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Sample records for clarifying cb2 receptor-dependent

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

    International Nuclear Information System (INIS)

    Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that Δ9-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p m) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher Ψm than did control cells. Since both Ψm and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of IκB-α and JNK was regulated in a CB2R- and THC

  2. Cannabinoid receptor CB2 modulates axon guidance

    DEFF Research Database (Denmark)

    Duff, Gabriel; Argaw, Anteneh; Cecyre, Bruno; Cherif, Hosni; Tea, Nicolas; Zabouri, Nawal; Casanova, Christian; Ptito, Maurice; Bouchard, Jean-François

    2013-01-01

    Navigation of retinal projections towards their targets is regulated by guidance molecules and growth cone transduction mechanisms. Here, we present in vitro and in vivo evidences that the cannabinoid receptor 2 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action ...

  3. Brain CB2 Receptors: Implications for Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Michelle Roche

    2010-08-01

    Full Text Available Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB2 receptor as a possible target for the treatment of neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations are also associated with neuropsychiatric disorders and polymorphisms in the CB2 gene have been reported in depression, eating disorders and schizophrenia. This review will examine the evidence to date for a role of brain CB2 receptors in neuropsychiatric disorders.

  4. Peripheral cannabinoid receptor, CB2, regulates bone mass

    Science.gov (United States)

    Ofek, Orr; Karsak, Meliha; Leclerc, Nathalie; Fogel, Meirav; Frenkel, Baruch; Wright, Karen; Tam, Joseph; Attar-Namdar, Malka; Kram, Vardit; Shohami, Esther; Mechoulam, Raphael; Zimmer, Andreas; Bab, Itai

    2006-01-01

    The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regulation of liver fibrosis and atherosclerosis. Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered. These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling. The CB2–/– phenotype is also characterized by increased activity of trabecular osteoblasts (bone-forming cells), increased osteoclast (the bone-resorbing cell) number, and a markedly decreased number of diaphyseal osteoblast precursors. CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. A CB2-specific agonist that does not have any psychotropic effects enhances endocortical osteoblast number and activity and restrains trabecular osteoclastogenesis, apparently by inhibiting proliferation of osteoclast precursors and receptor activator of NF-κB ligand expression in bone marrow-derived osteoblasts/stromal cells. The same agonist attenuates ovariectomy-induced bone loss and markedly stimulates cortical thickness through the respective suppression of osteoclast number and stimulation of endocortical bone formation. These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling. Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries. PMID:16407142

  5. CB2 Cannabinoid Receptor As Potential Target against Alzheimer's Disease

    Science.gov (United States)

    Aso, Ester; Ferrer, Isidro

    2016-01-01

    The CB2 receptor is one of the components of the endogenous cannabinoid system, a complex network of signaling molecules and receptors involved in the homeostatic control of several physiological functions. Accumulated evidence suggests a role for CB2 receptors in Alzheimer's disease (AD) and indicates their potential as a therapeutic target against this neurodegenerative disease. Levels of CB2 receptors are significantly increased in post-mortem AD brains, mainly in microglia surrounding senile plaques, and their expression levels correlate with the amounts of Aβ42 and β-amyloid plaque deposition. Moreover, several studies on animal models of AD have demonstrated that specific CB2 receptor agonists, which are devoid of psychoactive effects, reduce AD-like pathology, resulting in attenuation of the inflammation associated with the disease but also modulating Aβ and tau aberrant processing, among other effects. CB2 receptor activation also improves cognitive impairment in animal models of AD. This review discusses available data regarding the role of CB2 receptors in AD and the potential usefulness of specific agonists of these receptors against AD. PMID:27303261

  6. Stimulation of cannabinoid receptor 2 (CB2 suppresses microglial activation

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    Fernandez Francisco

    2005-12-01

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

  7. The numerical benchmark CB2-S, final evaluation

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Bouskila, Joseph; Javadi, Pasha; Casanova, Christian;

    2013-01-01

    presence of CB2R in the neural component of the retina. We therefore thoroughly examined the cellular localization of CB2R in the vervet monkey (Chlorocebus sabeus) retina, using confocal microscopy. Our results demonstrate that CB2R, like CB1R, is present throughout the retinal layers, but with striking...... dissimilarities. Double labeling of CB2R and glutamine synthetase shows that CB2R is restricted to Müller cell processes, extending from the internal limiting membrane, with very low staining, to the external limiting membrane, with heavy labeling. We conclude that CB2R is indeed present in the retina but...

  9. CB2 result evaluation (VVER-440 burnup credit benchmark)

    International Nuclear Information System (INIS)

    The second portion of the four-piece international calculational benchmark on the VVER burnup credit (CB2) prepared in the collaboration with the OECD/NEA/NSC Burnup Credit Criticality Benchmarks Working Group and proposed to the AER research community has been evaluated. The evaluated results of calculations performed by analysts from Cuba, the Czech Republic, Finland, Germany, Russia, Slovakia and the United Kingdom are presented. The goal of this study is to compare isotopic concentrations calculated by the participants using various codes and libraries for depletion of the VVER-440 fuel pin cell. No measured values were available for the comparison. (author)

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

    Directory of Open Access Journals (Sweden)

    Emmanuel S Onaivi

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

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

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    Balázs Csóka

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

  12. Results of the isotopic concentrations of VVER calculational burnup credit benchmark No. 2(CB2)

    International Nuclear Information System (INIS)

    Results of the nuclide concentrations are presented of VVER Burnup Credit Benchmark No. 2(CB2) that were performed in The Nuclear Technology Center of Cuba with available codes and libraries. The CB2 benchmark specification as the second phase of the VVER burnup credit benchmark is summarized. The CB2 benchmark focused on VVER burnup credit study proposed on the 97' AER Symposium. The obtained results are isotopic concentrations of spent fuel as a function of the burnup and cooling time. The depletion point 'ORIGEN2' code and other codes were used for the calculation of the spent fuel concentration. (author)

  13. The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

    Science.gov (United States)

    Bow, Eric W.; Rimoldi, John M.

    2016-01-01

    The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

  14. The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation.

    Science.gov (United States)

    Bow, Eric W; Rimoldi, John M

    2016-01-01

    The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (-)-Δ(9)-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure-CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure-activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure-activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

  15. Results of the isotopic concentrations of WWER calculation Burnup Credit Benchmark NO.2 (CB2)

    International Nuclear Information System (INIS)

    The purpose of this document is to present the results of the nuclide concentrations of the WWER Burnup Credit Benchmark NO.2 (CB2) that were performed in The Nuclear Technology Center of Cuba with available codes and libraries. The CB2 benchmark specification as the second phase of the WWER burnup credit benchmark is summarized in [1]. The CB2 benchmark focused on WWER burnup credit study proposed on the 97' Atomic Energy Research symposium [2]. The obtained results are isotopic concentrations of spent fuel as a function of the burnup and cooling time. The depletion point 'ORIGEN2'[3] code was used for the calculation of the spent fuel concentration. This work also comprises the results obtained by other codes [4]. (Author)

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

    OpenAIRE

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

    2011-01-01

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

  17. Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Joseph Bouskila

    2016-01-01

    Full Text Available The expression patterns of the cannabinoid receptor type 1 (CB1R and the cannabinoid receptor type 2 (CB2R are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells and CB2R is exclusively found in the retinal glia (Müller cells. However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp. in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function.

  18. Results of the isotopic concentrations of VVER calculational burnup credit benchmark no. 2(cb2

    International Nuclear Information System (INIS)

    The characterization of the irradiated fuel materials is becoming more important with the Increasing use of nuclear energy in the world. The purpose of this document is to present the results of the nuclide concentrations calculated Using Calculation VVER Burnup Credit Benchmark No. 2(CB2). The calculations were Performed in The Nuclear Technology Center of Cuba. The CB2 benchmark specification as the second phase of the VVER burnup credit benchmark is Summarized in [1]. The CB2 benchmark focused on VVER burnup credit study proposed on the 97' AER Symposium [2]. It should provide a comparison of the ability of various code systems And data libraries to predict VVER-440 spent fuel isotopes (isotopic concentrations) using Depletion analysis. This phase of the benchmark calculations is still in progress. CB2 should be finished by summer 1999 and evaluated results could be presented on the next AER Symposium. The obtained results are isotopic concentrations of spent fuel as a function of the burnup and Cooling time. The depletion point ORIGEN2[3] code was used for the calculation of the spent Fuel concentration. The depletion analysis was performed using the VVER-440 irradiated fuel assemblies with in-core Irradiation time of 3 years, burnup of the 30000 mwd/TU, and an after discharge cooling Time of 0 and 1 year. This work also comprises the results obtained by other codes[4].

  19. Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

    Science.gov (United States)

    Bouskila, Joseph; Harrar, Vanessa; Javadi, Pasha; Beierschmitt, Amy; Palmour, Roberta; Casanova, Christian; Bouchard, Jean-François; Ptito, Maurice

    2016-01-01

    The expression patterns of the cannabinoid receptor type 1 (CB1R) and the cannabinoid receptor type 2 (CB2R) are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells) and CB2R is exclusively found in the retinal glia (Müller cells). However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp.) in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function. PMID:27069692

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

    Science.gov (United States)

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

    2011-09-01

    Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist SR144528 blocked both antiallodynic effects of (R,S)-AM1241 self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241 self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain. PMID:21550725

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

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    Krishna Vukoti

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

  2. Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.

    Science.gov (United States)

    Hu, Jianping; Feng, Zhiwei; Ma, Shifan; Zhang, Yu; Tong, Qin; Alqarni, Mohammed Hamed; Gou, Xiaojun; Xie, Xiang-Qun

    2016-06-27

    Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse. The lack of an experimental three-dimensional CB2 structure has hindered not only the development of studies of conformational differences between the inactive and active CB2 but also the rational discovery of novel functional compounds targeting CB2. In this work, we constructed models of both inactive and active CB2 by homology modeling. Then we conducted two comparative 100 ns molecular dynamics (MD) simulations on the two systems-the active CB2 bound with both the agonist and G protein and the inactive CB2 bound with inverse agonist-to analyze the conformational difference of CB2 proteins and the key residues involved in molecular recognition. Our results showed that the inactive CB2 and the inverse agonist remained stable during the MD simulation. However, during the MD simulations, we observed dynamical details about the breakdown of the "ionic lock" between R131(3.50) and D240(6.30) as well as the outward/inward movements of transmembrane domains of the active CB2 that bind with G proteins and agonist (TM5, TM6, and TM7). All of these results are congruent with the experimental data and recent reports. Moreover, our results indicate that W258(6.48) in TM6 and residues in TM4 (V164(4.56)-L169(4.61)) contribute greatly to the binding of the agonist on the basis of the binding energy decomposition, while residues S180-F183 in extracellular loop 2 (ECL2) may be of importance in recognition of the inverse agonist. Furthermore, pharmacophore modeling and virtual screening were carried out for the inactive and active CB2 models in parallel. Among all 10 hits, two compounds exhibited novel scaffolds and can be used as novel chemical probes for future studies of CB2. Importantly, our studies show that the hits obtained from the inactive CB2 model mainly act as inverse agonist(s) or neutral

  3. Design, synthesis and evaluation of fluorescent CB2 cannabinoid receptor ligands

    OpenAIRE

    Holt, Christopher James

    2009-01-01

    Cannabis has been used as a medicinal and natural product for thousands of years. Whether it has been used to make rope or paper, or been used to treat pain or depression, cannabis has always had a place in human civilisation. With the isolation of the psychoactive compounds responsible for cannabis’ effects, the discovery of two human cannabinoid receptors and an expanding knowledge of the therapeutic uses of cannabis, interest in the development of novel cannabinoids grew. The CB2 cann...

  4. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists.

    Science.gov (United States)

    Altun, Ahmet; Yildirim, Kemal; Ozdemir, Ercan; Bagcivan, Ihsan; Gursoy, Sinan; Durmus, Nedim

    2015-09-01

    Cannabinoid CB1 and CB2 receptor antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance. The aim of this study was to investigate the effects of AM251 (a selective CB1 antagonist) and JTE907 (a selective CB2 antagonist) on morphine analgesia and tolerance in rats. Adult male Wistar albino rats weighing 205-225 g were used in these experiments. To constitute morphine tolerance, we used a 3 day cumulative dosing regimen. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated by analgesia tests. The analgesic effects of morphine (5 mg/kg), ACEA (a CB1 receptor agonist, 5 mg/kg), JWH-015 (a CB2 receptor agonist, 5 mg/kg), AM251 (1 mg/kg) and JTE907 (5 mg/kg) were considered at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. Our findings indicate that ACEA and JWH907 significantly increased morphine analgesia and morphine antinociceptive tolerance in the analgesia tests. In contrast, the data suggested that AM251 and JTE907 significantly attenuated the expression of morphine tolerance. In conclusion, we observed that co-injection of AM251 and JTE907 with morphine attenuated expression of tolerance to morphine analgesic effects and decreased the morphine analgesia. PMID:25894754

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

    Science.gov (United States)

    Dhopeshwarkar, Amey; Mackie, Ken

    2016-08-01

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

  6. CB2 receptor agonists protect human dopaminergic neurons against damage from HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Shuxian Hu

    Full Text Available Despite the therapeutic impact of anti-retroviral therapy, HIV-1-associated neurocognitive disorder (HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Recent work suggests that the nigrostriatal dopaminergic area is a critical brain region for the neuronal dysfunction and death seen in HAND and that human dopaminergic neurons have a particular sensitivity to gp120-induced damage, manifested as reduced function (decreased dopamine uptake, morphological changes, and reduced viability. Synthetic cannabinoids inhibit HIV-1 expression in human microglia, suppress production of inflammatory mediators in human astrocytes, and there is substantial literature demonstrating the neuroprotective properties of cannabinoids in other neuropathogenic processes. Based on these data, experiments were designed to test the hypothesis that synthetic cannabinoids will protect dopaminergic neurons against the toxic effects of the HIV-1 protein gp120. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, we were able to show that the CB1/CB2 agonist WIN55,212-2 blunts gp120-induced neuronal damage as measured by dopamine transporter function, apoptosis and lipid peroxidation; these actions were mediated principally by the CB2 receptor. Adding supplementary human microglia to our cultures enhances gp120-induced damage; WIN55,212-2 is able to alleviate this enhanced damage. Additionally, WIN55,212-2 inhibits gp120-induced superoxide production by purified human microglial cells, inhibits migration of human microglia towards supernatants generated from gp120-stimulated human mesencephalic neuronal/glial cultures and reduces chemokine and cytokine production from the human mesencephalic neuronal/glial cultures. These data suggest that synthetic cannabinoids are capable of protecting human dopaminergic neurons from

  7. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

    Directory of Open Access Journals (Sweden)

    Eleftheria Lakiotaki

    2015-01-01

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  8. Clarifying the Narrative Paradigm.

    Science.gov (United States)

    Fisher, Walter R.

    1989-01-01

    Replies to Rowland's article (same issue) on Fisher's views of the narrative paradigm. Clarifies the narrative paradigm by discussing three senses in which "narration" can be understood, and by indicating what the narrative paradigm is not. (SR)

  9. Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors.

    Science.gov (United States)

    Aghaei, Iraj; Rostampour, Mohammad; Shabani, Mohammad; Naderi, Nima; Motamedi, Fereshteh; Babaei, Parvin; Khakpour-Taleghani, Behrooz

    2015-11-01

    Epilepsy is one of the most common neurologic disorders. Though there are effective medications available to reduce the symptoms of the disease, their side effects have limited their usage. Palmitoylethanolamide (PEA) has been shown to attenuate seizure in different animal models. The objective of the current study was to evaluate the role of CB1 and CB2 receptors in this attenuation. Male wistar rats were used for the current experiment. PTZ was injected to induce chemical kindling in animals. After verification of kindling in animals, treatment was performed with PEA, AM251 and AM630 in different groups. Latency to induce seizure, seizure stages and latency and duration of fifth stage of seizure was recorded for each animal. Injection of PTZ led to seizure in the animals. Pretreatment with PEA increased the latency to initiate seizures and reduced the duration of seizure. Pretreatment with different dosages of AM251 had contrary effects so that at lower doses they increased the seizure in animals but at higher doses led to the attenuation of seizure. AM630 increased seizures in a dose dependent manner. Combination of the antagonists increased the seizure parameters and attenuated the effect of PEA on seizure. PEA attenuated the PTZ-induced seizures and pretreatment with CB1 and CB2 antagonists diminished this effect of PEA, but still PEA was effective, which might be attributed to the contribution of other receptors in PEA anti-epileptic properties. Findings of the current study implied that endocannabinoid signaling pathway might have an important role in the effects of PEA. PMID:26370914

  10. Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

    Science.gov (United States)

    Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. PMID:26577751

  11. Treatment with CB2 Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

    Directory of Open Access Journals (Sweden)

    Rodrigo Araujo Fraga-Silva

    2013-01-01

    Full Text Available Hypercholesterolemia is one of the most important risk factors for erectile dysfunction, mostly due to the impairment of oxidative stress and endothelial function in the penis. The cannabinoid system might regulate peripheral mechanisms of sexual function; however, its role is still poorly understood. We investigated the effects of CB2 activation on oxidative stress and fibrosis within the corpus cavernosum of hypercholesterolemic mice. Apolipoprotein-E-knockout mice were fed with a western-type diet for 11 weeks and treated with JWH-133 (selective CB2 agonist or vehicle during the last 3 weeks. CB2 receptor expression, total collagen content, and reactive oxygen species (ROS production within the penis were assessed. In vitro corpus cavernosum strips preparation was performed to evaluate the nitric oxide (NO bioavailability. CB2 protein expression was shown in cavernosal endothelial and smooth muscle cells of wild type and hypercholesterolemic mice. Treatment with JWH-133 reduced ROS production and NADPH-oxidase expression in hypercholesterolemic mice penis. Furthermore, JWH-133 increased endothelial NO synthase expression in the corpus cavernosum and augmented NO bioavailability. The decrease in oxidative stress levels was accompanied with a reduction in corpus cavernosum collagen content. In summary, CB2 activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice.

  12. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  13. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  14. Residues accessible in the binding site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor†

    OpenAIRE

    Nebane, Ntsang M.; Hurst, Dow P.; Carrasquer, Carl A.; Qiao, Zhuanhong; Reggio, Patricia H.; Song, Zhao-Hui

    2008-01-01

    We have used the substituted-cysteine accessibility method (SCAM) to map the residues in the sixth membrane-spanning segment of the CB2 cannabinoid receptor that contribute to the surface of the water-accessible binding-site crevice. Using a background of the mutant C2.59S which is relatively insensitive to the methanethiosulfonate (MTS) reagents, we mutated to cysteine, one at a time, 34 consecutive residues in TMH6 of the CB2 receptor. These mutant receptors were then expressed in HEK293 ce...

  15. Clarifying geothermal fluids

    Energy Technology Data Exchange (ETDEWEB)

    Dahlstrom, D.A.; Emmett, R.C.; Moore, R.W.

    1982-10-01

    The way a solids-contact clarifier for promoting crystal growth was tied in with a filter so that reinjection of the brines from geothermal wells, which requires separation of fine solids after desupersaturation of silica, could be achieved is described. The method involves utilizing a Reactor-Clarifier machine to reduce silica to the saturation point without addition of chemicals. Simultaneously, scaling was prevented by using the internally recycled solids as seed for crystal growth. By recirculating thickened solids to the pressure flash vessels and crystallizers employed for steam generation, scaling can be eliminated. Pressure filtration can be used to produce dewatered solids which can be disposed of in an environmentally acceptable way. Spent brine clarified by granular dual-media filters can be reinjected into the formation at a reasonably constant volumetric rate per unit of pressure drop. Inorganic by-products from the spent brine could be produced. Suggests that air-brine contact be prevented for brine reinjection to prevent precipitation of such compounds as ferric hydroxide. Concludes that total costs per kWh of electrical production appear reasonable.

  16. SEM, TEM and SLEEM (scanning low energy electron microscopy) of CB2 steel after creep testing

    International Nuclear Information System (INIS)

    The demand to produce electrical power with higher efficiency and with lower environmental pollution is leading to the use of new advanced materials in the production of power plant equipment. To understand the processes taking place in parts produced from these materials during their operation under severe conditions (such as high temperature, high stress, and environmental corrosion) requires detailed evaluation of their substructure. It is usually necessary to use transmission electron microscopy (TEM). However, this method is very exacting and time-consuming. So there is an effort to use new scanning electron microscopy techniques instead of TEM. One of them is scanning low energy electron microscopy (SLEEM). This paper deals with an assessment of the possibility to use SLEEM for describing the substructure of creep resistant steel CB2 after long-term creep testing. In the SLEEM images more information is contained about the microstructure of the material in comparison with standard scanning electron microscopy. Study of materials using slow and very slow electrons opens the way to better understanding their microstructures

  17. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

    2013-11-15

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  18. Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor.

    Science.gov (United States)

    Nebane, Ntsang M; Hurst, Dow P; Carrasquer, Carl A; Qiao, Zhuanhong; Reggio, Patricia H; Song, Zhao-Hui

    2008-12-30

    We have used the substituted-cysteine accessibility method (SCAM) to map the residues in the sixth membrane-spanning segment of the CB2 cannabinoid receptor that contribute to the surface of the water-accessible binding-site crevice. Using a background of the mutant C2.59S which is relatively insensitive to the methanethiosulfonate (MTS) reagents, we mutated to cysteine, one at a time, 34 consecutive residues in TMH6 of the CB2 receptor. These mutant receptors were then expressed in HEK293 cells. By incubating HEK293 cells stably transfected with CB2 receptors with the small, charged, hydrophilic, thiol-specific reagent methanethiosulfonate ethylammonium (MTSEA), [(3)H]CP55940 binding was significantly inhibited for six mutant receptors. All six of the mutants that reacted with MTSEA were protected from the reaction when pretreated with the cannabinoid agonist WIN55212-2, suggesting that MTSEA modification occurred within the binding crevice. Therefore, the side chains of the residues at these reactive loci (V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62) are on the water-accessible surface of the binding-site crevice. These residues are extracellular to the TMH6 CWXP hinge motif. The pattern of accessibility is consistent with a alpha-helical conformation for this segment of TMH6. Molecular modeling studies performed in the context of the CB2 model show that V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62 face into the CB2 binding pocket, further confirming our SCAM results. These results are similar to the accessibility patterns determined by SCAM studies of TMH6 in the opioid and dopamine D2 receptors. PMID:19053233

  19. Activation of Cannabinoid CB2 receptors Reduces Hyperalgesia in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis

    OpenAIRE

    Fu, Weisi; Taylor, Bradley K.

    2015-01-01

    Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. 4 weeks after induction of experimental autoimmune encephalomyelitis, we found that intrathecal administration of JWH-133 (10–100 μg...

  20. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors

    OpenAIRE

    Járai, Zoltán; Wagner, Jens A.; Varga, Károly; Lake, Kristy D.; Compton, David R.; Martin, Billy R.; Zimmer, Anne M.; Bonner, Tom I.; Buckley, Nancy E.; Mezey, Eva; Razdan, Raj K; Zimmer, Andreas; Kunos, George

    1999-01-01

    Cannabinoids, including the endogenous ligand arachidonyl ethanolamide (anandamide), elicit not only neurobehavioral but also cardiovascular effects. Two cannabinoid receptors, CB1 and CB2, have been cloned, and studies with the selective CB1 receptor antagonist SR141716A have implicated peripherally located CB1 receptors in the hypotensive action of cannabinoids. In rat mesenteric arteries, anandamide-induced vasodilation is inhibited by SR141716A, but other potent CB1 receptor agonists, suc...

  1. Biological characterization of PM226, a chromenoisoxazole, as a selective CB2 receptor agonist with neuroprotective profile.

    Science.gov (United States)

    Gómez-Cañas, M; Morales, P; García-Toscano, L; Navarrete, C; Muñoz, E; Jagerovic, N; Fernández-Ruiz, J; García-Arencibia, M; Pazos, M R

    2016-08-01

    Cannabinoids have emerged as promising neuroprotective agents due to their capability to activate specific targets, which are involved in the control of neuronal homeostasis and survival. Specifically, those ligands that selectively target and activate the CB2 receptor may be useful for their anti-inflammatory and neuroprotective properties in various neurological disorders, with the advantage of being devoid of psychotropic effects associated with the activation of CB1 receptors. The aim of this work has been to investigate the neuroprotective properties of 7-(1,1-dimethylheptyl)-4,4-dimethyl-9-methoxychromeno[3,4-d]isoxazole (PM226), a compound derived from a series of chromeno-isoxazoles and -pyrazoles, which seems to have a promising profile related to the CB2 receptor. The compound binds selectively to this receptor with an affinity in the nanomolar range (Ki=12.8±2.4nM). It has negligible affinity for the CB1 receptor (Ki>40000nM) and no activity at the GPR55. PM226 was also evaluated in GTPγS binding assays specific to the CB2 receptor showing agonist activity (EC50=38.67±6.70nM). In silico analysis of PM226 indicated that it has a good pharmacokinetic profile and a predicted ability to cross the blood-brain barrier. Next, PM226 was investigated in an in vitro model to explore its anti-inflammatory/neuroprotective properties. Conditioned media were collected from LPS-stimulated cultures of BV2 microglial cell line in the absence or presence of different doses of PM226, and then media were added to cultured M213-2O neuronal cells to record their influence on cell viability evaluated using MTT assays. As expected, cell viability was significantly reduced by the exposure to these conditioned media, while the addition of PM226 attenuated this reduction in a dose-dependent manner. This effect was reversed by co-incubating with the CB2 antagonist SR144528, thus confirming the involvement of CB2 receptors, whereas the addition of PM226 to neuronal cultures

  2. Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors.

    Science.gov (United States)

    Priller, J; Briley, E M; Mansouri, J; Devane, W A; Mackie, K; Felder, C C

    1995-08-01

    The recently discovered endogenous agonist for the cannabinoid receptor, anandamide (arachidonylethanolamide), can be formed enzymatically by the condensation of arachidonic acid with ethanolamine. 5Z,8Z,11Z-Eicosatrienoic acid (mead acid) has been found to substitute for arachidonic acid in the sn-2 position of phospholipids and accumulate during periods of dietary fatty acid deprivation in rats. In the present study, the chemically synthesized ethanolamide of mead acid was evaluated as a potential agonist at the two known subtypes of cannabinoid receptor: CB1 (central) and CB2 (peripheral). This compound was equipotent to anandamide in competing with [3H]CP55,940 binding to plasma membranes prepared from L cells expressing the human CB1 receptor and from ATt-20 cells expressing the human CB2 receptor. Mead ethanolamide was also equipotent to anandamide in inhibiting forskolin-stimulated cAMP accumulation in cells expressing the CB1 receptor. It inhibited N-type calcium currents with a lower potency than anandamide. Mead and arachidonic acid were equally efficacious as substrates for the enzymatic synthesis of their respective ethanolamides in rat and adult human hippocampal P2 membranes. Palmitic acid was not an effective substrate for the enzymatic synthesis of palmitoyl ethanolamide. Mead ethanolamide exhibits several characteristics of a novel agonist to CB1 and CB2 receptors and may represent another candidate endogenous ligand for the CB1 receptor. Due to the anticonvulsant properties of GABA and the positional similarity of L-serine to ethanolamine in membrane phospholipids, these compounds were synthetically coupled to arachidonic acid, and their resulting arachidonamides were tested as potential cannabinoid agonists. The arachidonamides of GABA and L-serine were inactive in both binding and functional assays at the CB1 receptor. PMID:7651362

  3. Targeting the cannabinoid CB2 receptor to attenuate the progression of motor deficits in LRRK2-transgenic mice.

    Science.gov (United States)

    Palomo-Garo, Cristina; Gómez-Gálvez, Yolanda; García, Concepción; Fernández-Ruiz, Javier

    2016-08-01

    Most of cases of Parkinson's disease (PD) have a sporadic origin, with their causes mostly unknown, although overexposure to some environmental factors has been found to occur in some cases. Other forms of parkinsonism are the consequence of dominant or recessive mutations in specific genes, e.g. α-synuclein, parkin and, more recently, leucine-rich repeat kinase 2 (LRRK2), whose G2019S mutation represents the most prevalent form of late-onset, autosomal dominant familial PD. A transgenic mouse model expressing the G2019S mutation of LRRK2 is already available and apparently may represent a valuable experimental model for investigating PD pathogenesis and novel treatments. We designed a long-term study with these animals aimed at: (i) elucidating the changes experienced by the endocannabinoid signaling system in the basal ganglia during the progression of the disease in these mice, paying emphasis in the CB2 receptor, which has emerged as a promising target in PD, and (ii) evaluating the potential of compounds selectively activating this CB2 receptor, as disease-modifying agents in these mice. Our results unequivocally demonstrate that LRRK2 transgenic mice develop motor impairment consisting of small anomalies in rotarod performance (presumably reflecting a deficit in motor coordination and dystonia) and a strong deficiency in the hanging-wire test (reflecting muscle weakness), rather than hypokinesia which was difficult to be demonstrated in the actimeter. These behavioral responses occurred in absence of any evidence of reactive gliosis and neuronal losses, as well as synaptic deterioration in the basal ganglia, except an apparent impairment in autophagy reflected by elevated LAMP-1 immunolabelling in the striatum and substantia nigra. Furthermore, there were no changes in the status of the CB2 receptor, as well as in other elements of the endocannabinoid signaling, in the basal ganglia, but, paradoxically, the selective activation of this receptor partially

  4. CALCULATION OF MAGNETIC OIL CLARIFIER

    OpenAIRE

    Puzik, S. O.; National Aviation University; Shevchuk, V. S.; National Aviation University; Baranivskiy, Y. O.; National Aviation University; Mykhailenko, O. O.; National Aviation University

    2013-01-01

    Technology of oil cleaning from iron-containing impurities that shows the feasibility of magnetic cleaners applying was investigated. Comparative analysis of the types of magnetic clarifier was carried out. Procedure of calculating the dimension type of oil clarifier, which makes it possible to obtain high purity grade oil, was offered.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-05

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

  6. Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.

    Science.gov (United States)

    Rock, Erin M; Boulet, Nathalie; Limebeer, Cheryl L; Mechoulam, Raphael; Parker, Linda A

    2016-09-01

    We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting. PMID:27263826

  7. Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment.

    Science.gov (United States)

    Martín-Saldaña, Sergio; Trinidad, Almudena; Ramil, Elvira; Sánchez-López, Antonio J; Coronado, Maria José; Martínez-Martínez, Esther; García, José Miguel; García-Berrocal, José Ramón; Ramírez-Camacho, Rafael

    2016-01-01

    We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2 receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways. PMID:27564061

  8. Method of operating centrifugal clarifier

    International Nuclear Information System (INIS)

    The present invention concerns a method of operating a centrifugal clarifier for spent nuclear fuel reprocessing. That is, clarified liquid containing useful ingredients dissolved therein and sludge ingredients are separated centrifugally by rotating a bottom-opened cylindrical bawl. In this case, the rotation of the cylindrical bawl is stopped to discharge and recover the clarified liquid remaining in the bawl from the bottom thereof. Further, sludge deposition layers are left in the bawl and they are rinsed to recover the useful ingredients. With this method, it is possible to reduce the amount of the rinsing liquid used as compared with the conventional method and also shorten the rinsing operation time compared with the conventional method. Furthermore, since useful ingredients contained in the sludge depositions, for example, U and Pu solutions can be recovered, their losses can be reduced remarkably. (I.S.)

  9. Clarifying the Construct of Perfectionism

    Science.gov (United States)

    Stairs, Agnes M.; Smith, Gregory T.; Zapolski, Tamika C. B.; Combs, Jessica L.; Settles, Regan E.

    2012-01-01

    The construct of perfectionism is related to many important outcome variables. However, the term "perfectionism" has been defined in many different ways, and items comprising the different existing scales appear to be very different in content. The overarching aim of the present set of studies was to help clarify the specific unidimensional…

  10. Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

    OpenAIRE

    Sisay, S.; Pryce, G.; Jackson, S. J.; Tanner, C.; Ross, R A; Michael, G. J.; Selwood, D. L.; Giovannoni, G; Baker, D.

    2013-01-01

    Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim)) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatmen...

  11. Continuation of the VVER burnup credit benchmark. Evaluation of CB1 results, overview of CB2 results to date, and specification of CB3

    International Nuclear Information System (INIS)

    A calculational benchmark focused on VVER-440 burnup credit, similar to that of the OECD/NEA/NSC Burnup Credit Benchmark Working Group, was proposed on the 96'AER Symposium. Its first part, CB1, was specified there whereas the second part, CB2, was specified a year later, on 97'AER Symposium in Zittau. A final statistical evaluation is presented of CB1 results and summarizes the CB2 results obtained to date. Further, the effect of an axial burnup profile of VVER-440 spent fuel on criticality ('end effect') is proposed to be studied in the CB3 benchmark problem of an infinite array of VVER-440 spent fuel rods. (author)

  12. CB2-Selective Cannabinoid Receptor Ligands: Synthesis, Pharmacological Evaluation, and Molecular Modeling Investigation of 1,8-Naphthyridin-2(1H)-one-3-carboxamides

    OpenAIRE

    Lucchesi, Valentina; Hurst, Dow P.; Shore, Derek M.; Bertini, Simone; Ehrmann, Brandie M.; Allarà, Marco; Lawrence, Lyle; Ligresti, Alessia; Minutolo, Filippo; Saccomanni, Giuseppe; Sharir, Haleli; Macchia, Marco; Di Marzo, Vincenzo; Abood, Mary E.; Reggio, Patricia H.

    2014-01-01

    We have recently identified 1,8-naphthyridin-2(1H)-one-3-carboxamide as a new scaffold very suitable for the development of new CB2 receptor potent and selective ligands. In this paper we describe a number of additional derivatives in which the same central scaffold has been variously functionalized in position 1 or 6. All new compounds showed high selectivity and affinity in the nanomolar range for the CB2 receptor. Furthermore, we found that their functional activity is controlled by the pr...

  13. Conscious observers clarify many worlds

    CERN Document Server

    Simon, Christoph

    2009-01-01

    In this brief note I argue that putting conscious observers at the center of the considerations clarifies and strengthens the many-worlds interpretation. The basic assumption, which seems extremely plausible based on our current understanding of the brain and of decoherence, is that quantum states corresponding to distinct conscious experiences have to be orthogonal. I show that, once this is accepted, probabilistic measurement outcomes corresponding to basis elements and following Born's rule emerge naturally from global unitary dynamics.

  14. HYDRAULIC CHARACTERISTICS OF ACTIVATED SLUDGE SECONDARY CLARIFIERS

    Science.gov (United States)

    This study documented the hydraulic characteristics of typical activated sludge clarifiers. Modifications to the clarifier structures were made in an attempt to improve clarifier hydraulic characteristics and performance. Innovative fluorometric dye tracer studies were used to ob...

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

    Directory of Open Access Journals (Sweden)

    Sofia Sisay

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

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

    Science.gov (United States)

    Sisay, Sofia; Pryce, Gareth; Jackson, Samuel J; Tanner, Carolyn; Ross, Ruth A; Michael, Gregory J; Selwood, David L; Giovannoni, Gavin; Baker, David

    2013-01-01

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

  17. Continuation of the WWER burnup credit benchmark: evaluation of CB1 results, overview of CB2 results to date, and specification of CB3

    International Nuclear Information System (INIS)

    A calculational benchmark focused on WWER-440 burnup credit, simular to that of the OECD/NEA/NSC Burnup Credit Criticality Benchmark Working Group, was proposed on the 96'AER Symposium. Its first part, CB1, was specified there whereas the second part, CB2, was specified a year later, on 97'AER Symposium in Zittau. This paper brings a final statistical evaluation of CB1 results and summarizes the CB2 results obtained to date. Further, the effect of an axial burnup profile of WWER-440 spent fuel on criticality ('end effect') is proposed to be studied in the CB3 benchmark problem of an infinite array of WWER-440 spent fuel rods as specified in the paper. (Authors)

  18. Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β Amyloid via Protein Kinase C

    Directory of Open Access Journals (Sweden)

    Ji Jia

    2016-01-01

    Full Text Available Background. Reducing β amyloid- (Aβ- induced microglial activation is considered to be effective in treating Alzheimer’s disease (AD. Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state or alternative activated state (M2 state; the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. Methods. We used Aβ1–42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA. Results. We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS expression and tumor necrosis factor α (TNF-α and interleukin- (IL- 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1 expression and brain-derived neurotrophic factor (BDNF release, in the Aβ-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC inhibitor partially abolished the nicotine-induced effects. Conclusion. These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Aβ via PKC.

  19. DENSITY CURRENTS IN ACTIVATED SLUDGE SECONDARY CLARIFIERS

    Science.gov (United States)

    Density currents form in activated sludge secondary clarifiers because the mixed liquor has a density greater than the treated wastewater in the clarifier. This causes the mixed liquor to plunge to the bottom of the clarifier establishing relatively high velocity currents within ...

  20. Sativex-like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Huntington's disease: role of CB1 and CB2 receptors.

