners (GPs provide CAM in their practices. This paper aims to explore the attitudes of GPs about the role of CAM in Germany, in relation to the healthcare system, quality of care, medical education and research. Furthermore, experiences of GPs integrating CAM in their daily practice were explored. Methods Using a qualitative methodological approach 3 focus groups with a convenience sample of 17 GPs were conducted. The discussions were transcribed verbatim and analysed using qualitative content analysis. Results The majority of the participating GPs had integrated one or more CAM therapies into their every-day practice. Four key themes were identified based on the topics covered in the focus groups: the role of CAM within the German healthcare system, quality of care, education and research. Within the theme 'role of CAM within the healthcare system' there were five categories: integration of CAM, CAM in the Statutory Health Insurance, modernisation of the Statutory Health Insurance Act, individual healthcare services and 'Heilpraktiker'. Regarding quality of care there were two broad groups of GPs: those who thought patients would benefit from standardizing CAM and those who feared that quality control would interfere with the individual approach of CAM. The main issues identified relating to research and education were the need for the development of alternative research strategies and the low quality of existing CAM education respectively. Conclusion The majority of the participating GPs considered CAM as a reasonable complementary approach within primary care. The study increased our understanding of GPs attitudes about the role of CAM within the German healthcare system and the use of

  8. Commitment to the CD4 lineage mediated by extracellular signal-related kinase mitogen-activated protein kinase and lck signaling. (United States)

    Sharp, L L; Hedrick, S M


    The development of T cells results in a concordance between the specificity of the TCR for MHC class I and class II molecules and the expression of CD8 and CD4 coreceptors. Based on analogy to simple metazoan models of organ development and lineage commitment, we sought to determine whether extracellular signal-related kinase (Erk) mitogen-activated protein (MAP) kinase pathway signaling acts as an inductive signal for the CD4 lineage. Here, we show that, by altering the intracellular signaling involving the Erk/MAP kinase pathway, T cells with specificity for MHC class I can be diverted to express CD4, and, conversely, T cells with specificity for MHC class II can be diverted to express CD8. Furthermore, we find that activation of the src-family tyrosine kinase, p56lck is an upstream mediator of lineage commitment. These results suggest a simple mechanism for lineage commitment in T cell development.

  9. Is complementary and alternative medicine (CAM cost-effective? a systematic review

    Directory of Open Access Journals (Sweden)

    Caspi Opher


    Full Text Available Abstract Background Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations. Methods The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding. Results A total of 56 economic evaluations (39 full evaluations of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36% studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with

  10. Design and fabrication of complete dentures using CAD/CAM technology (United States)

    Han, Weili; Li, Yanfeng; Zhang, Yue; lv, Yuan; Zhang, Ying; Hu, Ping; Liu, Huanyue; Ma, Zheng; Shen, Yi


    Abstract The aim of the study was to test the feasibility of using commercially available computer-aided design and computer-aided manufacturing (CAD/CAM) technology including 3Shape Dental System 2013 trial version, WIELAND V2.0.049 and WIELAND ZENOTEC T1 milling machine to design and fabricate complete dentures. The modeling process of full denture available in the trial version of 3Shape Dental System 2013 was used to design virtual complete dentures on the basis of 3-dimensional (3D) digital edentulous models generated from the physical models. The virtual complete dentures designed were exported to CAM software of WIELAND V2.0.049. A WIELAND ZENOTEC T1 milling machine controlled by the CAM software was used to fabricate physical dentitions and baseplates by milling acrylic resin composite plates. The physical dentitions were bonded to the corresponding baseplates to form the maxillary and mandibular complete dentures. Virtual complete dentures were successfully designed using the software through several steps including generation of 3D digital edentulous models, model analysis, arrangement of artificial teeth, trimming relief area, and occlusal adjustment. Physical dentitions and baseplates were successfully fabricated according to the designed virtual complete dentures using milling machine controlled by a CAM software. Bonding physical dentitions to the corresponding baseplates generated the final physical complete dentures. Our study demonstrated that complete dentures could be successfully designed and fabricated by using CAD/CAM. PMID:28072686

  11. Management of CAD/CAM information: Key to improved manufacturing productivity (United States)

    Fulton, R. E.; Brainin, J.


    A key element to improved industry productivity is effective management of CAD/CAM information. To stimulate advancements in this area, a joint NASA/Navy/Industry project designated Integrated Programs for Aerospace-Vehicle Design (IPAD) is underway with the goal of raising aerospace industry productivity through advancement of technology to integrate and manage information involved in the design and manufacturing process. The project complements traditional NASA/DOD research to develop aerospace design technology and the Air Force's Integrated Computer-Aided Manufacturing (ICAM) program to advance CAM technology. IPAD research is guided by an Industry Technical Advisory Board (ITAB) composed of over 100 repesentatives from aerospace and computer companies. The IPAD accomplishments to date in development of requirements and prototype software for various levels of company-wide CAD/CAM data management are summarized and plans for development of technology for management of distributed CAD/CAM data and information required to control future knowledge-based CAD/CAM systems are discussed.

  12. Tilting double-prism scanner driven by cam-based mechanism. (United States)

    Li, Anhu; Yi, Wanli; Sun, Wansong; Liu, Liren


    A pair of orthogonal tilting prisms has been explored in our previous work to perform the orientation and position tracking function with tracking accuracy better than submicroradian order. Crucial to the function implementation, however, is the real-time nonlinear control of the tilting angles of double prisms for tracking a given target trajectory. In previous papers [Proc. SPIE5892, 1-5 (2005).PSISDG0277-786X; Appl. Opt.45, 8063 (2006).PSISDG0277-786X; Proc. SPIE6709, 41 (2007).PSISDG0277-786X; Appl. Opt.51, 356 (2011).10.1364/AO.51.000356APOPAI1559-128X; Appl. Opt.53, 3712 (2014).10.1364/AO.53.003712APOPAI1559-128X], a new driving method by a cam-based mechanism, which can transfer the control problem to the design of corresponding cam configuration, is investigated. The design process of a cam-based mechanism is explained from the mapping relation between the tilting angles of a prism and the configuration curve of a corresponding cam. Based on the designed cam-based mechanism, a tracking error less than 0.375% is depicted between the tracking trajectory and the original one. Moreover, the dynamic characteristic of the tracking mechanism is discussed in detail as well as the impacts of different tilting speeds on the tracking trajectory. The proposed tracking mechanism of a tilting double-prism scanner can create a new avenue for passively tracking a given target.

  13. Expression of EpCam and Villin in Barrett’s Esophagus and in Gastric Cardia

    Directory of Open Access Journals (Sweden)

    Mario Anders


    Full Text Available In the current study we aimed to clarify the potential of EpCAM and villin as in vivo biomarkers for both Barrett esophagus (BE-associated neoplasia and BE versus cardiac mucosa. Immunohistochemical staining in BE with various degrees of intraepithelial neoplasia (IN, Barrett carcinoma (BC and in normal cardiac mucosa (CM revealed a lack of EpCam and villin in squamous esophageal epithelium. All specimens of IN and BC showed EpCam with varying staining intensities. In 57% of CM samples a weak signal was detected; the remainder displayed strong EpCam expression. Villin was found in 97% of BE specimens and in all those with IN; 37% of BC and 75% of CM specimens were also positive. We conclude that expression of EpCam and villin differs only between squamous epithelium and BE. Determination of these proteins does not allow discrimination between different degrees of neoplasia or between esophageal intestinal metaplasia and cardiac mucosa.

  14. Treatment Expectations for CAM Interventions in Pediatric Chronic Pain Patients and their Parents

    Directory of Open Access Journals (Sweden)

    Jennie C. I. Tsao


    Full Text Available Patient expectations regarding complementary and alternative medicine (CAM interventions have important implications for treatment adherence, attrition and clinical outcome. Little is known, however, about parent and child treatment expectations regarding CAM approaches for pediatric chronic pain problems. The present study examined ratings of the expected benefits of CAM (i.e. hypnosis, massage, acupuncture, yoga and relaxation and conventional medicine (i.e. medications, surgery interventions in 45 children (32 girls; mean age = 13.8 years ± 2.5 and parents (39 mothers presenting for treatment at a specialty clinic for chronic pediatric pain. Among children, medications and relaxation were expected to be significantly more helpful than the remaining approaches (P < 0.01. However, children expected the three lowest rated interventions, acupuncture, surgery and hypnosis, to be of equal benefit. Results among parents were similar to those found in children but there were fewer significant differences between ratings of the various interventions. Only surgery was expected by parents to be significantly less helpful than the other approaches (P < 0.01. When parent and child perceptions were compared, parents expected hypnosis, acupuncture and yoga, to be more beneficial than did children, whereas children expected surgery to be more helpful than did parents (P < 0.01. Overall, children expected the benefits of CAM to be fairly low with parents' expectations only somewhat more positive. The current findings suggest that educational efforts directed at enhancing treatment expectations regarding CAM, particularly among children with chronic pain, are warranted.

  15. Engineering task plan for rotary mode core sampling exhausters CAM high radiation interlock

    Energy Technology Data Exchange (ETDEWEB)

    BOGER, R.M.


    The Rotary Mode Core Sampling (RMCS) system is primarily made up of the Rotary Mode Core Sample Trucks (RMCST) and the RMCS Exhausters. During RMCS operations an Exhauster is connected to a tank riser and withdraws gases from the tank dome vapor space at approximately 200 Standard Cubic Feet per Minute (SCFM). The gases are passed through two High Efficiency Particulate Air (HEPA) filters before passing out the exhaust stack to the atmosphere. A Continuous Air Monitor (CAM) monitors the exhaust gases in the exhaust stack for beta particle and gamma radiation. The CAM has a high radiation alarm output and a detector fail alarm output. The CAM alarms are currently connected to the data logger only. The CAM alarms require operator response per procedure LMHC 1998 but no automatic functions are initiated by the CAM alarms. Currently, there are three events that can cause an automatic shut down of the Exhauster. These are, Low Tank Pressure, Highnow Stack Flow and High HEPA Filter Differential Pressure (DP).


    Labronici, Pedro José; Alves, Sergio Delmonte; da Silva, Anselmo Fernandes; Giuberti, Gilberto Ribeiro; de Azevedo Neto, Justino Nóbrega; Mezzalira Penedo, Jorge Luiz


    To analyze anatomical variations of the proximal end of femur that could cause a femoroacetabular impact. Methods: 199 skeletically mature anatomical specimens of femurs were used. The femurs were measured in order to determine the anteversion angle of the femoral neck, neckshaft angle, sphericity of the femoral head at anteroposterior and superoinferior, angle between epiphysis and the anterior femoral neck, angle between epiphysis and the neck at lateral plane, anteroposterior distance at 5mm of the head and neck junction and anteroposterior distance of the neck base. Results: we found that the impact subgroup presented a significantly larger junction diameter of 5mm (p = 0.0001) and cam-head (%) (p= 0.0001), while base-cam (%) (p = 0.0001) showed a significantly smaller diameter than the subgroup without impact. It was identified that cam-head (%) ≤ 80 e base-cam (%) ≤ 73 were identified as the optimal impact points. Conclusion: our study showed that the effect cam, caused by anatomical variations of the proximal femoral end focused the head-neck junction and base of the neck-junction head-neck. These rates can be predictive factors of the impact. PMID:26998462

  17. Phosphorylation of tau by death-associated protein kinase 1 antagonizes the kinase-induced cell apoptosis. (United States)

    Duan, Dong-Xiao; Chai, Gao-Shang; Ni, Zhong-Fei; Hu, Yu; Luo, Yu; Cheng, Xiang-Shu; Chen, Ning-Ning; Wang, Jian-Zhi; Liu, Gong-Ping


    The intracellular accumulation of hyperphosphorylated tau plays a crucial role in neurodegeneration of Alzheimer's disease (AD), but the mechanism is not fully understood. From the observation that tau hyperphosphorylation renders cells more resistant to chemically-induced cell apoptosis, we have proposed that tau-involved apoptotic abortion may be the trigger of neurodegeneration. Here, we further studied whether this phenomenon is also applicable for the cell death induced by constitutively expressed factors, such as death-associated protein kinase 1 (DAPK1). We found that DAPK1 was upregulated and accumulated in the brain of human tau transgenic mice. Overexpression of DAPK1 in HEK293 and N2a cells decreased cell viability with activation of caspase-3, whereas simultaneous expression of tau antagonized DAPK1-induced apoptotic cell death. Expression of DAPK1 induced tau hyperphosphorylation at Thr231, Ser262, and Ser396 with no effects on protein phosphatase 2A, glycogen synthase kinase-3β, protein kinase A, calcium/calmodulin dependent protein kinase II, cell division cycle 2, or cyclin dependent protein kinase 5. The phosphorylation level of microtubule affinity-regulating kinase 2 (MARK2) was increased by expression of DAPK1, but simultaneous downregulation of MARK2 did not affect the DAPK1-induced tau hyperphosphorylation. DAPK1 was co-immunoprecipitated with tau proteins both in vivo and in vitro, and expression of the kinase domain-truncated DAPK1 did not induce tau hyperphosphorylation. These data suggest that tau hyperphosphorylation at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the kinase-induced apoptotic cell death, providing new insights into the tau-involved apoptotic abortion in the course of chronic neurodegeneration.

  18. Specific MAP-kinase blockade protects against renal damage in homozygous TGR(mRen2)27 rats

    NARCIS (Netherlands)

    de Borst, MH; Navis, G; de Boer, RA; Vis, LM; van Gilst, WH; van Goor, H


    Angiotensin II (AngII) plays an important role in renal damage by acting on hemodynamics, cell-growth, proliferation, and fibrosis, mainly by effects on the AngII type 1 (AT,) receptor. The AT, receptor activates several intracellular signaling molecules such as mitogen-activated protein kinases ext

  19. Millora del camí que uneix Can Tintorer amb Molins de Rei


    Canalias Suquet, Ignasi


    El projecte té com a finalitat la millora del camí que uneix la població de Molins de Rei amb el restaurant de Can Tintorer. Aquest camí forma part del parc natural de Collserola i és molt utilitzat per accedir amb cotxe fins al restaurant i a l’hípica del Bosc que hi ha al costat seu; com també per molts usuaris del parc natural ja sigui per passejar-hi a peu, bicicleta o cavall. L’objectiu del projecte és donar solució als problemes que presenta el camí com són passos estrets pe...

  20. Soil diversity and hydration as observed by ChemCam at Gale crater, Mars. (United States)

    Meslin, P-Y; Gasnault, O; Forni, O; Schröder, S; Cousin, A; Berger, G; Clegg, S M; Lasue, J; Maurice, S; Sautter, V; Le Mouélic, S; Wiens, R C; Fabre, C; Goetz, W; Bish, D; Mangold, N; Ehlmann, B; Lanza, N; Harri, A-M; Anderson, R; Rampe, E; McConnochie, T H; Pinet, P; Blaney, D; Léveillé, R; Archer, D; Barraclough, B; Bender, S; Blake, D; Blank, J G; Bridges, N; Clark, B C; DeFlores, L; Delapp, D; Dromart, G; Dyar, M D; Fisk, M; Gondet, B; Grotzinger, J; Herkenhoff, K; Johnson, J; Lacour, J-L; Langevin, Y; Leshin, L; Lewin, E; Madsen, M B; Melikechi, N; Mezzacappa, A; Mischna, M A; Moores, J E; Newsom, H; Ollila, A; Perez, R; Renno, N; Sirven, J-B; Tokar, R; de la Torre, M; d'Uston, L; Vaniman, D; Yingst, A


    The ChemCam instrument, which provides insight into martian soil chemistry at the submillimeter scale, identified two principal soil types along the Curiosity rover traverse: a fine-grained mafic type and a locally derived, coarse-grained felsic type. The mafic soil component is representative of widespread martian soils and is similar in composition to the martian dust. It possesses a ubiquitous hydrogen signature in ChemCam spectra, corresponding to the hydration of the amorphous phases found in the soil by the CheMin instrument. This hydration likely accounts for an important fraction of the global hydration of the surface seen by previous orbital measurements. ChemCam analyses did not reveal any significant exchange of water vapor between the regolith and the atmosphere. These observations provide constraints on the nature of the amorphous phases and their hydration.


    Directory of Open Access Journals (Sweden)



    Full Text Available This paper addresses itself to a portion of a systematic investigation of a very simple intermittent motion mechanism consisting of a single roller crank and a single cam. The mechanism presented in this paper, being continuous contact type, does not have dynamic problems such as sudden jerk experienced in traditional genevamechanism. The cam being the output and the cam radius being a varying quantity, the conventional transmission angle cannot be used. A new rational transmission index is introduced in the present nvestigation. Here transmission index charts are developed as design aids in synthesizing a law of motion ( in general and not just forintermittent motion mechanisms . The variation of transmission index along the motion law curve may be readily seen by superimposing the chosen motion law on the transmission index chart. Appropriate changes may then be made in the motion law as found necessary.

  2. Design Alteration of Motor-Cycle Engine Cam for Pneumatic Operation

    Directory of Open Access Journals (Sweden)

    Jimil M. Shah


    Full Text Available Power produced by pressurized gases/air has been used in many applications since decades. The power produced by that means is pollution free too. Hence substitution of petrol/diesel in engines with compressed air will be a step towards pollution free engine. The 4-stroke IC engine is to be converted into a 2-stroke pneumatic engine. Various design changes in camshaft design were carried out. The valve timing diagram was derived for the same. The cam profile of a double lobed cam as required in the valve timing diagram was designed in Pro-e software and was cut on a wire cut machine. The cam and camshaft were manufactured separately and then assembled.

  3. Production and processing of spinel semi-porous sintered blocks to CAD-CAM with lanthanum-glass infiltration for dental applications; Producao e processamento de blocos sinterizados semi-porosos de espinelio para CAD-CAM com infiltracao de vidro de lantanio para aplicacoes dentarias

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, A.A.C.; Ogasawara, T.; Costa Neto, C.A.; Santos, F.V.C., E-mail: ogasawat@metalmat.ufrj.b [Universidade Federal do Rio de Janeiro (PEMM/COPPE/UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao em Engenharia. Programa de Engenharia Metalurgica e de Materiais


    The objective of this research was to obtain direct synthesis and sintering spinel by using powder mixing method for CAD-CAM ceramics manufacturing. Powders of alumina and magnesia (71.8 wt% Al2O3 and 28.2 wt% MgO) were mixed with 5 wt% of PVA and PEG binders and homogenized using ball mill (12h), then deagglomerated and submitted to uniaxial pressing into discs and plates (54 to 221.96 MPa), followed by isostatic pressing (186.03 MPa) and sintering at 1500 deg C(GrI) , 1600 C(GrII) and 1700 deg C(GrIII). Characterizations: XRD, density and four-point flexural strength and (for GrIII) elasticity modulus and Vickers microhardness. Lanthanum-glass was infiltrated into samples from all three Groups. Conclusions: (1) Plenty success for the pediatrician method; (2) Maximum density achieved for GrIII, best mechanical strength for GrII (compared to that of commercial product), this last one being the most indicated for In-Ceram manufacturing via CAD-CAM route; (3) The flexural strength of GrI might be improved a lot after Lanthanum-glass infiltration. (author)

  4. Management of CAD/CAM information: Key to improved manufacturing productivity (United States)

    Fulton, R. E.; Brainin, J.