    Science.gov (United States)

    Valdeolivas, Sara; Satta, Valentina; Pertwee, Roger G; Fernández-Ruiz, Javier; Sagredo, Onintza

    2012-05-16

    We have investigated whether a 1:1 combination of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation. We monitored the extent of this damage and the possible preservation of the striatal parenchyma by treatment with a Sativex-like combination of phytocannabinoids using different histological and biochemical markers. Results were as follows: (i) malonate increased the volume of edema measured by in vivo NMR imaging and the Sativex-like combination of phytocannabinoids partially reduced this increase; (ii) malonate reduced the number of Nissl-stained cells, while enhancing the number of degenerating cells stained with FluoroJade-B, and the Sativex-like combination of phytocannabinoids reversed both effects; (iii) malonate caused a strong glial activation (i.e., reactive microglia labeled with Iba-1, and astrogliosis labeled with GFAP) and the Sativex-like combination of phytocannabinoids attenuated both responses; and (iv) malonate increased the expression of inducible nitric oxide synthase and the neurotrophin IGF-1, and both responses were attenuated after the treatment with the Sativex-like combination of phytocannabinoids. We also wanted to establish whether targets within the endocannabinoid system (i.e., CB(1) and CB(2) receptors) are involved in the beneficial effects induced in this model by the Sativex-like combination of phytocannabinoids. This we did using selective antagonists for both receptor types (i.e., SR141716 and AM630) combined with the Sativex-like phytocannabinoid combination. Our results indicated that the effects of this

  1. COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord

    Directory of Open Access Journals (Sweden)

    Bountra Chas

    2006-03-01

    Full Text Available Abstract Background While multiple sclerosis (MS and amyotrophic lateral sclerosis (ALS are primarily inflammatory and degenerative disorders respectively, there is increasing evidence for shared cellular mechanisms that may affect disease progression, particularly glial responses. Cyclooxygenase 2 (COX-2 inhibition prolongs survival and cannabinoids ameliorate progression of clinical disease in animal models of ALS and MS respectively, but the mechanism is uncertain. Therefore, three key molecules known to be expressed in activated microglial cells/macrophages, COX-2, CB2 and P2X7, which plays a role in inflammatory cascades, were studied in MS and ALS post-mortem human spinal cord. Methods Frozen human post mortem spinal cord specimens, controls (n = 12, ALS (n = 9 and MS (n = 19, were available for study by immunocytochemistry and Western blotting, using specific antibodies to COX-2, CB2 and P2X7, and markers of microglial cells/macrophages (CD 68, ferritin. In addition, autoradiography for peripheral benzodiazepine binding sites was performed on some spinal cord sections using [3H] (R-PK11195, a marker of activated microglial cells/macrophages. Results of immunostaining and Western blotting were quantified by computerized image and optical density analysis respectively. Results In control spinal cord, few small microglial cells/macrophages-like COX-2-immunoreactive cells, mostly bipolar with short processes, were scattered throughout the tissue, whilst MS and ALS specimens had significantly greater density of such cells with longer processes in affected regions, by image analysis. Inflammatory cell marker CD68-immunoreactivity, [3H] (R-PK11195 autoradiography, and double-staining against ferritin confirmed increased production of COX-2 by activated microglial cells/macrophages. An expected 70-kDa band was seen by Western blotting which was significantly increased in MS spinal cord. There was good correlation between the COX-2 immunostaining

  2. Thiomonas sp. CB2 is able to degrade urea and promote toxic metal precipitation in acid mine drainage waters supplemented with urea

    OpenAIRE

    Farasin, Julien; Andres, Jérémy; Casiot, Corinne; Barbe, Valérie; Faerber, Jacques; Halter, David; Heintz, Dimitri; Koechler, Sandrine; Lièvremont, Didier; Lugan, Raphael; Marchal, Marie; Plewniak, Frédéric; Seby, Fabienne; Bertin, Philippe N; Arsène-Ploetze, Florence

    2015-01-01

    The acid mine drainage (AMD) in Carnoulès (France) is characterized by the presence of toxic metals such as arsenic. Several bacterial strains belonging to the Thiomonas genus, which were isolated from this AMD, are able to withstand these conditions. Their genomes carry several genomic islands (GEIs), which are known to be potentially advantageous in some particular ecological niches. This study focused on the role of the “urea island” present in the Thiomonas CB2 strain, which carry the gen...

  3. El flavonoide CB2 obtenido de chromolaena bullata induce activación de células dendríticas humanas

    OpenAIRE

    Sandra Paola Santander G; Claudia Urueña; Oscar E. Rodríguez; Rubén D. Torrenegra; Susana Fiorentino G

    2007-01-01

    CB2, al igual que los otros flavonoides obtenidos de Chromolaena bullata, fue evaluado sobre células dendríticas y células tumorales humanas, para determinar su actividad antitumoral o inmunorreguladora. Sobre las células tumorales (A375 melanoma humano) induce una depolarización temprana de la membrana mitocondrial, la cual es reversible y no conduce a la muerte. En contraste, el tratamiento de células dendríticas humanas obtenidas a partir de monocitos de sangre periférica...

  4. A method for regenerating clarifying coal

    Energy Technology Data Exchange (ETDEWEB)

    Parfent' yeva, N.A.; Barteneva, A.G.; Khal' kin, Yu.I.; Kravchenko, E.A.; Minakova, V.I.; Norinskaya, T.I.; Shkarbanov, N.A.

    1984-01-01

    A method is patented for regenerating ''clarifying coal'' which includes processing of the coal by a reagent with heating and subsequent washing with water. The method is distinguished by the fact that in order to increase the degree of regeneration, 70 to 100 percent H2S04 or oleum is used as the reagent and the process is conducted at 150 to 160 degrees. Example. Ten grams of a clarifying coal collactivite with a moisture content of 20 degrees, used for clarifying a hydrolizate, is processed by 13 grams per milliliter of 70 percent H2S04 at 160 degrees for 10 minutes, after which the mixture is washed off by 250 milliliters of water through repeated curing with subsequent filtration to an acidity level of 0.1 percent. 8.7 grams of regenerated coal with a clarifying capability of 91.7 percent are produced.

  5. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

    Directory of Open Access Journals (Sweden)

    O'Shea Esther

    2011-05-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

  6. Coagulation in clarifier with micro-sand

    International Nuclear Information System (INIS)

    As water treatment play key role in power generation at thermal and nuclear power station. This article is devoted to determine effectiveness of water clarifier with use of micro-sand at Thermal power stations. Efficiency of coagulation with application of aluminum sulphate and flocculants is experimentally detected. Presented the result of the tests of clarifier with micro-sand and given conclusion on these results. (author)

  7. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Science.gov (United States)

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

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

    Directory of Open Access Journals (Sweden)

    Deng Liting

    2012-09-01

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

  9. Crud removal equipment using a centrifugal clarifier

    International Nuclear Information System (INIS)

    Centrifugal clarifiers have been applied for the treatment of the radioactive liquid wastes in BWR nuclear power stations to reduce the amount of secondary waste, such as filter aid materials generated by pressure precoat filters. Two steps of the R and D programs have been performed before the full-scale operation of the centrifugal clarifiers installed in the Hamaoka NPS 2 radwaste system: one, a cold test at the laboratory, and the other, a pilot plant test at Hamaoka NPS 1. This paper describes the pilot plant test results and the experience gathered from the actual full-scale equipment operation, that is: concentration of the insoluble impurities of the treated liquid wastes has been kept to less than 0.5 ppm, while that of the fluent increased to approximately 100 ppm; sludge volume reduction by the equipment is approximately one tenth of that made by the pressure precoat filters

  10. New QSAR prediction models derived from GPCR CB2-antagonistic triaryl bis-sulfone analogues by a combined molecular morphological and pharmacophoric approach.

    Science.gov (United States)

    Chen, J-Z; Myint, K-Z; Xie, X-Q

    2011-01-01

    In order to build quantitative structure-activity relationship (QSAR) models for virtual screening of novel cannabinoid CB2 ligands and hit ranking selections, a new QSAR algorithm has been developed for the cannabinoid ligands, triaryl bis-sulfones, using a combined molecular morphological and pharmacophoric search approach. Both pharmacophore features and shape complementarity were considered using a number of molecular descriptors, including Surflex-Sim similarity and Unity Query fit, in addition to other molecular properties such as molecular weight, ClogP, molecular volume, molecular area, molecular polar volume, molecular polar surface area and dipole moment. Subsequently, partial least squares regression analyses were carried out to derive QSAR models linking bioactivity and the descriptors mentioned, using a training set of 25 triaryl bis-sulfones. Good prediction capability was confirmed for the best QSAR model by evaluation against a test set of a further 20 triaryl bis-sulfones. The pharmacophore and molecular shape-based QSAR scoring function now established can be used to predict the biological properties of virtual hits or untested compounds obtained from ligand-based virtual screenings. PMID:21714749

  11. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Lemtiri-Chlieh Fouad

    2011-12-01

    Full Text Available Abstract Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP, widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7, a Rho GDP/GTP exchange factor (Rho-GEF localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.

  12. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    KAUST Repository

    Lemtiri-Chlieh, Fouad

    2011-12-19

    Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.

  13. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.

    Science.gov (United States)

    Huang, Wendong; Ma, Ke; Zhang, Jun; Qatanani, Mohammed; Cuvillier, James; Liu, Jun; Dong, Bingning; Huang, Xiongfei; Moore, David D

    2006-04-14

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth. PMID:16614213

  14. Effect of Calpain inhibitor I on glucocorticoid receptor-dependent degradation and its transactivation ability

    Institute of Scientific and Technical Information of China (English)

    程晓刚; 粟永萍; 罗成基; 刘晓宏

    2004-01-01

    Objective: To investigate the effect of Calpain inhibitor I on glucocorticoid receptor-dependent proteasomal degradation and its transcriptional activity. Methods: After Raw-264.7 cells were treated with Calpain inhibitor I, dexamethasone, or both for about 12 h, the change of glucocorticoid receptor was detected by western blot analysis. COS-7 cells were transfected with PRsh-GRα expression vector and glucocorticoid-responsive receptor pMAMneo-CAT, then the effect of Calpain inhibitor I on glucocorticoid receptor transcriptional activation ability was determined by CAT activity. Results: The glucocorticoid receptor levels decreased after RAW-264.7 cells were treated with dexamethasone for 12 hours, which effect can be inhibited by Calpain inhibitor I to some extent. CAT activity assay showed that Calpain inhibitor I enhance glucocorticoid receptor transcriptional activity. Conclusion: Calpain inhibitor I can inhibit the down-regulation of dexamethasone on glucocoaicoid receptor, and enhances glucocorticoid receptor transactivation ability.

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

    OpenAIRE

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

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alter...

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

    OpenAIRE

    EDUARDO eBLANCO-CALVO; PATRICIA eRIVERA; SERGIO eARRABAL; ANTONIO eVARGAS; FRANCISCO JAVIER ePAVON; ANTONIA eSERRANO; PABLO eGALEANO; LETICIA eRUBIO; JUAN eSUAREZ; FERNANDO eRODRIGUEZ DE FONSECA

    2014-01-01

    Addiction to major drugs of abuse such as cocaine has been recently linked to alterations on adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulated this proliferative response since pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors by modulating not only neurogenesis but also cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation . To this...

  17. A Theoretical Study of the Relationships between Electronic Structure and CB1 and CB2 Cannabinoid Receptor Binding Affinity in a Group of 1-Aryl-5-(1-H-pyrrol-1-yl-1-H-pyrazole-3-carboxamides

    Directory of Open Access Journals (Sweden)

    Francisco Salgado-Valdés

    2014-01-01

    Full Text Available We report the results of a search for model-based relationships between hCB1 and hCB2 receptor binding affinity and molecular structure for a group of 1-aryl-5-(1-H-pyrrol-1-yl-1-H-pyrazole-3-carboxamides. The wave functions and local atomic reactivity indices were obtained at the B3LYP/6-31G(d,p levels of theory with full geometry optimization. Interaction pharmacophores were generated for both receptors. The main conclusions of this work are as follows. (1 We obtained statistically significant equations relating the variation of hCB1 and hCB2 receptor binding affinities with the variation of definite sets of local atomic reactivity indices. (2 The interaction of the molecules with the hCB1 and hCB2 receptors seems to be highly complex and mainly orbital controlled. (3 The interaction mechanisms seem to be different for each type of receptor. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.

  18. 21 CFR 178.3295 - Clarifying agents for polymers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Clarifying agents for polymers. 178.3295 Section... SANITIZERS Certain Adjuvants and Production Aids § 178.3295 Clarifying agents for polymers. Clarifying agents may be safely used in polymers that are articles or components of articles intended for use in...

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

    Directory of Open Access Journals (Sweden)

    EDUARDO eBLANCO-CALVO

    2014-01-01

    Full Text Available Addiction to major drugs of abuse such as cocaine has been recently linked to alterations on adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulated this proliferative response since pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors by modulating not only neurogenesis but also cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation . To this end we examined if pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg or CB2 receptors (AM630, 3 mg/kg affects cell proliferation (labeled with BrdU, found in the subventricular zone (SVZ of the lateral ventricles and the dentate subgranular zone (SGZ. In addition, we measured cell apoptosis (monitored by the expression of cleaved caspase-3 and glial activation ( by analizing the expression of GFAP and Iba-1 in the striatum and hippocampus, during acute or repeated (4 days cocaine administration (20 mg/kg. Results showed that acute cocaine decreased the number of BrdU+ cells in SVZ and SGZ. In contrast, repeated cocaine reduced the number of BrdU+ cells in SVZ only. Both acute and repeated cocaine increased the number of cleaved caspase-3+, GFAP+ and Iba1+ cells in the hippocampus, an effect counteracted by AM630 or Rimonabant that increased the number of BrdU+, GFAP+ and Iba1+ cells in the hippocampus. These results indicate that changes on neurogenic, apoptotic and gliosis processes, which were produced as a consequence of repeated cocaine administration, were normalized by the pharmacological blockade of CB1 and CB2. The restoring effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with a prevention of the induction of conditioned locomotion, but not of cocaine-induced sensitization.

  20. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model

    OpenAIRE

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Kondrat-Wrobel, Maria W.; Tutka, Piotr; Jarogniew J Luszczki

    2014-01-01

    The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were...

  1. Hydrodynamic Behavior of Flow in a Drinking Water Treatment Clarifier

    OpenAIRE

    Yang, Wen-Jie; Wu, Syuan-Jhih; Li, Yu-Hsuan; Liao, Hung-Chi; Yang, Chia-Yi; Shih, Keng-Lin; Wu, Rome-Ming

    2010-01-01

    Blanket floc volumetric concentration is an important parameter in understanding the performance of sludge blanket clarifiers. 3D simulations of a clarifier using four different geometric constructions were studied in this work. From the simulation results of effluent solid flux, it is suggested that under the same daily throughput the large inlet pipe can reduce the flow velocity in the clarifier, hence reduce effluent solid flux and improve the quality of water. According to this simulation...

  2. Verification modeling study for the influential factors of secondary clarifier

    OpenAIRE

    Gao, Haiwen

    2016-01-01

    A numerical Quasi 3-D model of secondary clarifier is applied to verify the data obtained through the literature and analyze the influential factors for secondary clarifiers. The data from the papers provide the input parameters for the model. During this study, several influential factors (density waterfall; surface overflow rate; solids loading rate; solids-settling characteristics; mixed liquor suspended solid; clarifier geometry) are tested. The results show that there are some difference...

  3. EVALUATION OF AN ACTIVATED SLUDGE SECONDARY CLARIFIER DISTRIBUTED INLET

    Science.gov (United States)

    Secondary clarifiers are crucial to the overall performance of the activated sludge process. Research over the last 40 years indicates that density currents are factors which degrade clarifier performance when not considered in design. However, present designs of most center-feed...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Hydrodynamic characteristics of high speed settling clarifiers by radiotracer method

    International Nuclear Information System (INIS)

    Results achieved in the evaluation of two high-speed settling cane juice Clarifiers, one denominated ICINAZ The Express and the other one with Low Residence Time (BTR), both located at the sugar factory Orlando Gonzalez employing the well established radiotracer method (Tc-99m) are presented. Several trials performed at the two Clarifiers demonstrated that the one identified as BTR was capable to assimilate the whole flow capacity of the factory with adequate characteristic of the pattern flux and residence time in the environment of 1 hour. In the other side, ICINAZ The Express Clarifier could only work at relative low flow capacity of the factory with residence time closely to the two hours and achieving occasionally a pattern flux seriously affected by fluctuations in the milling process. The radiotracer method was able to detect certain differences between the two clear juice outlet of the BTR Clarifier, probably due some problems in the construction of this equipment

  7. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cermanova, Jolana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Kadova, Zuzana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Zagorova, Marie [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Hroch, Milos [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Tomsik, Pavel [Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Nachtigal, Petr; Kudlackova, Zdenka [Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek [Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Laho, Tomas [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Micuda, Stanislav, E-mail: micuda@lfhk.cuni.cz [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic)

    2015-05-15

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

  8. Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

    Science.gov (United States)

    Cermanova, Jolana; Kadova, Zuzana; Zagorova, Marie; Hroch, Milos; Tomsik, Pavel; Nachtigal, Petr; Kudlackova, Zdenka; Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek; Laho, Tomas; Micuda, Stanislav

    2015-05-15

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. PMID:25771127

  9. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    International Nuclear Information System (INIS)

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

  10. Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.

    Science.gov (United States)

    Alaghband, Yasaman; O'Dell, Steven J; Azarnia, Siavash; Khalaj, Anna J; Guzowski, John F; Marshall, John F

    2014-12-01

    The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine

  11. Hydrodynamic characteristics of high speed settling clarifiers by radiotracer method

    International Nuclear Information System (INIS)

    Results achieved in the evaluation of two high-speed settling cane juice Clarifiers, one denominated ICINAZ The Express and the other one a modified SRI, both located at the sugar factory Orlando Gonzalez employing the well established radiotracer method (Tc-99m) are presented Several trials performed simultaneously at the two Clarifiers demonstrated that the modified SRI was capable to assimilate the whole flow capacity of the factory with adequate characteristic of the pattern flux and residence time in the environment of 1 hour. In the other side, ICINAZ The Express Clarifier could only work at relative low flow capacity of the factory with residence time closely to the two hours and achieving occasionally a pattern flux seriously affected by fluctuations in the milling process. The non-availability of a flow meter did not allow to extract more information related to some pattern flux anomalies, nevertheless, the radiotracer method was able to detect certain differences between the two clear juice outlet of the modified SRI Clarifier, probably due some problems in the construction of this equipment. This fact so as other goals achieved in this work, show once more the potentiality of the radiotracer method for this type of study related to the hydrodynamic characteristics of industrial facilities. (Author)

  12. ACTIVATED SLUDGE CLARIFIERS: DESIGN REQUIREMENTS AND RESEARCH PRIORITIES

    Science.gov (United States)

    The literature review of 320 references was conducted in an EPA-funded project to identify the needs for further research on activated sludge clarifier design and performance. The findings were summarized in a report and used as a basis of a 3-day research needs symposium. The pr...

  13. Radiotracer investigations of industrial waste water equalizer-clarifiers

    International Nuclear Information System (INIS)

    The methodology and results of radiotracer investigations of an industrial equalizer-clarifier for waste water treatment are presented. Potassium bromide activated in nuclear reactor for sewage labelling was used. The dynamic characteristics of the tank and principal parameters of its operation were determined. The waste water flow model in apparatus was proposed. (author)

  14. Clarifying Liability for Twenty-First-Century Payment Fraud

    OpenAIRE

    Dhameja, Sandeep; Jacob, Katy; Richard D. Porter

    2013-01-01

    This article examines the governance structure of retail payments in the United States, provides an overview of payment fraud, and discusses in depth the liability frameworks for fraud involving specific payment methods. It also presents a series of recommendations that describe how the public sector might work together with the private sector to reduce fraud risks by clarifying liability for fraud.

  15. Clarify: Software for Interpreting and Presenting Statistical Results

    OpenAIRE

    Michael Tomz; Jason Wittenberg; Gary King

    2003-01-01

    Clarify is a program that uses Monte Carlo simulation to convert the raw output of statistical procedures into results that are of direct interest to researchers, without changing statistical assumptions or requiring new statistical models. The program, designed for use with the Stata statistics package, offers a convenient way to implement the techniques described in: Gary King, Michael Tomz, and Jason Wittenberg (2000). "Making the Most of Statistical Analyses: Improving Interpretation and ...

  16. Improving secondary clarifier performance at the Oakville Oil Refinery

    International Nuclear Information System (INIS)

    The purpose of this study was threefold: to investigate the relationship between settleability and the physical properties of activated sludge, to correlate settleability and key operational parameters such as chemical oxygen demand (COD) concentration at the aeration basin inlet and to determine potential operational improvements to the Oakville Oil Refinery Wastewater Treatment Plant. Nine separate sets of stirred sludge-settling tests were conducted over a six-month period to measure settleability. The stirred sludge volume index (SSVI), the zone settling constants, and the Zheng-Bagley compression constants were determined. State point analyses were conducted to determine the maximum solids flux of the clarifiers. The concentrations of Al, Mn, Mg, Fe, Ca, Na, and K were determined to identify potential correlations to settling characteristics. Extracellular polymeric substances were extracted from the sludge and analyzed for the same reason. The performance of the clarifiers was highly variable during the period examined. As the refinery process flows and effluent streams changed, influent COD increased, from an average of 180mg/L to 600mg/L. Concurrently the settleability of the sludge decreased from excellent (SSVI = 68mL/g) to very poor (150mL/g), perhaps as the result of under aeration. State point analyses indicated that the clarifiers are under-sized for process upsets of this magnitude. (author)

  17. Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes.

    Science.gov (United States)

    Borza, Alexandra; Plöttner, Sabine; Wolf, Alexander; Behm, Claudia; Selinski, Silvia; Hengstler, Jan G; Roos, Peter H; Bolt, Hermann M; Kuhlmann, Jürgen; Föllmann, Wolfram

    2008-12-01

    Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes. PMID:18989657

  18. CB2 receptor agonist promotes cardiac stem/progenitor cell proliferation in a mouse model of myocardial infarction%大麻素Ⅱ型受体激动剂促进小鼠心肌梗死后心脏干/祖细胞增殖的作用

    Institute of Scientific and Technical Information of China (English)

    胡文星; 王亚斌; 刘通; 李秀娟; 马赛; 梁栋; 曹丰

    2014-01-01

    目的:探讨大麻素Ⅱ型受体(CB2)选择性激动剂AM1241对小鼠心肌梗死(MI)模型中心脏干/祖细胞增殖的作用.方法:40只雄性C57BL/6小鼠通过结扎小鼠心脏左冠状动脉前降支建立MI模型并随机分为4组,每组10只(n=10):①假手术(Sham)组;②MI组;③MI+CB2受体激动剂AM1241(MI+ AM1241)组;④MI+ CB2受体激动剂AM1241+ CB2受体拮抗剂AM630(MI+ AM1241+ AM630)组.采用小动物超声系统观察小鼠左室射血分数(LVEF)的变化.用免疫荧光染色法观察MI周边区表达干细胞生长因子受体(c-kit)、干细胞抗原1(Sca-1)的阳性细胞数,实时荧光定量PCR测定MI周边区c-kit、Sca-1和多药耐药蛋白P糖蛋白(MDR1)的表达水平.结果:与MI组相比,MI+ AM1241组小鼠7d和14 d心脏LVEF值显著提高(P<0.01).免疫荧光染色的结果提示,MI+AM1241组c-kit和Sca-1的表达较MI组增多(P<0.05).实时荧光定量PCR结果显示,MI+ AM1241组c-kit和Sca-1的基因表达水平明显高于MI组(P<0.05).同时,CB2受体拮抗剂AM630可阻断AM1241的上述作用.结论:CB2受体激活可促进梗死心肌干/祖细胞的增殖,改善心脏的收缩功能.

  19. Clarifying the Relation Between Extraversion and Positive Affect.

    Science.gov (United States)

    Smillie, Luke D; DeYoung, Colin G; Hall, Phillip J

    2015-10-01

    This article clarifies two sources of ambiguity surrounding the relation between extraversion and positive affect. First, positive affect is defined differently across major models of the structure of affect. Second, no previous research has examined potentially diverging associations of lower-order aspects of extraversion (i.e., assertiveness and enthusiasm) with positive affect. Australian (Study 1: N = 437, 78% female, Mage  = 20.41) and American (Study 2: N = 262, 39% female, Mage  = 33.86) participants completed multiple measures of extraversion and positive affect. Correlations were employed to examine relations among these measures. In both studies, extraversion was most clearly associated with positive affect as conceptualized within a major factor model of affect-specifically, as positive activation (Watson & Tellegen, 1985)-rather than the valence-based conceptualization of positive affect provided by a circumplex model of affect (Russell, 1980). This was also the case for the assertiveness and enthusiasm aspects of extraversion. Our findings clarify the nature of the positive affective component of extraversion, which is best described in terms of both positive valence and high activation. PMID:25234441

  20. Retrofitting conventional primary clarifiers to activated primary clarifiers to enhance nutrient removal and energy conservation in WWTPs in Beijing, China.

    Science.gov (United States)

    Wang, Jia-wei; Zhang, Tian-zhu; Chen, Ji-ning; Hu, Zhi-rong

    2011-01-01

    Biological nutrient removal requires sufficient carbon source. Meanwhile, the removal of organic matter in wastewater requires energy consumption in the aeration tank. Carbon source for nutrient removal in most wastewater treatment plants with conventional primary clarifier (CPC) is generally insufficient in China. In order to increase carbon source and to save energy, a part of the CPC may be retrofitted as an activated primary clarifier (APC). In this paper, a pilot scale experiment was conducted to examine the performance of primary sludge fermentation and its effect on nitrogen and phosphorus removal. Results show that the primary sludge fermentation in APC has produced a similar VFA/TP ratio but a higher BOD5/TN ratio compared with those in the CPC effluent, and the TN concentrations in the secondary effluent are at 8.0, 10.8, and 17.4 mg/L, while TP is at 0.45, 1.10, and 2.28 mg/L when the pilot test system was fed with (1) the APC effluent, (2) 50% from the APC effluent and 50% from the CPC effluent, and (3) the CPC effluent, respectively. Results also indicate that the BOD5/TN ratio is a more sensitive factor than the VFA/TP ratio for nutrient removal and energy conservation for the APC fermentation. PMID:21508549

  1. Mise en évidence de deux nouvelles fonctions du système endocannabinoïde dans la physiopathologie de la stéatose hépatique : propriétés stéatogènes du récepteur CB2 et profibrogéniques du récepteur CB1

    OpenAIRE

    Deveaux, Vanessa

    2008-01-01

    Les cannabinoïdes présents dans la marijuana agissent par l'intermédiaire de deux récepteurs, CB1 et CB2, qui sont également activés par des molécules endogènes, les endocannabinoïdes. Les récepteurs CB1, majoritairement exprimés dans le cerveau, relaient les effets psychoactifs du cannabis, mais exercent également de nombreux effets périphériques. Les récepteurs CB2 prédominent dans les cellules du système immunitaire et interviennent notamment dans la régulation de la réponse immune et infl...

  2. Clarifying some remaining questions in the anomaly puzzle

    International Nuclear Information System (INIS)

    We discuss several points that may help to clarify some questions that remain about the anomaly puzzle in supersymmetric theories. In particular, we consider a general N=1 supersymmetric Yang-Mills theory. The anomaly puzzle concerns the question of whether there is a consistent way in the quantized theory to put the R-current and the stress tensor in a single supermultiplet called the supercurrent, even though in the classical theory they are in the same supermultiplet. It was proposed that the classically conserved supercurrent bifurcates into two supercurrents having different anomalies in the quantum regime. The most interesting result we obtain is an explicit expression for the lowest component of one of the two supercurrents in 4-dimensional spacetime, namely the supercurrent that has the energy-momentum tensor as one of its components. This expression for the lowest component is an energy-dependent linear combination of two chiral currents, which itself does not correspond to a classically conserved chiral current. The lowest component of the other supercurrent, namely, the R-current, satisfies the Adler-Bardeen theorem. The lowest component of the first supercurrent has an anomaly, which we show is consistent with the anomaly of the trace of the energy-momentum tensor. Therefore, we conclude that there is no consistent way to construct a single supercurrent multiplet that contains the R-current and the stress tensor in the straightforward way originally proposed. We also discuss and try to clarify some technical points in the derivations of the two supercurrents in the literature. These latter points concern the significance of infrared contributions to the NSVZ β-function and the role of the equations of motion in deriving the two supercurrents. (orig.)

  3. Clarifying the relationship between impulsive delay discounting and nicotine dependence.

    Science.gov (United States)

    Amlung, Michael; MacKillop, James

    2014-09-01

    Impulsive delayed reward discounting (DRD) has been linked to nicotine dependence, but with some inconsistency. This may be related to the considerable variability in the literature with regard to the DRD assessments used, particularly in the case of the reward magnitudes assessed. In addition, previous studies have often not considered concurrent substance use when examining the relationship between DRD and nicotine dependence. The current study sought to further clarify the relationship between DRD and nicotine dependence by characterizing DRD across diverse reward magnitudes and incorporating other substance use. Daily smokers (N = 933) were assessed for DRD preferences across nine reward magnitudes (delayed reward range: $2.50-$850), comorbid substance use, and relevant demographic variables (age, education, income). A significant large effect size magnitude effect was found for DRD, reflecting steeper discounting for smaller delayed rewards, but significant correlations across magnitudes also suggested similar relative levels of discounting. Principal components analysis (PCA) was used to generate a single latent index of discounting across all magnitudes that accounted for 69% of the total variance. In correlation and regression analyses, steeper composite DRD was significantly associated with nicotine dependence severity. This relationship remained statistically significant after incorporating demographic variables and alcohol and illicit drug use. These findings provide evidence of a specific link between impulsive DRD and nicotine dependence and reveal that this association is robust across a broad range of monetary rewards. The study also demonstrates the utility of using PCA to generate latent indices of delay discounting across multiple magnitudes of delayed reward. PMID:24841186

  4. Compaction of bacterial genomic DNA: clarifying the concepts

    International Nuclear Information System (INIS)

    The unconstrained genomic DNA of bacteria forms a coil, whose volume exceeds 1000 times the volume of the cell. Since prokaryotes lack a membrane-bound nucleus, in sharp contrast with eukaryotes, the DNA may consequently be expected to occupy the whole available volume when constrained to fit in the cell. Still, it has been known for more than half a century that the DNA is localized in a well-defined region of the cell, called the nucleoid, which occupies only 15% to 25% of the total volume. Although this problem has focused the attention of many scientists in recent decades, there is still no certainty concerning the mechanism that enables such a dramatic compaction. The goal of this Topical Review is to take stock of our knowledge on this question by listing all possible compaction mechanisms with the proclaimed desire to clarify the physical principles they are based upon and discuss them in the light of experimental results and the results of simulations based on coarse-grained models. In particular, the fundamental differences between ψ-condensation and segregative phase separation and between the condensation by small and long polycations are highlighted. This review suggests that the importance of certain mechanisms, like supercoiling and the architectural properties of DNA-bridging and DNA-bending nucleoid proteins, may have been overestimated, whereas other mechanisms, like segregative phase separation and the self-association of nucleoid proteins, as well as the possible role of the synergy of two or more mechanisms, may conversely deserve more attention. (topical review)

  5. Springs as Ecosystems: Clarifying Groundwater Dependence and Wetland Status (Invited)

    Science.gov (United States)

    Stevens, L.; Springer, A. E.; Ledbetter, J. D.

    2013-12-01

    natural variation in flow, and many of the 12 springs types do not develop hydric soils or wetland vegetation. These factors and their normally small size preclude springs as jurisdictional wetlands by U.S. Environmental Protection Agency and Army Corps of Engineers criteria. Helocrenes (springfed wet meadows, cienegas, and some fens) are considered as wetlands, but the other 11 types of terrestrial springs often are not. The use of the phrase 'GDE' applies to any aquatic ecosystem supported by groundwater, and the utility of this phrase as a descriptor of springs is diluted by its application to all subterranean and surface aquatic habitats. The failure to recognize the importance of springs ecosystems has become a quiet but global crisis, in part due to inappropriate conceptual understanding and poor jurisdictional terminology. We clarify relationships between these concepts and terms to establish effective, consistent monitoring, assessment, restoration, management, and monitoring goals and protocols for improving springs stewardship.

  6. Variability and Intelligibility of Clarified Speech to Different Listener Groups

    Science.gov (United States)

    Silber, Ronnie F.

    Two studies examined the modifications that adult speakers make in speech to disadvantaged listeners. Previous research that has focused on speech to the deaf individuals and to young children has shown that adults clarify speech when addressing these two populations. Acoustic measurements suggest that the signal undergoes similar changes for both populations. Perceptual tests corroborate these results for the deaf population, but are nonsystematic in developmental studies. The differences in the findings for these populations and the nonsystematic results in the developmental literature may be due to methodological factors. The present experiments addressed these methodological questions. Studies of speech to hearing impaired listeners have used read, nonsense, sentences, for which speakers received explicit clarification instructions and feedback, while in the child literature, excerpts of real-time conversations were used. Therefore, linguistic samples were not precisely matched. In this study, experiments used various linguistic materials. Experiment 1 used a children's story; experiment 2, nonsense sentences. Four mothers read both types of material in four ways: (1) in "normal" adult speech, (2) in "babytalk," (3) under the clarification instructions used in the "hearing impaired studies" (instructed clear speech) and (4) in (spontaneous) clear speech without instruction. No extra practice or feedback was given. Sentences were presented to 40 normal hearing college students with and without simultaneous masking noise. Results were separately tabulated for content and function words, and analyzed using standard statistical tests. The major finding in the study was individual variation in speaker intelligibility. "Real world" speakers vary in their baseline intelligibility. The four speakers also showed unique patterns of intelligibility as a function of each independent variable. Results were as follows. Nonsense sentences were less intelligible than story

  7. Metabotropic Glutamate Receptor-dependent Long-term Depression is Impaired Due to Elevated ERK Signaling in the ΔRG Mouse Model of Tuberous Sclerosis Complex

    OpenAIRE

    Chévere-Torres, Itzamarie; Kaphzan, Hanoch; Bhattacharya, Aditi; Kang, Areum; Maki, Jordan M.; Michael J Gambello; Arbiser, Jack L.; Santini, Emanuela; Klann, Eric

    2011-01-01

    Tuberous sclerosis complex (TSC) and fragile X syndrome (FXS) are caused by mutations in negative regulators of translation. FXS model mice exhibit enhanced metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD). Therefore, we hypothesized that a mouse model of TSC, ΔRG transgenic mice, also would exhibit enhanced mGluR-LTD. We measured the impact of TSC2-GAP mutations on the mTORC1 and ERK signaling pathways and protein synthesis-dependent hippocampal synaptic plasticity ...

  8. THE ROLE OF DUCKWEED (LEMNA MINOR L.) IN SECONDARY CLARIFIER TANKS

    OpenAIRE

    Engin Gürtekin; Nusret Şekerdağ

    2008-01-01

    In this study, the effects of duckweed (Lemna minor L.) presence on the effluent water quality and settling characteristics in the secondary clarifier tank of a conventional biological treatment plant were investigated. For this purpose, the performances of the secondary clarifier with and without duckweed were compared. In the secondary clarifier tank with duckweed, COD, BOD5, ammonium and phosphate removal efficiencies were higher by 15, 25, 35 and 45%, respectively. SS concentration of eff...

  9. CRITICAL LITERATURE REVIEW AND RESEARCH NEEDED ON ACTIVATED SLUDGE SECONDARY CLARIFIERS

    Science.gov (United States)

    Secondary clarifiers are key to the successful performance of the activated sludge process. They serve to separate out the biological solids and produce a clear effluent and to concentrate the settled solids for return to the aeration basins. Clarifiers have served the purpose fo...

  10. THE ROLE OF DUCKWEED (LEMNA MINOR L. IN SECONDARY CLARIFIER TANKS

    Directory of Open Access Journals (Sweden)

    Engin Gürtekin

    2008-01-01

    Full Text Available In this study, the effects of duckweed (Lemna minor L. presence on the effluent water quality and settling characteristics in the secondary clarifier tank of a conventional biological treatment plant were investigated. For this purpose, the performances of the secondary clarifier with and without duckweed were compared. In the secondary clarifier tank with duckweed, COD, BOD5, ammonium and phosphate removal efficiencies were higher by 15, 25, 35 and 45%, respectively. SS concentration of effluent and values of sludge volume index (SVI were the same. The results showed that duckweed contributes to treatment efficiency of conventional biological treatment plant, which reduces the need of tertiary nutrients removal.

  11. Thermophysical properties of enzyme clarified Lime (Citrus aurantifolia L) juice at different moisture contents

    OpenAIRE

    Manjunatha, S. S.; Raju, P. S.; Bawa, A. S.

    2012-01-01

    Thermophysical properties of enzyme clarified lime (Citrus aurantifolia L.) juice were evaluated at different moisture contents ranging from 30.37 % to 89.30 % (wet basis) corresponding to a water activity range of 0.835 to 0.979. The thermophysical properties evaluated were density, Newtonian viscosity, thermal conductivity, specific heat and thermal diffusivity. The investigation showed that density and Newtonian viscosity of enzyme clarified lime juice decreased significantly (p 

  12. Investigation on Clarified Fruit Juice Composition by Using Visible Light Micro-Raman Spectroscopy

    OpenAIRE

    Maria Lepore; Damiano Gustavo Mita; Nadia Diano; Ines Delfino; Flora Zenone; Carlo Camerlingo

    2007-01-01

    Liquid samples of clarified apple and apricot juices at different production stages were investigated using visible light micro-Raman spectroscopy in order to assess its potential in monitoring fruit juice production. As is well-known, pectin plays a strategic role in the production of clarified juice and the possibility of using Raman for its detection during production was therefore evaluated. The data analysis has enabled the clear identification of pectin. In particular, Raman spectra of ...

  13. Clarifying Exercise Addiction: Differential Diagnosis, Co-occurring Disorders, and Phases of Addiction

    OpenAIRE

    Marilyn Freimuth; Kim, Shari R.; Sandy Moniz

    2011-01-01

    This paper sets out to clarify the unique features of exercise addiction. It begins by examining how this addiction can be distinguished from compulsions and impulse control disorders both of which, like an addiction, involve excessive behavior that creates adverse effects. Assessment of exercise addiction also requires that clinicians be attuned to other forms of excessive behavior, especially eating disorders that can co-occur with exercise. Finally in an effort to clarify exercise addictio...

  14. Utilization of water clarifier sludge for copper removal in a liquid fluidized-bed reactor

    International Nuclear Information System (INIS)

    A method was used to investigate the potential for using water clarifier sludge to remove copper in a fluidized-bed reactor (FBR). This study was conducted to evaluate the removal of copper in an aquatic system without prior treatment. Chemical analyses of water clarifier sludge through inductively coupled plasma-atomic emission spectrophotometry indicated that silicon, aluminum and iron oxides made up more than 84% of this average composition, similar to the composition of clay. The experimental results indicated that the copper removal efficiency was highly dependent on the pH. pH values also influence the character of the water clarifier sludge. After the copper was adsorbed by the water clarifier sludge, the pH of the solution was slightly increased. In the FBR, the copper removal efficiency reached 90% when the initial copper concentration was 20 mg/L, the pH was 4 and the operating time was 60 min. In addition, copper precipitation occured on the surface of clarifier sludge when the initial copper concentration was 20 mg/L and the pH was 7.0. The kinetics of copper ion adsorption at pH 5 showed that 94% copper ion was removed in 60 min and the adsorption equilibrium was attained in 5 h. The mechanisms of adsorption of copper ions on water clarifier sludge including the formation of surface complexation and surface precipitate

  15. Hook-up of GluA2, GRIP and liprin-α for cholinergic muscarinic receptor-dependent LTD in the hippocampus

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2009-06-01

    Full Text Available Abstract The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP, and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-α. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR, a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.

  16. Study of flow characteristics in a secondary clarifier by numerical simulation and radioisotope tracer technique

    International Nuclear Information System (INIS)

    Numerical simulation in a 2-D rectangular coordinate and experimental study have been performed to figure out the flow characteristics and concentration distribution of a large-scale rectangular final clarifier in wastewater treatment facility located in Busan, S. Korea. The purpose of numerical calculation is to verify the experimentally measured data by radioisotope tracer technique and further to understand the important physical feature occurring in a large-scale clarifier, in many cases which is not sufficient by the aid of limited number of experimental data. To this end, a comprehensive computer program is basically made by SIMPLE algorithm by Patankar with the special emphasis on the parametric evaluation of the various phenomenological models. Calculation results are successfully evaluated against experimental data obtained by the method of radioisotope tracer. Detailed comparison is made on the calculated residence time distribution (RTD) curves with measurement inside the clarifier as well as the exhaust. Further the calculation results predict well the well-known characteristics of clarifier flow such as the waterfall phenomenon at the front end of the clarifier, the bottom density current in the settling zone and the upward flow in the withdrawal zone. Thus it is believed that the flow calculation program and the data incorporation technique of radioisotope measurement employed in this study show the high possibility as a complementary tool of experiment in this area

  17. Characterizing shallow secondary clarifier performance where conventional flux theory over-estimates allowable solids loading rate.

    Science.gov (United States)

    Daigger, Glen T; Siczka, John S; Smith, Thomas F; Frank, David A; McCorquodale, J A

    2016-01-01

    The performance characteristics of relatively shallow (3.3 and 3.7 m sidewater depth in 30.5 m diameter) activated sludge secondary clarifiers were extensively evaluated during a 2-year testing program at the City of Akron Water Reclamation Facility (WRF), Ohio, USA. Testing included hydraulic and solids loading stress tests, and measurement of sludge characteristics (zone settling velocity (ZSV), dispersed and flocculated total suspended solids), and the results were used to calibrate computational fluid dynamic (CFD) models of the various clarifiers tested. The results demonstrated that good performance could be sustained at surface overflow rates in excess of 3 m/h, as long as the clarifier influent mixed liquor suspended solids (MLSS) concentration was controlled to below critical values. The limiting solids loading rate (SLR) was significantly lower than the value predicted by conventional solids flux analysis based on the measured ZSV/MLSS relationship. CFD analysis suggested that this resulted because mixed liquor entering the clarifier was being directed into the settled sludge blanket, diluting it and also creating a 'thin' concentration sludge blanket that overlays the thicker concentration sludge blanket typically expected. These results indicate the need to determine the allowable SLR for shallow clarifiers using approaches other than traditional solids flux analysis. A combination of actual testing and CFD analyses are demonstrated here to be effective in doing so. PMID:27438236

  18. Process waste treatment system upgrades: Clarifier startup at the nonradiological wastewater treatment plant

    Energy Technology Data Exchange (ETDEWEB)

    Lucero, A.J.; McTaggart, D.R.; Van Essen, D.C.; Kent, T.E.; West, G.D.; Taylor, P.A.

    1998-07-01

    The Waste Management Operations Division at Oak Ridge National Laboratory recently modified the design of a reactor/clarifier at the Nonradiological Wastewater Treatment Plant, which is now referred to as the Process Waste Treatment Complex--Building 3608, to replace the sludge-blanket softener/clarifier at the Process Waste Treatment Plant, now referred to as the Process Waste Treatment Complex-Building 3544 (PWTC-3544). This work was conducted because periodic hydraulic overloads caused poor water-softening performance in the PWTC-3544 softener, which was detrimental to the performance and operating costs of downstream ion-exchange operations. Over a 2-month time frame, the modified reactor/clarifier was tested with nonradiological wastewater and then with radioactive wastewater to optimize softening performance. Based on performance to date, the new system has operated more effectively than the former one, with reduced employee radiological exposure, less downtime, lower costs, and improved effluent quality.

  19. Process waste treatment system upgrades: Clarifier startup at the nonradiological wastewater treatment plant

    International Nuclear Information System (INIS)

    The Waste Management Operations Division at Oak Ridge National Laboratory recently modified the design of a reactor/clarifier at the Nonradiological Wastewater Treatment Plant, which is now referred to as the Process Waste Treatment Complex--Building 3608, to replace the sludge-blanket softener/clarifier at the Process Waste Treatment Plant, now referred to as the Process Waste Treatment Complex-Building 3544 (PWTC-3544). This work was conducted because periodic hydraulic overloads caused poor water-softening performance in the PWTC-3544 softener, which was detrimental to the performance and operating costs of downstream ion-exchange operations. Over a 2-month time frame, the modified reactor/clarifier was tested with nonradiological wastewater and then with radioactive wastewater to optimize softening performance. Based on performance to date, the new system has operated more effectively than the former one, with reduced employee radiological exposure, less downtime, lower costs, and improved effluent quality

  20. Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    Science.gov (United States)

    Chay, Andrew; Zamparo, Ilaria; Koschinski, Andreas; Zaccolo, Manuela; Blackwell, Kim T

    2016-02-01

    Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory. PMID:26901880

  1. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus.

    Science.gov (United States)

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K; Fiacco, Todd A

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8-20 weeks old) compared with juvenile (P15-P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  2. Ethanol withdrawal is required to produce persisting N-methyl-D-aspartate receptor-dependent hippocampal cytotoxicity during chronic intermittent ethanol exposure.

    Science.gov (United States)

    Reynolds, Anna R; Berry, Jennifer N; Sharrett-Field, Lynda; Prendergast, Mark A

    2015-05-01

    Chronic intermittent ethanol consumption is associated with neurodegeneration and cognitive deficits in preclinical laboratory animals and in the clinical population. While previous work suggests a role for neuroadaptations in the N-methyl-d-aspartate (NMDA) receptor in the development of ethanol dependence and manifestation of withdrawal, the relative roles of ethanol exposure and ethanol withdrawal in producing these effects have not been fully characterized. To examine underlying cytotoxic mechanisms associated with chronic intermittent ethanol (CIE) exposure, organotypic hippocampal slices were exposed to 1-3 cycles of ethanol (50 mM) in cell culture medium for 5 days, followed by 24 h of ethanol withdrawal, in which a portion of slices were exposed to competitive NMDA receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV; 40 μM). Cytotoxicity was assessed using immunohistochemical labeling of neuron-specific nuclear protein (NeuN; Fox-3), a marker of mature neurons, and thionine (2%) staining of Nissl bodies. Multiple cycles of CIE produced neurotoxicity, as reflected in persisting losses of neuron NeuN immunoreactivity and thionine staining in each of the primary cell layers of the hippocampal formation. Hippocampi aged in vitro were significantly more sensitive to the toxic effects of multiple cycles of CIE than were non-aged hippocampi. This effect was not demonstrated in slices exposed to continuous ethanol, in the absence of withdrawal, or to a single exposure/withdrawal regimen. Exposure to APV significantly attenuated the cytotoxicity observed in the primary cell layers of the hippocampus. The present findings suggest that ethanol withdrawal is required to produce NMDA receptor-dependent hippocampal cytotoxicity, particularly in the aging hippocampus in vitro. PMID:25746220

  3. On an extended clarifier-thickener model with singular source and sink term

    OpenAIRE

    2005-01-01

    A well-studied one-dimensional model for the operation of clarifier-thickener units in engineering applications can be expressed as a conservation law with a flux that is discontinuous with respect to the spatial variable. This model also includes a singular feed source. In this paper, the clarifier-thickener model is extended by a singular sink through which material is extracted from the unit. A difficulty is that in contrast to the singular source, the sink term cannot be incorporated into...

  4. A study of control strategies for a clarifier at an industry wastewater treatment plant

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Control of clarifier in the activated sludge process is critical for ensuring effective wastewater treatment. This paper is to study appropriate control strategies for a clarifier in an industrial wastewater treatment plant. Five control strategies are proposed, implemented and evaluated in a simulation software (West ++ ). The sludge blanket height and the effluent suspended solids concentration were proposed as the measured variable. The manipulated variable was the quantity of polymer added to the system. The strategies were evaluated in terms of their ability to maintain the sludge blanket height below 1.5m, their polymer requirements, their sensitivity to poor tuning and the required control action.

  5. Encouraging and Clarifying "Don't Know" Responses Enhances Interview Quality

    Science.gov (United States)

    Scoboria, Alan; Fisico, Stephanie

    2013-01-01

    Investigative interviewers seek to obtain complete and accurate accounts of events from witnesses. Two studies examined the influence of instructions about the use of don't know (DK) responses and of clarifying the meanings of DK responses on the quality of responding to questioning. Participants watched a video, and after a delay (Study 1, 30…

  6. REGULATION OF ACIDITY AND REDUCTION OF TURBIDITY IN THE CLARIFIED POMEGRANATE JUICE PRODUCTION

    OpenAIRE

    ESHMATOV FOZIL KHIDIROVICH; MAKSUMOVA DILRABO KUCHKAROVNA; DODAEVA LAYLO KUCHKAROVNA

    2016-01-01

    Regulation of acidity and reduction of turbidity in the clarified pomegranate juice production. From sour varieties of pomegranates may obtain normal natural pomegranate juice by anion-exchange resin. There are determined problems quantity of precipitate and unstable color in the pomegranate juice and concentrate by experimentally.

  7. Deception in Brand Names: Do Print Ads Clarify the Nutrition Claims?

    Science.gov (United States)

    Reece, Bonnie B.; Rifon, Nora J.

    To learn whether the problem of misunderstanding in brand names might be caused by the content of advertisements or whether it stemmed from a failure in the exposure-processing chain with respect to the effect of the ads on consumers, a study investigated the extent to which marketers provide information in their advertising that clarifies the…

  8. Clarifying the heterogeneity in psychopathic samples: Towards a new continuum of primary and secondary psychopathy

    NARCIS (Netherlands)

    Yildirim, B.O.; Derksen, J.J.L.

    2015-01-01

    Psychopathic individuals identified through contemporary instruments vary considerably in personality and etiological background, which creates confusion in practice and inconsistency in data. The goal of this paper is to clarify this heterogeneity and introduce a new typology to narrow down psychop

  9. Adequacy assessment studies of improved circular clarifier for type-II settling for storm water treatment.

    Science.gov (United States)

    Ahuja, Nandita; Pophali, Girish R

    2013-10-01

    The adequacy of an improved circular clarifier was assessed for solids-liquid separation of chemically treated storm water. The storm water was treated with alum and polyelectrolyte to enhance settling. The performance of the clarifier was studied under various operating conditions by varying suspended solids concentrations and turbidity, and the hydraulic retention time. It was observed that the clarifier worked at an optimum hydraulic retention time of 1.5 hours for initial suspended solids concentration of less than 500 mg/L. However, for treatment of storm water with suspended solids concentration more than 500 mg/L, the hydraulic retention time needs to be selected taking the required effluent turbidity and effluent usage into consideration, i.e. for high turbidity removal an optimum hydraulic retention time of 2 hours must be used against a hydraulic retention time of 1.5 hours for a relatively low turbidity removal. Thus, the clarifier can be effectively used on field scale for solids-liquid separation of flocculent suspensions. PMID:25906594

  10. Improvement performance of secondary clarifiers by a computational fluid dynamics model

    Science.gov (United States)

    Ghawi, Ali G.; Kriš, J.

    2011-12-01

    Secondary clarifier is one of the most commonly used unit operations in wastewater treatment plants. It is customarily designed to achieve the separation of solids from biologically treated effluents through the clarification of biological solids and the thickening of sludge. As treatment plants receive increasingly high wastewater flows, conventional sedimentation tanks suffer from overloading problems, which result in poor performance. Modification of inlet baffles through the use of an energy dissipating inlet (EDI) was proposed to enhance the performance in the circular clarifiers at the Al-Dewanyia wastewater treatment plant. A 3-dimensional fully mass conservative clarifier model, based on modern computational fluid dynamics theory, was applied to evaluate the proposed tank modification and to estimate the maximum capacity of the existing and modified clarifiers. A Computational Fluid Dynamics (CFD) model was formulated to describe the tank is performance, and design parameters were obtained based on the experimental results. The study revealed that velocity and (suspended solids) SS is a better parameter than TS (total solids), (Biochemical Oxygen Demand) BOD, (Chemical Oxygen Demand) COD to evaluate the performance of sedimentation tanks and that the removal efficiencies of the suspended solids, biochemical oxygen demand, and chemical oxygen demand were higher in the baffle.

  11. 75 FR 68249 - Policy Clarifying Definition of “Actively Engaged” for Purposes of Inspector Authorization

    Science.gov (United States)

    2010-11-05

    ...'s Web page at http://www.gpoaccess.gov/fr/index.html . You can also get a copy by sending a request... Federal Aviation Administration 14 CFR Part 65 Policy Clarifying Definition of ``Actively Engaged'' for.... Availability of This Proposed Policy You can get an electronic copy using the Internet by-- (1) Searching...

  12. An Experiential Approach to Teaching Communication Theory: Incorporating Contemporary Media To Clarify Theoretical Concepts.

    Science.gov (United States)

    Lamoureux, Elizabeth R.

    For professors who have been assigned the task of teaching communication theory, carefully chosen examples of films, videos, TV clips, or music can be productively used to support instruction. Both research and experience have shown that the visual and aural channels are excellent forms of amplifying, clarifying, and justifying theoretical…

  13. Attenuation of Aβ25–35-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    International Nuclear Information System (INIS)

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ25–35-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ25–35 (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ25–35 treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ25–35 treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ25–35-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ25–35-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens or gypenosides. - Highlights:

  14. Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum

    OpenAIRE

    Tovar-Moll, Fernanda; Monteiro, Myriam; Andrade, Juliana; Bramati, Ivanei E.; Vianna-Barbosa, Rodrigo; Marins, Theo; Rodrigues, Erika; Dantas, Natalia; Behrens, Timothy E. J.; de Oliveira-Souza, Ricardo; Moll, Jorge; Lent, Roberto

    2014-01-01

    Individuals subjected to surgical transection of the corpus callosum (“split-brains”) fail to transfer information between the cerebral hemispheres, a condition known as “disconnection syndrome.” On the other hand, subjects born without the callosum (callosal dysgenesis, CD) typically show preserved interhemispheric communication. To clarify this paradox, which has defied neuroscientists for decades, we investigated CD subjects using functional and structural neuroimaging and neuropsychologic...

  15. To clarify features of photoplethysmography in monitoring balanced anesthesia, compared with Cerebral State Index

    OpenAIRE

    Zhang, Lieliang; Xu, Lei; Zhu, Juan; Gao, Yujie; Luo, Zhonghua; Wang, Hongyu; Zhu, Zhongliang; Yu, Yi; Shi, Hongwei; Bao, Hongguang

    2014-01-01

    Background Although photoplethysmography and cerebral state index (CSI) have been used as indices in monitoring vital signs perioperatively, there are only a few reports comparing the performance of photoplethysmography with CSI in monitoring anaesthesia depth. The aim of the present study was to clarify features of photoplethysmography in monitoring balanced general anesthesia compared with CSI. Material/Methods Forty-five patients undergoing elective operation under general anaesthesia were...

  16. Hydrodynamic evaluation of a hydraulic clarifier through hydraulic behaviour indicators and simplified flow models

    OpenAIRE

    Paola Patiño; Camilo Cruz; Patricia Torres; Santiago Laín

    2012-01-01

    Hydrodynamic phenomena take place within water treatment plants associated with physical, operational and environmental factors which can affect the water quality. This study evaluated a hydraulic clarifier’s hydrodynamic pattern using sludge recirculation through continuous tracer test leading to determining hydraulic behaviour indicators and simplified flow models. The clarifier had dual flow with a predominantly complete mixture during the hours in which higher temperatures were reported f...

  17. The alphabet soup of perfusion CT and MR imaging: terminology revisited and clarified in five questions

    Energy Technology Data Exchange (ETDEWEB)

    Leiva-Salinas, Carlos [University of Virginia, Department of Radiology, Neuroradiology Division, Charlottesville, VA (United States); Hospital Universitario y Politecnico la Fe, Department of Radiology, Neuroradiology Division, Valencia (Spain); Universidad Autonoma de Barcelona, Department of Medicine, Barcelona (Spain); Provenzale, James M. [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Emory University School of Medicine, Departments of Radiology, Oncology and Biomedical Engineering, Atlanta, GA (United States); Kudo, Kohsuke; Sasaki, Makoto [Iwate Medical University, Division of Ultra-high Field MRI, Institute for Biomedical Sciences, Morioka (Japan); Wintermark, Max [University of Virginia, Department of Radiology, Neuroradiology Division, Charlottesville, VA (United States); University of Virginia Medical Center, Department of Radiology, Neuroradiology Division, 1215 Lee Street-New Hospital, 1st Floor, Room 1011, PO Box 800170, Charlottesville, VA (United States)

    2012-09-15

    The five questions answered in this article revolve around the different parameters resulting from perfusion imaging processing, and this clarifies the frequently confusing terminology used to describe these parameters. More specifically, the article discusses the different imaging techniques and main mathematical models behind perfusion imaging, reviews the perfusion attributes of brain tissue, and proposes a standardized parameter terminology to facilitate understanding and avoid common misinterpretations. (orig.)

  18. A model of continuous sedimentation of flocculated suspensions in clarifier-thickener units

    OpenAIRE

    2004-01-01

    The chief purpose of this paper is to formulate and partly analyze a new mathematical model for continuous sedimentation-consolidation processes of flocculated suspensions in clarifier-thickener units. This model appears in two variants for cylindrical and variable cross-sectional area units, respectively (Models 1 and 2). In both cases, the governing equation is a scalar, strongly degenerate parabolic equation in which both the convective and diffusion fluxes depend on parameters that are di...

  19. Evaluation of commercial chromatographic adsorbents for the direct capture of polyclonal rabbit antibodies from clarified antiserum

    DEFF Research Database (Denmark)

    Bak, Hanne; Thomas, O.R.T.

    2007-01-01

    We have carried out a rigorous evaluation of eight commercially available packed bed chromatography adsorbents for direct capture and purification of immumoglobulins from clarified rabbit antiserum. Three of these materials featured rProtein A (rProtein A Sepharose Fast Flow, Mabselect, Prosep rProtein...... evaluated on the basis of dynamic binding capacity, recovery, and purity) were obtained, which allowed clear recommendations concerning the choice of adsorbents best suited for antibody capture from rabbit antisera, to be made....

  20. The alphabet soup of perfusion CT and MR imaging: terminology revisited and clarified in five questions

    International Nuclear Information System (INIS)

    The five questions answered in this article revolve around the different parameters resulting from perfusion imaging processing, and this clarifies the frequently confusing terminology used to describe these parameters. More specifically, the article discusses the different imaging techniques and main mathematical models behind perfusion imaging, reviews the perfusion attributes of brain tissue, and proposes a standardized parameter terminology to facilitate understanding and avoid common misinterpretations. (orig.)

  1. Sustainable or Distributed Energy—or both? Clarifying the Basic Concepts of Reforming the Energy Sector

    OpenAIRE

    Pekka Peura; Patrik Sjöholm

    2015-01-01

    This paper clarifies the concepts of Sustainable Energy (SE) and Distributed Energy (DE) including their related synonyms, by discussing, analyzing and presenting recommendations. This is important because these concepts are crucial in the on-going transformation from the fossil carbon based to renewable energy based societies, but still the use of the concepts has been confusing. SE consists of the integration of rational use of energy (energy saving, energy efficiency, use of renewable ener...

  2. Anaerobic co-digestion of sewage sludge and primary clarifier skimmings for increased biogas production.

    Science.gov (United States)

    Alanya, S; Yilmazel, Y D; Park, C; Willis, J L; Keaney, J; Kohl, P M; Hunt, J A; Duran, M

    2013-01-01

    The objective of the study was to identify the impact of co-digesting clarifier skimmings on the overall methane generation from the treatment plant and additional energy value of the increased methane production. Biogas production from co-digesting clarifier skimmings and sewage sludge in pilot-scale fed-batch mesophilic anaerobic digesters has been evaluated. The digester was fed with increasing quantities of clarifier skimmings loads: 1.5, 2.6, 3.5 and 7.0 g COD equivalent/(L·d) (COD: chemical oxygen demand). Average volatile solids reduction of 65% was achieved in the scum-fed digester, compared with 51% in the control digester. Average 69% COD removal was achieved at highest scum loading (7 g COD eq/(L·d)) with approximate methane yield of 250 L CH(4)/kg COD fed (4 ft(3)/lb COD fed). The results show that scum as co-substrate in anaerobic digestion systems improves biogas yields while a 29% increase in specific CH(4) yield could be achieved when scum load is 7 g COD eq/(L·d). Based on the pilot-scale study results and full-scale data from South East Water Pollution Control Plant and Northeast Water Pollution Control Plant the expected annual energy recovery would be approximately 1.7 billion BTUs or nearly 0.5 million kWh. PMID:23128636

  3. The clarification of uranium pregnant solution at Buffelsfontein by a circulator-clarifier

    International Nuclear Information System (INIS)

    Owing to the strategic value of organic solvents, an investigation was conducted on the reduction of solvent losses at the Buffelsfontein solvent-extraction plant. It was established that the major cause of the high solvent losses was the high content of suspended solids in the uranium pregnant solution. To improve the clarification of the pregnant solution, it was decided to replace the conventional sand clarifiers that were being used at that stage. After pilot-plant tests had been conducted, a circulator-clarifier 16 m in diameter was installed to treat 9000 m3 per day of pregnant solution containing approximately 500 p.p.m. of suspended solids. The clarifier was commissioned successfully, and yielded an overflow containing approximately 80 p.p.m. of suspended solids compared with the previous value of 250 p.p.m. This reduction in suspended solids immediately resulted in a decreasing trend in losses of organic solvent, finally yielding a reduction in these losses of approximately 50 per cent

  4. Electroflotation clarifier to enhance nitrogen removal in a two-stage alternating aeration bioreactor.

    Science.gov (United States)

    Cho, Kangwoo; Chung, Chong Min; Kim, Yun Jung; Hoffmann, Michael R; Chung, Tai Hak

    2013-01-01

    Stringent water treatment criteria and rapidly growing pollutant loads provoke the demand for retrofitting wastewater treatment plants towards a higher capacity. In this study, we assess a two stage alternating aeration (AA) bioreactor equipped with electroflotation (EF) clarifier, for nitrogen removal within a short hydraulic retention time (HRT). The EF under steady solids loading required a minimum unit height and gas: solids ratio of 0.006 for efficient clarification. The separated sludge blanket was further thickened with retaining stability when the cyclic solids loading was smaller than 1.0 kg m(-2). In the continuous operation of the bioreactor, the returned activated sludge concentration increased to more than 18,000 mg L(-1), while the effluent suspended solids concentration was lowered below 5 mg L(-1). Under influent chemical oxygen demand (COD)/total inorganic nitrogen (TIN) concentration of 300/30 mg L(-1), the TIN removal efficiency was near 70% with cycle time ratios of 0.17 and 0.27. Under higher influent COD concentration of 500mg L(-1), TIN removal efficiency was found to be 73.4% at a carbon:nitrogen (C:N) ratio of 10 and even higher (80.4%) at a C:N ratio of 16.6. The increased mixed liquor suspended solids concentrations (> 6000 mg L(-1)) under the high COD loading were efficiently maintained by using the EF clarifier. The results of this study demonstrate that an EF clarifier with a HRT of less than 1 h can support reliable nitrogen removal in the AA process that has a HRT of 6 h, even under increasing influent loadings. PMID:24527640

  5. Clarifying the role of actor network theory (ANT) for the accounting of information system in Iran

    OpenAIRE

    DEHKORDI, Bahareh Banitalebi; ROODPOSHTI, Fraydoon Rahnamay; NIKOMARAM, Hashem; TALEBNIA, Ghodratollah

    2015-01-01

    Abstract. In this research is paid to clarify the role of actor network theory (ANT) for the accounting of information system in Iran with the aim of the determining of the human and non-human actors effective on the accounting information systems, the analysis of relationships between the human and non-human actors on the net and to determine the effective factors on the accounting information systems in terms of types of actors for the first time in Iran. In this research which is done in t...

  6. Clarifying the Relationship between Average Excesses and Average Effects of Allele Substitutions.

    Science.gov (United States)

    Alvarez-Castro, José M; Yang, Rong-Cai

    2012-01-01

    Fisher's concepts of average effects and average excesses are at the core of the quantitative genetics theory. Their meaning and relationship have regularly been discussed and clarified. Here we develop a generalized set of one locus two-allele orthogonal contrasts for average excesses and average effects, based on the concept of the effective gene content of alleles. Our developments help understand the average excesses of alleles for the biallelic case. We dissect how average excesses relate to the average effects and to the decomposition of the genetic variance. PMID:22509178

  7. Clarifying the relationship between average excesses and average effects of allele substitutions

    Directory of Open Access Journals (Sweden)

    Jose M eÁlvarez-Castro

    2012-03-01

    Full Text Available Fisher’s concepts of average effects and average excesses are at the core of the quantitative genetics theory. Their meaning and relationship have regularly been discussed and clarified. Here we develop a generalized set of one-locus two-allele orthogonal contrasts for average excesses and average effects, based on the concept of the effective gene content of alleles. Our developments help understand the average excesses of alleles for the biallelic case. We dissect how average excesses relate to the average effects and to the decomposition of the genetic variance.

  8. Modelling of the Secondary Clarifier Combined with the Activated Sludge Model no. 1

    DEFF Research Database (Denmark)

    Dupont, René; Henze, Mogens

    1992-01-01

    Modelling of activated sludge wastewater treatment plants is today generally based on the Activated Sludge Model No. 1 combined with a very simple model for the secondary settler. This paper describes the development of a model for the secondary clarifier based on the general flux theory for zone...... model is a purely empirical model, which connects the effluent quality with the hydraulic load, suspended solids load and the nitrate load. The paper describes the model and gives some basic examples on computer simulations and verification of the model....

  9. 40 CFR 180.1161 - Clarified hydrophobic extract of neem oil; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... neem oil; exemption from the requirement of a tolerance. Clarified hydrophobic extract of neem oil is... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Clarified hydrophobic extract of neem oil; exemption from the requirement of a tolerance. 180.1161 Section 180.1161 Protection...

  10. Enhanced biological nitrogen removal in MLE combined with post-denitrification process and EF clarifier.

    Science.gov (United States)

    Chung, C M; Cho, K W; Kim, Y J; Yamamoto, K; Chung, T H

    2012-05-01

    A modified ludzack ettinger reactor (MLE) combined with a post-denitrification reactor (PDMLE) using electroflotation (EF) as a secondary clarifier was investigated on its feasibility and process performance. Results indicated that higher mixed liquor suspended solids (MLSS) concentrations in bioreactor (5,350 ± 352 mg L(-1)) were maintained via the highly concentrated return sludge (16,771 ± 991 mg L(-1)) from the EF clarifier and the effluent suspended solids (SS) concentrations continued relatively low, representing effluent SS concentration of 1.71 ± 1.16 mg L(-1), compared with GS-A2O process during the operation of four months. The denitrification was improved by combining MLE process with post-denitrification based on endogenous decay (i.e. no additional carbon source was added), resulting in the removal efficiencies of TN were about 91 and 59% for the influent C/N ratio of 10 and 5, respectively, revealing relatively high nitrogen removal as compared with EF-A2O and gravity settling (GS)-A2O processes as a control. The nitrogen balance analysis indicates that pre-denitrification and post-denitrification contributed to 78 and 22% of TN removed, respectively. PMID:21947625

  11. Investigation on Clarified Fruit Juice Composition by Using Visible Light Micro-Raman Spectroscopy

    Science.gov (United States)

    Camerlingo, Carlo; Zenone, Flora; Delfino, Ines; Diano, Nadia; Mita, Damiano Gustavo; Lepore, Maria

    2007-01-01

    Liquid samples of clarified apple and apricot juices at different production stages were investigated using visible light micro-Raman spectroscopy in order to assess its potential in monitoring fruit juice production. As is well-known, pectin plays a strategic role in the production of clarified juice and the possibility of using Raman for its detection during production was therefore evaluated. The data analysis has enabled the clear identification of pectin. In particular, Raman spectra of apple juice samples from washed and crushed fruits revealed a peak at 845 cm-1 (typical of pectin) which disappears in the Raman spectra of depectinised samples. The fructose content was also revealed by the presence of four peaks at 823 cm-1, 872 cm-1, 918 cm-1 and 975 cm-1. In the case of apricot juice, several Raman fingerprints of β-carotene at 1008, 1159 and 1520 cm-1 were also highlighted. Present results resulted interesting for the exclusive use of optical methods for the quantitative determination of the above-mentioned substances in place of the biochemical assays generally used for this purpose, which are time consuming and require different chemical reagents for each of them.

  12. Investigation on Clarified Fruit Juice Composition by Using Visible Light Micro-Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Maria Lepore

    2007-10-01

    Full Text Available Liquid samples of clarified apple and apricot juices at different productionstages were investigated using visible light micro-Raman spectroscopy in order to assessits potential in monitoring fruit juice production. As is well-known, pectin plays a strategicrole in the production of clarified juice and the possibility of using Raman for its detectionduring production was therefore evaluated. The data analysis has enabled the clearidentification of pectin. In particular, Raman spectra of apple juice samples from washedand crushed fruits revealed a peak at 845 cm-1 (typical of pectin which disappears in theRaman spectra of depectinised samples. The fructose content was also revealed by thepresence of four peaks at 823 cm-1, 872 cm-1, 918 cm-1 and 975 cm-1. In the case of apricotjuice, several Raman fingerprints of β-carotene at 1008, 1159 and 1520 cm-1 were alsohighlighted. Present results resulted interesting for the exclusive use of optical methods forthe quantitative determination of the above-mentioned substances in place of thebiochemical assays generally used for this purpose, which are time consuming and requiredifferent chemical reagents for each of them.

  13. Tree ring effects and ice core acidities clarify the volcanic record of the 1st millennium

    Directory of Open Access Journals (Sweden)

    M. G. L. Baillie

    2014-04-01

    Full Text Available Various attempts have been made to link tree-ring and ice-core records, something vital for the understanding of the environmental response to major volcanic eruptions in the past. Here we demonstrate that, by taking note of the spacing between events, it is possible to clarify linkages between tree-response, as witnessed by frost rings in bristlecone pines from Western North America and volcanic acid deposition in ice cores. The results demonstrate that in the 6th and 7th centuries of the current era, and presumably for all earlier dates, the key European ice chronologies from the North Greenland Ice Core Project, namely Dye3, GRIP, NGRIP and NEEM appear to have been wrongly dated by 7 years, with the ice dates being too old. Similar offsets are observed for the Antarctic Law Dome and West Antarctic Ice Sheet Divide WDC06A ice-core chronologies that have been linked to the Greenland record. Importantly, the results clarify which frost rings in bristlecone pines are related to volcanic activity and which may be the result of other causes. In addition, it is possible to show that ice core researchers have used inappropriate linkages to tree effects to justify their chronology.

  14. Effect of gas sparging on flux enhancement and phytochemical properties of clarified pineapple juice by microfiltration

    KAUST Repository

    Laorko, Aporn

    2011-08-01

    Membrane fouling is a major obstacle in the application of microfiltration. Several techniques have been proposed to enhance the permeate flux during microfiltration. Gas sparging is a hydrodynamic method for improving the performance of the membrane process. In this study, a 0.2 μm hollow fiber microfiltration membrane was used to study the effect of cross flow velocity (CFV) and gas injection factor () on the critical and limiting flux during microfiltration of pineapple juice. In addition, the phytochemical properties of clarified juice were investigated. In the absence of gas sparging, the critical and limiting flux increased as the CFV or shear stress number increased. The use of gas sparging led to a remarkable improvement in both the critical and limiting flux but it was more effective at the lower CFV (1.5 m s-1), compared to those at higher CFV (2.0 and 2.5 m s-1). When the gas injection factor was applied at 0.15, 0.25 and 0.35 with a CFV of 1.5 m s -1, the enhancement of 55.6%, 75.5% and 128.2% was achieved for critical flux, while 65.8%, 69.7% and 95.2% was achieved for limiting flux, respectively. The results also indicated that the use of gas sparging was an effective method to reduce reversible fouling and external irreversible fouling rather than internal irreversible fouling. In addition, the CFV and gas sparging did not affect pH, total soluble solids, colour, total phenolic content and the antioxidant property of the clarified juice. The l-ascorbic acid and total vitamin C were significantly decreased when the higher CFV and high gas injection factor were applied. The results also indicated that the use of gas sparging with low CFV was beneficial for flux enhancement while most of the phytochemical properties of the clarified juice was preserved. © 2011 Elsevier B.V. All rights reserved.

  15. Clarifying the atrioventricular junctional anatomy in the setting of double outlet right atrium

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Gupta

    2015-01-01

    Full Text Available Double outlet atrium is a rare cardiac anomaly wherein one of the atriums, most frequently the right atrium, opens into both the ventricles. Although seen more commonly in the setting of atrioventricular septal defect, this arrangement can also be found when one of the atrioventricular connections is atretic due to absence of the atrioventricular connection and the other atrioventricular valve straddles the muscular ventricular septum. It is the specific anatomy and connections of the atrioventricular junction that clarifies the situation and distinguishes between these two types of double outlet atrium. In this report, we present a case of double outlet right atrium co-existing with the absence of left atrioventricular connection. We then discuss the morphologic aspects of this interesting anomaly.

  16. Hydrodynamic evaluation of a hydraulic clarifier through hydraulic behaviour indicators and simplified flow models

    Directory of Open Access Journals (Sweden)

    Paola Patiño

    2012-04-01

    Full Text Available Hydrodynamic phenomena take place within water treatment plants associated with physical, operational and environmental factors which can affect the water quality. This study evaluated a hydraulic clarifier’s hydrodynamic pattern using sludge recirculation through continuous tracer test leading to determining hydraulic behaviour indicators and simplified flow models. The clarifier had dual flow with a predominantly complete mixture during the hours in which higher temperatures were reported for affluent water compared to those reported inside the reactor, causing the formation of density currents promoting mixing in the reactor and increased turbidity in the effluent. The hydraulic indicators and the Wolf-Resnick model had higher sensitivity to the influence of temperature on reactor hydrodynamics.