    A key element to improved industry productivity is effective management of CAD/CAM information. To stimulate advancements in this area, a joint NASA/Navy/industry project designated Intergrated Programs for Aerospace-Vehicle Design (IPAD) is underway with the goal of raising aerospace industry productivity through advancement of technology to integrate and manage information involved in the design and manufacturing process. The project complements traditional NASA/DOD research to develop aerospace design technology and the Air Force's Integrated Computer-Aided Manufacturing (ICAM) program to advance CAM technology. IPAD research is guided by an Industry Technical Advisory Board (ITAB) composed of over 100 representatives from aerospace and computer companies.

  5. Calibrating the ChemCam LIBS for carbonate minerals on Mars

    Energy Technology Data Exchange (ETDEWEB)

    Wiens, Roger C [Los Alamos National Laboratory; Clegg, Samuel M [Los Alamos National Laboratory; Ollila, Ann M [Los Alamos National Laboratory; Barefield, James E [Los Alamos National Laboratory; Lanza, Nina [Los Alamos National Laboratory; Newsom, Horton E [Los Alamos National Laboratory


    The ChemCam instrument suite on board the NASA Mars Science Laboratory (MSL) rover includes the first LIBS instrument for extraterrestrial applications. Here we examine carbonate minerals in a simulated martian environment using the LIDS technique in order to better understand the in situ signature of these materials on Mars. Both chemical composition and rock type are determined using multivariate analysis (MVA) techniques. Composition is confirmed using scanning electron microscopy (SEM) techniques. Our initial results suggest that ChemCam can recognize and differentiate between carbonate materials on Mars.

  6. Mathematical model of the Beta Rand Cam{trademark} engine vane seals

    Energy Technology Data Exchange (ETDEWEB)

    Braden, C.H.; Thompson, G.J.; Smith, J.E.; Mucino, V.H. [West Virginia Univ., Morgantown, WV (United States)


    A mathematical model of the vane sealing mechanism is presented to determine how the loading on the seals will affect the performance of the Rand Cam{trademark} engine. Within the Rand Cam{trademark} engine, sacrificial linear seals in the vane are used as the main sealing mechanism to prevent blowby from one chamber to the next. Throughout this investigation a kinetostatic analysis, based upon Yamamoto`s Wankel apex seal analysis, is extended into three dimensions. The input data to the model can be varied to study the effects of seal dimensions, seal material, seal dynamics, and friction.

  7. 28th International Conference on CAD/CAM, Robotics and Factories of the Future

    CERN Document Server

    Syan, Chanan


    This volume is based on the proceedings of the 28th International Conference on CAD/CAM, Robotics and Factories of the Future. This book specially focuses on the positive changes made in the field of robotics, CAD/CAM and future outlook for emerging manufacturing units. Some of the important topics discussed in the conference are product development and sustainability, modeling and simulation, automation, robotics and handling systems, supply chain management and logistics, advanced manufacturing processes, human aspects in engineering activities, emerging scenarios in engineering education and training. The contents of this set of proceedings will prove useful to both researchers and practitioners.

  8. Calibrating the ChemCam LIBS for Carbonate Minerals on Mars (United States)

    Wiens, Roger C.; Clegg, Samuel M.; Ollila, Ann M.; Barefield, James E.; Lanza, Nina; Newsom, Horton E.


    The ChemCam instrument suite on board the NASA Mars Science Laboratory (MSL) rover includes the first LIBS instrument for extraterrestrial applications. Here we examine carbonate minerals in a simulated martian environment using the LIDS technique in order to better understand the in situ signature of these materials on Mars. Both chemical composition and rock type are determined using multivariate analysis (MVA) techniques. Composition is confirmed using scanning electron microscopy (SEM) techniques. Our initial results suggest that ChemCam can recognize and differentiate between carbonate materials on Mars.



    Rojas Lazo, Oswaldo; Ingeniero industrial de la UNMSM.


    El diseño y fabricación asistida con computadora comúnmente denominado CAD/CAM (Computer Aided Desing / Computer Aided Manufacturing) es una tecnología indispensable en los procesos productivos que se encuentran sometidos al alto nivel de competitividad en el mercado nacional e internacional, debido fundamentalmente a que las compañías necesitan abatir sus tiempos de diseño y manufactura con altos niveles de calidad. Design and Computer Aided Manufacturing commonly called CAD / CAM ...

  10. Calcium Sulfate Characterized by ChemCam/Curiosity at Gale Crater, Mars (United States)

    Nachon, M.; Clegg, S. N.; Mangold, N.; Schroeder, S.; Kah, L. C.; Dromart, G.; Ollila, A.; Johnson, J. R.; Oehler, D. Z.; Bridges, J. C.; LeMouelic, S.; Forni, O.; Wiens, R. C.; Rapin, W.; Anderson, R. B.; Blaney, D. L.; Bell, J. F. , III; Clark, B.; Cousin, A.; Dyar, M. D.; Ehlmann, B.; Fabre, C.; Gasnault, O.; Grotzinger, J.; Lasue, J.; Lewin, E.; Leveille, R.; McLennan, S.; Maurice, S.; Meslin, P.-Y.; Rice, M.; Squyres, S. W.; Stack, K.; Sumner, D. Y.; Vaniman, D.; Wellington, D.


    Onboard the Mars Science Laboratory (MSL) Curiosity rover, the ChemCam instrument consists of :(1) a Laser-Induced Breakdown Spectrometer (LIBS) for elemental analysis of the targets [1;2] and (2) a Remote Micro Imager (RMI), for the imaging context of laser analysis [3]. Within the Gale crater, Curiosity traveled from Bradbury Landing through the Rocknest region and into Yellowknife Bay (YB). In the latter, abundant light-toned fracture-fill material were seen [4;5]. ChemCam analysis demonstrate that those fracture fills consist of calcium sulfates [6].

  11. ERK kinases modulate the activation of PI3 kinase related kinases (PIKKs) in DNA damage response. (United States)

    Lin, Xiaozeng; Yan, Judy; Tang, Damu


    DNA damage response (DDR) is the critical surveillance mechanism in maintaining genome integrity. The mechanism activates checkpoints to prevent cell cycle progression in the presence of DNA lesions, and mediates lesion repair. DDR is coordinated by three apical PI3 kinase related kinases (PIKKs), including ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR), and DNA-PKcs (the catalytic subunit of the DNA dependent protein kinase). These kinases are activated in response to specific DNA damage or lesions, resulting in checkpoint activation and DNA lesion repair. While it is clear that the pathways of ATM, ATR, and DNA-PK are the core components of DDR, there is accumulating evidence revealing the involvement of other cellular pathways in regulating DDR; this is in line with the concept that in addition to being a nuclear event DDR is also a cellular process. One of these pathways is the extracellular signal-regulated kinase (ERK) MAPK (mitogen-activated protein kinase) pathway. ERK is a converging point of multiple signal transduction pathways involved in cell proliferation, differentiation, and apoptosis. Adding to this list of pathways is the recent development of ERK in DDR. The ERK kinases (ERK1 and ERK2) contribute to the proper execution of DDR in terms of checkpoint activation and the repair of DNA lesions. This review summarizes the contributions of ERK to DDR with emphasis on the relationship of ERK kinases with the activation of ATM, ATR, and DNA-PKcs.

  12. Eye tracking method on improved CamShift algorithm%改进CamShift算法的眼动跟踪方法

    Institute of Scientific and Technical Information of China (English)

    HUANG Yuan-gang; SANG Nan; HAO Zong-bo; JIANG Wei


    Since the CamShift algorithm only adopted color feature, which would result in the inaccuracy or failure of eye tracking in the situation of similar color objects,rapid movement of the head or deformation of the iris, this paper proposed an eye tracking m%针对CamShift跟踪算法仅采用颜色特征,在存在颜色相近干扰目标、头部快速运动或者虹膜发生形变等情况易发生眼动跟踪不准确或失败等问题,提出一种基于改进CamShift算法的眼动跟踪方法。在CamShift算法中,计算边缘直方图分布,在颜色特征基础上融合边缘特征,同时通过分析饱和度分量抑制噪声影响,并利用基于边缘特征的自定义方法判断虹膜是否发生形变。当发生形变时,自动更新模板,根据历史运动轨迹预测虹膜中心。实验表明,该方法能有效改善眼动跟踪性能,且定位虹膜精确、错误率低、速度快,预测虹膜中心与实际虹膜中心

  13. Evaluating the prevalence, content and readability of complementary and alternative medicine (CAM) web pages on the internet. (United States)

    Sagaram, Smitha; Walji, Muhammad; Bernstam, Elmer


    Complementary and alternative medicine (CAM) use is growing rapidly. As CAM is relatively unregulated, it is important to evaluate the type and availability of CAM information. The goal of this study is to deter-mine the prevalence, content and readability of online CAM information based on searches for arthritis, diabetes and fibromyalgia using four common search engines. Fifty-eight of 599 web pages retrieved by a "condition search" (9.6%) were CAM-oriented. Of 216 CAM pages found by the "condition" and "condition + herbs" searches, 78% were authored by commercial organizations, whose pur-pose involved commerce 69% of the time and 52.3% had no references. Although 98% of the CAM information was intended for consumers, the mean read-ability was at grade level 11. We conclude that consumers searching the web for health information are likely to encounter consumer-oriented CAM advertising, which is difficult to read and is not supported by the conventional literature.