  17. Clarifying the link between childhood abuse history and psychopathic traits in adult criminal offenders.

    Science.gov (United States)

    Dargis, Monika; Newman, Joseph; Koenigs, Michael

    2016-07-01

    Childhood abuse is a risk factor for the development of externalizing characteristics and disorders, including antisocial personality disorder and psychopathy. However, the precise relationships between particular types of childhood maltreatment and subsequent antisocial and psychopathic traits remain unclear. Using a large sample of incarcerated adult male criminal offenders (n = 183), the current study confirmed that severity of overall childhood maltreatment was linked to severity of both psychopathy and antisocial personality disorder in adulthood. Moreover, this relationship was particularly strong for physical abuse and the antisocial facet of psychopathy. Sexual abuse history was uniquely related to juvenile conduct disorder severity, rather than adult psychopathy or antisocial behaviors. Additionally, there was a significantly stronger relationship between childhood maltreatment and juvenile conduct disorder than between childhood maltreatment and ASPD or psychopathy. These findings bolster and clarify the link between childhood maltreatment and antisocial behavior later in life. (PsycINFO Database Record PMID:26389621

  18. Verification method for CFD models on clarifier of wastewater treatment plants using radioisotope tracer techniques

    International Nuclear Information System (INIS)

    The rectangular clarifier in laboratory was simulated on computational fluid dynamics by which the flow patterns of suspended particle and water in a specific condition can be predicted. In order to validate the simulation model, the tracer experiment has been carried out using radiotracer, 113mIn, which is produced from Sn/In generator. As a result of converting the radiotracer data into the graphs of contour maps, the experimental data was visualized looking like a simulation result and it was fairly useful for understanding the general characteristics of flow. For more quantitative verification, however, the simulation data should be processed to make concentration-time curves corresponding to RTD curves of radiotracer experiment. (author)

  19. Improved waste water polishing in the North Anna clarifier using Durasil ion exchange media

    International Nuclear Information System (INIS)

    On December 26, 1985, forty-one cubic feet of ion exchange media provided by Duratek was loaded into the North Anna clarifier demineralizer. As of the writing of this manuscript (February 6, 1986), processing using this single loading has continued for 42 straight days without breakthrough. To date, some 5.89 million gallons have been processed at an average flow rate of 140,200 gal/day. Throughputs are 143,700 gal/cu.ft. and still climbing. These figures represent improvements of a factor 20 over the run times experienced with organic resins immediately prior to the introduction of the new materials. This paper describes the testing program of Durasil ion exchange media carried out at North Anna by Duratek which lead to this dramatic improvement in performance

  20. Modeling of slow sand filtration for disinfection of secondary clarifier effluent.

    Science.gov (United States)

    Langenbach, K; Kuschk, P; Horn, H; Kästner, M

    2010-01-01

    Due to increasing water scarcity, appropriate technologies are needed for disinfection of wastewater to enable safe reuse. Research on hygienisation of secondary effluent using slow sand filters is very limited but promising with removal of fecal indicator bacteria of >2log-units. A quantitative description of the processes leading to bacteria removal is lacking and therefore a model was developed for E. coli removal from secondary clarifier effluent in slow sand filters. Removal was successfully simulated for sands of variable grain size distribution and under a range of hydraulic loading rates compared to data obtained at pilot-scale filters. The most important process was retention of bacteria at the "schmutzdecke" and sand surface leading to an enrichment by a factor of up to 600 compared to the surrounding bulk phase. Bacteria elimination and inactivation both in the bulk phase and the schmutzdecke can be described by a first order kinetic. PMID:19833374

  1. Mathematical Modeling for the Clarifier Units and Turbidity Parameters in AL-KARAMA Treatment Plant

    Directory of Open Access Journals (Sweden)

    Hayder Mohammed Abdul-Hameed

    2005-01-01

    Full Text Available The high cost of chemical analysis of water has necessitated various researches into finding alternative method of determining portable water quality. This paper is aimed at modelling the turbidity value as a water quality parameter. Mathematical models for turbidity removal were developed based on the relationships between water turbidity and other water criteria. Results showed that the turbidity of water is the cumulative effect of the individual parameters/factors affecting the system. A model equation for the evaluation and prediction of a clarifier’s performance was developed:Model: T = T0(-1.36729 + 0.037101∙10λpH + 0.048928t + 0.00741387∙alkThe developed model will aid the predictive assessment of water treatment plant performance. The limitations of the models are as a result of insufficient variable considered during the conceptualization.

  2. Secondary clarifier hybrid model calibration in full scale pulp and paper activated sludge wastewater treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sreckovic, G.; Hall, E.R. [British Columbia Univ., Dept. of Civil Engineering, Vancouver, BC (Canada); Thibault, J. [Laval Univ., Dept. of Chemical Engineering, Ste-Foy, PQ (Canada); Savic, D. [Exeter Univ., School of Engineering, Exeter (United Kingdom)

    1999-05-01

    The issue of proper model calibration techniques applied to mechanistic mathematical models relating to activated sludge systems was discussed. Such calibrations are complex because of the non-linearity and multi-model objective functions of the process. This paper presents a hybrid model which was developed using two techniques to model and calibrate secondary clarifier parts of an activated sludge system. Genetic algorithms were used to successfully calibrate the settler mechanistic model, and neural networks were used to reduce the error between the mechanistic model output and real world data. Results of the modelling study show that the long term response of a one-dimensional settler mechanistic model calibrated by genetic algorithms and compared to full scale plant data can be improved by coupling the calibrated mechanistic model to as black-box model, such as a neural network. 11 refs., 2 figs.

  3. CONSTITUTIVE ANDROSTANE RECEPTOR DEPENDENT AND INDEPENDENT MODULATION OF CYP3A2, CYP1A2 BY PHENOBARBITAL AND FIBRATE IN RATS’ LIVER

    Directory of Open Access Journals (Sweden)

    Zein Shaban Ibrahim

    2013-01-01

    Full Text Available Cytochrome P450 enzymes, CYP3A and CYP1A are major drug metabolizing enzymes in the liver. CYP3A enzymes have a major role in the metabolism of 30-40% of all used drugs. CYP1A2 is a key enzyme having an important role in the metabolic clearance of 5% of currently marketed drugs. CYP1A2 participates in the metabolic activation of chemical mutagens in cooked food, therefore its activity is suspected to be one of the possible risk factors determining the carcinogenicity of heterocyclic amines in human beings. In a previous report, we have reported the induction of CYP3A2 and the inhibition of CYP1A2 by Fibrate (CFA and proved CYP1A2 inhibition to be PPARα-dependent. CYP3A2 and CYP1A2 have been reported to be induced in the liver by Phenobarbital (PB while Fibrates was reported to induce CYP3A2. However the exact mechanism of the induction of CYP3A2 by CFA and PB and induction of CYP1A2 by PB has not been clarified yet whether it is through Constitutive Androstane Receptor (CAR or other receptor as PPARα or Pregnane X Receptor (PXR. We treated Wistar female rats (with normal expression of CAR protein and Wistar femal Kyoto rats (with low expression of CAR protein with PB and Clofibric Acid (CFA. PB caused a high CYP3A2 induction in Wistar female rats and a low induction in (WKY indicating that PB induced CYP3A2 in a CAR-dependent manner. Interestingly, PB treatment induced CYP1A2 in Wistar female rats and failed to induce it in (WKY indicating that the induction of CYP1A2 by PB to be CAR-dependent. Moreover CFA induced CYP3A2 protein similarly in both rat strains indicating that CYP3A2 induction by Fibrates is CAR-independent and most probably to be PXR or PPARα-dependent. For the best of our knowledge this is the first report that shows a clear evidence of the CAR-dependent induction of CYP1A2 and CYP3A2 by PB and the CAR-independent induction of CYP3A2 by fibrates.

  4. Isotopic tracer method in the investigation of the scraper work in the clarifier of the biological sewage-treatment plant

    International Nuclear Information System (INIS)

    A method of investigation of the velocity of sediment transport in a clarifier of the biological sewage- treatment plant is described. It is based on the tracking of the motion of sediment portion containing 32P or 140La. (author)

  5. N2O emissions from secondary clarifiers and their contribution to the total emissions of the WWTP.

    Science.gov (United States)

    Mikola, Anna; Heinonen, Mari; Kosonen, Heta; Leppänen, Maarit; Rantanen, Pirjo; Vahala, Riku

    2014-01-01

    Recent studies have indicated that the emissions of nitrous oxide, N2O, constitute a major part of the carbon footprint of wastewater treatment plants (WWTPs). Denitrification occurring in the secondary clarifier basins has been observed by many researchers, but until now N2O emissions from secondary clarifiers have not been widely reported. The objective of this study was to measure the N2O emissions from secondary clarifiers and weigh the portion they could represent of the overall emissions at WWTPs. Online measurements over several days were carried out at four different municipal WWTPs in Finland in cold weather conditions (March) and in warm weather conditions (June-July). An attempt was made to define the conditions in which N2O emissions from secondary clarifiers may occur. It was evidenced that large amounts of N2O can be emitted from the secondary clarifiers, and that the emissions have long-term variation. It was assumed that part of the N2O released in secondary clarification was originally formed in the activated sludge basin. The emissions from secondary clarification thus seem to be dependent on conditions of the nitrification and denitrification accomplished in the denitrification-nitrification process and on the amount of sludge stored in the secondary clarifiers. PMID:25116504

  6. Clarifying appeals to dignity in medical ethics from an historical perspective.

    Science.gov (United States)

    Van Der Graaf, Rieke; Van Delden, Johannes Jm

    2009-03-01

    Over the past few decades the concept of (human) dignity has deeply pervaded medical ethics. Appeals to dignity, however, are often unclear. As a result some prefer to eliminate the concept from medical ethics, whereas others try to render it useful in this context. We think that appeals to dignity in medical ethics can be clarified by considering the concept from an historical perspective. Firstly, on the basis of historical texts we propose a framework for defining the concept in medical debates. The framework shows that dignity can occur in a relational, an unconditional, a subjective and a Kantian form. Interestingly, all forms relate to one concept since they have four features in common: dignity refers, in a restricted sense, to the 'special status of human beings'; it is based on essential human characteristics; the subject of dignity should live up to it; and it is a vulnerable concept, it can be lost or violated. We argue that being explicit about the meaning of dignity will prevent dignity from becoming a conversation-stopper in moral debate. Secondly, an historical perspective on dignity shows that it is not yet time to dispose of dignity in medical ethics. At least Kantian and relational dignity can be made useful in medical ethics. PMID:19161568

  7. Clarifying concepts of food parenting practices. A Delphi study with an application to snacking behavior.

    Science.gov (United States)

    Gevers, D W M; Kremers, S P J; de Vries, N K; van Assema, P

    2014-08-01

    Inconsistencies in measurements of food parenting practices continue to exist. Fundamental to this problem is the lack of clarity about what is understood by different concepts of food parenting practices. The purpose of this study was to clarify food parenting practice concepts related to snacking. A three round Delphi study among an international group of experts (n = 63) was conducted. In the first round, an open-ended survey was used to collect food parenting practice descriptions and concept labels associated with those practices. In the second round, participants were asked to match up descriptions with the appropriate concept labels. The third and final round allowed participants to reconsider how descriptions and concept labels were matched, taking into account the opinions expressed in round two. Round one produced 408 descriptions of food parenting practices and 110 different concept names. Round two started with 116 descriptions of food parenting practices and 20 concept names. On 40 descriptions, consensus regarding the underlying concept name was reached in round two. Of the remaining 76 descriptions, consensus on 47 descriptions regarding the underlying concept name was reached in round three. The present study supports the essential process of consensus development with respect to food parenting practices concepts. PMID:24732407

  8. Development of Laboratory Experimental System to Clarify Solar Wind Charge Exchange Mechanism with TES Microcalorimeter

    Science.gov (United States)

    Enoki, T.; Ishisaki, Y.; Akamatsu, H.; Ezoe, Y.; Ohashi, T.; Kanda, T.; Ishida, T.; Tanuma, H.; Ohashi, H.; Shinozaki, K.; Mitsuda, K.

    2012-06-01

    Significant fraction of the cosmic diffuse soft X-ray emission (0.1-1 keV) is caused by the Solar Wind Charge eXchange (SWCX) process between the solar wind ion (C q+, N q+, O q+ etc.) and the interplanetary neutral matter. It is difficult to identify spectral features of SWCX with the spectral resolution of existing X-ray astronomy satellites. We are developing a laboratory experimental system with transition edge sensor (TES) X-ray microcalorimeters, in order to clarify the SWCX mechanism. This experiment is designed to measure Charge eXchange (CX) X-rays using Electron Cyclotron Resonance Ion Source (ECRIS) that generates multi-charged ions. Emission lines (OVIII: 2p→1s; 654 eV) by CX between O8+ and neutral He atom is aimed to be measured with energy resolution better than 10 eV. The TES microcalorimeter is cooled by a double-stage adiabatic demagnetization refrigerator (DADR), however, our TES microcalorimeter are not working potentially due to magnetic field contamination. This paper reports our experimental system, present results, and future prospects.

  9. Alternatives for clarifying glucose syrup obtained by enzymatic hydrolysis of starch

    Directory of Open Access Journals (Sweden)

    Gloria Teresa Cruz Guerrero

    2010-03-01

    Full Text Available The present paper studies some routes for separating and purifying glucose syrup obtained by enzymatic hydrolysis of potato starch. The clarifying process is done in three stages. The first one (solids remotion is done by applying conventional solid-liquid separation techniiques such as sedimentation, centrifugation and filtration, as well as studying the effect of using flocculant and coagulant agents, prior to the already mentioned operations. Purification is done by adding decolouring agents, followed by ultrafiltration of the syrup. The last step (concentration is done by vacuum evaporation. The results showed that separation, centrifuging and sedimation reached 50% yield whilst filtration and ultrafiltration achieved 78% and 98% respectively. It was found that adsorbent agents such as activated carbon and diatomaceous earth were effective in removing colour during the purification stage. The most suitable alternative for separation can be suggested from the foregoing, allowing a syrup to be obtained having similar characteristics and propierties to the commercial product. The most appropriate technological module for carrying out the operation is also represented.

  10. Crud removal equipment using a centrifugal clarifier in Hamaoka Nuclear Power Station

    International Nuclear Information System (INIS)

    Although pressurized precoat type filters had been used so far as the liquid waste treatment equipment in the radwaste treatment systems for BWR type nuclear power stations, the experiences in Hamaoka No. 1 plant revealed that the above mentioned filters required the filter aids of about ten times as much as liquid waste to remove mainly insoluble corrosion products (called crud), and this occupied the large part of waste production. Therefore the separating cone type centrifugal clarifier (called crud separator) which can remove crud in the field of centrifugal force was adopted, and the proving test for two-years has been performed in Hamaoka No. 1 nuclear power plant. The system configuration, testing details, the concentration and composition of crud, crystal form and particle size distribution are thoroughly reported. As for equipment drain, it was possible to satisfy the criteria for reuse in the plant, using only the crud separator. Waste production was able to be reduced to 1/10 or less as compared with conventional pressurized precoat filters. The crud separator is easy to make the automatic operation and results in the reduction of burden of operators. The performance for crud removal was not deteriorated by piling up of scale or blocking, even if the liquid wastes containing much microorganism, Ga compounds and others have been processed. The effect of concentrating crud was also large. (Wakatsuki, Y.)

  11. Innovative use of lamella clarifiers for central stormwater treatment in separate sewer systems.

    Science.gov (United States)

    Weiss, Gebhard

    2014-01-01

    Lamella settlers have been used in the past few years for the sedimentation of particles in wastewater and stormwater applications. A new and very innovative approach for the treatment of stormwater flows is proposed which extends the portfolio of solutions beyond traditional settling tanks. Surface runoff is stored in a sewer or a basin and finally treated in a small but continuously operated lamella clarifier. The low throughput flow will yield good treatment efficiency at a small footprint. The possibilities of using existing storage volume in a storm sewer, as well as the structural flexibility of the arrangement are decisive benefits. As a large operational advantage, the lamellae may be cleaned mechanically, e.g. by pivoting under water. Finally, the flow and the sludge which will be sent to the downstream treatment plant will be minimized. A new comparative simulation method is proposed in order to assess an equivalent degree of stormwater treatment, either by achieving an equal annual volume of treated stormwater or, more directly, an equal amount of spilled pollutant load. The new solution is compared with a traditional settling tank according to current German design rules. Additionally, a case study from a real installation will be presented. PMID:24759518

  12. Suppression of phosphorus release from sediments using water clarifier sludge as capping material.

    Science.gov (United States)

    Ichihara, Makiko; Nishio, Takayuki

    2013-01-01

    Water clarifier sludge was assessed as a capping material for preventing release of phosphorus from eutrophic pond sediments. Sediment incubation experiments were carried out over two months using five capping materials (sludge, sludge sintered respectively at 200, 400 and 600 degrees C, and sea sand) to evaluate the effect of sintering temperature. We also examined reduction in the nitrogen eluted from the sludge. Sludge, sludge sintered at 400 and 600 degrees C, and sea sand suppressed phosphorus release from sediments into the overlying water, whereas sludge and sludge sintered at 200 degrees C increased nitrogen release relative to that without capping. Sludge sintered at 600 degrees C was the most effective in reducing total nitrogen (TN) flux. Our experiments revealed that nitrogen and organic substances must be removed completely from sludge in order to avoid their release. The phosphate removal efficiency of sludge (including sintered sludge) was expressed in terms of Freundlich adsorption isotherms. The results showed that sludge sintered at 600 degrees C was suitable for use as a capping material since (1) its organic content (ignition loss) and TN were low (1.1% and 0.014 mg g(-1) dry, respectively), (2) its phosphorus adsorption capacity was 2.2 times higher than that ofunsintered sludge, and (3) it was effective in suppressing the diffusion of phosphorus and NH4+-N from sediments when used as a capping material. PMID:24350484

  13. Clarifying the best interests standard: the elaborative and enumerative strategies in public policy-making.

    Science.gov (United States)

    Lim, Chong-Ming; Dunn, Michael C; Chin, Jacqueline J

    2016-08-01

    One recurring criticism of the best interests standard concerns its vagueness, and thus the inadequate guidance it offers to care providers. The lack of an agreed definition of 'best interests', together with the fact that several suggested considerations adopted in legislation or professional guidelines for doctors do not obviously apply across different groups of persons, result in decisions being made in murky waters. In response, bioethicists have attempted to specify the best interests standard, to reduce the indeterminacy surrounding medical decisions. In this paper, we discuss the bioethicists' response in relation to the state's possible role in clarifying the best interests standard. We identify and characterise two clarificatory strategies employed by bioethicists -elaborative and enumerative-and argue that the state should adopt the latter. Beyond the practical difficulties of the former strategy, a state adoption of it would inevitably be prejudicial in a pluralistic society. Given the gravity of best interests decisions, and the delicate task of respecting citizens with different understandings of best interests, only the enumerative strategy is viable. We argue that this does not commit the state to silence in providing guidance to and supporting healthcare providers, nor does it facilitate the abuse of the vulnerable. Finally, we address two methodological worries about adopting this approach at the state level. The adoption of the enumerative strategy is not defeatist in attitude, nor does it eventually collapse into (a form of) the elaborative strategy. PMID:27145811

  14. Disturbance-driven Hillslope Diffusion Scales and Values Clarified by Extant Surface Roughness

    Science.gov (United States)

    Doane, T.; Furbish, D. J.

    2015-12-01

    In low-relief landscapes, the hillslope diffusion equation approximates the rate of topographic evolution due to disturbance driven sediment transport. Whereas this expression is appealing and performs well, the physical meaning of a hillslope diffusivity remains unclear. Here, a study of the disturbances that redistribute sediment on hillslopes clarifies a physical interpretation. We conceptualize the cumulative hillslope diffusivity, which is a rate constant for topographic degradation at large scales, as the aggregate of all surface disturbing processes. A numerical model that generates pit and mound topography from tree throw events illustrates this idea. Using the diffusion equation, we model the degradation of pits and mounds by all smaller scale disturbances. However, when examined at a larger scale, the effective hillslope diffusivity is composed of the small scale diffusivity plus the effect of tree throw. We also present a method to determine the background hillslope diffusivity using the extant hillslope roughness and rates of roughness production. Numerical simulations show that the variance of the surface roughness of a hillslope as introduced by pit and mound topography reaches a steady state when the rate of variance production (tree throw) is constant. The magnitude of the steady state variance is a function of variance production and decay (small scale diffusivity), so there is an opportunity to determine hillslope diffusivity values if the rates of variance production are known. This method yields estimates of the modern hillslope diffusivity which are useful in problems involving the human and climate change time scales.

  15. Clarifying inflation models: The precise inflationary potential from effective field theory and the WMAP data

    International Nuclear Information System (INIS)

    We clarify inflaton models by considering them as effective field theories in the Ginzburg-Landau spirit. In this new approach, the precise form of the inflationary potential is constructed from the present WMAP data, and a useful scheme is prepared to confront with the forthcoming data. In this approach, the WMAP statement excluding the pure φ4 potential implies the presence of an inflaton mass term at the scale m∼1013 GeV. Chaotic, new and hybrid inflation models are studied in an unified way. In all cases the inflaton potential takes the form V(φ)=m2MPl2v(φ/MPl), where all coefficients in the polynomial v(φ) are of order one. If such potential corresponds to supersymmetry breaking, the corresponding susy breaking scale is √(mMPl)∼1016 GeV which turns to coincide with the grand unification (GUT) scale. The inflaton mass is therefore given by a seesaw formula m∼MGUT2/MPl. The observables turn to be two-valued functions: one branch corresponds to new inflation and the other to chaotic inflation, the branch point being the pure quadratic potential. For red tilted spectrum, the potential which fits the best the present data (vertical bar 1-ns vertical bar s of scalar perturbations: 106(m/MPl)=127√(r vertical bar 1-ns vertical bar) where the numerical coefficient is fixed by the WMAP amplitude of adiabatic perturbations. Implications for string theory are discussed

  16. Sustainable or Distributed Energy—or both? Clarifying the Basic Concepts of Reforming the Energy Sector

    Directory of Open Access Journals (Sweden)

    Pekka Peura

    2015-06-01

    Full Text Available This paper clarifies the concepts of Sustainable Energy (SE and Distributed Energy (DE including their related synonyms, by discussing, analyzing and presenting recommendations. This is important because these concepts are crucial in the on-going transformation from the fossil carbon based to renewable energy based societies, but still the use of the concepts has been confusing. SE consists of the integration of rational use of energy (energy saving, energy efficiency, use of renewable energy sources and sustainability management for anticipating, avoiding and reducing adverse impacts. The best consensus for defining DE is “facilities connected to the distribution network or on the customer side of the meter”. Devices using fossil fuels but otherwise falling under this umbrella cannot be excluded from DE. This paper explores definitions of wind power in relation to its grid connections via DE. SE is more comprehensive embracing the whole field of energy management, with the exception of distributed fossil generation. SE is valuable for understanding, planning and implementing energy strategies in the transition process of the energy sector. SE also includes centralized energy. It is useful for planning at national or sub-national geographic regions. The combination Sustainable Distributed Energy (SDE is excellent for regional contexts and for creating regional renewable energy self-sufficiency, integrated with society-wide energy saving and energy efficiency programs.

  17. [THE MODE OF CLARIFYING DIAGNOSTIC OF PROGRESSING FORMS OF OVARIAN CARCINOMA].

    Science.gov (United States)

    Dolgova, D R; Gening, T P; Abakumova, T V; Antoneeva, I I; Butov, A A; Korchagina, I A; Tuzeeva, A Yu; Fomina, A V

    2015-10-01

    The ovarian carcinoma is the most frequent cause of death because of malignant neoplasins in women. At that, there is no pathognomonic symptoms permitting diagnosing stage of process with sufficient degree of confidence. This is a determinative not only for choosing treatment regimen but also for correlation of expected results of treatments with economic factors with purpose to evaluate cost effectiveness under monitoring of these patients. The study was carried out to develop mode of clarifying diagnostic of progressing forms of ovarian carcinoma on the basis of evaluation of oxidative modification of proteins in blood plasma. In 100 female patients with primary ovarian carcinoma (stage III and IV according FIGO,) in blood plasma 21 indicators were determined in blood plasma using standardized techniques: absolute number of leukocytes, absolute and relative number of neutrophils, products of oxidative modification of proteins of basic and ketonic character (under wavelength of 356, 370, 430, 530 nm), Her-2/neu CA-125, matrix metalloproteinase 2 and 9 in blood serum and neutrophils, interleukin-6, interleukin-10, interleukin-1β, interferon-γ, tumor necrosis factor-α, malonic dialdehyde, catalase, glutaihione transferase, glutathione reductase. The least squares method was applied to every parameter to appmximnate relative rates by density of Rayleigh distribution. For every indicator likelihood ratio functions of likelihood ratio were constructed and intervals at every stage were determined. The reliability of approximation was proved under testing with Pirson criterion hypothesis of compliance of practical values of parameters to theoretical law of density of distribution. The results permit to assert that level of oxidative modification of proteins cab be used as a reliable indicator for differentiated diagnostic of stage III and IV of ovarian carcinoma. PMID:26841670

  18. Elements to clarify the shale gas debate. Committee on Energy Prospective

    International Nuclear Information System (INIS)

    Shale gases have been the centre of heated debates for a few years. The opinions range from an outright ban on their exploitation to the notion that they might in an unexpected and almost miraculous way restore growth in our country and create jobs. In view of the importance of the questions raised by this topic, the Comite de Prospective en Energie de l'Academie des Sciences (CPE) provides elements to help clarify the debate and to formulate recommendations with the aim in particular of reducing current uncertainties. This report first describes the various contextual elements and then some recommendations that have been formulated. The first four recommendations concern research and exploration; the following five concern the exploitation of shale gases which could be potentially undertaken provided that necessary conditions, in particular for reducing environmental risks, are fulfilled. 1. Launch a research effort involving academic laboratories and major organizations to study all the scientific issues arising from the exploration and exploitation of shale gases. 2. Prepare exploration by making use of existing or archived geological, geophysical and geochemical data and involve geologists in the evaluation of reserves. 3. Develop studies and experiments aimed at evaluating and reducing the environmental impact of any potential exploitation. 4. Create an independent and multidisciplinary scientific authority to monitor actions taken to evaluate resources and their methods of exploitation. 5. Address issues of water management, a major problem in the exploitation of shale gases. 6. Implement environmental monitoring before, during and after exploitation. 7. Launch developments to improve the processes of hydraulic fracturing and develop alternative methods. 8. Initiate a research program to develop appropriate regulations to address the long-term tightness issues in exploitation drilling. 9. Full-scale tests should be carried out under conditions that

  19. Clarifying CLARITY: quantitative optimization of the diffusion based delipidation protocol for genetically labelled tissue

    Directory of Open Access Journals (Sweden)

    Chiara eMagliaro

    2016-04-01

    Full Text Available Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine the optimum clearing time for genetically labeled neurons from thick murine brain slices using CLARITY2 is described. In particular, as the main objective of the delipidation treatment is to clarify tissues, while limiting loss of fluorescent signal, the goodness of clarification was evaluated by considering the bulk tissue clarification index (BTCi and the fraction of the fluorescent marker retained in the slice as easily quantifiable macroscale parameters. Here we describe the approach, illustrating an example of how it can be used to determine the optimum clearing time for 1 mm-thick cerebellar slice from transgenic L7GFP mice, in which Purkinje neurons express the GFP (green fluorescent protein tag. To validate the method, we evaluated confocal stacks of our samples using standard image processing indices (i.e. the mean pixel intensity of neurons and the contrast-to-noise ratio as figures of merit for image quality.The results show that detergent-based delipidation for more than five days does not increase tissue clarity but the fraction of GFP in the tissue continues to diminish. The optimum clearing time for 1 mm-thick slices was thus identified as five days, which is the best compromise between the increase in light penetration depth due to removal of lipids and a decrease in fluorescent signal as a consequence of protein loss: further clearing does not improve tissue transparency, but only leads to more protein removal or degradation. The rigorous

  20. Clarifying CLARITY: Quantitative Optimization of the Diffusion Based Delipidation Protocol for Genetically Labeled Tissue.

    Science.gov (United States)

    Magliaro, Chiara; Callara, Alejandro L; Mattei, Giorgio; Morcinelli, Marco; Viaggi, Cristina; Vaglini, Francesca; Ahluwalia, Arti

    2016-01-01

    Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine the optimum clearing time for genetically labeled neurons from thick murine brain slices using CLARITY2 is described. In particular, as the main objective of the delipidation treatment is to clarify tissues, while limiting loss of fluorescent signal, the "goodness" of clarification was evaluated by considering the bulk tissue clarification index (BTCi) and the fraction of the fluorescent marker retained in the slice as easily quantifiable macroscale parameters. Here we describe the approach, illustrating an example of how it can be used to determine the optimum clearing time for 1 mm-thick cerebellar slice from transgenic L7GFP mice, in which Purkinje neurons express the GFP (green fluorescent protein) tag. To validate the method, we evaluated confocal stacks of our samples using standard image processing indices (i.e., the mean pixel intensity of neurons and the contrast-to-noise ratio) as figures of merit for image quality. The results show that detergent-based delipidation for more than 5 days does not increase tissue clarity but the fraction of GFP in the tissue continues to diminish. The optimum clearing time for 1 mm-thick slices was thus identified as 5 days, which is the best compromise between the increase in light penetration depth due to removal of lipids and a decrease in fluorescent signal as a consequence of protein loss: further clearing does not improve tissue transparency, but only leads to more protein removal or degradation. The rigorous quantitative approach

  1. Clarifying the association of genes within the major histocompatibility complex with narcolepsy

    Energy Technology Data Exchange (ETDEWEB)

    Acton, R.T.; Watson, B.; Rivers, C. [Univ. of Alabama, Birmingham, AL (United States)] [and others

    1994-09-01

    HLA-DR2 and DQwl has been reported to be strongly associated with narcolepsy. The particular phenotype and strength of these associations varies between races. For example DQB*0601 has been reported associated with some African American (AA) narcoleptics while some Caucasian American (CA) narcoleptics do not possess DR2 or DQw1. We have sought to clarify the relationship of MHC genes with narcolepsy in the local CA and AA population. There was no significant difference in the frequency of DR phenotypes in CA or AA narcoleptics compared to race, age, sex and geographic region-matched controls. DR2 was increased in CA cataplexy positive (Cat+) narcoleptics compared to controls (p=0.028, odds ratio (OR)=2.4) and to Cat- narcoleptics (p=<0.001, OR=8.8). DR11 was increased in AA Cat+ narcoleptics compared to controls (p=0.004, OR=11.2) and to Cat- narcoleptics (p=0.002). DQB1*0601 was not significantly associated with narcolepsy in our AA population. We have assessed the frequency of the TNFa (13 alleles, 1.1Mb telomeric to DQ{alpha}), D6S105 (13 alleles, 1kb telomeric of HLA-A), and GLP-1R (19 alleles, 18.5 Mb centromeric of DQ{alpha}), dinucleotide repeats in narcoleptics compared to controls. The TNFa allele 117 was increased in CA Cat+ vs. controls (p=0.003). The GLP-1R allele 144 was increased in CA Cat- vs. controls (p=0.02). In AA narcoleptics, the TNFa allele 109 was significantly increased (p=0.04) along with the D6S105 allele 130 (p=0.02) compared to controls. The D6S105 allele 130 was increased in AA Cat- vs. controls (p=0.03). The GLP-1R allele 154 was significantly decreased in AA Cat+ vs. Cat- (p=0.04). These data suggest that DR and/or DQ genes are not responsible for narcolepsy and that cataplexy is associated with different regions around the MHC in various racial groups.

  2. Involving students in learning and health promotion processes--clarifying why? what? and how?

    Science.gov (United States)

    Jensen, Bjarne Bruun; Simovska, Venka

    2005-01-01

    The concept of student participation is currently a popular notion in health promoting schools as well as in general education. However, phrases such as 'involvement', 'participation', 'co-determination' and 'influence' are frequently used without careful definition. In this article two models, developed in the context of health promoting schools in two different cultures, are presented and discussed. The first model makes a fundamental distinction between token and genuine participation. Token participation in health promotion is characterised by focusing on prescribed knowledge, closed and convergent outcomes and targeting individuals isolated from the surrounding environment. In contrast, genuine participation stresses students' own construction of knowledge, open and divergent outcomes and targeting individuals in their context. Genuine participation is in accordance with a democratic health promoting school aiming at students' empowerment and action competence. The second model clarifies a number of different categories of students' participation in health promotion. The different categories illustrate how the teacher in various ways can play an active role in participatory approaches as a responsible professional. The more the students are involved in health projects, the more important it will be for the teacher to provide support, insight and knowledge to facilitate the learning processes. Furthermore, the different participation categories have to be related to a number of decisions which are normally included in a school health project. The model illustrates that participation should always be viewed in relation to the context and that it makes no sense to establish a single ideal way of working with participation in a health promoting school. The theoretical models are illuminated by concrete examples from health promoting schools. The overall conclusion is that participation is a complex term and rather than providing definitive answers, the models can

  3. Clarifying CLARITY: Quantitative Optimization of the Diffusion Based Delipidation Protocol for Genetically Labeled Tissue

    Science.gov (United States)

    Magliaro, Chiara; Callara, Alejandro L.; Mattei, Giorgio; Morcinelli, Marco; Viaggi, Cristina; Vaglini, Francesca; Ahluwalia, Arti

    2016-01-01

    Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine the optimum clearing time for genetically labeled neurons from thick murine brain slices using CLARITY2 is described. In particular, as the main objective of the delipidation treatment is to clarify tissues, while limiting loss of fluorescent signal, the “goodness” of clarification was evaluated by considering the bulk tissue clarification index (BTCi) and the fraction of the fluorescent marker retained in the slice as easily quantifiable macroscale parameters. Here we describe the approach, illustrating an example of how it can be used to determine the optimum clearing time for 1 mm-thick cerebellar slice from transgenic L7GFP mice, in which Purkinje neurons express the GFP (green fluorescent protein) tag. To validate the method, we evaluated confocal stacks of our samples using standard image processing indices (i.e., the mean pixel intensity of neurons and the contrast-to-noise ratio) as figures of merit for image quality. The results show that detergent-based delipidation for more than 5 days does not increase tissue clarity but the fraction of GFP in the tissue continues to diminish. The optimum clearing time for 1 mm-thick slices was thus identified as 5 days, which is the best compromise between the increase in light penetration depth due to removal of lipids and a decrease in fluorescent signal as a consequence of protein loss: further clearing does not improve tissue transparency, but only leads to more protein removal or degradation. The rigorous quantitative

  4. Further Clarifying Proximal Withdrawal States and the Turnover Criterion Space: Comment on Hom, Mitchell, Lee, and Griffeth (2012)

    Science.gov (United States)

    Maertz, Carl P., Jr.

    2012-01-01

    In "Reviewing Employee Turnover: Focusing on Proximal Withdrawal States and an Expanded Criterion," Hom, Mitchell, Lee, and Griffeth (2012) brought together many of the most important content and process factors in the employee turnover literature. In this paper, I attempt to clarify the true contributions of this framework for the turnover area…

  5. ENVIRONMENTAL TECHNOLOGY VERIFICATION: Separation of Manure Solids from Flushed Swine Waste. Hoffland Environmental Inc. Drag Screen and Clarifier

    Science.gov (United States)

    Verification testing of the Hoffland Drag Screen and Clarifier was conducted at the North Carolina State University's Lake Wheeler Road Field Laboratory, in Raleigh, North Carolina. The farm is designed to operate as a research and teaching facility with the capacity for 250 so...

  6. Use of Moringa oleífera Lamarck leaf extract as sugarcane juice clarifier: effects on clarifed juice and sugar

    Directory of Open Access Journals (Sweden)

    Gustavo Henrique Gravatim Costa

    2014-03-01

    Full Text Available The objective of this study was to evaluate the effect of Moringa oleifera Lam. leaf extract on the sedimentation of impurities in the treatment of sugarcane juice and the effects on sugar quality and on the clarified juice. The experimental design used was a 4x2 factorial arrangement with four replications. The main treatments performed included the extracted original sugarcane juice, the synthetic polyelectrolyte (Flomex 9076, the leaf extract, and a control. The secondary treatments consisted of the sugarcane varieties RB92579 and RB867515. The clarification process used was simple defecation, in which the flocculating agents and the juice, limed and heated, were poured simultaneously into a decanter. The microbiological and chemico-technological characteristics of the extracted and clarified juices were evaluated. The clarified juice was concentrated up to 60° Brix (syrup and subjected to boiling in a pilot pan using seeds to perform the graining: The sugar was recovered by centrifugation and analyzed for microbiological and chemico-technological characteristics. It was concluded that the use of the Moringa oleifera Lam. leaves extract resulted in a better quality of clarified juice and sugar.