  14. Use of Complementary and Alternative Medicine (CAM) in Autism Spectrum Disorder (ASD): Comparison of Chinese and Western Culture (Part A) (United States)

    Wong, V. C. N.


    A cross-sectional survey of the use of CAM by children was undertaken in the Duchess of Kent Children's Hospital in Hong Kong (March-December 2006). A questionnaire survey concerning the use of CAM was administered to chief caretakers (only the mothers) who accompanied children with neurodevelopmental disabilities followed up in our…

  15. Criterios para Seleccionar Sistemas de Diseño y Manufactura Asistidos por Computadora (CAD/CAM Criteria for the Selection of Computer Aided Design and Manufacturing Systems (CAD/CAM

    Directory of Open Access Journals (Sweden)

    R.R. Martínez


    Full Text Available Este estudio tiene como objetivo presentar en forma clara los principios fundamentales que se requieren para tener un criterio sobre las bondades e inconvenientes de los sistemas Diseño y Manufactura Asistidos por Computadora (CAD/CAM. La inquietud nació por algunos problemas presentados en la primera adquisición de un sistema de CAD/CAM. Se adaptó a una máquina de Control Numérico por Computadora (CNC las dos modalidades de CAM, el primero con el sistema de CAD integrado y la otra con interacción en AutoCAD. Del análisis se determinó la indiferencia de usar un software de CAD desarrollado por la misma compañía del CAM. El resultado de estos experimentos y observaciones proporciona una herramienta fundamental para seleccionar un sistema de CAD/CAM eficienteThe objective of this study was to present in clear form the fundamental principles required to obtain a criterion of the advantages and disadvantages of computer aided design and manufacturing systems (CAD/CAM. The idea for setting these selection criteria were obtained during the initial acquisition of a CAD/CAM system. A Numerical Control by Computer (CNC machine was adapted to two modalities of CAM, the first with an integrated CAD system and another with AutoCAD interaction. From the analysis it was determined that it was immaterial whether or not the use of CAD software was from the same company that produced the CAM software. The results of these experiments and observations provide a fundamental tool for selecting an efficient CAD/CAM system

  16. Complementary and alternative medicine (CAM) use in an Italian cohort of pediatric headache patients: the tip of the iceberg. (United States)

    Dalla Libera, D; Colombo, B; Pavan, G; Comi, G


    The use of complementary alternative medicine (CAM) in paediatric populations is considerably increased, especially for pain and chronic conditions, as demonstrated by epidemiological surveys both in Europe and in the USA. In our study, CAM was used in 76 % patients of a cohort of 124 children affected by headache (age 4-16 years; 67 % female; 70 % migraine without aura, 12 % migraine with aura, 18 % tensive headache according to IHS criteria) consecutively recruited at a Pediatric Headache University Center. CAM was used as preventive treatment in 80 % cases. The main reasons for seeking CAM were: the wish of avoiding chronic use of drugs with their related side effects, the desire of an integrated approach, the reported inefficacy of conventional medicine, and a more suitable children disposition to CAM than to pharmacological compound. Female gender, younger age, migraine without aura, parents' higher educational status, maternal use of CAM and other associated chronic conditions, correlated with CAM use (p insomnia, muscle-scheletric disorders and dysmenorrhoea). The most assumed CAM were: herbal remedies (64 %) such as Valeriana, Ginkgo biloba, Boswellia serrata, Vitex agnus-castus, passion flower, Linden tree; vitamins/minerals supplements (40 %) with magnesium, 5-Hydroxytryptophan, vitamin B6 or B12, Multivitamin compounds; Homeopathy (47 %) with Silicea, Ignatia Amara, Pulsatilla, Aconitum, Nux Vomica, Calcarea phosphorica; physical treatment (45 %) such as Ayurvedic massage, shiatsu, osteopathy; yoga (33 %); acupuncture (11 %). CAM-often integrated with conventional care-was auto-prescribed in 30 % of the cases, suggested by non-physician in 22 %, by the General Practitioner in 24 % and by paediatrician in 24 %. Both general practitioners and neurologists were mostly unaware of their patients' CAM use. In conclusion, neurologists should inquire for CAM use and be prepared to learn about CAM therapies or to directly interact with CAM trained experts, in

  17. A review of dental CAD/CAM: current status and future perspectives from 20 years of experience. (United States)

    Miyazaki, Takashi; Hotta, Yasuhiro; Kunii, Jun; Kuriyama, Soichi; Tamaki, Yukimichi


    In this article, we review the recent history of the development of dental CAD/CAM systems for the fabrication of crowns and fixed partial dentures (FPDs), based on our 20 years of experience in this field. The current status of commercial dental CAD/CAM systems developed around the world is evaluated, with particular focus on the field of ceramic crowns and FPDs. Finally, we discuss the future perspectives applicable to dental CAD/CAM. The use of dental CAD/CAM systems is promising not only in the field of crowns and FPDs but also in other fields of dentistry, even if the contribution is presently limited. CAD/CAM technology will contribute to patients' health and QOL in the aging society.

  18. Predictable aesthetic replacement of a metal-ceramic crown using CAD/CAM technology: a case report. (United States)

    Poticny, Daniel; Conrad, Robert


    The currently available CAD/CAM technologies present clinicians with various clinical benefits that include durability, marginal adaptation, and precision aesthetics. The clinical and laboratory procedures associated with these CAD/CAM systems differ from one another, and practitioners must understand the indications for each. Office-based systems, as demonstrated in the following case presentation, allow excellent results to be achieved in a single patient visit and provide a viable alternative for today's practice. This case report describes the associated sequences for a posterior CAD/CAM restoration. Learning Objectives This article discusses a protocol for the use of CAD/CAM restorations in the aesthetic replacement of defective posterior crowns. Upon reading this article, the reader should have: * Greater understanding of the in-office CAD/CAM procedures used to fabricate single-visit crowns. * Improved awareness of the bonding protocol used for these all-ceramic crowns.

  19. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    YongliangZhang; ChenDong


    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses. Cellular & Molecular Immunology. 2005;2(1):20-27.

  20. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong


    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  1. Abscisic acid activates a Ca2+-calmodulin-stimulated protein kinase involved in antioxidant defense in maize leaves

    Institute of Scientific and Technical Information of China (English)

    Shucheng Xu


     The role of a calcium-dependent and calmodulin(CaM)stimulated protein kinase in abscisic acid(ABA)-induced antioxidant defense was determined in leaves of maize (Zea mays).In-gel kinase assays showed that treatments with ABA or H2O2 induced the activation of a 49-kDa protein kinase and a 52-kDa protein kinase significantly.Furthermore,we showed that the 52-kDa protein kinase has the characteristics of CaM-stimulating activity and is sensitive to calcium-CaM-dependent protein kinase Ⅱ (CaMK Ⅱ)inhibitor KN-93 or CaM antagonist W-7.Treatments with ABA or H2O2 not only induced the acti vation of the 52-kDa protein kinase,but also enhanced the total activities of the antioxidant enzymes,including catalase,ascorbate peroxidase,glutathione reductase,and superoxide dismutase.Such enhancements were blocked by pretreatment with a CaMK inhibitor and a reactive oxygen species(ROS)inhibitor or scavenger.Pretreatment with the CaMK inhibitor also substantially arrested the ABA-induced H2O2 production.Kinase activity enhancements induced by ABA were attenuated by pretreatment with an ROS inhibitor or scavenger.These results suggest that the 52-kDa CaMK is involved in ABA-induced antioxidant defense and that cross-talk between CaMK and H2O2 plays a pivotal role in ABA signaling.We infer that CaMK acts both upstream and downstream of H2O2,but mainly acts between ABA and H2O2 in ABA-induced antioxidant-defensive signaling.

  2. Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitor. (United States)

    Hanyu, Yuichiro; Imai, Kumiko K; Kawasaki, Yosuke; Nakamura, Takahiro; Nakaseko, Yukinobu; Nagao, Koji; Kokubu, Aya; Ebe, Masahiro; Fujisawa, Asuka; Hayashi, Takeshi; Obuse, Chikashi; Yanagida, Mitsuhiro


    Calcium/calmodulin-dependent protein kinase (CaMK) is required for diverse cellular functions, and similar kinases exist in fungi. Although mammalian CaMK kinase (CaMKK) activates CaMK and also evolutionarily-conserved AMP-activated protein kinase (AMPK), CaMKK is yet to be established in yeast. We here report that the fission yeast Schizosaccharomyces pombe Ssp1 kinase, which controls G2/M transition and response to stress, is the putative CaMKK. Ssp1 has a CaM binding domain (CBD) and associates with 14-3-3 proteins as mammalian CaMKK does. Temperature-sensitive ssp1 mutants isolated are defective in the tolerance to limited glucose, and this tolerance requires the conserved stretch present between the kinase domain and CBD. Sds23, multi-copy suppressor for mutants defective in type 1 phosphatase and APC/cyclosome, also suppresses the ssp1 phenotype, and is required for the tolerance to limited glucose. We demonstrate that Sds23 binds to type 2A protein phosphatases (PP2A) and PP2A-related phosphatase Ppe1, and that Sds23 inhibits Ppe1 phosphatase activity. Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common beta-(Amk2) and gamma-(Cbs2) subunits.

  3. Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling. (United States)

    Holopainen, Tanja; Räsänen, Markus; Anisimov, Andrey; Tuomainen, Tomi; Zheng, Wei; Tvorogov, Denis; Hulmi, Juha J; Andersson, Leif C; Cenni, Bruno; Tavi, Pasi; Mervaala, Eero; Kivelä, Riikka; Alitalo, Kari


    Cardiac hypertrophy accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease, and it is a strong predictor of increased cardiovascular morbidity and mortality. Deletion of bone marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has been shown to inhibit cardiac hypertrophy in mice. This finding raised the possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced cardiac hypertrophy is significantly reduced in mice deficient in Bmx and in mice with inactivated Bmx tyrosine kinase compared with WT mice. Genome-wide transcriptomic profiling showed that Bmx inactivation suppresses myocardial expression of genes related to Ang II-induced inflammatory and extracellular matrix responses whereas expression of RNAs encoding mitochondrial proteins after Ang II administration was maintained in Bmx-inactivated hearts. Very little or no Bmx mRNA was expressed in human cardiomyocytes whereas human cardiac endothelial cells expressed abundant amounts. Ang II stimulation of endothelial cells increased Bmx phosphorylation, and Bmx gene silencing inhibited downstream STAT3 signaling, which has been implicated in cardiac hypertrophy. Furthermore, activation of the mechanistic target of rapamycin complex 1 pathway by Ang II treatment was decreased in the Bmx-deficient hearts. Our results demonstrate that inhibition of the cross-talk between endothelial cells and cardiomyocytes by Bmx inactivation suppresses Ang II-induced signals for cardiac hypertrophy. These results suggest that the endothelial Bmx tyrosine kinase could provide a target to attenuate the development of cardiac hypertrophy.

  4. Thermography of semi-transparent materials by a FLIR ThermaCAM SC3000 infrared camera

    NARCIS (Netherlands)

    Van der Tempel, L.


    An acceptance test for thermography of semi-transparent materials by a FLIR ThermaCAM SC3000 infrared camera with 8.0 µm low-wavelength-pass filter has been developed and performed on polycarbonate, PEN, quartz, Corning 1737 glass, G427 cone glas, G443 screen glass, Schott Zerodur, silicon and a bl

  5. Education & Training for CAD/CAM: Results of a National Probability Survey. Krannert Institute Paper Series. (United States)

    Majchrzak, Ann

    A study was conducted of the training programs used by plants with Computer Automated Design/Computer Automated Manufacturing (CAD/CAM) to help their employees adapt to automated manufacturing. The study sought to determine the relative priorities of manufacturing establishments for training certain workers in certain skills; the status of…

  6. Classroom Experiences in an Engineering Design Graphics Course with a CAD/CAM Extension. (United States)

    Barr, Ronald E.; Juricic, Davor


    Reports on the development of a new CAD/CAM laboratory experience for an Engineering Design Graphics (EDG) course. The EDG curriculum included freehand sketching, introduction to Computer-Aided Design and Drafting (CADD), and emphasized 3-D solid modeling. Reviews the project and reports on the testing of the new laboratory components which were…

  7. ESA ExoMars: Pre-launch PanCam Geometric Modeling and Accuracy Assessment (United States)

    Li, D.; Li, R.; Yilmaz, A.


    ExoMars is the flagship mission of the European Space Agency (ESA) Aurora Programme. The mobile scientific platform, or rover, will carry a drill and a suite of instruments dedicated to exobiology and geochemistry research. As the ExoMars rover is designed to travel kilometres over the Martian surface, high-precision rover localization and topographic mapping will be critical for traverse path planning and safe planetary surface operations. For such purposes, the ExoMars rover Panoramic Camera system (PanCam) will acquire images that are processed into an imagery network providing vision information for photogrammetric algorithms to localize the rover and generate 3-D mapping products. Since the design of the ExoMars PanCam will influence localization and mapping accuracy, quantitative error analysis of the PanCam design will improve scientists' awareness of the achievable level of accuracy, and enable the PanCam design team to optimize its design to achieve the highest possible level of localization and mapping accuracy. Based on photogrammetric principles and uncertainty propagation theory, we have developed a method to theoretically analyze how mapping and localization accuracy would be affected by various factors, such as length of stereo hard-baseline, focal length, and pixel size, etc.

  8. Effects of Complementary and Alternative Medicines (CAM) on the Metabolism and Transport of Anticancer Drugs

    NARCIS (Netherlands)

    Mooiman, K.D.


    The use of complementary and alternative medicines (CAM), such as herbs and dietary supplements, has become more popular among cancer patients. Cancer patients use these supplements for different reasons such as reduction of side effects and improvement of their quality of life. In general, the use

  9. The Cyborg Astrobiologist: porting from a wearable computer to the Astrobiology Phone-cam (United States)

    Bartolo, Alexandra; McGuire, Patrick C.; Camilleri, Kenneth P.; Spiteri, Christopher; Borg, Jonathan C.; Farrugia, Philip J.; Ormö, Jens; Gómez-Elvira, Javier; Rodriguez-Manfredi, José Antonio; Díaz-Martínez, Enrique; Ritter, Helge; Haschke, Robert; Oesker, Markus; Ontrup, Jörg


    We have used a simple camera phone to significantly improve an `exploration system' for astrobiology and geology. This camera phone will make it much easier to develop and test computer-vision algorithms for future planetary exploration. We envision that the `Astrobiology Phone-cam' exploration system can be fruitfully used in other problem domains as well.

  10. Input torque balancing using a cam-based centrifugal pendulum: design procedure and example (United States)

    Demeulenaere, Bram; Spaepen, Pieter; De Schutter, Joris


    Input torque balancing is a well-known way to reduce drive speed fluctuations in high-speed machinery and combustion engines. This paper introduces a cam-based centrifugal pendulum (CBCP) and a design procedure for it which results in quasi-perfect balancing of inertial torques for any drive speed. The CBCP combines the centrifugal pendulum vibration absorber, well-known in mechanical vibration literature, with a torque balancing principle well-known in mechanism literature, that is, the use of cams to generate arbitrary torques. For given design parameters (such as the link lengths and link inertial parameters), the cam design is governed by a nonlinear, second-order, explicit differential equation. This differential equation is numerically solved by reformulating it as a nonlinear least-squares problem. The design parameters themselves are determined by means of an optimization problem, the goal of which is to minimize the (constant) equivalent inertia of the combined system, consisting of the original mechanism to be balanced and the CBCP. Application of the CBCP to torque balance a high-speed, purely inertial cam-follower mechanism, driving the sley of a weaving loom, shows that the optimization results in a compact and technologically feasible mechanism.

  11. The C.A.M.S. 54 G.R. transatlantic seaplane (French) (United States)

    Ide, John Jay


    Tested at the end of March, 1928, the C.A.M.S. 54 G.R. was built for the purpose of crossing the Atlantic from Europe by way of the azores. It has a biplane construction with wings mounted above the hull. It is powered by two new series 500 HP. geared Hispano Suiza V type engines.

  12. EpCAM Expression in Lymph Node and Bone Metastases of Prostate Carcinoma : A Pilot Study

    NARCIS (Netherlands)

    Campos, Anna K.; Hoving, Hilde D.; Rosati, Stefano; van Leenders, Geert J. L. H.; de Jong, Igle J.


    There is an urgent need for new imaging modalities in prostate carcinoma staging. A non-invasive modality that can assess lymph node and bone metastases simultaneously is preferred. Epithelial cell adhesion molecule (EpCAM) is a membranous protein of interest as an imaging target since it is overexp

  13. EpCAM expression in lymph node and bone metastases of prostate carcinoma: A pilot study

    NARCIS (Netherlands)

    Campos, A.K. (Anna K.); Hoving, H.D. (Hilde D.); S. Rosati (Stefano); G.J.H.L. Leenders (Geert); I.J. de Jong (Igle)


    textabstractThere is an urgent need for new imaging modalities in prostate carcinoma staging. A non-invasive modality that can assess lymph node and bone metastases simultaneously is preferred. Epithelial cell adhesion molecule (EpCAM) is a membranous protein of interest as an imaging target since i

  14. Motorized CPM/CAM physiotherapy device with sliding-mode Fuzzy Neural Network control loop. (United States)

    Ho, Hung-Jung; Chen, Tien-Chi


    Continuous passive motion (CPM) and controllable active motion (CAM) physiotherapy devices promote rehabilitation of damaged joints. This paper presents a computerized CPM/CAM system that obviates the need for mechanical resistance devices such as springs. The system is controlled by a computer which performs sliding-mode Fuzzy Neural Network (FNN) calculations online. CAM-type resistance force is generated by the active performance of an electric motor which is controlled so as to oppose the motion of the patient's leg. A force sensor under the patient's foot on the device pedal provides data for feedback in a sliding-mode FNN control loop built around the motor. Via an active impedance control feedback system, the controller drives the motor to behave similarly to a damped spring by generating and controlling the amplitude and direction of the pedal force in relation to the patient's leg. Experiments demonstrate the high sensitivity and speed of the device. The PC-based feedback nature of the control loop means that sophisticated auto-adaptable CPM/CAM custom-designed physiotherapy becomes possible. The computer base also allows extensive data recording, data analysis and network-connected remote patient monitoring.

  15. Perapation of mica-based glassceramics for denta CAD/CAM system

    Institute of Scientific and Technical Information of China (English)

    LI Hong; RAN Junguo; GOU Li; ZHAO Yunfeng


    @@ Ceramic materials have received considerable application in biomedical and dental restoration because of their relative higher mechanical properties, excellent biocompatibility and good natural aesthetics. Development of machinable glass-ceramicsin dental CAD/CAM maching system have provided a new impetus for fabrication ofceramic restorations.