  7. Straight from the Mouths of Horses and Tapirs: Using Fossil Teeth to Clarify How Ancient Environments Have Changed over Time

    Science.gov (United States)

    DeSantis, Larisa

    2009-01-01

    Clarifying ancient environments millions of years ago is necessary to better understand how ecosystems change over time, providing insight as to the potential impacts of current global warming. This module engages middle school students in the scientific process, asking them to use tooth measurement to test the null hypothesis that horse and tapir…

  8. 75 FR 41078 - Revisions to the Commerce Control List To Update and Clarify Crime Control License Requirements

    Science.gov (United States)

    2010-07-15

    ...This rule updates and clarifies export and reexport license requirements on striking weapons, restraint devices, shotguns and parts, optical sighting devices, and electric shock devices. It also adds equipment designed for the execution of humans to the Commerce Control List. This rule makes no changes to the longstanding policy of denial of applications to export or reexport specially......

  9. Valuating report on radionuclide concentrations in the waste water and mixed slurry from the Vienna main clarifying plant for 1988

    International Nuclear Information System (INIS)

    Sample preparation- and measuring methods, and results on 16 nuclides from the Vienna clarifying plant for 1988 are presented. Comparisons with the 1987 values are made and hypotheses about the sources of radionuclides - natural, atmospheric atomic weapons tests, Chernobyl accident and medical applications - are presented. An estimation of the activity transferred to the surface waters (Danube) over 1988 is also made. 16 refs., 8 figs., 6 tabs. (qui)

  10. Do we care about the distance to the CMB?:clarifying the impact of second-order lensing

    OpenAIRE

    Bonvin, Camille; Clarkson, Chris; Durrer, Ruth.; Maartens, Roy; Umeh, Obinna

    2015-01-01

    It has recently been shown that second-order corrections to the background distance-redshift relation can build up significantly at large redshifts, due to an aggregation of gravitational lensing events. This shifts the expectation value of the distance to the CMB by 1%. In this paper we show that this shift is already properly accounted for in standard CMB analyses. We clarify the role that the area distance to the CMB plays in the presence of second-order lensing corrections.

  11. Do we care about the distance to the CMB? Clarifying the impact of second-order lensing

    CERN Document Server

    Bonvin, Camille; Durrer, Ruth; Maartens, Roy; Umeh, Obinna

    2015-01-01

    It has recently been shown that second-order corrections to the background distance-redshift relation can build up significantly at large redshifts, due to an aggregation of gravitational lensing events. This shifts the expectation value of the distance to the CMB by 1%. In this paper we show that this shift is already properly accounted for in standard CMB analyses. We clarify the role that the distance to the CMB plays in the presence of second-order lensing corrections.

  12. Descriptive epidemiology of spot urine sodium-to-potassium ratio clarified close relationship with blood pressure level: the Nagahama study.

    OpenAIRE

    Tabara, Yasuharu; Takahashi, Yoshimitsu; Kumagai, Kyoko; Setoh, Kazuya; Kawaguchi, Takahisa; Takahashi, Meiko; Muraoka, Yuki; Tsujikawa, Akitaka; Gotoh, Norimoto; Terao, Chikashi; Yamada, Ryo; Kosugi, Shinji; Sekine, Akihiro; Yoshimura, Nagahisa; Nakayama, Takeo

    2015-01-01

    [Objectives]: We undertook descriptive epidemiology of spot urine sodium-to-potassium ratio (Na/K) in a population sample to clarify the close relationship between Na/K and blood pressure level independently of potential confounding factors. [Methods]: Study participants consisted of 9144 apparently healthy citizens (aged 54 ± 13 years). All clinical parameters were obtained at baseline. [Results]: Na/K was significantly higher in hypertensive individuals irrespective of antihypertensive medi...

  13. Effect of treatment with adsorbent resin on the volatile profile and physicochemical characteristics of clarified cashew apple juice

    Directory of Open Access Journals (Sweden)

    Adriana Dutra Sousa

    2013-12-01

    Full Text Available Increased preference for healthy and functional foods could be an opportunity to increase the consumption of clarified cashew apple juice. Given its level of fructose, glucose, and vitamin C, it can be used as a base in blends. However, its characteristic odor can interfere with the acceptance of these formulations, especially by consumers who are not familiar with cashew aroma. The aim of this study was to evaluate the effect of treatment with macroporous resins (FPA54, FPX66, XAD761, and XAD4 on the volatile profile and physicochemical characteristics of clarified cashew apple juice. After the treatment with the resins, the volatile profile was evaluated using solid-phase microextraction (SPME and gas chromatography/mass spectrometry (GC/MS. The physicochemical analyses performed were: pH, soluble solids (ºBrix, total titrable acidity, reducing sugars, and vitamin C. Gas chromatography analyses showed that XAD4 and FPX66 led to a reduction of the initial amount of volatile compounds to 14.05% and 15.72%, respectively. These two resins also did not affect the physicochemical characteristics of the clarified cashew apple juice.

  14. Selective detection of adenosine A1 receptor-dependent G-protein activity in basal and stimulated conditions of rat brain [35S]guanosine 5minutes or feet-(γ-thio)triphosphate autoradiography

    International Nuclear Information System (INIS)

    [35S]Guanosine 5minutes or feet-(γ-thio)triphosphate autoradiography is a novel technique to detect receptor-dependent activation of G-proteins in brain tissue sections. While an increasing number of reports using this approach are beginning to appear, little effort has been directed to the identification of factors responsible for the heterogeneously distributed [35S]guanosine 5minutes or feet-(γ-thio)triphosphate signal in basal conditions. The present study demonstrates that endogenously formed adenosine generates a widespread and prominent adenosine A1 receptor-dependent signal in basal conditions using this technique. Treatment of rat brain tissue sections with the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine dose-dependently (ec5035S]guanosine 5minutes or feet-(γ-thio)triphosphate binding in a region-specific manner, an effect fully mimicked by the adenosine-depleting enzyme adenosine deaminase, and less so by the A1 antagonist cirsimarin and by caffeine. That adenosine was continuously formed during the incubation is supported by the constant requirements of adenosine deaminase in order to suppress basal radioligand binding and further by the fact that low micromolar concentrations of adenine nucleotides evoked only adenosine-mimicking and fully 8-cyclopentyl-1,3-dipropylxanthine-sensitive binding responses. In the presence of adenosine deaminase, all responses to adenine nucleotides were abolished, indicating that prior conversion to adenosine was required. Upon stimulation, this technique selectively detected A1 receptor-activated G-proteins, as the non-selective agonists adenosine and 2-chloroadenosine and the A1-selective agonist N6-p-sulfophenyladenosine all evoked only 8-cyclopentyl-1,3-dipropylxanthine-sensitive responses in identical gray matter areas, and also in several white matter areas such as the corpus callosum, anterior commissure, optic tract and cerebellar white matter. Dose-response studies revealed region

  15. Residue-Ligand Interaction Energy (ReLIE on a Receptor-Dependent 3D-QSAR Analysis of S- and NH-DABOs as Non-Nucleoside Reverse Transcriptase Inhibitors

    Directory of Open Access Journals (Sweden)

    Monique Araújo de Brito

    2012-06-01

    Full Text Available A series of 74 dihydroalkoxybenzyloxopyrimidines (DABOs, a class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs, was retrieved from the literature and studied by receptor-dependent (RD three-dimensional quantitative structure-activity relationship (3D-QSAR analysis to derive RD-3D-QSAR models. The descriptors in this new method are the steric and electrostatic interaction energies of the protein-ligand complexes (per residue simulated by molecular dynamics, an approach named Residue-Ligand Interaction Energy (ReLIE. This study was performed using a training set of 59 compounds and the MKC-442/RT complex structure as reference. The ReLIE-3D-QSAR models were constructed and evaluated by genetic algorithm (GA and partial least squares (PLS. In the best equations, at least one term is related to one of the amino acid residues of the p51 subunit: Asn136, Asn137, Glu138, and Thr139. This fact implies the importance of interchain interaction (p66-p51 in the equations that best describe the structure-activity relationship for this class of compounds. The best equation shows q2 = 0.660, SEcv = 0.500, r2 = 0.930, and SEE = 0.226. The external predictive ability of this best model was evaluated using a test set of 15 compounds. In order to design more potent DABO analogues as anti-HIV/AIDS agents, substituents capable of interactions with residues like Ile94, Lys101, Tyr181, and Tyr188 should be selected. Also, given the importance of the conserved Asn136, this residue could become an attractive target for the design of novel NNRTIs with improved potency and increased ability to avoid the development of drug-resistant viruses.

  16. Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects

    OpenAIRE

    Bocci Velio; Zanardi Iacopo; Travagli Valter

    2011-01-01

    Abstract Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, l...

  17. WELL-POSEDNESS IN BVt AND CONVERGENCE OF A DIFFERENCE SCHEME FOR CONTINUOUS SEDIMENTATION IN IDEAL CLARIFIER-THICKENER UNITS

    OpenAIRE

    2003-01-01

    We consider a scalar conservation law modeling the settling of particles in an ideal clarifier-thickener unit. The conservation law has a nonconvex flux which is spatially dependent on two discontinuous parameters. We suggest to use a Kruzkov-type notion of entropy solution for this conservation law and prove iniqueness ($L_1$ stability) of the entropy solution in the $BV_t$ class (functions $W(x,t)$ with $\\partial_tW$ being a finite measure). The existence of a $BV_t$ entropy solution is est...

  18. CRIEPI's research results (2006-2011) and clarified future issues on alteration behavior of bentonite barrier by alkaline solutions

    International Nuclear Information System (INIS)

    In radioactive waste disposal facilities, bentonite barrier would be altered by alkaline solutions which arise by leaching of cementitious materials. Consequently suitable properties of the bentonite barrier would be degraded for a long time period. In CRIEPI, the investigation on the alteration of the bentonite under alkaline conditions was started in 2006, and several CRIEPI reports have been published. Specifically, we have investigated the kinetics of montmorillonite dissolution, the mineralogical alteration of compacted bentonite (with high- and low-dry density) and the change of permeability of the compacted bentonite (with high- and low-dry density) during alteration under the alkaline conditions. Furthermore, stability of saponite, which has similar physical properties to the bentonite, under the alkaline conditions was also examined. In this report, we show the outline of those research results, and lay out the clarified future issues extracted from our results. Ten clarified future issues were divided three categories as follows: 1) the estimation of the alteration behavior of the bentonite by alkaline solutions, 2) the elucidation of the mechanism of physical properties (e.g., permeability, swelling properties and mechanistic properties) change of the compacted bentonites during alteration, and 3) the development of the model building and simulation technology concerning the change in physical properties during alteration under alkaline conditions. (author)

  19. Attenuation of Aβ{sub 25–35}-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangbao; Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Guibo, E-mail: sunguibo@126.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Ye, Jingxue [Jilin Agricultural University, Changchun, Jilin 130021 (China); Zhou, Yanhui [Center of Cardiology, People' s Hospital of Jilin Province, Changchun, 130021, Jilin (China); Dong, Xi [Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Wang, Tingting; Lu, Shan [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China); Sun, Xiaobo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193 (China)

    2014-08-15

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ{sub 25–35}-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ{sub 25–35} (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ{sub 25–35} treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ{sub 25–35} treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ{sub 25–35}-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ{sub 25–35}-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens

  20. Courts Clarify Holiday Conflicts.

    Science.gov (United States)

    Nolte, M. Chester

    1979-01-01

    Outlines the case in which a judge held that Sioux Falls, South Dakota, Christmas assemblies were constitutional. Presents part of the school district policy on the observance of religious holidays. (IRT)

  1. Codependency: Clarifying the Construct.

    Science.gov (United States)

    Springer, Carrie A.; Britt, Thomas W.; Schlenker, Barry R.

    1998-01-01

    College students (N=217) completed questionnaires to examine associations between codependency, relationship quality, and personality characteristics. Codependency was associated with lower self-esteem and lower perception of interpersonal control. Codependency was also found to be associated with greater self-consciousness, social anxiety, and…

  2. Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects

    Directory of Open Access Journals (Sweden)

    Bocci Velio

    2011-04-01

    Full Text Available Abstract Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, like vascular diseases. However, ozone therapy is mostly in practitioners' hands and some recent developments for increasing cost effectiveness and speed of treatment are neither standardized, nor evaluated toxicologically. Hence, the aim of this article is to emphasize the need to objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in the hope that ozone therapy will be accepted by orthodox medicine in the near future.

  3. Estimation and modeling of direct rapid sand filtration for total fecal coliform removal from secondary clarifier effluents.

    Science.gov (United States)

    Li, Yi; Yu, Jingjing; Liu, Zhigang; Ma, Tian

    2012-01-01

    The filtration of fecal coliform from a secondary clarifier effluent was investigated using direct rapid sand filters as tertiary wastewater treatment on a pilot scale. The effect of the flocculation dose, flow loading rate, and grain size on fecal coliform removal was determined. Direct rapid sand filters can remove 0.6-1.5 log-units of fecal coliform, depending on the loading rate and grain size distribution. Meanwhile, the flocculation dose has little effect on coliform removal, and increasing the loading rate and/or grain size decreases the bacteria removal efficiency. A model was then developed for the removal process. Bacteria elimination and inactivation both in the water phase and the sand bed can be described by first-order kinetics. Removal was successfully simulated at different loading rates and grain size distributions and compared with the data obtained using pilot-scale filters. PMID:22508124

  4. Characterization of clarified medium from submerse and semisolid cultivation of OF Aspergillus awamori NRRL3112 by size-exclusion chromatography

    Directory of Open Access Journals (Sweden)

    MINAMI N.M.

    1999-01-01

    Full Text Available In this study, a preparative size-exclusion chromatography of two different clarified media obtained from submerse and semisolid culture of the mold Aspergillus awamori was carried out. Characterization and comparison of the quantities of glucoamylase and contaminant proteins present in these media were possible. Glucoamylase is the protein with the higher molecular weight in both media analyzed, varying from 72 to 80kDa in the submerse culture and from 68 to 90kDa in the semisolid culture. Also, glucoamylase protein concentration is higher in the submerse culture than in the semisolid culture. The other proteins in the submerse culture presented molecular weights lower than 12kDa and in the semisolid culture their molecular weights varied from 21 to 37kDa and below 10kDa.

  5. Oxygen/ozone as a medical gas mixture. A critical evaluation of the various methods clarifies positive and negative aspects

    Science.gov (United States)

    2011-01-01

    Besides oxygen, several other gases such as NO, CO, H2, H2S, Xe and O3 have come to age over the past few years. With regards to O3, its mechanisms of action in medicine have been clarified during the last two decades so that now a comprehensive framework for understanding and recommending ozone therapy in various pathologies is available. O3 used within the determined therapeutic window is absolutely safe and more effective than golden standard medications in numerous pathologies, like vascular diseases. However, ozone therapy is mostly in practitioners' hands and some recent developments for increasing cost effectiveness and speed of treatment are neither standardized, nor evaluated toxicologically. Hence, the aim of this article is to emphasize the need to objectively assess the pros and cons of oxygen/ozone as a medical gas mixture in the hope that ozone therapy will be accepted by orthodox medicine in the near future. PMID:22146387

  6. Rancièrean Atomism: Clarifying the Debate between Jacques Rancière and Alain Badiou

    Directory of Open Access Journals (Sweden)

    Joseph M. Spencer

    2015-12-01

    Full Text Available In the late 1970s and the 1980s, a number of radical left political theorists focused their philosophical attention on the relevance of ancient atomism, revitalizing a tradition that went back to Karl Marx's work on his dissertation. This essay looks at the uses of atomism by two thinkers in particular, Jacques Rancière and Alain Badiou, in order to see how their discussions of and references to ancient materialism help to shed light on their fundamental disagreements about the nature of community and equality.First, this paper argues that what Badiou and Rancière most obviously share in their assessments of atomism is a negative judgment regarding the post-swerve constitution of the world, while what most obviously distinguishes their positions is their differing judgments regarding the preswerve rain of the atoms in the void (which Badiou assesses negatively and Rancière positively. Becoming clear both about how Badiou and Rancière respond to what comes before and after the atomistic swerve helps to clarify an implicit response on Rancière’s part to what has become Badiou’s chief objection to Rancière’s political theory. Second, this paper argues that the fact that Badiou assesses both what comes before and what comes after the swerve as negative, while Rancière assesses only what comes after the swerve as negative (because he assesses the pre-swerve rain of the atoms in the void positively, makes clear that their most essential point of difference concerns the status of the swerve that mediates between before and after. Working through the complexities of Badiou’s analysis of the swerve and uncovering Rancière’s extremely subtle analysis of the swerve helps to clarify a major aspect of what has become Rancière’s chief criticism of Badiou’s conception of philosophy.

  7. Consumption of clarified grapefruit juice ameliorates high-fat diet induced insulin resistance and weight gain in mice.

    Directory of Open Access Journals (Sweden)

    Rostislav Chudnovskiy

    Full Text Available To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25-50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ, ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13-17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet.

  8. Immunoregulation of a CB2 Receptor Agonist in a Murine Model of NeuroAIDS

    OpenAIRE

    Gorantla, Santhi; Makarov, Edward; Roy, Deepa; Finke-Dwyer, Jennifer; Murrin, L. Charles; Gendelman, Howard E; Poluektova, Larisa

    2010-01-01

    Chronic HIV-1 infection commonly affects behavioral, cognitive, and motor functions in the infected human host and is commonly referred to as HIV-1-associated neurocognitive disorders (HAND). This occurs, in measure, as a consequence of ingress of leukocytes into brain perivascular regions. Such cells facilitate viral infection and disease by eliciting blood–brain barrier and neuronal network dysfunctions. Previous works demonstrated that the endocannabinoid system modulates neuroimmunity and...

  9. How Can I Clarify My Responsibility as a Headteacher as I Provide Opportunities to Enable All Children in the School to Create Talents?

    Science.gov (United States)

    Cripps, Louise

    2013-01-01

    In this account I explore and clarify my responsibility as I explain how I have come to my current understanding of talent creation, and why I feel it is so important to develop an inclusive approach to talent creation which provides opportunities for all the children to develop talents through their time at school, and to have them recognised and…

  10. Investigation on the hydrodynamic behaviors of the clarifier with an interior baffle in WWTP by using of radiotracer 99mTc

    International Nuclear Information System (INIS)

    The hydrodynamic behaviors of the clarifier with an interior baffle in a wastewater treatment plant was investigated by using a radiotracer 99mTc(30 40 mCi) to verify the results of CFD(Computational Fluid Dynamics) modelling in the previous study. The clarifier model was manufactured with consideration to the hydraulic similarity(1/21) of a plant(L x W x H : 2.6 x 0.4 x 0.2 m). By installation of an interior baffle to the clarifier, the strong density current at the bottom of the clarifier decreased substantially and increased the area of sludge settling zone, which were visualized successfully from the radiotracer experiment. Also the portion of short circuit stream changed from 48% to 32% and the mean residence time of sludge decreased from 940 sec to 810 sec, which corresponds to the results of CFD modelling. As a result, it is anticipated that radiotracer technology can be used as important tool for designing new wastewater treatment plants and verifying their performances after structural modifications

  11. A Framework for Clarifying “Participation” in Participatory Research to Prevent its Rejection for the Wrong Reasons

    Directory of Open Access Journals (Sweden)

    Katherine A. Daniell

    2010-06-01

    Full Text Available Participatory research relies on stakeholder inputs to obtain its acclaimed benefits of improved social relevance, validity, and actionability of research outcomes. We focus here on participatory research in the context of natural resource management. Participants’ acceptance of participatory research processes is key to their implementation. Our first assumption is that this positive view and acceptance of participation in research processes is a public good for the whole participatory research community. We also assume that the diversity of participatory forms of research is rarely considered by potential participants when they make their decisions about whether or not to participate in a proposed process. We specifically address how to avoid stakeholders’ reluctance to be involved in participatory research projects based on disillusion with past experiences. We argue that the disappointment experienced by stakeholders and other participants (i.e., researchers and policy makers can be avoided by being upfront and precise about how “participation” will be implemented, and what kind of involvement is expected from participants. Such a collective effort from the research community can also clarify the variety of possible implementations for potential participants. Building on earlier efforts to characterize and categorize the diversity of participatory research approaches, we develop a conceptual analytic procedural framework to make participants’ roles explicit in the implementation of different participatory research processes. This framework consists of three facets: (1 the flows of information among participants and the control over these flows for each step in a process, i.e., who will be expected to produce information, who will use this information, and who will receive the results; (2 the timing of the involvement of participants in the different steps of the research process, and the framing power that is associated with each

  12. Integrating fluorescent dye flow-curve testing and acoustic Doppler velocimetry profiling for in situ hydraulic evaluation and improvement of clarifier performance.

    Science.gov (United States)

    Tarud, F; Aybar, M; Pizarro, G; Cienfuegos, R; Pastén, P

    2010-08-01

    Enhancing the performance of clarifiers requires a thorough understanding of their hydraulics. Fluorescence spectroscopy and acoustic doppler velocimeter (ADV) profiling generally have been used separately to evaluate secondary settlers. We propose that simultaneous use of these techniques is needed to obtain a more reliable and useful evaluation. Experiments were performed on laboratory- and full-scale clarifiers. Factors affecting Fluorescein and Rhodamine 6G properties were identified. Underestimations up to 500% in fluorescence intensities may be derived from differential fluorescence quenching by oxygen. A careful control and interpretation of fluorescent dye experiments is needed to minimize artifacts in real settings. While flow-curve tests constructed under controlled conditions provided a more accurate overall quantitative estimation of the hydraulic performance, ADV velocity and turbulence profiling provided a detailed spatial understanding of flow patterns that was used to troubleshoot and fix the causes of hydraulic short-circuits. PMID:20853746

  13. An iTRAQ-Based Proteomics Approach to Clarify the Molecular Physiology of Somatic Embryo Development in Prince Rupprecht's Larch (Larix principis-rupprechtii Mayr)

    OpenAIRE

    Zhao, Jian; Li, Hui; Fu, Shuangbin; Chen, Bo; Sun, Wenting; Zhang, Junqi; Zhang, Jinfeng

    2015-01-01

    Prince Rupprecht's larch (Larix principis-rupprechtii Mayr) is a native high-value forest tree species in North China whose clonal propagation through somatic embryogenesis (SE) has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. To date, research has focused on clarifying the molecular mechanism of SE, but proteomic studies are still in the early stages. In this study, isobaric tags for relative and...

  14. Clarifying the mechanism of triplet-triplet annihilation in phosphorescent organic host-guest systems: A combined experimental and simulation study

    Science.gov (United States)

    Zhang, L.; van Eersel, H.; Bobbert, P. A.; Coehoorn, R.

    2016-05-01

    At high brightness, triplet-triplet annihilation (TTA) reduces the efficiency of organic light-emitting diodes. Triplet diffusion may considerably enhance this effect, which is otherwise limited by the rate of long-range interactions. Although its role can be clarified by studying the emissive dye concentration dependence of the TTA loss, we demonstrate here the practical applicability of a more direct method, requiring a study for only a single dye concentration. The method uses transient photoluminescence yield measurements, for a wide initial excitation density range. The analysis is applied to an iridium complex and is supported by the results of kinetic Monte Carlo simulations.

  15. Eclipses could clarify axion mystery

    CERN Multimedia

    2007-01-01

    "Physicists in Europe have proposed an outlandish experiment that could determine once and for all whether ultralight particles called axions - one of the leading candidates for dark matter - exist." (1/2 page)

  16. Clarifying Resilience: an invited comment

    OpenAIRE

    Deeming, Hugh

    2013-01-01

    So, we all know what resilience is, don’t we? The National Academies recently said building disaster resilience capacity in our communities should be a national imperative (National Academies 2012).So resilience must be a tangible thing, right?

  17. Estrogen receptor-dependent effects of bisphenol a

    Directory of Open Access Journals (Sweden)

    P. Bulzomi

    2011-01-01

    Full Text Available Bisphenol A (BPA, commonly used as building block of polycarbonate plastics, significantly affects human and animal health interfering with the action of natural hormones. Within BPA disrupting effects, a mitogenic activity and, consequently, an increased incidence of neoplastic transformations has been reported in exposed organisms. Among the several mechanisms proposed for the mitogenic BPA effects, its ability to bind to estrogen receptors (ERα and ERβ deserves particular attention. Aim of this work is to investigate ERα- and ERβ-dependent mechanisms underlying BPA proliferative effect. Binding assay confirms that BPA binds to both ERs. Cell vitality assay and Western blot analysis of protein involved in cell proliferation demonstrate that BPA acts as a double side disruptor of estrogenic effects. In fact in the presence of ERα, BPA mimics E2, increasing cell proliferation. On the contrary, in the presence of ERβ, BPA acts as an E2 antagonist preventing the hormone-induced cancer cells apoptosis. These two divergent aspects could act synergistically in the exposed organisms leading to the disruption of the balance between proliferation and apoptosis typical of E2 effects.

  18. Aryl Hydrocarbon Receptor-Dependent Pathways in Immune Regulation.

    Science.gov (United States)

    Gargaro, M; Pirro, M; Romani, R; Zelante, T; Fallarino, F

    2016-08-01

    The idea of possible involvement of the aryl hydrocarbon receptor (AhR) in transplant tolerance can be traced back >30 years, when very low doses of dioxin-the most potent AhR ligand-were found to markedly reduce the generation of cytotoxic T lymphocytes in response to alloantigen challenge in vivo. AhR is a ligand-activated transcription factor that is activated by dioxins and other environmental pollutants. We now know that AhR can bind a broad variety of activating ligands that are disparate in nature, including endogenous molecules and those formed in the gut from food and bacterial products. Consequently, in addition to its classical role as a toxicological signal mediator, AhR is emerging as a transcription factor involved in the regulation of both innate and adaptive immune responses in various immune cell types, including lymphocytes and antigen-presenting cells (APCs). Allograft rejection is mostly a T cell-mediated alloimmune response initiated by the recognition of alloantigens presented by donor and recipient APCs to recipient CD4(+) and CD8(+) T cells. Based on those findings, AhR may function as a critical sensor of outside and inside environments, leading to changes in the immune system that may have relevance in transplantation. PMID:26751261

  19. Metabotropic Glutamate Receptor Dependent Cortical Plasticity in Chronic Pain.

    Science.gov (United States)

    Koga, Kohei; Li, Shermaine; Zhuo, Min

    2016-01-01

    Many cortical areas play crucial roles in higher order brain functions such as pain and emotion-processing, decision-making, and cognition. Among them, anterior cingulate cortex (ACC) and insular cortex (IC) are two key areas. Glutamate mediates major excitatory transmission during long-term plasticity in both physiological and pathological conditions. Specifically related to nociceptive or pain behaviors, metabotropic glutamate subtype receptors (mGluRs) have been involved in different types of synaptic modulation and plasticity from periphery to the spinal cord. However, less is known about their functional roles in plasticity related to pain and its related behaviors within cortical regions. In this review, we first summarized previous studies of synaptic plasticity in both the ACC and IC, and discussed how mGluRs may be involved in both cortical long-term potentiation (LTP) and long-term depression (LTD)-especially in LTD. The activation of mGluRs contributes to the induction of LTD in both ACC and IC areas. The loss of LTD caused by peripheral amputation or nerve injury can be rescued by priming ACC or IC with activations of mGluR1 receptors. We also discussed the potential functional roles of mGluRs for pain-related behaviors. We propose that targeting mGluRs in the cortical areas including the ACC and IC may provide a new therapeutic strategy for the treatment of chronic pain, phantom pain or anxiety. PMID:27296638

  20. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  1. A rapid reversed-phase thin layer chromatographic protocol for detection of adulteration in ghee (clarified milk fat) with vegetable oils.

    Science.gov (United States)

    Rani, Anupama; Sharma, Vivek; Arora, Sumit; Lal, Darshan; Kumar, Anil

    2015-04-01

    Detection of milk fat adulteration with foreign fats/oils continues to be a challenge for the dairy industry as well as food testing laboratories, especially in the present scenario of rampant adulteration using the scientific knowledge by unscrupulous persons involved in the trade. In the present investigation a rapid reversed-phase thin layer chromatographic (RP-TLC) protocol was standardized to ascertain the purity of milk fat. RP-TLC protocol did not show any false positive results in the genuine ghee (clarified butter fat) samples of known origin. Adulteration of ghee with coconut oil up to 7. 5 %, soybean oil, sunflower oil and groundnut oil up to 1 %, while, designer oil up to 2 % level could be detected using the standardized RP-TLC protocol. The protocol standardized is rapid and convenient to use. PMID:25825547

  2. One of the Possible Causes for Diatom Appearance in Ariake Bay Area in Japan In the Winter from 2010 to 2015 (Clarified with AQUA/MODIS

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2016-10-01

    Full Text Available One of the possible causes for diatom appearance in Ariake bay area I Japan in the winter seasons from 2010 to 2015 is clarified with AQUA/MODIS of remote sensing satellite. Two months (January and February AQUA/MODIS derived chlorophyll-a concentration are used for analysis of diatom appearance. Match-up data of AQUA/MODIS with the evidence of the diatom appearance is extracted from the MODIS database. Through experiments, it is found that diatom appears after a long period time of relatively small size of red tide appearance. Also, it depends on the weather conditions and tidal effect as well as water current in the bay area in particular.

  3. Biodegradation of multiple microcystins and cylindrospermopsin in clarifier sludge and a drinking water source: Effects of particulate attached bacteria and phycocyanin.

    Science.gov (United States)

    Maghsoudi, Ehsan; Fortin, Nathalie; Greer, Charles; Duy, Sung Vo; Fayad, Paul; Sauvé, Sébastien; Prévost, Michèle; Dorner, Sarah

    2015-10-01

    The effects of particulate attached bacteria (PAB) and phycocyanin on the simultaneous biodegradation of a mixture of microcystin-LR, YR, LY, LW, LF and cylindrospermopsin (CYN) was assessed in clarifier sludge of a drinking water treatment plant (DWTP) and in a drinking water source. The biomass from lake water and clarifier sludge was able to degrade all microcystins (MCs) at initial concentrations of 10µgL(-1) with pseudo-first order reaction half-lives ranging from 2.3 to 8.8 days. CYN was degraded only in the sludge with a biodegradation rate of 1.0×10(-1)d(-1) and a half-life of 6.0 days. This is the first study reporting multiple MCs and CYN biodegradation in the coagulation-flocculation sludge of a DWTP. The removal of PAB from the lake water and the sludge prolonged the lag time substantially, such that no biodegradation of MCLY, LW and LF was observed within 24 days. Biodegradation rates were shown to increase in the presence of C-phycocyanin as a supplementary carbon source for indigenous bacteria, a cyanobacterial product that accompanies cyanotoxins during cyanobacteria blooms. MCs in mixtures degraded more slowly (or not at all) than if they were degraded individually, an important outcome as MCs in the environment are often present in mixtures. The results from this study showed that the majority of the bacterial biomass responsible for the biodegradation of cyanotoxins is associated with particles or biological flocs and there is a potential for extreme accumulation of cyanotoxins within the DWTP during a transient bloom. PMID:26122734

  4. Ground and CHAMP observations of field-aligned current circuits generated by lower atmospheric disturbances and expectations to the SWARM to clarify their three dimensional structure

    Science.gov (United States)

    Iyemori, Toshihiko; Nakanishi, Kunihito; Aoyama, Tadashi; Lühr, Hermann

    2014-05-01

    Acoustic gravity waves propagated to the ionosphere cause dynamo currents in the ionosphere. They divert along geomagnetic field lines of force to another hemisphere accompanying electric field and then flow in the ionosphere of another hemisphere by the electric field forming closed current circuits. The oscillating current circuits with the period of acoustic waves generate magnetic variations on the ground, and they are observed as long period geomagnetic pulsations. This effect has been detected during big earthquakes, strong typhoons, tornados etc. On a low-altitude satellite orbit, the spatial distribution (i.e., structure) of the current circuits along the satellite orbit should be detected as temporal magnetic oscillations, and the effect is confirmed by a CHAMP data analysis. On the spatial structure, in particular, in the longitudinal direction, it has been difficult to examine by a single satellite or from ground magnetic observations. The SWARM satellites will provide an unique opportunity to clarify the three dimensional structure of the field-aligned current circuits.

  5. 187-gene phylogeny of protozoan phylum Amoebozoa reveals a new class (Cutosea) of deep-branching, ultrastructurally unique, enveloped marine Lobosa and clarifies amoeba evolution.

    Science.gov (United States)

    Cavalier-Smith, Thomas; Chao, Ema E; Lewis, Rhodri

    2016-06-01

    Monophyly of protozoan phylum Amoebozoa, and subdivision into subphyla Conosa and Lobosa each with different cytoskeletons, are well established. However early diversification of non-ciliate lobose amoebae (Lobosa) is poorly understood. To clarify it we used recently available transcriptomes to construct a 187-gene amoebozoan tree for 30 species, the most comprehensive yet. This robustly places new genus Atrichosa (formerly lumped with Trichosphaerium) within lobosan class Tubulinea, not Discosea as previously supposed. We identified an earliest diverging lobosan clade comprising marine amoebae armoured by porose scaliform cell-envelopes, here made a novel class Cutosea with two pseudopodially distinct new families. Cutosea comprise Sapocribrum, ATCC PRA-29 misidentified as 'Pessonella', plus from other evidence Squamamoeba. We confirm that Acanthamoeba and ATCC 50982 misidentified as Stereomyxa ramosa are closely related. Discosea have a strongly supported major subclade comprising Thecamoebida plus Glycostylida (suborders Dactylopodina, Stygamoebina; Vannellina) phylogenetically distinct from Centramoebida. Stygamoeba is sister to Dactylopodina. Himatismenida are either sister to Centramoebida or deeper branching. Discosea usually appear holophyletic (rarely paraphyletic). Paramoeba transcriptomes include prokinetoplastid Perkinsela-like endosymbiont sequences. Cunea, misidentified as Mayorella, is closer to Paramoeba than Vexillifera within holophyletic Dactylopodina. Taxon-rich site-heterogeneous rDNA trees confirm cutosan distinctiveness, allow improved conosan taxonomy, and reveal previous dictyostelid tree misrooting. PMID:27001604

  6. An iTRAQ-based proteomics approach to clarify the molecular physiology of somatic embryo development in Prince Rupprecht's larch (Larix principis-rupprechtii Mayr).

    Science.gov (United States)

    Zhao, Jian; Li, Hui; Fu, Shuangbin; Chen, Bo; Sun, Wenting; Zhang, Junqi; Zhang, Jinfeng

    2015-01-01

    Prince Rupprecht's larch (Larix principis-rupprechtii Mayr) is a native high-value forest tree species in North China whose clonal propagation through somatic embryogenesis (SE) has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. To date, research has focused on clarifying the molecular mechanism of SE, but proteomic studies are still in the early stages. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) analysis was performed on three developmental stages of SE in L. principis-rupprechtii in an attempt to identify a wide range of proteins that are regulated differentially during this process. Proteins were extracted and analyzed from the pro-embryogenic mass (PEM), globular embryo (GE), and cotyledon embryo (CE) stages of embryo development. We detected 503 proteins in total and identified 96 proteins expressed differentially during different developmental stages. The identified proteins were analyzed further to provide information about their expression patterns and functions during SE. Four clusters of proteins based on shared expression profiles were generated. Functional analysis showed that proteins involved in primary metabolism, phosphorylation, and oxidation reduction were upregulated during somatic embryo development. This work provides novel insights into the process of larch embryo development in vitro and a basis for further study of the biological process and opportunities for practical application of this knowledge. PMID:25781987

  7. An iTRAQ-based proteomics approach to clarify the molecular physiology of somatic embryo development in Prince Rupprecht's larch (Larix principis-rupprechtii Mayr.

    Directory of Open Access Journals (Sweden)

    Jian Zhao

    Full Text Available Prince Rupprecht's larch (Larix principis-rupprechtii Mayr is a native high-value forest tree species in North China whose clonal propagation through somatic embryogenesis (SE has the potential to rapidly capture the benefits of breeding or genetic engineering programs and to improve raw material uniformity and quality. To date, research has focused on clarifying the molecular mechanism of SE, but proteomic studies are still in the early stages. In this study, isobaric tags for relative and absolute quantitation (iTRAQ analysis was performed on three developmental stages of SE in L. principis-rupprechtii in an attempt to identify a wide range of proteins that are regulated differentially during this process. Proteins were extracted and analyzed from the pro-embryogenic mass (PEM, globular embryo (GE, and cotyledon embryo (CE stages of embryo development. We detected 503 proteins in total and identified 96 proteins expressed differentially during different developmental stages. The identified proteins were analyzed further to provide information about their expression patterns and functions during SE. Four clusters of proteins based on shared expression profiles were generated. Functional analysis showed that proteins involved in primary metabolism, phosphorylation, and oxidation reduction were upregulated during somatic embryo development. This work provides novel insights into the process of larch embryo development in vitro and a basis for further study of the biological process and opportunities for practical application of this knowledge.

  8. Examination of sludge accumulation rates and sludge characteristics for a decentralized community wastewater treatment systems with individual primary clarifier tanks located in Wardsville (Ontario, Canada).

    Science.gov (United States)

    Lossing, Heather; Champagne, Pascale; McLellan, P James

    2010-01-01

    In conventional septic systems, settling and partial treatment via anaerobic digestion occurs in the septic tank. One of the byproducts of solids separation in the septic tank is a semi-liquid material known as septage, which must be periodically pumped out. Septage includes the liquid portion within the tank, as well as the sludge that settles at the bottom of the tank and the scum that floats to the surface of the liquid layer. A number of factors can influence septage characteristics, as well as the sludge and scum accumulation rates within the tank. This paper presents the results of a 2007 field sampling study conducted in Wardsville (Ontario, Canada). The field study examined 29 individual residential two-chamber septic tanks in a community serviced by a decentralized wastewater treatment system in operation for approximately 7 years without septage removal. The field investigation provided a comprehensive data set that allowed for statistical analysis of the data to assess the more critical factors influencing solids accumulation rates within each of the clarifier chambers. With this data, a number of predictive models were developed using water usage data for each residence as an explanatory variable. PMID:21123926

  9. Clarifying relationships between persistent organic pollutant concentrations and age in wildlife biomonitoring: individuals, cross-sections, and the roles of lifespan and sex.

    Science.gov (United States)

    Binnington, Matthew J; Wania, Frank

    2014-06-01

    Relationships between persistent organic pollutant (POP) levels and age in wildlife biomonitoring are often interpreted as changes in contaminant burden as organisms age. However, cross-sectional body burden-age trends (CBATs) obtained from biomonitoring studies, which sample individuals of different ages at the same time, should not be confused with longitudinal body burden-age trends (LBATs) obtained by sampling the same individuals repeatedly through time. To clarify how CBATs and LBATs for wildlife species deviate from each other, and describe any impact of lifespan and sex, we used mechanistic bioaccumulation models to estimate historic longitudinal exposures of polar cod, ringed seals, beluga whales, and bowhead whales to polychlorinated biphenyl congener 153. Cross-sectional body burden-age trends were then produced by sampling resultant LBATs of successive birth cohorts at specific time points. As found previously for humans, the year of sampling relative to the year of peak environmental contamination was a critical parameter in determining male CBAT shapes. However, a similar cohort effect was not apparent for reproductive females because efficient POP loss through lactation prevented their lipids from retaining a memory of past exposure levels. Thus, lactation loss was not only responsible for the large differences between the CBATs of males and females of the same species, but also the lack of female CBAT variability through time. Cross-sectional body burden-age trend shapes varied little between species by lifespan, as long as equivalent age scales were used. However, lifespan relative to the timescale of environmental contaminant level changes did determine the extent to which CBATs resembled LBATs for males. We suggest that accounting for birth cohort and sex effects is essential when interpreting age trends in POP biomonitoring studies of long-lived species. PMID:24619475

  10. Towards a review of the EC Recommendation for a definition of the term "nanomaterial": Part 3: Scientific-technical evaluation of options to clarify the definition and to facilitate its implementation

    OpenAIRE

    Rauscher, Hubert; Roebben, Gert; BOIX SANFELIU Ana; Emons, Hendrik; Gibson, Peter; KOEBER Robert; Linsinger, Thomas; Rasmussen, Kirsten; RIEGO SINTES Juan; SOKULL-KLUETTGEN Birgit; STAMM Hermann

    2015-01-01

    This report provides the JRC's scientific-technical evaluation of options to clarify the EC Recommendation on a definition of nanomaterial, published in 2011 (EC Recommendation 2011/696/EU). It is a follow-up report of two previous JRC publications, which compiled feedback on the experiences of stakeholders with the EC nanomaterial definition collected by JRC in 2013 and early 2014 (EUR 26567 EN, 2014), and provided an assessment of the collected information (EUR 26744 EN, 2014). The three JR...

  11. Efeito dos complexos enzimáticos clarificantes Clarex e CEC1-CTAA sobre a qualidade do suco de banana Effect of enzymatic clarifier complexes Clarex and CEC1-CTAA on the quality of banana juice

    Directory of Open Access Journals (Sweden)

    Marisa Helena Cardoso

    1999-05-01

    Full Text Available Neste trabalho foi observado o efeito dos complexos enzimáticos clarificantes Clarex e CEC1-CTAA, adicionados na proporção de 0,03% v/p sobre purê de banana (Musa cavendishii, em condições amenas de hidrólise (40ºC, 15 minutos visando determinar a qualidade, aqui representada pelos indicadores: rendimento; viscosidade; Brix; pH; composição centesimal; contagens de bolores e leveduras e de mesófilos, e propriedades sensoriais de cor, aroma, sabor e corpo dos sucos de banana clarificados. O suco clarificado com Clarex apresentou-se significativamente (p The effect of the clarifier enzymatic complexes Clarex and CEC1-CTAA, used in the proportion 0.03% v/w in industrialized banana (Musa cavendishii pulp, at the conditions of gentle hydrolysis 40 degree Celsius, 15 minutes, was observed to determine the quality here represented by indicators such as yield, viscosity, Brix, pH, centesimal composition, counts of moulds and yeasts and of mesophilics, and sensorial properties of color, aroma, flavor and body by both clarified banana juices. The juice clarified by Clarex was significantly (p < 0.01 more yellow, less grey, less opaque and less viscous than that obtained with CEC1-CTAA. There was no significant difference between the means of aroma of fresh banana and flavor in these juices. Furthermore, the values obtained for flavor for both juices were judged good (6.72 and 6.05 for the juices clarified with Clarex and CEC1- CTAA, respectively, because they were up the middle of the scale (from 0 to 10.

  12. Effects of the Use of Different Clarifiers on the Clarification and Quality of Cherry Wine%不同澄清剂对樱桃酒澄清效果与质量的影响

    Institute of Scientific and Technical Information of China (English)

    魏晓华

    2015-01-01

    选择啤酒单宁-明胶、五倍子单宁-明胶、壳聚糖和皂土4种澄清剂处理樱桃发酵原酒,比较处理后樱桃酒的澄清效果(透光率、色度)、理化指标(酒精度、干浸出物、总糖、总酸、pH值、总酚、花色苷)和感官特征,并进行樱桃酒稳定性实验。结果表明,4种澄清剂的最佳使用量分别为0.30 g/L啤酒单宁和0.10 g/L明胶,0.30 g/L五倍子单宁和0.30 g/L明胶,0.10 g/L壳聚糖,2.0 g/L皂土。与其他3种澄清剂相比,皂土澄清保证澄清效果的同时有利于樱桃酒理化指标和感官质量的维持。樱桃酒不稳定,易氧化,蛋白质稳定性差,间歇式冷冻处理可提高樱桃酒的稳定性。%In this study, four kinds of clarifiers including beer tannins-gelatin, gallnut tannin-gelatin, chitosan and bentonite were used respec-tively for the clarification of cherry base wine. The clarifying effects (light transmittance and chroma), physiochemical indexes (alcohol con-tent, dry extract, total sugar content, pH value, total phenol content, and anthocyanin content), and sensory characteristics of the clarified wine samples were compared. Besides, the stability test of cherry wine was done. The results suggested that, the best use level of the four clarifiers were 0.30 g/L beer tannins and 0.10 g/L gelatin, 0.30 g/L gallnut tannin and 0.30 g/L gelatin, 0.10 g/L chitosan, and 2.0 g/L bentonite, respec-tively. Compared with other three clarifiers, the use of bentonite was beneficial to maintaining good physiochemical indexes and sensory quali-ty of cherry wine, meanwhile, it had the best clarifying effects. Cherry wine is unstable and easily-oxidized with poor protein stability. Accord-ingly, intermittent freezing treatment could improve the stability of cherry wine.

  13. O uso da internet como ferramenta de apoio ao esclarecimento de dúvidas durante a gestação
    The use of the Internet as a support tool to clarify questions during pregnancy

    OpenAIRE

    Taiara Maestro Calderon; Maria Elisa Wotzasek Cestari; Alyni Cristiny Dobkowski; Mariana Digieri Cavalheiro

    2016-01-01

    Introduction: Pregnancy is a period of doubts and anxiety for most pregnant women. Objective: To evaluate the use of the Internet as a support tool to clarify doubts raised by women during pregnancy. Methods: An exploratory and descriptive study. Sample based on accidentalness, for 241 users who responded to the on-line form, built with Google Docs and made available in  one Blog. Results: 98% of pregnant women were between 19 and 39 years, 97% with schooling above 9 years, 99% had follow up ...

  14. Clarifying concepts: cultural humility or competency.

    Science.gov (United States)

    Isaacson, Mary

    2014-01-01

    Cultural competency in the delivery of health care to diverse population groups has become an urgent need in the United States. Yet, despite the incorporation of cultural competency education into nursing curricula, inequities in health care remain. The purpose of this mixed-method study was to identify if differences in perceptions of cultural competence were present in senior nursing students (N = 11) before and after cultural immersion experiences on an Indian reservation. Preimmersion results revealed that the majority considered themselves culturally competent, whereas after immersion, there was a downward shift in scores. Triangulation of the quantitative results alongside a hermeneutic phenomenological analysis of the students' reflective journals revealed a paradox. Students perceived themselves as culturally competent, yet their journals demonstrated many negative stereotypes. Three common themes emerged: seeing with closed eyes, seeing through a fused horizon, and disruption to reshaping. These combined results revealed the misperceptions regarding the concept of cultural competency. Efforts must be made in nursing education to teach students the importance of adopting an ethic of cultural humility, where we emphasize attentive listening and openness to other cultures, and stress the importance of self-reflection and self-critique in our interactions with others. PMID:24939335

  15. A critical review of clarifier modelling

    DEFF Research Database (Denmark)

    Plósz, Benedek; Nopens, Ingmar; Rieger, Leiv; Griborio, Alonso; Clercq, Jeriffa De; Vanrolleghem, Peter A.; Daigger, Glen T.; Takacs, Imre; Wicks, Jim; Ekama, George A.

    This outline paper aims to provide a critical review of secondary settling tank (SST) modelling approaches used in current wastewater engineering and develop tools not yet applied in practice. We address the development of different tier models and experimental techniques in the field with a part...

  16. GLOBALISATION, INTERNATIONALISATION, MONDIALISATION : DES CONCEPTS À CLARIFIER

    OpenAIRE

    Dumont, Gérard-François

    2001-01-01

    Au seuil du XXIe siècle, le contexte mondial est dominé par trois phénomènes nouveaux ou de nature nouvelle dans l’Histoire de l’humanité : la globalisation, l’internationalisation et la mondialisation. S’interroger sur la situation planétaire actuelle et future suppose une clarification préalable de ces trois concepts sans laquelle il est impossible de comprendre le monde contemporain et les changements actuels.

  17. Clarifying the role of the IAEA

    International Nuclear Information System (INIS)

    The IAEA has many roles in promoting the role of nuclear energy for peaceful purposes. The most significant role that the IAEA undertakes is the development and application of safeguards to nuclear material, other material, equipment and facilities; this work consumes about 35% of the IAEA budget. The authority, procedures and limitations for the application of safeguards were described together with the relationship between the IAEA and the States where safeguards are in effect. Claims that the IAEA is not adequately fulfilling its safeguard role are usually based on misunderstandings of its role and authority. The IAEA's relationship to inspected States is not adversarial, regulatory, or guarding. It provides assurance to all States that peaceful nuclear activities are not diverted to a military program and in so doing enhances the reputation of States to whom safeguards are applied. Safeguards would be only one of many factors that would be involved in a States embarking on a military nuclear program. If proliferation of nuclear weapons occurs, this may be due in entirety or in part to these other factors. Many States could now undertake a military program but do not do so, because of their enlightened viewpoint that such activities are not in their own, or the world's best interests. However, any trend to further proliferation of nuclear weapons could be diminished by: -a lessening of political and economic tension between States, -restrictions on the supply of required technology, equipment, and material, and -an effective IAEA safeguard regime. There has been a regrettable trend to politicization in the direction and operation of the IAEA. It is hoped that this trend will be reversed and that IAEA will return to its earlier more technical role. There is a pressing need for the general public and governments to more fully understand the IAEA's role and its limitations

  18. Social Identity: Clarifying its Dimensions across Cultures

    Directory of Open Access Journals (Sweden)

    Maritza R. Salazar

    2012-12-01

    Full Text Available Social identity has been linked to a number of work-relevant constructs. Specifically, researchers have investigated the role of social identity in cross-function teams, its impact on team performance and willingness to engage in OCBs, just to name a few. Furthermore, this construct has been cited as one of the most relevant constructs when understanding inter-group relations (Sohrabi, Gholipour, & Amiri, 2011. Given the theoretical and empirical importance of this construct, this paper reviews the construct of social identity and theorizes about how this construct may differ across cultures. First, we review social identity dimensions and propose how they may have different meanings and be perceived differently across cultures. Next, we delineate ways to pursue the measurement of social identity when conducting cross-cultural research. We conclude by providing insight for future research that compares social identity across cultures.

  19. Development of Compound Clarifying Vegetable Drinks Made from Pumpkin, Carrot and Tomato%南瓜-胡萝卜-西红柿复合澄清蔬菜汁饮料的研制

    Institute of Scientific and Technical Information of China (English)

    徐君飞; 耿倩

    2015-01-01

    以南瓜、胡萝卜、西红柿为原料,制备复合澄清蔬菜汁饮料.结果表明,分别添加南瓜汁240 g/L、胡萝卜汁140 g/L、西红柿汁100 g/L,混匀,补加蔗糖80 g/L、柠檬酸2.0 g/L、果胶酶0.8 g/L、蛋白酶0.6 g/L,调节pH 4.0,45℃保温1 h,室温保存7 d,该复合澄清蔬菜汁饮料的透光率为65.0%;以此为基础,添加羧甲基纤维素钠0.5 g/L、海藻酸钠0.6 g/L、魔芋胶0.6 g/L,该复合澄清蔬菜汁饮料的透光率达95.0%,产品甜酸可口,营养丰富,澄清稳定.%Compound clarifying vegetable drinks were made from pumpkin , carrot and tomato. The optimum formula were pumpkin juice 240 g/L, carrot juice 140 g/L, tomato juice 100 g/L, sugar 80 g/L and citric acid 2.0 g/L, pectinase 0.8 g/L, protease 0.6 g/L, respectively. In this conditions, the author adjusted the compound clarifying vegetable drinks's pH 4.0, at 45℃,1 h, then at indoor temperature, 7 d, their transmittance were 65.0%. On these basis, the author added sodium carboxyl methyl cellulose 0.5 g/L, sodium alginate 0.6 g/L, konjac gum 0.6 g/L, their transmittance increased to 95.0%. The compound clarifying vegetable drinks were sweet and tasty, nutritious and stabilize.

  20. Bebida mista com propriedade estimulante à base de água de coco e suco de caju clarificado Mixed drink with stimulating properties consisting of coconut water and clarified cashew apple juice

    Directory of Open Access Journals (Sweden)

    Joelia Marques de Carvalho

    2005-12-01

    Full Text Available Na indústria de bebidas, uma alternativa para acrescentar valor nutricional ou simplesmente desenvolver novos sabores é a mistura de diferentes sucos de frutas na formulação de bebidas mistas. Este trabalho teve como objetivo o desenvolvimento de uma bebida à base de água de coco e suco de caju clarificado (cajuína, com adição de cafeína, conferindo-lhe propriedades estimulantes. Foram avaliadas cinco formulações, com diferentes proporções de cajuína, tendo sido padronizados previamente o pH, teor de sólidos solúveis e cafeína. As formulações foram submetidas à caracterização físico-química (pH, sólidos solúveis, acidez, açúcares redutores, não redutores e totais e vitamina C, análises microbiológicas e avaliação sensorial de aceitação (atributos de cor, sabor, avaliação global e intenção de compra. Todas as formulações em estudo apresentaram boa aceitação sensorial, não havendo diferença entre as médias dos atributos avaliados. Na intenção de compra, a formulação mais aceita foi ACC 20 (20% de cajuína e 80% de água de coco. A incorporação de vitamina C na bebida através da adição da cajuína foi mais evidente até a formulação ACC 20. Os resultados indicaram que a formulação ACC 20 foi a mais viável para elaboração da bebida mista. Todas as formulações apresentaram padrões microbiológicos satisfatórios.In the beverage industry, an alternative to add nutritional quality or simply to develop new tastes is the blending of different kinds of fruit juices. The objective of this work was the development of blends consisting of coconut water and clarified cashew apple juice with the addition of caffeine so as to provide stimulating properties to the beverage. Five formulations with different concentration of clarified cashew apple juice and previously standardized for pH, total soluble solids and caffeine concentration were evaluated. The formulations were submitted to

  1. The application of integrated water clarifier on treatment of water flushing cinder - dust of boiler%一体化净水器在锅炉冲渣冲灰水处理中的应用

    Institute of Scientific and Technical Information of China (English)

    黄文

    2012-01-01

    锅炉冲渣冲灰水的悬浮物高达3000mg/L,原有处理工艺造成平流沉淀池出水悬浮物仍然高达1000mg/L,因此在平流沉淀池出水加压送人一体化净水器进一步的处理,出水悬浮物降到10mg/L以下,净化后的废水主要回用于锅炉烟气水膜除尘器及冲渣冲灰,废水零排放;闭路循环;回收冲渣冲灰水达到100%,去除悬浮物大于99%以上。%The suspended matter in water flushing cinder and dust of boiler was up to 3000mg/L, that in effluent water of a fluent - flow sedimentation tank was still up to 1000mg/L as old treating process. As the effluent wa- ter of a fluent - flow sedimentation tank was further treated by compressed into a integrated water clarifier, so that suspended matter in effluent water decreased to less than 10mg/L. The clarified waste water could re - use to be water dust scrubber for boiler exhaust gas and to flush cinder and dust, waste water was zero released and closed - circult, recovery of water flushing cinder and dust was 100%, dislodged suspended matter was more than 99%.

  2. O uso da internet como ferramenta de apoio ao esclarecimento de dúvidas durante a gestaçãoThe use of the Internet as a support tool to clarify questions during pregnancy

    Directory of Open Access Journals (Sweden)

    Taiara Maestro Calderon

    2016-03-01

    Full Text Available Introduction: Pregnancy is a period of doubts and anxiety for most pregnant women. Objective: To evaluate the use of the Internet as a support tool to clarify doubts raised by women during pregnancy. Methods: An exploratory and descriptive study. Sample based on accidentalness, for 241 users who responded to the on-line form, built with Google Docs and made available in  one Blog. Results: 98% of pregnant women were between 19 and 39 years, 97% with schooling above 9 years, 99% had follow up with healthcare providers. Regarding the use of the Internet, 99% said they usually search for the pregnancy questions. The doubts consisted mostly in the search for information about the development of the baby, then how to deal with the discomforts of pregnancy, the changes in the woman’s body and feeding care. The choice of the sites, according to the interviewees, occurred mainly through the indication of social networks, friends and acquaintances. Regarding to the resolution of doubts, 97% reported that after the Internet search doubts were resolved. Conclusion: The Internet has been a tool of support for pregnant women who seek effective support on the World Wide Web to clarify their doubts. The significant standard for clarification and education reflected a customer that will search and possibly question the procedures and practices that are performed during prenatal care. However, the search for sites has been based on independent research guidance by health professionals, something which does not ensure the credibility of the sites surveyed by users.

  3. Evaluation of the specificity of antibodies raised against cannabinoid receptor type 2 in the mouse retina.

    Science.gov (United States)

    Cécyre, Bruno; Thomas, Sébastien; Ptito, Maurice; Casanova, Christian; Bouchard, Jean-François

    2014-02-01

    Cannabinoid receptors (CB1R and CB2R) are among the most abundant G protein-coupled receptors in the central nervous system. The endocannabinoid system is an attractive therapeutic target for immune system modulation and peripheral pain management. While CB1R is distributed in the nervous system, CB2R has traditionally been associated to the immune system. This dogma is currently a subject of debate since the discovery of CB2R expression in neurons using antibody-based methods. The localization of CB2R in the central nervous system (CNS) could have a significant impact on drug development because it would mean that in addition to its effects on the peripheral pain pathway, CB2R could also mediate some central effects of cannabinoids. In an attempt to clarify the debate over CB2R expression in the CNS, we tested several commercially or academically produced CB2R antibodies using Western blot and immunohistochemistry on retinal tissue obtained from wild-type mice and mice lacking CB2R (cnr2 (-/-) ). One of the antibodies tested exhibited a valuable specificity as it marked a single band near the predicted molecular weight in Western blot and produced no staining in cnr2 (-/-) mice retina sections. The other antibodies tested detected multiple bands in Western blot and labeled unidentified proteins when used with their immunizing peptide or on cnr2 (-/-) retinal sections. We conclude that many commonly used antibodies raised against CB2R are not specific for use in immunohistochemistry, at least in the context of the mouse retina. Moreover, some of them tested presented significant lot-to-lot variability. Hence, caution should be used when interpreting prior and future studies using CB2R antibodies. PMID:24185999

  4. Inhibition of guinea-pig and human sensory nerve activity and the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation

    OpenAIRE

    Patel, Hema J; Birrell, Mark A; Crispino, Natascia; Hele, David J.; Venkatesan, Priya; Barnes, Peter J; Yacoub, Magdi H.; Belvisi, Maria G.

    2003-01-01

    There is considerable interest in novel therapies for cough, since currently used agents such as codeine have limited beneficial value due to the associated side effects. Sensory nerves in the airways mediate the cough reflex via activation of C-fibres and RARs. Evidence suggests that cannabinoids may inhibit sensory nerve-mediated responses.We have investigated the inhibitory actions of cannabinoids on sensory nerve depolarisation mediated by capsaicin, hypertonic saline and PGE2 on isolated...

  5. Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors.

    Science.gov (United States)

    Staiano, Rosaria I; Loffredo, Stefania; Borriello, Francesco; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Orlando, Pierangelo; Secondo, Agnese; Granata, Francescopaolo; Lepore, Maria Teresa; Fiorelli, Alfonso; Varricchi, Gilda; Santini, Mario; Triggiani, Massimo; Di Marzo, Vincenzo; Marone, Gianni

    2016-04-01

    Macrophages are pivotal effector cells in immune responses and tissue remodeling by producing a wide spectrum of mediators, including angiogenic and lymphangiogenic factors. Activation of cannabinoid receptor types 1 and 2 has been suggested as a new strategy to modulate angiogenesis in vitro and in vivo. We investigated whether human lung-resident macrophages express a complete endocannabinoid system by assessing their production of endocannabinoids and expression of cannabinoid receptors. Unstimulated human lung macrophage produce 2-arachidonoylglycerol,N-arachidonoyl-ethanolamine,N-palmitoyl-ethanolamine, andN-oleoyl-ethanolamine. On LPS stimulation, human lung macrophages selectively synthesize 2-arachidonoylglycerol in a calcium-dependent manner. Human lung macrophages express cannabinoid receptor types 1 and 2, and their activation induces ERK1/2 phosphorylation and reactive oxygen species generation. Cannabinoid receptor activation by the specific synthetic agonists ACEA and JWH-133 (but not the endogenous agonist 2-arachidonoylglycerol) markedly inhibits LPS-induced production of vascular endothelial growth factor-A, vascular endothelial growth factor-C, and angiopoietins and modestly affects IL-6 secretion. No significant modulation of TNF-α or IL-8/CXCL8 release was observed. The production of vascular endothelial growth factor-A by human monocyte-derived macrophages is not modulated by activation of cannabinoid receptor types 1 and 2. Given the prominent role of macrophage-assisted vascular remodeling in many tumors, we identified the expression of cannabinoid receptors in lung cancer-associated macrophages. Our results demonstrate that cannabinoid receptor activation selectively inhibits the release of angiogenic and lymphangiogenic factors from human lung macrophage but not from monocyte-derived macrophages. Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation. PMID:26467187

  6. Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β Amyloid via Protein Kinase C

    OpenAIRE

    Ji Jia; Jie Peng; Zhaoju Li; Youping Wu; Qunlin Wu; Weifeng Tu; Mingchun Wu

    2016-01-01

    Background. Reducing β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation ...

  7. Elaboração de bebida composta por mistura de garapa parcialmente clarificada-estabilizada e sucos de frutas ácidas Elaboration of beverage composed by blends of clarified-stabilized sugar cane and juice's acid fruits

    Directory of Open Access Journals (Sweden)

    Patricia Prati

    2005-03-01

    Full Text Available O Brasil é grande produtor e consumidor de sucos de frutas, além de ser o maior produtor mundial de cana-de-açúcar. O caldo de cana, também conhecido popularmente como garapa, é uma bebida de grande aceitação pelo consumidor brasileiro, e nos vendedores ambulantes, normalmente é comercializada em misturas com sucos de frutas ácidas. O trabalho teve como objetivo avaliar físico-química e sensorialmente as misturas de garapa parcialmente clarificada-estabilizada com sucos de limão, abacaxi e maracujá, e posteriormente eleger a bebida preferida do ponto de vista sensorial. Foram realizados Testes Sensoriais de Aceitação e de Intenção de Compra. As outras determinações foram pH, ºBrix, acidez, relação ºBrix/Acidez, teor de ácido ascórbico, cor e turbidez. Os resultados das análises sensoriais indicaram que a mistura preferida foi aquela elaborada com garapa clarificada e 5% de suco de maracujá, seguida da mistura que continha 10% de suco de abacaxi. No entanto, pelo Teste de Intenção de Compra a maioria dos consumidores afirmaram que "possivelmente compraria" todas as misturas avaliadas. Todos os produtos apresentaram boa retenção nos níveis de vitamina C após o tratamento térmico. Microbiologicamente todas as bebidas apresentaram-se adequadas para consumo.Brazil is a great producer and consumer of fruit juices, in addition to being the World's largest producer of sugar cane. Sugar cane juice, popularly known as garapa, is a beverage highly appreciated by the Brazilian population and the street vendors usually sell it in mixtures with acid fruit juices. The objective of this study was the sensory and physical-chemical evaluation of partially clarified-stabilized sugar cane juice in mixtures with lemon, pineapple and passion fruit juices, aimed at choosing the most appreciated beverage from the sensory point of view. The sensory analyses were those of acceptance and intention to buy and the remaining determinations

  8. 新型磁化斜板澄清器在钢铁工业浊环水中的应用研究%The Research of a New Magnetization Inclined Plate Clarifier Using in the Steel Industry Turbid Water

    Institute of Scientific and Technical Information of China (English)

    王莉

    2014-01-01

    本文介绍一种新型磁化斜板澄清器的工作原理、工艺组成以及技术特点等,该设备采用斜板沉淀和过滤技术相结合,通过药磁的作用,促使颗粒间互相吸引,凝聚成大颗粒物,进入斜板区加速沉淀,沉淀出水进入过滤区进一步处理,细小悬浮物进一步被拦截去除,其采用气水反洗技术。具有占地面积少、出水水质好、自动化程度高、易操作、投资省等优点,是一种具药磁、斜板沉淀和过滤一体化的新型水处理设备,具有广阔的应用前景。%This article describes a new type of magnetization inclined plate clarifier,introduce the process, composition and technical features, etc. The device uses inclined plate sedimentation and filtration technology, by the action of magnetic and drug, prompting the mutual attraction between the particles, condensed into big particles. The water enter into inclined plate sedimentation area to accelerate precipitation, after the water flow into the filter area for further processing, Small suspended solids can be blocked,The device use air and water backwash technology.It has small occupation area, good water quality , high degree of automation, easy operation, low investment , etc. The device is a new water treatment equipment which has drug and magnetic, inclined plate sedimentation and filtration integration, it has broad application prospects.

  9. Pramipexole inhibits MPTP toxicity in mice by dopamine D3 receptor dependent and independent mechanisms.

    Science.gov (United States)

    Ramirez, Andres D; Wong, Stephen K-F; Menniti, Frank S

    2003-08-15

    The role of dopamine D3 receptors was investigated in mediating the neuroprotective effect of the dopamine D2/D3 receptor agonist (S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole (pramipexole) in vivo. Pramipexole retained the ability to inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion in mice in which the dopamine D3 receptor had been deleted. However, the neuroprotective efficacy was reduced in the dopamine D3 receptor-deleted mice compared to that in littermates expressing the wildtype receptor. Furthermore, the dopamine D3 receptor selective antagonist 2-(3-[4-(2-tert-butyl-6-trifluoromethyl-4-pyrimidinyl)-1-piperazinyl]propylthio)-4-pyrimidinol (A-437203) partially inhibited the neuroprotective effect of pramipexole in dopamine D3 receptor expressing mice but not in receptor-deleted mice. These results indicate that pramipexole protects dopamine neurons from MPTP-induced toxicity by mechanisms that are both dependent and independent of an interaction with dopamine D3 receptors. PMID:12954356

  10. Experimental Evidence of Persistent Androgen-Receptor-Dependency in Castration-Resistant Prostate Cancer

    OpenAIRE

    Osamu Ogawa; Tomomi Kamba; Takahiro Inoue; Takashi Kobayashi

    2013-01-01

    In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent subli...

  11. Yops of Yersinia enterocolitica Inhibit Receptor-Dependent Superoxide Anion Production by Human Granulocytes

    OpenAIRE

    Visser, L.G.; Seijmonsbergen, E.; Nibbering, P H; van den Broek, P J; van Furth, R

    1999-01-01

    The virulence plasmid-borne genes encoding Yersinia adhesin A (YadA) and several Yersinia secreted proteins (Yops) are involved in the inhibition of phagocytosis and killing of Yersinia enterocolitica by human granulocytes. One of these Yops, YopH, dephosphorylates multiple tyrosine-phosphorylated proteins in eukaryotic cells and is involved in the inhibition of phagocytosis of Y. enterocolitica by human granulocytes. We investigated whether antibody- and complement-opsonized plasmid-bearing ...

  12. GABA[sub A] Receptor-Dependent Synchronization Leads to Ictogenesis in the Human Dysplastic Cortex

    Science.gov (United States)

    D'Antuono, M.; Louvel, J.; Kohling, R.; Mattia, D.; Bernasconi, A.; Olivier, A.; Turak, B.; Devaux, A.; Pumain, R.; Avoli, M.

    2004-01-01

    Patients with Taylor's type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K[superscript +]-selective recordings in neocortical slices obtained from epileptic…

  13. Adolescent social rejection alters pain processing in a CB1 receptor dependent manner.

    Science.gov (United States)

    Schneider, Peggy; Pätz, Monique; Spanagel, Rainer; Schneider, Miriam

    2016-07-01

    Experiences of social rejection represent a major source of distress and in particular peer rejection during adolescence has been implicated in various psychiatric disorders. Moreover, experimentally induced acute social rejection alters pain perception in humans, implicating overlapping neurocircuits for social and physical pains. We recently demonstrated that rearing of adolescent Wistar rats with inadequate, less playful play partners (Fischer 344) persistently decreases pain sensitivity, although the detailed mechanisms mediating the aversiveness during the social encounter remained unsettled. With the present study we examined the behavioral performance during acute interaction of female adolescent Wistar rats with either age-matched same-strain partners or rats from the Fischer 344 strain. We here identify the low responsiveness upon playful attacks, which appears to be characteristic for social play in the Fischer 344 strain, as one of the main aversive components for adolescent Wistar animals during cross-strain encounters, which subsequently diminishes thermal pain reactivity. A detailed behavioral analysis further revealed increased ultrasonic vocalization at 50kHz and an increased frequency of playful attacks for adolescent Wistar animals paired with a Fischer 344 rat compared to same-strain control pairs. Finally, an acute injection of a subthreshold dose of the cannabinoid type 1 receptor inverse agonist/antagonist SR141716 before the social encounter abolished enhanced play-soliciting behavior in Wistar/Fischer 344 pairs as well as the behavioral consequences of the rejection experience in adolescent Wistar rats, further emphasizing an important modulatory role of the endocannabinoid system in mediating the effects of social behavior and social pain. PMID:27157075

  14. β2-Adrenergic Receptor-Dependent Sexual Dimorphism For Murine Leukocyte Migration

    OpenAIRE

    de Coupade, Catherine; Brown, Adrienne S.; Dazin, Paul F; Levine, Jon D.; Green, Paul G.

    2007-01-01

    In wild-type FVB mice, leukocyte recruitment to lipopolysaccharide was sexually dimorphic, with a greater number of leukocytes recruited in females. In male β2-adrenergic receptor knock out mice (bred on a congenic FVB background) the number leukocytes recruited was increased ~4-fold, while in females there was no change, eliminating sexual dimorphism in leukocyte migration. While there were significantly fewer recruited CD62L+ and CD11a+ leukocytes in wild-type males, only in male β2-adrener...

  15. Mechanism of estrogen receptor-dependent transcription in a cell-free system.

    OpenAIRE

    Elliston, J F; Fawell, S E; Klein-Hitpass, L; Tsai, S. Y.; Tsai, M J; Parker, M G; O'Malley, B W

    1990-01-01

    RNA synthesis was stimulated directly in a cell-free expression system by crude preparations of recombinant mouse estrogen receptor (ER). Receptor-stimulated transcription required the presence of estrogen response elements (EREs) in the test template and could be specifically inhibited by addition of competitor oligonucleotides containing EREs. Moreover, polyclonal antibodies directed against the DNA-binding region of ER inhibited ER-dependent transcription. In our cell-free expression syste...

  16. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions...

  17. NMDA receptor-dependent glutamate excitotoxicity in human embryonic stem cell-derived neurons

    OpenAIRE

    Gupta, K.; Hardingham, G. E.; Chandran, S

    2013-01-01

    Thanks to the development of efficient differentiation strategies, human pluripotent stem cells (HPSC) offer the opportunity for modelling neuronal injury and dysfunction in human neurons in vitro. Critically, the effective use of HPSC-derived neural cells in disease-modelling and potentially cell replacement therapies hinges on an understanding of the biology of these cells, specifically their development, subtype specification and responses to neurotoxic signalling mediators. Here, we gener...

  18. Functions of human bitter taste receptors depend on N-glycosylation.

    Science.gov (United States)

    Reichling, Claudia; Meyerhof, Wolfgang; Behrens, Maik

    2008-08-01

    Human bitter taste receptors of the TAS2R gene family play a crucial role as warning sensors against the ingestion of toxic food compounds. Moreover, the genetically highly polymorphic hTAS2Rs recognize an enormous number of structurally diverse toxic and non-toxic bitter substances, and hence, may substantially influence our individual eating habits. Heterologous expression in mammalian cells is a useful tool to investigate interactions between these receptors and their agonists. However, many bitter taste receptors are poorly expressed at the cell surface of heterologous cells requiring the addition of plasma membrane export promoting epitopes to the native receptor proteins. Currently, nothing is known about amino acid motifs or other receptor-intrinsic features of TAS2Rs affecting plasma membrane association. In the present study, we analyzed the Asn-linked glycosylation of hTAS2Rs at a consensus sequence in the second extracellular loop, which is conserved among all 25 hTAS2Rs. Non-glycosylated receptors exhibit substantially lower cell surface localization and reduced association with the cellular chaperone calnexin. As the auxiliary factors receptor transporting proteins 3 and 4 are able to restore the function of non-glycosylated hTAS2R16 partially, we conclude that glycosylation is important for receptor maturation but not for its function per se. PMID:18466324

  19. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

    International Nuclear Information System (INIS)

    At date the major neuroreceptors i.e. γ-aminobutyric acidA (GABAAR) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABAAR agonist (muscimol, MUS; 0,1 μg/g body weight) and/or its antagonist bicuculline (BIC; 1 μg/g body weight) have corroborated a GABAAergic role on motor behaviors. In particular, MUS induced moderate (p AR was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABAAR inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

  20. Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

    Directory of Open Access Journals (Sweden)

    Seii eOHKA

    2012-04-01

    Full Text Available In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV via the blood-brain barrier (BBB. After the virus enters the central nervous system (CNS, it replicates in neurons, especially in motor neurons (MNs, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155-transgenic (Tg mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. Recently, we identified transferrin receptor 1 (TfR1 of mouse brain capillary endothelial cells as a binding protein to PV, implicating that TfR1 is a possible receptor for PV to permeate the BBB.

  1. PLK1 Signaling in Breast Cancer Cells Cooperates with Estrogen Receptor-Dependent Gene Transcription

    Directory of Open Access Journals (Sweden)

    Michael Wierer

    2013-06-01

    Full Text Available Polo-like kinase 1 (PLK1 is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 mediates estrogen receptor (ER-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. Performing large-scale phosphoproteomics of estradiol-treated MCF7 cells in the presence or absence of the specific PLK1 inhibitor BI2536, we identified several PLK1 end targets involved in transcription, including the histone H3K4 trimethylase MLL2, the function of which on ER target genes was impaired by PLK1 inhibition. Our results propose a mechanism for the tumor-suppressive role of PLK1 in mammals as an interphase transcriptional regulator.