  16. The RCCM 2009 Survey: Mapping Doctoral and Postdoctoral CAM Research in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Nicola Robinson


    Full Text Available Complementary and Alternative Medicine (CAM is widely available in the UK and used frequently by the public, but there is little high quality research to sustain its continued use and potential integration into the NHS. There is, therefore, a need to develop rigorous research in this area. One essential way forward is to train and develop more CAM researchers so that we can enhance academic capacity and provide the evidence upon which to base strategic healthcare decisions. This UK survey identified 80 research active postgraduates registered for MPhils/PhDs in 21 universities and were either current students or had completed their postgraduate degree during the recent UK Research Assessment Exercise (RAE 2001–2008. The single largest postgraduate degree funder was the university where the students registered (26/80. Thirty-two projects involved randomized controlled trials and 33 used qualitative research methods. The UK RAE also indicates a significant growth of postdoctoral and tenured research activity over this period (in 2001 there were three full time equivalents; in 2008 there were 15.5 with a considerable improvement in research quality. This mapping exercise suggests that considerable effort is currently being invested in developing UK CAM research capacity and thus inform decision making in this area. However, in comparative international terms UK funding is very limited. As in the USA and Australia, a centralized and strategic approach by the National Institute of Health Research to this currently uncoordinated and underfunded activity may benefit CAM research in the UK.

  17. Leadless Chip Carrier Packaging and CAD/CAM-Supported Wire Wrap Interconnect Technology for Subnanosecond ECL. (United States)


    Aided Manufacturing Software J. M. Dubin : CAD/CAM Demonstration Circuit Design, Fabrica- tion, and Test L. M. Krueger: ECL Design Protocols R. D...the electro - plating fingers is further compounded by the presence of yet another set of plating fingers, which may be detected in Figure 24 between the

  18. Soil diversity and hydration as observed by ChemCam at Gale Crater, Mars

    NARCIS (Netherlands)

    Meslin, P.-Y.; Gasnault, O.; Forni, O.; Schröder, S.; Cousin, A.; Berger, G.; Clegg, S.M.; Lasue, J.; Maurice, S.; Sautter, V.; Le Mouélic, S.; Wiens, R.C.; Fabre, C.; Goetz, W.; Bish, D.; Mangold, N.; Ehlmann, B.; Lanza, N.; Harri, A.-M.; Anderson, R.; Rampe, E.; McConnochie, T.H.; Pinet, P.; Blaney, D.; Léveillé, R.; Archer, D.; Barraclough, B.; Bender, S.; Blake, D.; Blank, J.G.; Bridges, N.; Clark, B.C.; DeFlores, L.; Delapp, D.; Dromart, G.; Dyar, M.D.; Fisk, M.; Gondet, B.; Grotzinger, J.; Herkenhoff, K.; Johnson, J.; Lacour, J.-L.; Langevin, Y.; Leshin, L.; Lewin, E.; Madsen, M.B.; Melikechi, N.; Mezzacappa, A.; Mischna, M.A.; Moores, J.E.; Newsom, H.; Ollila, A.; Perez, R.; Renno, N.; Sirven, J.-B.; Tokar, R.; De La Torre, M.; D'Uston, L.; Vaniman, D.; Yingst, A.; MSL Science Team, the


    The ChemCam instrument, which provides insight into martian soil chemistry at the submillimeter scale, identified two principal soil types along the Curiosity rover traverse: a fine-grained mafic type and a locally derived, coarse-grained felsic type. The mafic soil component is representative of wi

  19. Monitoring the photometric behavior of OmegaCAM with Astro-WISE

    CERN Document Server

    Kleijn, Gijs A Verdoes; Valentijn, Edwin A; Boxhoorn, Danny R; Begeman, Kor G; Deul, Erik R; Helmich, Ewout M; Rengelink, Roeland


    The OmegaCAM wide-field optical imager is the sole instrument on the VLT Survey Telescope at ESO's Paranal Observatory. The instrument, as well as the telescope, have been designed for surveys with very good, natural seeing-limited image quality over a 1 square degree field. OmegaCAM was commissioned in 2011 and has been observing three ESO Public Surveys in parallel since October 15, 2011. We use the Astro-WISE information system to monitor the calibration of the observatory and to produce the Kilo Degree Survey (KiDS). Here we describe the photometric monitoring procedures in Astro-WISE and give a first impression of OmegaCAM's photometric behavior as a function of time. The long-term monitoring of the observatory goes hand in hand with the KiDS survey production in Astro-WISE. KiDS is observed under partially non-photometric conditions. Based on the first year of OmegaCAM operations it is expected that a $\\sim 1%-2%$ photometric homogeneity will be achieved for KiDS.

  20. CLIC main beam quadrupole active pre-alignment based on cam movers

    CERN Document Server

    Kemppinen, J; Leuxe, R; Mainaud Durand, H; Sandomierski, J; Sosin, M


    Compact Linear Collider (CLIC) is a study for a future 48 km long linear electron-positron collider in the multi TeV range. Its target luminosity can only be reached if the main beam quadrupoles (MB quads) are actively pre-aligned within 17 µm in sliding windows of 200 m with respect to a straight reference line. In addition to the positioning requirement, the pre-alignment system has to provide a rigid support for the nano-stabilization system to ensure that the first eigenfrequency is above 100 Hz. Re-adjustment based on cam movers was chosen for detailed studies to meet the stringent pre-alignment requirements. There are four different types of MB quads in CLIC. Their lengths and masses vary so that at least two types of cam movers have to be developed. The validation of the cams with less stringent space restrictions has proceeded to a test setup in 5 degrees of freedom (DOF). Prototypes of the more demanding, smaller cams have been manufactured and they are under tests in 1 DOF. This paper describes the...


    Directory of Open Access Journals (Sweden)



    Full Text Available A computer assisted procedure for the cinematic analysis of the mechanism of a cam is essential in making a certain type of research operations. They mainly refer to the optimization of operations running on specific machinery, or to the re-design of the mechanism, in order to make the mechanism digital. This analysis seems even more important, when we consider the fact that most of the machines used in shoe industry nowadays use a cam mechanism. The paper is devided in two parts. In first part, it is elaborated a method of finding of a function G(x, belonging to a Fourier series, which approximates the numerical values {xi, yi}, with the biggest accuracy. Finding the function that approximates the most accurately the data set, for the position parameters of the follower S(ω, ( will lead to a complete kinematic and dynamic analysis of the cam mechanism. These values repeat with T = 2π period. In second part, the method is tasted using MatCAD work sessions which allow a numerical and graphical analysis of the mathematical relations involved, in order to test the reability of the method. The set of experimental data are resulted after measuring a cam mechanism of a machine used in shoemaking.

  2. A distributed data base management facility for the CAD/CAM environment (United States)

    Balza, R. M.; Beaudet, R. W.; Johnson, H. R.


    Current/PAD research in the area of distributed data base management considers facilities for supporting CAD/CAM data management in a heterogeneous network of computers encompassing multiple data base managers supporting a variety of data models. These facilities include coordinated execution of multiple DBMSs to provide for administration of and access to data distributed across them.

  3. Comparison of CAD-CAM and hand made sockets for PTB prostheses. (United States)

    Köhler, P; Lindh, L; Netz, P


    The aim of the present study was to compare sockets for below-knee (BK) prostheses made by Computer Aided Design-Computer Aided Manufacture (CAD-CAM) to those made by hand. The patients in the study were provided with two prostheses each, which apart from the sockets, were identical. One socket was made by the CAD-CAM technique developed at the Bioengineering Centre, Roehampton, University College London and one was made by hand at the OT-Centre, Stockholm, Sweden. The results were based on investigation of eight unilateral below-knee amputees evaluating their own sockets by Visual Analogous Scale with respect to comfort, pressure, and pain. The sockets were evaluated on seven occasions, at two tests, on delivery, after use every second day for six days and every second week for two weeks. All CAD-CAM sockets except one had to be changed once as compared to the hand made of which only two had to be changed. As to comfort it could not be demonstrated that there was any significant difference between the two types of sockets and both types were well accepted by all patients. Differences in pressure and pain were rarely reported. There were obvious differences between the two types of socket with respect to height, width, and inner surface configuration. The authors feel that CAD-CAM will in the near future be an excellent tool for design and manufacture of prosthetic sockets.

  4. An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy

    NARCIS (Netherlands)

    McLaughlin, PMJ; Kroesen, BJ; Dokter, WHA; van der Molen, H; de Groot, M; Brinker, MGL; Kok, K; Ruiters, MHJ; Buys, CHCM; de Leij, LFMH


    The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), also known as 17-1A or EpCAM, is a 38-kDa transmembrane antigen, commonly used for targeted immunotherapy of carcinomas. Although strongly expressed by most carcinomas, EGP-2 is also expressed in most simple epithelia. To evaluate

  5. Winning in the Rural Zone: How Cam Henderson Invented the Zone Defense. (United States)

    Barnett, Bob


    Assesses the distinguished coaching career of Cam Henderson, who won over 611 games in 36 seasons of college basketball and coached over 151 college football wins at West Virginia colleges, mainly at Marshall University (Huntington). His influence has been so pervasive that Marshall University's basketball arena is named in his honor. (LP)

  6. Development of Integrated ASR Model Forcing Data and Their Applications to Improve CAM

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Minghua [Research Foundation of the State University of New York, Albany, NY (United States)


    In this project, we have (1) improved the constrained variational analysis algorithm of ARM model forcing data, and (2) used the ARM forcing data to identify systematic biases in clouds and radiation in the CAM5 and design new physical parameterizations to improve it.