  2. Cigarette smoke condensate induces aryl hydrocarbon receptor-dependent changes in gene expression in spermatocytes.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Moley, Kelle H

    2012-12-01

    Cigarette smoke contains numerous compounds that cause oxidative stress and alter gene expression in many tissues, and cigarette smoking is correlated with male infertility. To identify mechanisms by which this occurs, we evaluated expression of antioxidant genes in mouse spermatocytes in response to cigarette smoke condensate (CSC). CSC exposure led to oxidative stress and dose-dependent up-regulation of Hsp90aa1, Ahr, Arnt, Sod1, Sod2, and Cyp1a1 expression in a mouse spermatocyte cell line. An antagonist of the aryl hydrocarbon receptor (AHR) abrogated several CSC-mediated changes in mRNA and protein levels. Consistent with these results, spermatocytes isolated by laser-capture microdissection from CSC-treated mice showed increased expression of several antioxidant genes. In vivo exposure to CSC was genotoxic to spermatocytes, resulting in apoptosis and disruptions to the seminiferous tubules. Our in vivo and in vitro data indicate that CSC-mediated damage to murine spermatocytes is AHR-dependent and is mediated by oxidative stress. PMID:23069111

  3. HDACs class II-selective inhibition alters nuclear receptor-dependent differentiation

    DEFF Research Database (Denmark)

    Nebbioso, Angela; Dell'Aversana, Carmela; Bugge, Anne Skovsø;

    2010-01-01

    Epigenetic deregulation contributes to diseases including cancer, neurodegeneration, osteodystrophy, cardiovascular defects, and obesity. For this reason, several inhibitors for histone deacetylases (HDACs) are being validated as novel anti-cancer drugs in clinical studies and display important a...

  4. β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle.

    Science.gov (United States)

    Nuber, Susanne; Zabel, Ulrike; Lorenz, Kristina; Nuber, Andreas; Milligan, Graeme; Tobin, Andrew B; Lohse, Martin J; Hoffmann, Carsten

    2016-03-31

    (β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor-β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling. PMID:27007855

  5. Receptor-dependent regulation of the CYP3A4 gene

    International Nuclear Information System (INIS)

    A CYP3A4 promoter-reporter gene construct has been used to assess the ability of 16 known (in vivo) and putative (in vitro) inducers to transactivate a CYP3A4 reporter gene in HepG2 cells. With the exception of pravastatin, the remaining 15 compounds transactivated the CYP3A4 reporter gene with differing inductive abilities (Imax:EC50) over two orders of magnitude, ranging from 1.1 (phenytoin) to 222.9 (lovastatin) in a receptor-supplemented system and it is proposed that the lack of response to pravastatin is due to loss of the known hepatic uptake transporter in HepG2 cells. In addition, reporter gene assays were used to investigate two promoter mutants namely a T to C change at -191 bp in the hepatic nuclear factor 3 binding site (HNF-3, -187 to -194 bp) and an A to G change at -205 bp in the oestrogen response element (ERE, -202 to -212 bp), which conferred differential responsiveness to steroid and xenobiotic inducers

  6. The Role of Homer1c in Metabotropic Glutamate Receptor-dependent Long-Term Potentiation

    Science.gov (United States)

    O’Riordan, Kenneth; Gerstein, Hilary; Hullinger, Rikki; Burger, Corinna

    2016-01-01

    Group I metabotropic glutamate receptors (mGluR1/5) play a role in synaptic plasticity and they demonstrate direct interactions with the neuronal Homer1c protein. We have previously shown that Homer1c can restore the plasticity deficits in Homer1 knockout mice (H1-KO). Here, we investigated the role of Homer1c in mGluR-dependent synaptic plasticity in wild-type mice, H1-KO, and H1-KO mice overexpressing Homer1c (KO+H1c). We used a form of plasticity induced by activation of mGluR1/5 that transforms short-term potentiaion (STP) induced by a subthreshold theta burst stimulation into long-term potentiation (LTP). We have shown that although acute hippocampal slices from wild-type animals can induce LTP using this stimulation protocol, H1-KO only show STP. Gene delivery of Homer1c into the hippocampus of H1-KO mice rescued LTP to wild-type levels. This form of synaptic plasticity was dependent on mGluR5 but not mGluR1 activation both in wild-type mice and in KO+H1c. mGluR1/5-dependent LTP was blocked with inhibitors of the MEK-ERK and PI3K-mTOR pathways in KO+H1c mice. Moreover, blocking Homer1c–mGluR5 interactions prevented the maintenance of LTP in acute hippocampal slices from KO+H1c. These data indicate that Homer1c–mGluR5 interactions are necessary for mGluR-dependent LTP, and that mGluR1/5-dependent LTP involves PI3K and ERK activation. PMID:24167026

  7. Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

  8. Forskolin induces NMDA receptor-dependent potentiation at a central synapse in the leech.

    Science.gov (United States)

    Grey, Kathryn B; Burrell, Brian D

    2008-05-01

    In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique for inducing chemical long-term potentiation (cLTP) that is N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin induces a similar potentiation in invertebrate synapses. Therefore, we examined whether forskolin plus rolipram treatment could induce potentiation at a known glutamatergic synapse in the leech (Hirudo sp.), specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of isolated ganglia with forskolin (50 muM) in conjunction with rolipram (0.1 muM) in Mg(2+)-free saline significantly potentiated the P-to-AP excitatory postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100 muM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to-AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic cell, but not by BAPTA injection into the presynaptic neuron, indicating a requirement for postsynaptic elevation of intracellular Ca(2+). Application of db-cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of protein kinase A, blocked forskolin-induced potentiation. Potentiation was also blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a requirement for activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII). Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking of glutamate receptors also plays a role in this form of synaptic plasticity. These experiments demonstrate that techniques used to induce cLTP in vertebrate synapses also induce NMDAR-dependent potentiation in the leech CNS and that many of the cellular processes that mediate LTP are conserved between vertebrate and invertebrate phyla. PMID:18337371

  9. Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum.

    Science.gov (United States)

    Whittaker, Matthew T; Gibbs, Terrell T; Farb, David H

    2008-10-01

    Neuromodulators that alter the balance between lower-frequency glutamate-mediated excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABA(A) receptor mediated synaptic transmission. The enzymes necessary for PS synthesis and degradation are found in brain tissue of several species including human and rat, and up to 5 nM PS has been detected in extracts of postmortem human brain. Here, we ask whether PS could modulate transmitter release from nerve terminals located in the striatum. Superfusion of a preparation of striatal nerve terminals comprised of mixed synaptosomes and synaptoneurosomes with brief-duration (2 min) pulses of 25 nM PS demonstrates that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that it specifically affects the transmitter release mechanism. The PS-induced [3H]DA release occurs via an NMDA receptor (NMDAR) dependent mechanism as it is blocked by D-2-amino-5-phosphonovaleric acid. PS modulates DA release with very high potency, significantly increasing [3H]DA release at PS concentrations as low as 25 pM. This first report of a selective direct enhancement of synaptosomal dopamine release by PS at picomolar concentrations via an NMDAR dependent mechanism raises the possibility that dopaminergic axon terminals may be a site of action for this neurosteroid. PMID:18710414

  10. Regulation of Toll-like receptors-dependent inflammatory response 

    Directory of Open Access Journals (Sweden)

    Ewa Kowalczyk

    2013-03-01

    Full Text Available Toll-like receptors (TLRs are a pivotal part of our innate immune response. They recognize a wide variety of pathogens and instigate an immune response, thus facilitating the removal of the disease-causing agent. Due to the intense nature of this response its strict control is of keyimportance, as a prolonged inflammatory signal leads to carcinogenesis and autoimmune disorders. The signaling cascade initiated by the activated TLR is complex and consists of multiple stages. It involves a variety of adaptor proteins, protein kinases and effector transcription factors. The number of stages in this process enables many possible checkpoints and ways of regulation. Signal modulation involves differentiated expression of TLRs, splicing variants of their adaptorproteins, enzymes modifying proteins engaged in the cascade and many more. This review focuses on endogenous factors responsible for controlling the TLR-dependent inflammatory response as well as on pharmacological therapies designed for regulating the innate immune response.  

  11. Impact of Sorbic Acid on Germinant Receptor-Dependent and -Independent Germination Pathways in Bacillus cereus▿

    OpenAIRE

    Melis,, Rosanna; Nierop Groot, M.N.; Abee, T.

    2011-01-01

    Amino acid- and inosine-induced germination of Bacillus cereus ATCC 14579 spores was reversibly inhibited in the presence of 3 mM undissociated sorbic acid. Exposure to high hydrostatic pressure, Ca-dipicolinic acid (DPA), and bryostatin, an activator of PrkC kinase, negated this inhibition, pointing to specific blockage of signal transduction in germinant receptor-mediated germination.

  12. Neuregulin and BDNF Induce a Switch to NMDA Receptor-Dependent Myelination by Oligodendrocytes

    OpenAIRE

    Iben Lundgaard; Aryna Luzhynskaya; Stockley, John H.; Zhen Wang; Evans, Kimberley A.; Matthew Swire; Katrin Volbracht; Gautier, Hélène O. B.; Franklin, Robin J. M.; David Attwell; Káradóttir, Ragnhildur T.

    2013-01-01

    Author Summary Myelination acts as an insulator for neurons and as such is essential for normal brain function, ensuring fast neuronal communication. Oligodendrocytes are the cells that wrap their membrane around nerve cell axons to form the myelin sheath that enables fast action potential propagation. However, what determines whether an individual axon becomes myelinated remains unknown. We show that there are two distinct modes of myelination: one that is independent of neuronal activity an...

  13. T cell receptor-dependent translational control of GATA-3 enhances Th2 differentiation1

    OpenAIRE

    Kevin D. Cook; Miller, Jim

    2010-01-01

    The differentiation of CD4+ T cells into the Th2 subset is controlled by the transcription factor, GATA-3. GATA-3 is both necessary and sufficient for Th2 differentiation and works through the induction of chromatin remodeling at the Th2 effector cytokine loci. We show here that IL-4 stimulation induces GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are enhanced by concomitant TCR ...

  14. 把握马克思主义人的解放理论需要澄清的三个问题%Three Questions Grasping the Marxism Theory of Human Liberation Need to Be Clarified

    Institute of Scientific and Technical Information of China (English)

    丁增锋

    2014-01-01

    在国内学界,人的解放作为马克思主义的主题已成基本共识,似乎已经没有再度言说的必要。但是,无论从这个问题所面临的理论挑战,还是就其实践意义在当代的充分开显,深入思考马克思主义人的解放理论仍须解决一些至关重要的问题,其中包括厘清青年马克思人的解放理论与马克思主义人的解放学说之间的关系,准确把握马克思主义人的解放理论与西方传统解放理论的根本区别,以及澄明马克思主义人的解放理论的当代性。这对于我们更加深入准确地理解马克思主义的人的解放理论无疑具有重要的意义和价值。%In the domestic academic circles, Human liberation as the theme of Marxism has become a basic consensus, there doesn't seem to be necessary to speak again. However, no matter to face the chal‐lenge from the theory of the problem, or with respect to its practical meaning in contemporary full opening show, think deeply about the Marxist human liberation theory still has to solve some crucial problems, in‐cluding clarifying young Marx’s human liberation theory and the relationship between Marxist theory of human liberation, accurately grasping the human liberation theory of Marxism and the Western traditional theory of liberation, the fundamental difference between and transparent of the contemporary Marxism theory of human liberation. It is undoubtedly important significance and value for us to understand more accurately Marxist human liberation theory.

  15. Comment on: "Recent revisions of phosphate rock reserves and resources: a critique" by Edixhoven et al. (2014) - clarifying comments and thoughts on key conceptions, conclusions and interpretation to allow for sustainable action

    Science.gov (United States)

    Scholz, R. W.; Wellmer, F.-W.

    2016-02-01

    , innovation for exploiting low-grade deposits, etc.) is acknowledged, but the right conclusions are not drawn, including the mixing of finiteness and staticness, and the way in which the critique of the USGS upgrading of the Moroccan reserves has been linked to Peak P. In particular, we clarify that reserves are primarily company data that serve mining companies for their strategic planning and may, by no means, be used as proxy data for providing global Peak P estimates. Likewise, we elaborate that drilling plans for assessing reserves have to be adjusted to site characteristics, in particular, in the case of four plateaus in Morocco and the Western Sahara comprising an area greater than 10 000 km2. We reconstruct the IFDC and USGS estimates and conclude that there is no evidence for considering the somewhat surprising increase to 50 Gt phosphate concentrate to be an unreasonable estimate for Moroccan reserves. However, the partial mixing of different units (e.g., phosphate ore and phosphate concentrate or marketable product) in the USGS data may be avoided by improving the database and using proper conversion factors. When applying these factors and assessing all reserves of marketable Gt of phosphate rock (PR-M), which is a common scale for measuring annual consumption, the magnitude of the 2014 USGS estimates of 67 Gt PR reserves does not change essentially but decreases from 64 (IFDC assessment) to 57.5 Gt PR-M (a worst-case calculation). We agree that a better harmonization of the (national) classification systems is meaningful. The discussion includes several ideas and thoughts that go beyond the paper by Edixhoven et al. (2014). We suggest that the discrepancies in the resource estimates are often caused by missing system understandings, different conceptions of sciences, and diverging world views. Finally, we suggest the establishment of a solidly funded, international standing committee that regularly analyzes global geopotential for assuring long-term supply

  16. Microstructural banding effects clarified through micrographic digital image correlation

    International Nuclear Information System (INIS)

    Microstructural banding is commonly observed in commercial steels, but its effect on the global mechanical properties is still disputed in the literature. This letter investigates the influence of band morphology and banding phase properties from tensile tests for two limit cases (continuous hard band vs. discontinuous softer band), analysed from digital image correlation of in situ electron microscopy micrographs. The effects of band continuity and hardness are elucidated, yielding a clear detrimental influence especially for hard bands with a continuous morphology.

  17. Clarifying Differences between Reading Skills and Reading Strategies

    Science.gov (United States)

    Afflerbach, Peter; Pearson, P. David; Paris, Scott G.

    2008-01-01

    The terms "reading skill" and "reading strategy" are central to how we conceptualize and teach reading. Despite their importance and widespread use, the terms are not consistently used or understood. This article examines the current and historical uses of the terms, defines them, and describes their differences, similarities, and relationships.…

  18. Commentary: Clarifying Medical Decisionmaking-Who, How, and Why?

    Science.gov (United States)

    Gibb, Tyler S; Redinger, Michael J

    2016-07-01

    In its simplest interpretation, this is a case about goals of care and appropriate code status. At the outset, we must confess that we found this case to be extremely interesting-not for the novelty of the issues or its ethical complexity but because it is truly a case of the ordinary. Too often when teaching or discussing clinical ethics cases, we are distracted by the exotic and the unusual and ignore the mundane cases that every practicing clinical ethicist must be able to competently manage. 1,2,3. PMID:27348842

  19. Clarifying the role of sodium in the silica oligomerization reaction

    NARCIS (Netherlands)

    A. Pavlova; T.T. Trinh; R.A. Santen; E.J. Meijer

    2013-01-01

    Silica oligomerization is the key reaction in zeolite synthesis. NaOH is a common additive in the zeolite synthesis that decreases the reaction rate of smaller silica oligomers and also affects the final structure of the zeolite. Here we report a study of the role of sodium in the initial stages of

  20. Blur Clarified: A review and Synthesis of Blur Discrimination

    Science.gov (United States)

    Watson, Andrew B.; Ahumada, Albert J.

    2011-01-01

    Blur is an important attribute of human spatial vision, and sensitivity to blur has been the subject of considerable experimental research and theoretical modeling. Often these models have invoked specialized concepts or mechanisms, such as intrinsic blur, multiple channels, or blur estimation units. In this paper we review the several experimental studies of blur discrimination and find they are in broad empirical agreement. But contrary to previous modeling efforts, we find that the essential features of blur discrimination are fully accounted for by a visible contrast energy model (ViCE), in which two spatial patterns are distinguished when the integrated difference between their masked local contrast energy responses reaches a threshold value.

  1. Clarifying the relation between bullying and social cognition

    OpenAIRE

    Failows Neyestani, Laura

    2010-01-01

    In an effort to resolve a current conflict in the literature, this project investigated the relation between social cognition and bullying by assessing theory of mind, emotion understanding, empathy, moral emotions, and bullying for aggressive children compared to prosocial children. A new measure was developed to assess the social cognitive constructs; bullying was assessed via self, peer, and teacher reports. Participants were 18 second graders, with the results presented in a descriptive...

  2. Assessing tolerance for wildlife: Clarifying relations between concepts and measures

    Science.gov (United States)

    Bruskotter, Jeremy T.; Singh, Ajay; Fulton, David C.; Slagle, Kristina

    2015-01-01

    Two parallel lines of inquiry, tolerance for and acceptance of wildlife populations, have arisen in the applied literature on wildlife conservation to assess probability of successfully establishing or increasing populations of controversial species. Neither of these lines is well grounded in social science theory, and diverse measures have been employed to assess tolerance, which inhibits comparability across studies. We empirically tested behavioral measures of tolerance against self-reports of previous policy-relevant behavior and behavioral intentions. Both composite behavioral measures were strongly correlated (r > .70) with two attitudinal measures of tolerance commonly employed in the literature. The strong correlation between attitudinal and behavioral measures suggests existing attitudinal measures represent valid, parsimonious measures of tolerance that may be useful when behavioral measures are too cumbersome or misreporting of behavior is anticipated. Our results demonstrate how behavioral measures of tolerance provide additional, useful information beyond general attitudinal measures.

  3. The Case for Empiricism: Clarifying Fundamental Issues in Communication Theory.

    Science.gov (United States)

    Bostrom, Robert; Donohew, Lewis

    1992-01-01

    Focuses on recent critiques of empiricism. Discusses the present state of communication research and theory. Asserts that examining levels of language and explanation helps to solve logical inconsistencies that have appeared to present philosophical problems in the past. (PRA)

  4. Clarifying the Relationship between Emotion Regulation, Gender, and Depression

    OpenAIRE

    Sumida, Emi

    2010-01-01

    This study investigates the relation between emotion regulation problems and clinical depression. One goal of the present study was to bring increased clarity and parsimony to how emotion regulation is presently measured by consolidating three widely used instruments. In addition, of interest was an investigation of whether particular emotion regulation problems and management strategies interact with gender to predict either severity of overall depression symptoms or the presence of a formal...

  5. Teachers’ professional vision: exploring and clarifying the concept

    Directory of Open Access Journals (Sweden)

    Tomáš Janík

    2012-06-01

    Full Text Available This theoretical study introduces the concept of professional vision into Czech academic discourse as one of the potential concepts that can be used when contemplating (teacher professionalization. At the beginning the authors mention selected attempts to define characteristics of a profession and introduce their view of the issue of teacher professionality that is built on three dimensions – professional vision, professional knowledge and professional action. They further suggest the relationships among these dimensions in the model of pedagogical reasoning and action (Shulman, 1986 and the ALACT model of reflection (Korthagen, 2011.Professional vision in general and specifically in the teaching profession is discussedand its existing conceptualizations are described. Based on other theoretical and empirical studies connected to this issue, the authors then suggest their own approach to teachers’ professional vision. The relationship between professional vision and reflection on the spiral of pedagogical reasoning and action is elaborated on. In the end,the usability of the concept of professional vision in teacher education is discussed, specifically in the process of development of an e-learning (videoenvironment for(prospective teachers.

  6. Clarifying the anatomy of the fifth arch artery

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Gupta

    2016-01-01

    Full Text Available The artery allegedly forming in the fifth pharyngeal arch has increasingly been implicated as responsible for various vascular malformations in patients with congenitally malformed hearts. Observations from studies on developing embryos, however, have failed to provide support to substantiate several of these inferences such that the very existence of the fifth arch artery remains debatable. To the best of our knowledge, in only a solitary human embryo has a vascular channel been found that truly resembled the artery of the fifth arch. Despite the meager evidence to support its existence, the fifth arch artery has been invoked to explain the morphogenesis of double-barreled aorta, some unusual forms of aortopulmonary communications, and abnormalities of the brachiocephalic arteries. In most of these instances, the interpretations have proved fallible when examined in the light of existing knowledge of cardiac development. In our opinion, there are more plausible alternative explanations for the majority of these descriptions. Double-barreled aorta is more likely to result from retention of the recently identified dorsal collateral channels while abnormalities of brachiocephalic arteries are better explained on the basis of extensive remodeling of aortic arches during fetal development. Some examples of aortopulmonary communications, nonetheless, may well represent persistence of the developing artery of the fifth pharyngeal arch. We here present one such case - a patient with tetralogy of Fallot and pulmonary atresia, in whom the fifth arch artery provided a necessary communication between the ascending aorta and the pulmonary arteries. In this light, we discuss the features we consider to be essential before attaching the tag of "fifth arch artery" to a candidate vascular channel.

  7. Schopenhauer's Contraction of Reason: Clarifying Kant and Undoing German Idealism

    OpenAIRE

    Gardner, S.

    2012-01-01

    Schopenhauer's claim that the essence of the world consists in Wille encounters well-known difficulties. Of particular importance is the conflict of this metaphysical claim with his restrictive account of conceptuality. This paper attempts to make sense of Schopenhauer's position by restoring him to the context of post-Kantian debate, with special attention to the early notebooks and Fourfold Root of the Principle of Sufficient Reason. On the reconstruction suggested here, Schopenhauer's phil...

  8. The Terrorist War against Islam: Clarifying Academic Confusions

    Science.gov (United States)

    Schwartz, Stephen

    2011-01-01

    Since the terrorist atrocities of September 11, 2001, Westerners have been challenged to understand the ideological and theological concepts, derived from Islam, that motivated the actions of Al-Qaida on that day and in other attacks before and since. Differences in taxonomy have proven to be a major issue. In the author's view, it is insufficient…

  9. Clarifying the relationship between ostracism and relational devaluation.

    Science.gov (United States)

    Gerber, J P; Wheeler, Ladd

    2014-01-01

    We examine how three perspectives on relational devaluation relate to needs threat following ostracism. In two experiments with 179 first-year psychology students, distress was greatest when participants were ostracized without any prior throws, and distress decreased linearly with increasing prior inclusion. In Experiment 3, using 76 first-year psychology students, we manipulated expectations of exclusion and found expectations predicted distress following ostracism, suggesting ostracism's distress can be influenced by norm-based expectations of inclusion, and that progressive relational devaluation is not a necessary condition for ostracism's distress. PMID:24689334

  10. Toward a new electromagnetics part 4: Vectors and mechanisms clarified

    International Nuclear Information System (INIS)

    The authors have released a number of powerful mechanisms that result from the new technological concepts. Many of these were originally discovered - at least in rudimentary form - by Nikola Tesla. In the West, the suppression of Tesla led to the suppression of these effects. And the knowledge of them went to the grave with Tesla. After World War II, the Soviet Union mounted a massive campaign to obtain all the scientific literature of the West and thoroughly digest it. Great centers were set up, and thousands of PhDs devoted to this purpose. Gradually they synthesized this technology from the errors in EM foundations they uncovered, and from obscure, ignored papers published in the orthodox Western scientific literature. They rediscovered the technology of Tesla, Moray, and Rogers. And they have highly weaponized the effects, and adjusted and aligned the weapons upon us

  11. Andragogy in Practice: Clarifying the Andragogical Model of Adult Learning.

    Science.gov (United States)

    Holton, Elwood F., III; Swanson, Richard A.; Naquin, Sharon S.

    2001-01-01

    Discusses aspects of andragogy that are important for performance improvement professionals. Topics include the core andragogical model that presents core principles of adult learning; andragogy as an individual-transactional framework; individual learner differences; situational differences; and the Andragogy in Practice Model. (Contains 70…

  12. Use of talc as low-cost clarifier for wastewater.

    Science.gov (United States)

    Grafia, Ana L; Castillo, Luciana A; Barbosa, Silvia E

    2014-01-01

    Talc is proposed as a low-cost mineral for wastewater clarification. In this sense, adsorption of methylene blue (MB) from aqueous solutions was studied comparatively by using sepiolite (qualified as very good adsorbent) and two talc samples with different particle size and purity degree. The MB adsorption was assessed by determining remnant dye in the supernatant using UV-vis spectroscopy and by detecting dye adsorbed on mineral samples through thermogravimetric analysis and infrared spectroscopy. Both isothermal curves and kinetic studies demonstrate that talc is a good dye adsorbent. Particularly, with dye concentrations similar to those of textile wastewater, talc was demonstrated to adsorb the same dye content of sepiolite at similar times. Natural talc could be employed as a low-cost alternative in wastewater treatment for the removal of cationic dyes. PMID:24552739

  13. REMOVAL OF SOLUBLE BOD(5) IN PRIMARY CLARIFIERS

    Science.gov (United States)

    This project was directed to evaluating means for increasing BOD removal from primary treatment systems treating pulp and paper wastes. An improved understanding of the optimal conditions for soluble and colloidal BOD removal should permit increasing efficiency in total organic r...

  14. Clarifying how defocus blur and disparity affect the perceived depth

    OpenAIRE

    Wang, Junle; Barkowsky, Marcus; Ricordel, Vincent; Le Callet, Patrick

    2011-01-01

    Human visual system takes advantage of different cues simultaneously to provide us the perception of depth. When 3D images are shown on a planar stereoscopic display, binocular disparity becomes a pre-eminent depth cue. But it induces simultaneously the conflict between accommodation and vergence, which is often considered as a main reason for visual discomfort. If we limit this visual discomfort by decreasing the disparity, the apparent depth also decreases. We propose to decrease the (binoc...

  15. Finite Element Modelling Used to Clarify Separate Effects

    International Nuclear Information System (INIS)

    1D and 1.5D fuel behaviour codes include either mechanistic or empirical models for the physical phenomena occurring in the fuel rods. Since it is in the nature of integral tests and of real-life situations (e.g. licensing) not to provide detailed, local pre-characterisation of the rods, some sort of statistical averaging is inherently included in the modelling of the processes. Often applied averaging leads to assumptions of e.g. • uniformity, • homogeneity, • axisymmetry. Finite element codes make it possible to account for 3D and local phenomena, e.g. • PCMI including the effect of cracks in the pellets, • PCI with a mixture of boded cladding areas. Moreover, the basic assumption on the homogeneity and uniformity of the cladding can be lifted and the effect of inhomogeneities and slight variation in thickness can be studied in e.g. LOCA conditions. MTA EK has started research to study such local phenomena in order to better understand and reproduce experimental data. The results are promising: the stress distribution in a cladding with bonded and unbonded areas differs significantly from the azimuthally symmetric case. The shape of the ballooned area of a fuel rod subjected to LOCA can only be reproduced if the above averaging assumptions are lifted, which leads to a new, second order approach. (author)

  16. Toward Clarifying the Meanings of "Gender" in Mathematics Education Research

    Science.gov (United States)

    Damarin, Suzanne; Erchick, Diana B.

    2010-01-01

    The importance of clarity in definitions of gender is discussed and several conceptual models of gender are presented. Four of these models begin with biological sex differences but draw attention to other aspects of gender. Four models set biology aside and are based on social and cultural theories. Some of the advantages of the latter for…

  17. Clarifying possible misconceptions in the foundations of general relativity

    Science.gov (United States)

    Brown, Harvey R.; Read, James

    2016-05-01

    We discuss what we take to be three possible misconceptions in the foundations of general relativity, relating to: (a) the interpretation of the weak equivalence principle and the relationship between gravity and inertia; (b) the connection between gravitational redshift results and spacetime curvature; and (c) the Einstein equivalence principle and the ability to "transform away" gravity in local inertial coordinate systems.

  18. Immigration and National Wages: Clarifying the Theory and the Empirics

    OpenAIRE

    Ottaviano, Gianmarco I. P.; Giovanni PERI

    2008-01-01

    This paper estimates the effects of immigration on wages of native workers at the national U.S. level. Following Borjas (2003) we focus on national labor markets for workers of different skills and we enrich his methodology and refine previous estimates. We emphasize that a production function framework is needed to combine workers of different skills in order to evaluate the competition as well as cross-skill complementary effects of immigrants on wages. We also emphasize the importance (and...

  19. Using Key Distance to Clarify a Theory on the SNARC.

    Science.gov (United States)

    Schiller, Florian; Eloka, Owino; Franz, Volker H

    2016-01-01

    The most prominent explanation for the spatial numerical association of response codes (SNARC) effect is the direct mapping account (DMA). The DMA assumes that (a) numbers are represented on a mental number line, (b) this mental number line is mapped to external space, and (c) the better the mapping location corresponds to the response location, the faster the response. The DMA leaves open whether a variation of response locations can (ceteris paribus) influence the location to which numbers are mapped in external space. In order to investigate this question, we varied response key distance during a standard parity judgment and a magnitude judgment task. We found that even drastic manipulations of response key distance did not modulate the SNARC effect. Power and meta-analyses show that this null effect is not due to insufficient statistical power or a poor experimental setup. Thus, our results indicate that, in order for the DMA to explain the SNARC effect, it must assume that the mapping from the mental number line to external space is anchored to response location. For future research, our results suggest that it is not necessary to control the horizontal separation of the response keys in basic SNARC experiments. PMID:26822868

  20. Ionian Sea circulation as clarified by assimilation of glider observations

    OpenAIRE

    Dobricic, S.; Istituto Nazionale di Geofisica e Vulcanologia, Sezione Bologna, Bologna, Italia; Pinardi, N.; Istituto Nazionale di Geofisica e Vulcanologia, Sezione Bologna, Bologna, Italia; Testor, P.; Send, U.; Istituto Nazionale di Geofisica e Vulcanologia, Sezione CNT, Roma, Italia

    2008-01-01

    Glider observations of temperature and salinity in the Ionian Sea (Eastern Mediterranean Sea), made in the period October 2004-December 2004, were assimilated into an operational forecasting model together with other in-situ and satellite observations. The impact of glider data on the estimation of the circulation is studied and it is found that the assimilation of glider data significantly improve the vertical structure of temperature and salinity fields and remove biases. The...

  1. L2 Extensive Reading and Flow: Clarifying the Relationship

    Science.gov (United States)

    Kirchhoff, Cheryl

    2013-01-01

    Among foreign language educators interest in extensive reading is growing along with questions about learner motivation to read. Maintaining learner motivation over long periods of time is influenced by many variables suggesting that multiple means of stimulating motivation is needed. The psychological theory of flow has been suggested to…

  2. Reading Motivation and Reading Engagement: Clarifying Commingled Conceptions

    Science.gov (United States)

    Unrau, Norman J.; Quirk, Matthew

    2014-01-01

    The constructs of motivation for reading and reading engagement have frequently become blurred and ambiguous in both research and discussions of practice. To address this commingling of constructs, the authors provide a concise review of the literature on motivation for reading and reading engagement and illustrate the blurring of those concepts…

  3. Clarifying students' feedback-seeking behaviour in clinical clerkships

    NARCIS (Netherlands)

    Bok, H.G.; Teunissen, P.W.; Spruijt, A.; Fokkema, J.P.; Beukelen, P. van; Jaarsma, D.A.; Vleuten, C.P.M. van der

    2013-01-01

    CONTEXT: Why and how do students seek feedback on their performance in the clinical workplace and which factors influence this? These questions have remained largely unanswered in research into workplace learning during clinical clerkships. Research on feedback has focused mainly on feedback provide

  4. Cyber bullying: Clarifying Legal Boundaries for School Supervision in Cyberspace

    OpenAIRE

    Shariff, Shaheen; Hoff, Dianne L.

    2007-01-01

    Abstract Cyber bullying is a psychologically devastating form of social cruelty among adolescents. This paper reviews the current policy vacuum of the legal obligations and expectations of schools to monitor and supervise online discourse, while balancing student safety, education, and interaction in virtual space. The paper opens with a profile and conditions of cyber bullying using an analogy to Golding’s (1954), Lord of the Flies. The anarchy and deterioration of unsupervised ado...

  5. Clarifying and Measuring Filial Concepts across Five Cultural Groups

    OpenAIRE

    Jones, Patricia S.; Lee, Jerry W.; Zhang, Xinwei E.

    2011-01-01

    Literature on responsibility of adult children for aging parents reflects lack of conceptual clarity. We examined filial concepts across five cultural groups: African-, Asian-, Euro-, Latino-, and Native Americans. Data were randomly divided for scale development (n = 285) and cross-validation (n = 284). Exploratory factor analysis on 59 items identified three filial concepts: Responsibility, Respect, and Care. Confirmatory factor analysis on a 12-item final scale showed data fit the three-fa...

  6. Outdoor Education in Senior Schooling: Clarifying the Body of Knowledge

    Science.gov (United States)

    Martin, Peter

    2008-01-01

    Australia has a state-based educational system. In some of these states, outdoor education exists as part of the formal accredited secondary school curriculum. In this paper I analyse the content of these senior secondary school outdoor courses as a means to help delineate and describe the body of knowledge of outdoor education. I suggest outdoor…

  7. "Measurement" and "Construct" Need to Be Clarified First. Commentary on Newton, P. E. "Clarifying the Consensus Definition of Validity"

    Science.gov (United States)

    Bramley, Tom

    2012-01-01

    There is something about the topic of validity that seems to provoke dissatisfaction in many of those who encounter it--a sense that something is not right, and that something needs to be done to sort it out. Paul E. Newton in his target essay does not attempt a radical reconstruction of the validity edifice. His position is that the "consensus…

  8. Antibody limits in vivo murid herpesvirus-4 replication by IgG Fc receptor-dependent functions

    OpenAIRE

    Wright, Debbie E.; Colaco, Susanna; Colaco, Camilo; Stevenson, Philip G.

    2009-01-01

    Antibody is an important antiviral defence. However, it is considered to do little against human gamma-herpesviruses, which establish predominantly latent infections regulated by T cells. One limitation on analysing these infections has been that latency is already well-established at clinical presentation; early infection may still be accessible to antibody. Here, using murid herpesvirus-4 (MuHV-4), we tested the impact of adoptively transferred antibody on early gamma-herpesvirus infection....

  9. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1, smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP induces both NKx-2.5 and NF-kappaB translocations. Conclusion This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders.

  10. Aryl hydrocarbon receptor-dependent enrichment of a megakaryocytic precursor with a high potential to produce proplatelets.

    Science.gov (United States)

    Strassel, Catherine; Brouard, Nathalie; Mallo, Lea; Receveur, Nicolas; Mangin, Pierre; Eckly, Anita; Bieche, Ivan; Tarte, Karin; Gachet, Christian; Lanza, François

    2016-05-01

    The mechanisms regulating megakaryopoiesis and platelet production (thrombopoiesis) are still incompletely understood. Identification of a progenitor with enhanced thrombopoietic capacity would be useful to decipher these mechanisms and to improve our capacity to produce platelets in vitro. Differentiation of peripheral blood CD34(+) cells in the presence of bone marrow-human mesenchymal stromal cells (MSCs) enhanced the production of proplatelet-bearing megakaryocytes (MKs) and platelet-like elements. This was accompanied by enrichment in a MK precursor population exhibiting an intermediate level of CD41 positivity while maintaining its expression of CD34. Following sorting and subculture with MSCs, this CD34(+)CD41(low) population was able to efficiently generate proplatelet-bearing MKs and platelet-like particles. Similarly, StemRegenin 1 (SR1), an antagonist of the aryl hydrocarbon receptor (AhR) transcription factor known to maintain CD34 expression of progenitor cells, led to an enriched CD34(+)CD41(low) fraction and to an increased capacity to generate proplatelet-producing MKs and platelet-like elements ultrastructurally and functionally similar to circulating platelets. The effect of MSCs, like that of SR1, appeared to be mediated by an AhR-dependent mechanism because both culture conditions resulted in repression of its downstream effector CYP1B1. This newly described isolation of a precursor exhibiting strong MK potential could be exploited to study normal and abnormal thrombopoiesis and for in vitro platelet production. PMID:26966088

  11. Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, Emelia [Department of Medicine, McGill University, Montreal, Quebec (Canada); Zago, Michela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Sarill, Miles [Department of Medicine, McGill University, Montreal, Quebec (Canada); Rico de Souza, Angela [Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Gomez, Alvin; Matthews, Jason [Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON (Canada); Hamid, Qutayba; Eidelman, David H. [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Baglole, Carolyn J., E-mail: Carolyn.baglole@McGill.ca [Department of Medicine, McGill University, Montreal, Quebec (Canada); Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec (Canada)

    2014-11-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR{sup −/−}) and wild-type (AhR{sup +/+}) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR{sup −/−} cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR{sup −/−} compared to AhR{sup +/+} cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR{sup +/+} fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR{sup +/+} lung fibroblasts in response to serum, corresponding to a decrease in p27{sup KIP1} protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27{sup KIP1} in AhR{sup −/−} fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the expression of the microRNA miR-196a independent of xenobiotics. • AhR ligands decrease miR-196a concomitant with reduced AhR protein expression. • AhR regulation of miR-196a expression suppresses cigarette smoke-induced apoptosis. • Control of miRNA expression represents a potential new endogenous function of the AhR.

  12. Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

    Science.gov (United States)

    Sathler, Matheus Figueiredo; Stutz, Bernardo; Martins, Robertta Silva; Dos Santos Pereira, Maurício; Pecinalli, Ney Roner; Santos, Luis E; Taveira-da-Silva, Rosilane; Lowe, Jennifer; de Freitas, Isis Grigorio; de Melo Reis, Ricardo Augusto; Manhães, Alex C; Kubrusly, Regina C C

    2016-08-01

    Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC. PMID:27208619

  13. Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission

    OpenAIRE

    Park, Hye Jin; Lee, Seungheon; Jung, Ji Wook; Lee, Young Choon; Choi, Seong-Min; Kim, Dong hyun

    2016-01-01

    Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. ...