  7. OmegaCAM: the 16k × 16k Survey Camera for the VLT Survey Telescope

    NARCIS (Netherlands)

    Deul, Erik; Kuijken, Konrad; Valentijn, Edwin A.; Tyson, J. Anthony; Wolff, Sidney


    OmegaCAM, a 16k×16k-pixel wide field optical camera, and the VLT Survey Telescope (VST) that is to host it, will constitute a major sky surveying machine that becomes operational in 2004 at ESO"s Paranal Observatory. It maps one square degree of sky with 0.21 arcsec sized pixels. Both individual pro

  8. Force Analysis of Geneva Wheel and Face Cam Used In Automat

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    Madhoo G


    Full Text Available Glazerol Automat is a dedicated machine used in the Insulator pre assembly line. This automat is driven using single motor for different operations. Here the focus is on two main parts they are Geneva wheel and Face cam which are used for their respective operations. Geneva Wheel is used to index the drum which consists of 96 spindles. Due to this Geneva mechanism each of the spindles will hold the ceramic body when the drum is being indexed. Due to which there is a force which is generated in the Geneva wheel in maximum and minimum position. Face cam which is used while indexing the work piece carrier There are 2 tangential forces which are acting, one at the indexing side and the other at the driving side /cam side. The effective resultant force which is acting on the face cam while indexing work piece carrier is calculated. And these forces are analyzed using ansys and their respective Von Mises stresses and displacement plots are obtained for both the conditions based on boundary and loading conditions.

  9. Child/Adolescent Anxiety Multimodal Study (CAMS: rationale, design, and methods

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    Waslick Bruce D


    Full Text Available Abstract Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS, a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT, sertraline (SRT, and their combination (COMB against pill placebo (PBO for the treatment of separation anxiety disorder (SAD, generalized anxiety disorder (GAD and social phobia (SoP in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488 children and adolescents (ages 7-17 years with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT and pharmacologic (SSRI treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results

  10. The prevalence, patterns of usage and people's attitude towards complementary and alternative medicine (CAM among the Indian community in Chatsworth, South Africa

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    Raidoo Deshandra M


    Full Text Available Abstract Background The purpose of this study was to determine, among the Indian community of Chatsworth, South Africa, the prevalence and utilisation patterns of complementary and alternative medicine (CAM, attitudes associated with CAM use and communication patterns of CAM users with their primary care doctors. Methods Face-to-face structured interviews were conducted in Chatsworth, a suburb of Durban in which South Africans of Indian origin predominantly reside. Participants were 200 randomly selected adult English-speaking Indian residents. Results The prevalence of CAM usage for period 2000/2001 was 38.5% (95% confidence interval 31.7% to 45.6%. Spiritual healing and herbal/natural medicines, including vitamins were the most common types of CAM used, accounting for 42.8% and 48.1% respectively of overall CAM usage. People used CAM to treat conditions including diabetes mellitus, headaches, arthritis and joint pains, stress, skin disorders, backaches, hypertension and nasal disorders. Half of the CAM users used allopathic medicines concurrently. The cost of CAM utilization over this 1-year period, incurred by 80.5% of users for the duration of therapy for their most troublesome condition was below R500 (approximately US$50. Age, sex, marital status, religion, level of education and income were shown not to influence the use of CAM. Greater than half (51.9% of CAM users did so either upon the advice of someone they knew, or after noticing a CAM advertisement in the local press. Seventy-nine percent of CAM users indicated that they had positive outcomes with their treatments. Fifty four percent of CAM users (excluding those using spiritual healing only failed to inform their doctors that they used CAM. The main reason given by half of this group was that informing their doctors did not seem necessary. Conclusion The prevalence of CAM in Chatsworth is similar to findings in other parts of the world. Although CAM was used to treat many different

  11. Discoloration of various CAD/CAM blocks after immersion in coffee (United States)

    Lauvahutanon, Sasipin; Shiozawa, Maho; Iwasaki, Naohiko; Oki, Meiko; Finger, Werner J.; Arksornnukit, Mansuang


    Objectives This study evaluated color differences (ΔEs) and translucency parameter changes (ΔTPs) of various computer-aided design/computer-aided manufacturing (CAD/CAM) blocks after immersion in coffee. Materials and Methods Eight CAD/CAM blocks and four restorative composite resins were evaluated. The CIE L*a*b* values of 2.0 mm thick disk-shaped specimens were measured using the spectrophotometer on white and black backgrounds (n = 6). The ΔEs and ΔTPs of one day, one week, and one month immersion in coffee or water were calculated. The values of each material were analyzed by two-way ANOVA and Tukey's multiple comparisons (α = 0.05). The ΔEs after prophylaxis paste polishing of 1 month coffee immersion specimens, water sorption and solubility were also evaluated. Results After one month in coffee, ΔEs of CAD/CAM composite resin blocks and restorative composites ranged from 1.6 to 3.7 and from 2.1 to 7.9, respectively, and ΔTPs decreased. The ANOVA of ΔEs and ΔTPs revealed significant differences in two main factors, immersion periods and media, and their interaction except for ΔEs of TEL (Telio CAD, Ivoclar Vivadent). The ΔEs significantly decreased after prophylaxis polishing except GRA (Gradia Block, GC). There was no significant correlation between ΔEs and water sorption or solubility in water. Conclusions The ΔEs of CAD/CAM blocks after immersion in coffee varied among products and were comparable to those of restorative composite resins. The discoloration of CAD/CAM composite resin blocks could be effectively removed with prophylaxis paste polishing, while that of some restorative composites could not be removed. PMID:28194359

  12. Status of the photomultiplier-based FlashCam camera for the Cherenkov Telescope Array (United States)

    Pühlhofer, G.; Bauer, C.; Eisenkolb, F.; Florin, D.; Föhr, C.; Gadola, A.; Garrecht, F.; Hermann, G.; Jung, I.; Kalekin, O.; Kalkuhl, C.; Kasperek, J.; Kihm, T.; Koziol, J.; Lahmann, R.; Manalaysay, A.; Marszalek, A.; Rajda, P. J.; Reimer, O.; Romaszkan, W.; Rupinski, M.; Schanz, T.; Schwab, T.; Steiner, S.; Straumann, U.; Tenzer, C.; Vollhardt, A.; Weitzel, Q.; Winiarski, K.; Zietara, K.


    The FlashCam project is preparing a camera prototype around a fully digital FADC-based readout system, for the medium sized telescopes (MST) of the Cherenkov Telescope Array (CTA). The FlashCam design is the first fully digital readout system for Cherenkov cameras, based on commercial FADCs and FPGAs as key components for digitization and triggering, and a high performance camera server as back end. It provides the option to easily implement different types of trigger algorithms as well as digitization and readout scenarios using identical hardware, by simply changing the firmware on the FPGAs. The readout of the front end modules into the camera server is Ethernet-based using standard Ethernet switches and a custom, raw Ethernet protocol. In the current implementation of the system, data transfer and back end processing rates of 3.8 GB/s and 2.4 GB/s have been achieved, respectively. Together with the dead-time-free front end event buffering on the FPGAs, this permits the cameras to operate at trigger rates of up to several ten kHz. In the horizontal architecture of FlashCam, the photon detector plane (PDP), consisting of photon detectors, preamplifiers, high voltage-, control-, and monitoring systems, is a self-contained unit, mechanically detached from the front end modules. It interfaces to the digital readout system via analogue signal transmission. The horizontal integration of FlashCam is expected not only to be more cost efficient, it also allows PDPs with different types of photon detectors to be adapted to the FlashCam readout system. By now, a 144-pixel mini-camera" setup, fully equipped with photomultipliers, PDP electronics, and digitization/ trigger electronics, has been realized and extensively tested. Preparations for a full-scale, 1764 pixel camera mechanics and a cooling system are ongoing. The paper describes the status of the project.

  13. Diagnosing delirium in elderly Thai patients: Utilization of the CAM algorithm

    Directory of Open Access Journals (Sweden)

    Lerttrakarnnon Peerasak


    Full Text Available Abstract Background Delirium is a common illness among elderly hospitalized patients. However, under-recognition of the condition by non-psychiatrically trained personnel is prevalent. This study investigated the performance of family physicians when detecting delirum in elderly hospitalized Thai patients using the Thai version of the Confusion Assessment Method (CAM algorithm. Methods A Thai version of the CAM algorithm was developed, and three experienced Thai family physicians were trained in its use. The diagnosis of delirium was also carried out by four fully qualified psychiatrists using DSM-IV TR criteria, which can be considered the gold standard. Sixty-six elderly patients were assessed with MMSE Thai 2002, in order to evaluate whether they had dementia upon admission. Within three days of admission, each patient was interviewed separately by a psychiatrist using DSM-IV TR, and a family physician using the Thai version of the CAM algorithm, with both sets of interviewers diagnosing for delirium. Results The CAM algorithm tool, as used by family physicians, demonstrated a sensitivity of 91.9% and a specificity of 100.0%, with a PPV of 100.0% and an NPV of 90.6%. Interrater agreement between the family physicians and the psychiatrists was good (Cohen's Kappa = 0.91, p Conclusions Family physicians performed well when diagnosing delirium in elderly hospitalized Thai patients using the Thai version of the CAM algorithm, showing that this measurement tool is suitable for use by non-psychiatrically trained personnel, being short, quick, and easy to administer. However, proper training on use of the algorithm is required.

  14. Cloning and Characterization of a Homologous Ca2+/Calmodulin-Dependent Protein Kinase PSKH1 from Pearl Oyster Pinctada fucata

    Institute of Scientific and Technical Information of China (English)

    DAI Yiping; XIE Liping; XIONG Xunhao; CHEN Lei; FAN Weimin; ZHANG Rongqing


    Many of the effects of Ca2+ signaling are mediated through the Ca2+/calmodulin complex and its acceptors, the Ca2+/calmodulin-dependent protein kinases, including PSKH1. Studies of the proteins involved in the calcium metabolism in oysters will help elucidate the pearl formation mechanism. This paper describes a full-length PSKH1 cDNA isolated from pearl oyster Pinctada fucata. Oyster PSKH1 shares 65% homology with human PSKH1 and 48% similarity with rat CaM kinase I in the amino acid sequence, and contains a calmodulin-binding domain. The results of semi-quantitative reverse transcription-polymerase chain reaction and in situ hybridization revealed that oyster PSKH1 mRNA is highly expressed in the outer epithelial cells of the mantle pallial and in the gill epithelial cells. These studies provide important information describing the complex Ca2+ signaling mechanism in oyster calcium metabolism.

  15. Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells. (United States)

    Kwon, Taeho; Bak, Yesol; Park, Young-Ho; Jang, Gyu-Beom; Nam, Jeong-Seok; Yoo, Jeong Eun; Park, Young Nyun; Bak, In Seon; Kim, Jin-Man; Yoon, Do-Young; Yu, Dae-Yeul


    Redox regulation in cancer stem cells (CSCs) is viewed as a good target for cancer therapy because redox status plays an important role in cancer stem-cell maintenance. Here, we investigated the role of Peroxiredoxin II (Prx II), an antioxidant enzyme, in association with maintenance of liver CSCs. Our study demonstrates that Prx II overexpressed in liver cancer cells has high potential for self-renewal activity. Prx II expression significantly corelated with expression of epithelial-cell adhesion molecules (EpCAM) and cytokerain 19 in liver cancer tissues of hepatocellular carcinoma (HCC) patients. Downregulation of Prx II in Huh7 cells with treatment of siRNA reduced expression of EpCAM and CD133 as well as Sox2 in accordance with increased ROS and apoptosis, which were reversed in Huh7-hPrx II cells. Huh7-hPrx II cells exhibited strong sphere-formation activity compared with mock cells. Vascular endothelial growth factor (VEGF) exposure enhanced sphere formation, cell-surface expression of EpCAM and CD133, and pSTAT3 along with activation of VEGF receptor 2 in Huh7-hPrx II cells. The result also emerged in Huh7-H-ras(G12V) and SK-HEP-1-H-ras(G12V) cells with high-level expression of Prx II. Prx II was involved in regulation of VEGF driving cancer stem cells through VEGFR-2/STAT3 signaling to upregulate Bmi1 and Sox2. In addition, knockdown of Prx II in Huh7-H-ras(G12V) cells showed significant reduction in cell migration in vitro and in tumorigenic potential in vivo. Taken together, all the results demonstrated that Prx II plays a key role in the CSC self-renewal of HCC cells through redox regulation. Stem Cells 2016;34:1188-1197.

  16. Bilgisayar destekli diş hekimliği ve güncel CAD/CAM sistemleri

    Directory of Open Access Journals (Sweden)

    Gözde Çelik


    Full Text Available

    CAD/CAM systems (computer aided design/computer aided manufacturing has been used in dentistry since 1987. In the past 25 years, development of various high quality chairside and laboratory CAD/CAM systems has been continued with the progress of technology. This article describes currently used CAD/CAM systems.

    Keywords: Dental, CAD/CAM systems.



    CAD/CAM sistemleri (bilgisayar destekli tasarım/bilgisayar destekli üretim diş hekimliğinde 1987 yılından beri kullanılmaktadır. Son 25 yılda teknolojinin de ilerlemesiyle üstün özellikte çeşitli klinik ve laboratuvar CAD/CAM sistemleri geliştirilmeye devam etmektedir. Bu makalede günümüzde kullanılan CAD/CAM sistemleri anlatılmaktadır.

  17. Concurrent Complementary and Alternative Medicine CAM and Conventional Rehabilitation Therapy in the Management of Children with Developmental Disorders

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    Soo Yeon Kim


    Full Text Available Background. We investigated the concurrent use of conventional rehabilitations and complementary and alternative medicine (CAM therapies for the long-term management of children with developmental disorders (DDs. Methods. The parents or caregivers of 533 children with DDs (age range, 1–19 years who visited the rehabilitation centers were surveyed using in depth face-to-face interviews. Results. Of the 533 patients enrolled, 520 completed the questionnaire (97% response rate. A total of 292 (56% children were receiving multiple therapies, more than two conventional rehabilitations and CAM, at the time of the interview. A total of 249 (48% children reported lifetime CAM use, 23% used CAM at the time of the interview, and 62% of the patients planned to use CAM therapy in the future. Conventional rehabilitation therapies used at the time of the interview included physical therapy (30%, speech therapy (28%, and occupational therapy (19%, and the CAM therapies included herbal medicine (5% and acupuncture or moxibustion (3%. The respondents indicated that in the future they planned to use acupuncture or moxibustion (57%, occupational therapy (18%, cognitive behavioral therapy (16%, speech therapy (10%, and physical therapy (8%. Conclusion. Concurrent management as conventional rehabilitations and CAM therapies is widely used by children with DDs.

  18. A focus Group Study of Medical Students’ Views of an Integrated Complementary and Alternative Medicine (CAM Curriculum: Students Teaching Teachers

    Directory of Open Access Journals (Sweden)

    Désirée Lie, M.D


    Full Text Available Background: Student views of new curricula can shape training outcomes. This qualitative study elicited student opinions of CAM instruction to examine and distill best strategies.Methods: 49 second, third and fourth year students participated in focus groups using a predefined question route. Interviews were audio taped and transcribed.Results: Students successfully differentiated CAM curricula from other academic content and were supportive of a longitudinal integrated approach. They had positive disposition toward CAM use for themselves but this did not necessarily translate into patient recommendations. They agreed that goals of the CAM curriculum should center on awareness of patient use and evidence and information relevant to clinical practice. They advocated a case-based, hands-on, experiential strategy vs lectures. Students proposed greater institutional commitment to strengthen curricular effectiveness. The majority did not intend to practice CAM modalities but valued skills to assess them. Patient-centeredness was recognized. As training progressed, students exhibited a growing tendency to evaluate CAM efficacy, and therefore value, exclusively according to evidence.Conclusions: In-depth student input allowed examination of the effectiveness of a CAM curriculum,permitting improvement and assessment of program effectiveness.

  19. Implant-supported fixed dental prostheses with CAD/CAM-fabricated porcelain crown and zirconia-based framework. (United States)

    Takaba, Masayuki; Tanaka, Shinpei; Ishiura, Yuichi; Baba, Kazuyoshi


    Recently, fixed dental prostheses (FDPs) with a hybrid structure of CAD/CAM porcelain crowns adhered to a CAD/CAM zirconia framework (PAZ) have been developed. The aim of this report was to describe the clinical application of a newly developed implant-supported FDP fabrication system, which uses PAZ, and to evaluate the outcome after a maximum application period of 36 months. Implants were placed in three patients with edentulous areas in either the maxilla or mandible. After the implant fixtures had successfully integrated with bone, gold-platinum alloy or zirconia custom abutments were first fabricated. Zirconia framework wax-up was performed on the custom abutments, and the CAD/CAM zirconia framework was prepared using the CAD/CAM system. Next, wax-up was performed on working models for porcelain crown fabrication, and CAD/CAM porcelain crowns were fabricated. The CAD/CAM zirconia frameworks and CAD/CAM porcelain crowns were bonded using adhesive resin cement, and the PAZ was cemented. Cementation of the implant superstructure improved the esthetics and masticatory efficiency in all patients. No undesirable outcomes, such as superstructure chipping, stomatognathic dysfunction, or periimplant bone resorption, were observed in any of the patients. PAZ may be a potential solution for ceramic-related clinical problems such as chipping and fracture and associated complicated repair procedures in implant-supported FDPs.

  20. EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. (United States)

    Xie, Xiaodong; Li, Fengqiao; Zhang, Huijuan; Lu, Yusheng; Lian, Shu; Lin, Hang; Gao, Yu; Jia, Lee


    Targeted delivery of anticancer agents by functional nanoparticles is an attractive strategy to increase their therapeutic efficacy while reducing toxicity. In this work, doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) were modified with aptamer (Ap) against the epithelial cell adhesion molecule (EpCAM) for targeted delivery of DOX to colon cancer cells. These nanoparticles (Ap-MSN-DOX) were characterized by particle size, zeta potential, aptamer conjugation efficiency, drug encapsulation efficiency, and drug release properties. The in vitro cell recognition, cellular uptake, EpCAM protein inhibition efficiency, and cytotoxicity of Ap-MSN-DOX were also studied. Results demonstrated that EpCAM conjugation increased binding of Ap-MSN-DOX to EpCAM over-expressing SW620 colon cancer cells but not EpCAM-negative Ramos cells, resulting in enhanced cellular uptake and increased cytotoxicity of the DOX in SW620 cells when compared to non-Ap-modified nanoparticles (MSN-DOX). Additionally, Ap-MSN-DOX exhibited significant inhibition effects on the expression of EpCAM on SW620 cells. These results suggested that Ap-MSN-DOX has the potential for the targeted delivery of therapeutic agents into EpCAM positive colon cancer cells to improve therapeutic index while reducing side effects.