  14. 99mTc labeled plumbagin. Estrogen receptor dependent examination against breast cancer cells and comparison with PLGA encapsulated form

    International Nuclear Information System (INIS)

    Plant origin products having anticancer properties come into prominence due to widespread of cancer. Plumbagin has various biological activities like anticancer activity. Estrogen receptor (ER) specificity of plumbagin (PL) and radiolabeled PL investigated by in vitro studies on ER+ and ER- adenocarcinoma cells. Additionally, PLGA encapsulation was carried out to reduce toxicity of plumbagin and encapsulation effect was investigated. Plumbagin radiolabeled with 100 % in yields and had ER specificity. Furthermore, PLGA encapsulation effected positively on properties of plumbagin; reduced toxicity, increased stability and ER specificity. A promising agent for the diagnosis of ER+ breast cancer is suggested. (author)

  15. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Xinyi [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Department of Histology and Embryology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016 (China); Liao, Xinggui; Chen, Xuemei; Li, Yanli; Wang, Meirong; Shen, Cha; Zhang, Xue; Wang, Yingxiong; Liu, Xueqing [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); He, Junlin, E-mail: hejunlin_11@aliyun.com [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China)

    2015-11-15

    Highlights: • DEHP inhibits primordial folliculogenesis in vivo and in vitro. • Estrogen receptors participate in the effect of DEHP on early ovarian development. • DEHP exposure impairs the expression of Notch2 signaling components. • DEHP exposure disrupts the proliferation of pregranulosa precursor cells. - Abstract: Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development.

  16. Bidirectional effects of fentanyl on dendritic spines and AMPA receptors depend upon the internalization of mu opioid receptors

    OpenAIRE

    Lin, Hang; Higgins, Paul; Loh, Horace H.; Law, Ping-Yee; Liao, Dezhi

    2009-01-01

    Fentanyl is a frequently used and abused opioid analgesic and can cause internalization of mu opioid receptors (MORs). Receptor internalization modulates the signaling pathways of opioid receptors. Because changes in dendritic spines and synaptic AMPA receptors play important roles in addiction and memory loss, we investigated how fentanyl affects dendritic spines and synaptic AMPA receptors in cultured hippocampal neurons. Fentanyl at low concentrations (0.01 and 0.1 µM) caused collapse of d...

  17. Trace and Contextual Fear Conditioning Require Neural Activity and NMDA Receptor-Dependent Transmission in the Medial Prefrontal Cortex

    Science.gov (United States)

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…

  18. Both neurons and astrocytes exhibited tetrodotoxin-resistant metabotropic glutamate receptor-dependent spontaneous slow Ca2+ oscillations in striatum.

    Directory of Open Access Journals (Sweden)

    Atsushi Tamura

    Full Text Available The striatum plays an important role in linking cortical activity to basal ganglia outputs. Group I metabotropic glutamate receptors (mGluRs are densely expressed in the medium spiny projection neurons and may be a therapeutic target for Parkinson's disease. The group I mGluRs are known to modulate the intracellular Ca(2+ signaling. To characterize Ca(2+ signaling in striatal cells, spontaneous cytoplasmic Ca(2+ transients were examined in acute slice preparations from transgenic mice expressing green fluorescent protein (GFP in the astrocytes. In both the GFP-negative cells (putative-neurons and astrocytes of the striatum, spontaneous slow and long-lasting intracellular Ca(2+ transients (referred to as slow Ca(2+ oscillations, which lasted up to approximately 200 s, were found. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca(2+ oscillation. Depletion of the intracellular Ca(2+ store and the blockade of inositol 1,4,5-trisphosphate receptors greatly reduced the transient rate of the slow Ca(2+ oscillation, and the application of an antagonist against mGluR5 also blocked the slow Ca(2+ oscillation in both putative-neurons and astrocytes. Thus, the mGluR5-inositol 1,4,5-trisphosphate signal cascade is the primary contributor to the slow Ca(2+ oscillation in both putative-neurons and astrocytes. The slow Ca(2+ oscillation features multicellular synchrony, and both putative-neurons and astrocytes participate in the synchronous activity. Therefore, the mGluR5-dependent slow Ca(2+ oscillation may involve in the neuron-glia interaction in the striatum.

  19. Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells.

    Science.gov (United States)

    Klein, Diana; Yaghootfam, Afshin; Matzner, Ullrich; Koch, Bettina; Braulke, Thomas; Gieselmann, Volkmar

    2009-01-01

    Metachromatic leukodystrophy is a lysosomal disorder caused by the deficiency of arylsulfatase A (ASA). This leads to the storage of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide) in various cell types, such as renal tubular cells. Examination of mannose 6-phosphate receptor (MPR300)-dependent endocytosis revealed that uptake of lysosomal enzymes is more than two-fold increased in sulfatide-storing kidney cells. Expression of MPR300 and its internalization rate is increased in these cells, whereas the recycling rate is decreased. Similar alterations can be found for the transferrin receptor, indicating that sulfatide storage leads to a general alteration of the endocytotic pathway. These data allow calculating that the endosomal pool from which receptors can recycle is 1.4- to 2-fold increased in lipid-storing cells. Immunocytochemistry demonstrates that the MPR300 in lipid-storing cells does not co-localize with accumulated sulfatide, suggesting that the kinetics of internalization and recycling appear to be altered indirectly. PMID:19007310

  20. Transitions in Oral and Intestinal Microflora Composition and Innate Immune Receptor-Dependent Stimulation during Mouse Development▿ †

    OpenAIRE

    Hasegawa, Mizuho; Osaka, Toshifumi; Tawaratsumida, Kazuki; Yamazaki, Takashi; Tada, Hiroyuki; Chen, Grace Y.; Tsuneda, Satoshi; Núñez, Gabriel; Inohara, Naohiro

    2009-01-01

    Commensal bacteria possess immunostimulatory activities that can modulate host responses to affect development and homeostasis in the intestine. However, how different populations of resident bacteria stimulate the immune system remains largely unknown. We characterized here the ability of intestinal and oral microflora to stimulate individual pattern recognition receptors (PRRs) in bone marrow-derived macrophages and mesothelial cells. The intestinal but not oral microflora elicited age- and...

  1. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of strong long-term memories because the activation of hippocampal GRs after learning is coupled to the recruitment of the growth and pro-survival BDNF/cAMP response element-binding protein (CREB) pathway, which is well-know to be a general mechanism required for long-term memory formation. We will then speculate about how these results may explain the negative effects of traumatic or chronic stress on memory and cognitive functions. PMID:24113652

  2. H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a purinergic receptor-dependent pathway.

    Science.gov (United States)

    Cortier, Marion; Boina-Ali, Rahamata; Racoeur, Cindy; Paul, Catherine; Solary, Eric; Jeannin, Jean-François; Bettaieb, Ali

    2015-03-30

    High doses of the organic nitrate glyceryl trinitrate (GTN), a nitric oxide (NO) donor, are known to trigger apoptosis in human cancer cells. Here, we show that such a cytotoxic effect can be obtained with subtoxic concentrations of GTN when combined with H89, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide.2HCl. This synergistic effect requires the generation of reactive oxygen species (ROS) from H89 and NO from GTN treatment that causes cGMP production and PKG activation. Furthermore, the GTN/H89 synergy was attenuated by inhibition of P2-purinergic receptors with suramin and competition with ATP/UDP. By down-regulating genes with antisense oligonucleotides, P2-purinergic receptors P2X3, P2Y1, and P2Y6 were found to have a role in creating this cytotoxic effect. Thus, H89 likely acts as an ATP mimetic synergizing with GTN to trigger apoptosis in aggressive cancer cells. PMID:25762630

  3. DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

    International Nuclear Information System (INIS)

    Highlights: • DEHP inhibits primordial folliculogenesis in vivo and in vitro. • Estrogen receptors participate in the effect of DEHP on early ovarian development. • DEHP exposure impairs the expression of Notch2 signaling components. • DEHP exposure disrupts the proliferation of pregranulosa precursor cells. - Abstract: Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development

  4. Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

    OpenAIRE

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increase...

  5. Memory retrieval in response to partial cues requires NMDA receptor-dependent neurotransmission in the medial prefrontal cortex.

    Science.gov (United States)

    Jo, Yong Sang; Choi, June-Seek

    2014-03-01

    The medial prefrontal cortex (mPFC) has been suggested to play a crucial role in retrieving detailed contextual information about a previous learning episode in response to a single retrieval cue. However, few studies investigated the neurochemical mechanisms that mediate the prefrontal retrieval process. In the current study, we examined whether N-methyl-D-aspartate receptors (NMDARs) in the mPFC were necessary for retrieval of a well-learned spatial location on the basis of partial or degraded spatial cues. Rats were initially trained to find a hidden platform in the Morris water maze using four extramaze cues in the surrounding environment. Their retrieval performance was subsequently tested under different cue conditions. Infusions of DL-2-amino-5-phosphonovaleric acid (APV), a NMDAR antagonist, significantly disrupted memory retrieval when three of the original cues were removed. By contrast, APV injections into the mPFC did not affect animals' retrieval performance when the original cues were presented or when three novels landmarks were added alongside the original cues. These results indicate that prefrontal NMDARs are required for memory retrieval when allocentric spatial information is degraded. NMDAR-dependent neurotransmission in the mPFC may facilitate an active retrieval process to reactivate complete contextual representations associated with partial retrieval cues. PMID:24269352

  6. Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells

    DEFF Research Database (Denmark)

    Grigg, Jonathan; Walters, Haydn; Sohal, Sukhwinder Singh;

    2012-01-01

    BACKGROUND: Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association is unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of...... active-smokers by immunostaining. RESULTS: In A549 cells, CSE 1% increased pneumococcal adhesion (p<0.05 vs control), PAFR transcript level (p<0.01), and PAFR expression (p<0.01). Pneumococcal adhesion to A549 cells was attenuated by CV-3988 (p<0.001). CSE 1% stimulated pneumococcal adhesion to BEAS2-B...... cells and HBEpC (p<0.01 vs control). CSE 1% increased PAFR expression in BEAS2-B (p<0.01), and in HBEpC (p<0.05). Lung PAFR transcript level was increased in mice exposed to CS in vivo (p<0.05 vs room air). Active smokers (n=16) had an increased percentage of bronchial epithelium with PAFR...

  7. Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission.

    Science.gov (United States)

    Park, Hye Jin; Lee, Seungheon; Jung, Ji Wook; Lee, Young Choon; Choi, Seong-Min; Kim, Dong Hyun

    2016-07-01

    Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 μg/ml) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol. PMID:27257009

  8. Role of endoplasmic reticulum stress in alpha-TEA mediated TRAIL/DR5 death receptor dependent apoptosis.

    Directory of Open Access Journals (Sweden)

    Richa Tiwary

    Full Text Available BACKGROUND: Alpha-TEA (RRR-alpha-tocopherol ether-linked acetic acid analog, a derivative of RRR-alpha-tocopherol (vitamin E exhibits anticancer actions in vitro and in vivo in variety of cancer types. The objective of this study was to obtain additional insights into the mechanisms involved in alpha-TEA induced apoptosis in human breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: alpha-TEA induces endoplasmic reticulum (ER stress as indicated by increased expression of CCAAT/enhancer binding protein homologous protein (CHOP as well as by enhanced expression or activation of specific markers of ER stress such as glucose regulated protein (GRP78, phosphorylated alpha subunit of eukaryotic initiation factor 2 (peIF-2alpha, and spliced XBP-1 mRNA. Knockdown studies using siRNAs to TRAIL, DR5, JNK and CHOP as well as chemical inhibitors of ER stress and caspase-8 showed that: i alpha-TEA activation of DR5/caspase-8 induces an ER stress mediated JNK/CHOP/DR5 positive amplification loop; ii alpha-TEA downregulation of c-FLIP (L protein levels is mediated by JNK/CHOP/DR5 loop via a JNK dependent Itch E3 ligase ubiquitination that further serves to enhance the JNK/CHOP/DR5 amplification loop by preventing c-FLIP's inhibition of caspase-8; and (iii alpha-TEA downregulation of Bcl-2 is mediated by the ER stress dependent JNK/CHOP/DR5 signaling. CONCLUSION: Taken together, ER stress plays an important role in alpha-TEA induced apoptosis by enhancing DR5/caspase-8 pro-apoptotic signaling and suppressing anti-apoptotic factors c-FLIP and Bcl-2 via ER stress mediated JNK/CHOP/DR5/caspase-8 signaling.

  9. Analysis of Physical Human–Robot Interaction for Motor Learning with Physical Help

    OpenAIRE

    Shuhei Ikemoto; Takashi Minato; Hiroshi Ishiguro

    2008-01-01

    In this paper, we investigate physical human–robot interaction (PHRI) as an important extension of traditional HRI research. The aim of this research is to develop a motor learning system that uses physical help from a human helper. We first propose a new control system that takes advantage of inherent joint flexibility. This control system is applied on a new humanoid robot called CB2. In order to clarify the difference between successful and unsuccessful interaction, we conduct an experimen...

  10. Echinacea-induced cytosolic Ca2+ elevation in HEK293

    Directory of Open Access Journals (Sweden)

    Nikolau Basil J

    2010-11-01

    Full Text Available Abstract Background With a traditional medical use for treatment of various ailments, herbal preparations of Echinacea are now popularly used to improve immune responses. One likely mode of action is that alkamides from Echinacea bind to cannabinoid type 2 (CB2 receptors and induce a transient increase in intracellular Ca2+. Here, we show that unidentified compounds from Echinacea purpurea induce cytosolic Ca2+ elevation in non-immune-related cells, which lack CB2 receptors and that the Ca2+ elevation is not influenced by alkamides. Methods A non-immune human cell line, HEK293, was chosen to evaluate E. purpurea root extracts and constituents as potential regulators of intracellular Ca2+ levels. Changes in cytosolic Ca2+ levels were monitored and visualized by intracellular calcium imaging. U73122, a phospholipase C inhibitor, and 2-aminoethoxydiphenyl borate (2-APB, an antagonist of inositol-1,4,5-trisphosphate (IP3 receptor, were tested to determine the mechanism of this Ca2+ signaling pathway. E. purpurea root ethanol extracts were fractionated by preparative HPLC, screened for bioactivity on HEK293 cells and by GC-MS for potential constituent(s responsible for this bioactivity. Results A rapid transient increase in cytosolic Ca2+ levels occurs when E. purpurea extracts are applied to HEK293 cells. These stimulatory effects are phospholipase C and IP3 receptor dependent. Echinacea-evoked responses could not be blocked by SR 144528, a specific CB2 receptor antagonist, indicating that CB2 is not involved. Ca2+ elevation is sustained after the Echinacea-induced Ca2+ release from intracellular Ca2+ stores; this longer-term effect is abolished by 2-APB, indicating a possible store operated calcium entry involvement. Of 28 HPLC fractions from E. purpurea root extracts, six induce cytosolic Ca2+ increase. Interestingly, GC-MS analysis of these fractions, as well as treatment of HEK293 cells with known individual and combined chemicals, indicates the

  11. The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

    International Nuclear Information System (INIS)

    Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their effects were significantly reduced in cells expressing a dominant-negative AhR mutant (dnAhR). Roscovitine, a chemical inhibitor of cdk2, abolished the induction of cell proliferation by BbF. However, neither BaA nor BbF modulated expression of the principal cdk inhibitor involved in maintenance of contact inhibition, p27Kip1, or pRb phosphorylation. The strongly mutagenic BaP induced apoptosis, a decrease in total cell numbers and significantly higher percentage of cells entering S-phase than either BaA or BbF. Given that BaP induced high levels of Cyclin A/cdk2 activity, downregulation of p27Kip1 and hyperphosphorylation of pRb, the accumulation of cells in S-phase was probably due to cell proliferation, although S-phase arrest due to blocked replication forks can not be excluded. Both types of effects of BaP were significantly attenuated in dnAhR cells. Transfection of WB-F344 cells with siRNA targeted against AhR decreased induction of Cyclin A induced by BbF or BaP, further supporting the role of AhR in proliferative effects of PAHs. This suggest that activation of AhR plays a significant role both in disruption of contact inhibition by weakly mutagenic PAHs and in genotoxic effects of BaP possibly leading to enhanced cell proliferation. Thus, PAHs may increase proliferative rate and the likelihood of fixation of mutations

  12. The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Andrysik, Zdenek [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Vondracek, Jan [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic) and Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic)]. E-mail: vondracek@ibp.cz; Machala, Miroslav [Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Krcmar, Pavel [Department of Chemistry and Toxicology, Veterinary Research Institute, 621 32 Brno (Czech Republic); Svihalkova-Sindlerova, Lenka [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Kranz, Anne [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Weiss, Carsten [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Faust, Dagmar [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany); Kozubik, Alois [Laboratory of Cytokinetics, Institute of Biophysics, 612 65 Brno (Czech Republic); Dietrich, Cornelia [Institute of Toxicology, Johannes Gutenberg-University, 55131 Mainz (Germany)

    2007-02-03

    Disruption of cell proliferation control by polycyclic aromatic hydrocarbons (PAHs) may contribute to their carcinogenicity. We investigated role of the aryl hydrocarbon receptor (AhR) in disruption of contact inhibition in rat liver epithelial WB-F344 'stem-like' cells, induced by the weakly mutagenic benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF) and by the strongly mutagenic benzo[a]pyrene (BaP). There were significant differences between the effects of BaA and BbF, and those of the strongly genotoxic BaP. Both BaA and BbF increased percentage of cells entering S-phase and cell numbers, associated with an increased expression of Cyclin A and Cyclin A/cdk2 complex activity. Their effects were significantly reduced in cells expressing a dominant-negative AhR mutant (dnAhR). Roscovitine, a chemical inhibitor of cdk2, abolished the induction of cell proliferation by BbF. However, neither BaA nor BbF modulated expression of the principal cdk inhibitor involved in maintenance of contact inhibition, p27{sup Kip1}, or pRb phosphorylation. The strongly mutagenic BaP induced apoptosis, a decrease in total cell numbers and significantly higher percentage of cells entering S-phase than either BaA or BbF. Given that BaP induced high levels of Cyclin A/cdk2 activity, downregulation of p27{sup Kip1} and hyperphosphorylation of pRb, the accumulation of cells in S-phase was probably due to cell proliferation, although S-phase arrest due to blocked replication forks can not be excluded. Both types of effects of BaP were significantly attenuated in dnAhR cells. Transfection of WB-F344 cells with siRNA targeted against AhR decreased induction of Cyclin A induced by BbF or BaP, further supporting the role of AhR in proliferative effects of PAHs. This suggest that activation of AhR plays a significant role both in disruption of contact inhibition by weakly mutagenic PAHs and in genotoxic effects of BaP possibly leading to enhanced cell proliferation. Thus, PAHs may increase proliferative rate and the likelihood of fixation of mutations.

  13. Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

    International Nuclear Information System (INIS)

    The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with NG-nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: ► Puerarin induced the phosphorylation of eNOS and the production of NO. ► Puerarin activated eNOS through ER-dependent PI3-kinase and Ca2+-dependent AMPK. ► Puerarin-induced NO was involved in the inhibition of NF-kB activation. ► Puerarin may help for prevention of vascular dysfunction and diabetes.

  14. The aryl hydrocarbon receptor-dependent deregulation of cell cycle control induced by polycyclic aromatic hydrocarbons in rat liver epithelial cells

    Czech Academy of Sciences Publication Activity Database

    Andrysík, Zdeněk; Vondráček, Jan; Machala, M.; Krčmář, P.; Šindlerová, Lenka; Kranz, A.; Weiss, C.; Faust, D.; Kozubík, Alois; Dietrich, C.

    2007-01-01

    Roč. 615, č. 1-2 (2007), s. 87-97. ISSN 0027-5107 R&D Projects: GA AV ČR(CZ) KJB6004407 Institutional research plan: CEZ:AV0Z50040702 Keywords : aryl hydrocarbon receptor * contact inhibition * polycyclic aromatic hydrocarbons Subject RIV: BO - Biophysics Impact factor: 4.159, year: 2007

  15. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  16. Leptin Induces a Novel Form of NMDA Receptor-Dependent LTP at Hippocampal Temporoammonic-CA1 Synapses 1,2,3

    OpenAIRE

    Luo, Xiao; McGregor, Gemma; Irving, Andrew J; Harvey, Jenni

    2015-01-01

    Abstract It is well documented that the hormone leptin regulates many central functions and that hippocampal CA1 pyramidal neurons are a key target for leptin action. Indeed, leptin modulates excitatory synaptic transmission and synaptic plasticity at the Schaffer-collateral input to CA1 neurons. However the impact of leptin on the direct temporoammonic (TA) input to CA1 neurons is not known. Here we show that leptin evokes a long-lasting increase [long-term potentiation (LTP)] in excitatory ...

  17. Retinoic acid receptor-dependent, cell-autonomous, endogenous retinoic acid signaling and its target genes in mouse collecting duct cells.

    Directory of Open Access Journals (Sweden)

    Yuen Fei Wong

    Full Text Available BACKGROUND: Vitamin A is necessary for kidney development and has also been linked to regulation of solute and water homeostasis and to protection against kidney stone disease, infection, inflammation, and scarring. Most functions of vitamin A are mediated by its main active form, all-trans retinoic acid (tRA, which binds retinoic acid receptors (RARs to modulate gene expression. We and others have recently reported that renal tRA/RAR activity is confined to the ureteric bud (UB and collecting duct (CD cell lineage, suggesting that endogenous tRA/RARs primarily act through regulating gene expression in these cells in embryonic and adult kidney, respectively. METHODOLOGY/PRINCIPAL FINDINGS: To explore target genes of endogenous tRA/RARs, we employed the mIMCD-3 mouse inner medullary CD cell line, which is a model of CD principal cells and exhibits constitutive tRA/RAR activity as CD principal cells do in vivo. Combining antagonism of RARs, inhibition of tRA synthesis, exposure to exogenous tRA, and gene expression profiling techniques, we have identified 125 genes as candidate targets and validated 20 genes that were highly regulated (Dhrs3, Sprr1a, and Ppbp were the top three. Endogenous tRA/RARs were more important in maintaining, rather than suppressing, constitutive gene expression. Although many identified genes were expressed in UBs and/or CDs, their exact functions in this cell lineage are still poorly defined. Nevertheless, gene ontology analysis suggests that these genes are involved in kidney development, renal functioning, and regulation of tRA signaling. CONCLUSIONS/SIGNIFICANCE: A rigorous approach to defining target genes for endogenous tRA/RARs has been established. At the pan-genomic level, genes regulated by endogenous tRA/RARs in a CD cell line have been catalogued for the first time. Such a catalogue will guide further studies on molecular mediators of endogenous tRA/RARs during kidney development and in relation to renal defects associated with vitamin A deficiency.

  18. Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1

    International Nuclear Information System (INIS)

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. The phytoestrogen puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicines for thousands of years. Recent studies have indicated that the estrogen receptor (ER), through interaction with p85, regulates phosphoinositide 3-kinase (PI3K) activity, revealing a physiologic, non-nuclear function of ER that may be relevant in cytoprotection. In this study, we demonstrate that the phytoestrogen puerarin inhibits tert-butyl hydroperoxide (t-BHP)-induced oxidative injury via an ER-dependent Gβ1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of Hepa1c1c7 and HepG2 cells with puerarin significantly reduced t-BHP-induced caspase-3 activation and subsequent cell death. Also, puerarin up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-BHP. Moreover, puerarin induced Nrf2 nuclear translocation, which is upstream of puerarin-induced HO-1 expression, and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Puerarin-induced up-regulation of HO-1 and cytoprotection against t-BHP were abolished by silencing Nrf2 expression with specific siRNA. Also, puerarin-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that puerarin augments cellular antioxidant defense capacity through ER-dependent HO-1 induction via the Gβ1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress

  19. Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-β/δ- and retinoic acid receptor-dependent mechanisms

    OpenAIRE

    Yao, Pei-Li; Chen, Li Ping; Dobrzański, Tomasz P.; Phillips, Dylan A.; Zhu, Bokai; Kang, Boo-Hyon; Frank J. Gonzalez; Peters, Jeffrey M.

    2015-01-01

    Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has important physiological functions in control of cell growth, lipid and glucose homeostasis, differentiation and inflammation. To investigate the role of PPARβ/δ in cancer, stable human testicular embryonal carcinoma cell lines were developed that constitutively express PPARβ/δ. Expression of PPARβ/δ caused enhanced activation of the receptor, and this significantly decreased proliferation, migration, invasion, anchorage-independent ...

  20. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion

    Energy Technology Data Exchange (ETDEWEB)

    Bui, Peter; Solaimani, Parrisa [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States); Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Wu, Xiaomeng [Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Hankinson, Oliver, E-mail: ohank@mednet.ucla.edu [Molecular Toxicology Program, University of California, Los Angeles, California 90095 (United States); Dept of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095 (United States); Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095 (United States); Molecular Biology Institute, University of California, Los Angeles, California 90095 (United States)

    2012-03-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A{sub 2} to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved. -- Highlights: ► TCDD treatment increases the levels of many eicosanoids in several mouse organs. ► Products of both the cytochrome P450 and classical lipoxygenase pathways are increased. ► These increases are dependent on the aryl hydrocarbon receptor. ► Cyp1a1, Cyp1a2 and Cyp1b1 appear to be responsible for much but not all of the increases.

  1. Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway.

    Science.gov (United States)

    Esposito, Giuseppe; Gigli, Stefano; Seguella, Luisa; Nobile, Nicola; D'Alessandro, Alessandra; Pesce, Marcella; Capoccia, Elena; Steardo, Luca; Cirillo, Carla; Cuomo, Rosario; Sarnelli, Giovanni

    2016-08-01

    Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 µM) in the presence or absence of ketoconazole (10 µM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 µM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-α (HIF-1α), p70S6K and NF-κB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool. PMID:27279570

  2. Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function.

    Science.gov (United States)

    Weiser, Michael J; Foradori, Chad D; Handa, Robert J

    2010-06-01

    Neuropsychiatric disorders such as anxiety and depression have formidable economic and societal impacts. A dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis leading to elevated endogenous glucocorticoid levels is often associated with such disorders. Chronically high glucocorticoid levels may act upon the central nucleus of the amygdala (CeA) to alter normally adaptive responses into those that are maladaptive and detrimental. In addition to glucocorticoids, other steroid hormones such as estradiol and androgens can also modify hormonal and behavioral responses to threatening stimuli. In particular, estrogen receptor beta (ERbeta) agonists have been shown to be anxiolytic. Consequently, these experiments addressed the hypothesis that the selective stimulation of glucocorticoid receptor (GR) in the CeA would increase anxiety-like behaviors and HPA axis reactivity to stress, and further, that an ERbeta agonist could modulate these effects. Young adult female Sprague-Dawley rats were ovariectomized and bilaterally implanted via stereotaxic surgery with a wax pellet containing the selective GR agonist RU28362 or a blank pellet, to a region just dorsal to the CeA. Four days later, animals were administered the ERbeta agonist S-DPN or vehicle (with four daily sc injections). Anxiety-type behaviors were measured using the elevated plus maze (EPM). Central RU28362 implants caused significantly higher anxiety-type behaviors in the EPM and greater plasma CORT levels than controls given a blank central implant. Moreover, S-DPN treated animals, regardless of type of central implant, displayed significantly lower anxiety-type behaviors and post-EPM plasma CORT levels than vehicle treated controls or vehicle treated animals implanted with RU28362. These results indicate that selective activation of GR within the CeA is anxiogenic, and peripheral administration of an ERbeta agonist can overcome this effect. These data suggest that estradiol signaling via ERbeta prevents glucocorticoid-dependent effects of the CeA on behavior and neuroendocrine function. PMID:20381466

  3. NMDA receptor-dependent GABA(B) receptor internalization via CaMKII phosphorylation of serine 867 in GABA(B1)

    Czech Academy of Sciences Publication Activity Database

    Guetg, N.; Aziz, S. A.; Holbro, N.; Tureček, Rostislav; Rose, T.; Seddik, R.; Gassmann, M.; Moes, S.; Jenoe, P.; Oertner, T.G.; Casanova, E.; Bettler, B.

    2010-01-01

    Roč. 107, č. 31 (2010), s. 13924-13929. ISSN 0027-8424 Grant ostatní: EU(XE) LSHM-CT-2005-019055 Institutional research plan: CEZ:AV0Z50390512 Keywords : gamma-aminobutyric acid * spines * trafficking Subject RIV: FH - Neurology Impact factor: 9.771, year: 2010

  4. Intranasal Administration of dsRNA Analog Poly(I:C) Induces Interferon-α Receptor-Dependent Accumulation of Antigen Experienced T Cells in the Airways

    OpenAIRE

    McNally, Beth; Willette, Meredith; Ye, Fang; Partida-Sanchez, Santiago; Flaño, Emilio

    2012-01-01

    Polyriboinosinic-polyribocytoidylic acid (pIC), a synthetic dsRNA, acts as an adjuvant that boosts immune responses and protection. Intranasal (IN) administration of pIC has recently been used to adjuvant influenza virus vaccines; however, the effects of IN pIC administration on pulmonary T cell responses remain unclear. Here we show that a single IN administered dose of dsRNA into mice induced local Th1 chemokine production in the lungs and airways, and generated a biphasic and sustained mig...

  5. Beta-Naphthoflavone and 3'-methoxy-4'-nitroflavone exert ambiguous effects on Ah receptor-dependent cell proliferation and gene expression in rat liver 'stem-like' cells

    Czech Academy of Sciences Publication Activity Database

    Zatloukalová, Jiřina; Šindlerová, Lenka; Kozubík, Alois; Krčmář, P.; Machala, M.; Vondráček, Jan

    2007-01-01

    Roč. 73, č. 10 (2007), s. 1622-1634. ISSN 0031-7012 R&D Projects: GA ČR(CZ) GA524/06/0517; GA AV ČR(CZ) KJB6004407 Institutional research plan: CEZ:AV0Z50040702 Keywords : flavony * aryl hydrocarbon receptor * cell proliferation Subject RIV: BO - Biophysics Impact factor: 1.195, year: 2007

  6. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; Eijkeren JCH van; LBO

    1997-01-01

    The interspecies extrapolation of chemical toxicity is traditionally based on the daily administered dose of the chemical. However, in the case of compounds with strong bioaccumulating properties, such as 2,3,7,8-TetraChloroDibenzo-p-Dioxin (TCDD), chronic toxicity is expected to scale better with t

  7. Modeling of Ah-receptor dependent P450 induction I. Cellular model definition and its incorporation in a PBPK model of 2,3,7,8-TCDD

    NARCIS (Netherlands)

    Zeilmaker MJ; van Eijkeren JCH; LBO

    1997-01-01

    De extrapolatie van de toxiciteit van chemische stoffen van proefdieren naar de mens vindt traditioneel plaats op basis van de dagelijks toegediende hoeveelheid van een stof. Echter, voor stoffen met sterk accumulerende eigenschappen zoals 2,3,7,8-TetraChloroDibenzo-p-Dioxine (TCDD) ligt een extrap

  8. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway

    OpenAIRE

    Ardiani, Andressa; Gameiro, Sofia R.; Kwilas, Anna R.; Donahue, Renee N.; Hodge, James W.

    2014-01-01

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone r...

  9. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway.

    Science.gov (United States)

    Ardiani, Andressa; Gameiro, Sofia R; Kwilas, Anna R; Donahue, Renee N; Hodge, James W

    2014-10-15

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone render prostate tumor cells more sensitive to T cell-mediated lysis through immunogenic modulation, and that these immunomodulatory activities are androgen receptor (AR)-dependent. In studies reported here, the NAIP gene was significantly down-regulated in human prostate tumor cells treated in vitro and in vivo with enzalutamide. Functional analysis revealed that NAIP played a critical role in inducing CTL sensitivity. Amplification of AR is a major mechanism of resistance to androgen-deprivation therapy (ADT). Here, we show that enzalutamide enhances sensitivity to immune-mediated killing of prostate tumor cells that overexpress AR. The immunomodulatory properties of enzalutamide and abiraterone provide a rationale for their use in combination with immunotherapeutic agents in CRPC, especially for patients with minimal response to enzalutamide or abiraterone alone, or for patients who have developed resistance to ADT. PMID:25344864

  10. The calcium-sensing receptor-dependent regulation of cell-cell adhesion and keratinocyte differentiation requires Rho and Filamin A

    OpenAIRE

    Tu, Chia-Ling; Chang, Wenhan; Bikle, Daniel D.

    2011-01-01

    Extracellular Ca2+ (Ca2+o) acting through the calcium-sensing receptor (CaR) induces E-cadherin mediated cell-cell adhesion and cellular signals mediating cell differentiation in epidermal keratinocytes. Previous studies indicate that the CaR regulates cell-cell adhesion through the Fyn/Src tyrosine kinases. Here we investigate whether Rho GTPase is a part of the CaR-mediated signaling cascade regulating cell adhesion and differentiation. Suppressing endogenous Rho A expression by small inter...

  11. Adenosine A{sub 2A} receptor-dependent proliferation of pulmonary endothelial cells is mediated through calcium mobilization, PI3-kinase and ERK1/2 pathways

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Aftab, E-mail: Aftab.Ahmad@UCDenver.edu [Pediatric Airway Research Center, Department of Pediatrics, Aurora, CO (United States); Schaack, Jerome B. [Department of Microbiology, University of Colorado Denver, Aurora, CO (United States); White, Carl W.; Ahmad, Shama [Pediatric Airway Research Center, Department of Pediatrics, Aurora, CO (United States)

    2013-05-10

    Highlights: •A{sub 2A} receptor-induced pulmonary endothelial growth is mediated by PI3K and ERK1/2. •Cytosolic calcium mobilization is also critical for pulmonary endothelial growth. •Effectors of A{sub 2A} receptor, like tyrosine kinases and cAMP increase PI3K/Akt signaling. •Activation of A{sub 2A} receptor can contribute to vascular remodeling. -- Abstract: Hypoxia and HIF-2α-dependent A{sub 2A} receptor expression and activation increase proliferation of human lung microvascular endothelial cells (HLMVECs). This study was undertaken to investigate the signaling mechanisms that mediate the proliferative effects of A{sub 2A} receptor. A{sub 2A} receptor-mediated proliferation of HLMVECs was inhibited by intracellular calcium chelation, and by specific inhibitors of ERK1/2 and PI3-kinase (PI3K). The adenosine A{sub 2A} receptor agonist CGS21680 caused intracellular calcium mobilization in controls and, to a greater extent, in A{sub 2A} receptor-overexpressing HLMVECs. Adenoviral-mediated A{sub 2A} receptor overexpression as well as receptor activation by CGS21680 caused increased PI3K activity and Akt phosphorylation. Cells overexpressing A{sub 2A} receptor also manifested enhanced ERK1/2 phosphorylation upon CGS21680 treatment. A{sub 2A} receptor activation also caused enhanced cAMP production. Likewise, treatment with 8Br-cAMP increased PI3K activity. Hence A{sub 2A} receptor-mediated cAMP production and PI3K and Akt phosphorylation are potential mediators of the A{sub 2A}-mediated proliferative response of HLMVECs. Cytosolic calcium mobilization and ERK1/2 phosphorylation are other critical effectors of HLMVEC proliferation and growth. These studies underscore the importance of adenosine A{sub 2A} receptor in activation of survival and proliferative pathways in pulmonary endothelial cells that are mediated through PI3K/Akt and ERK1/2 pathways.

  12. Genetic evidence for a protein-kinase-A-mediated presynaptic component in NMDA-receptor-dependent forms of long-term synaptic potentiation

    OpenAIRE

    Huang, Yan-You; Zakharenko, Stanislav S.; Schoch, Susanne; Kaeser, Pascal S.; JANZ, ROGER; Südhof, Thomas C; Siegelbaum, Steven A.; Kandel, Eric R.

    2005-01-01

    The synaptic vesicle protein Rab3A is a small GTP-binding protein that interacts with rabphilin and RIM1α, two presynaptic substrates of protein kinase A (PKA). Mice lacking RIM1α and Rab3A have a defect in PKA-dependent and NMDA receptor (NMDAR)-independent presynaptic long-term potentiation (LTP) at hippocampal mossy-fiber and cerebellar parallel-fiber synapses. In contrast, the NMDAR-dependent and PKA-independent early phase of LTP at hippocampal CA3–CA1 synapses does not require these pre...

  13. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    Directory of Open Access Journals (Sweden)

    Jacob Aude

    2011-08-01

    Full Text Available Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP or Δ9-tetrahydrocannabinol (Δ9-THC. Results After ex vivo exposure to TCDD (a highly potent AhR ligand for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold and Cyp1b1 protein (2-fold in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ9-THC once daily for 7 seven days had no effect on Cyp1b1 expression Conclusions Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

  14. Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and Substantia Nigra

    Directory of Open Access Journals (Sweden)

    A. Harkavyi

    2013-01-01

    Full Text Available Glucagon-like peptide-1 receptor (GLP-1R activation by exendin-4 (EX-4 is effective in preclinical models of Parkinson’s disease (PD and appears to promote neurogenesis even in severely lesioned rats. In the present study, we determined the effects of EX-4 on cellular BrdU incorporation in the rat subventricular zone (SVZ and substantia nigra (SN. We also determined the specificity of this effect with the GLP-1R antagonist EX-(9-39 as well as the potential role of dopamine (DA D3 receptors. Rats were administered 6-OHDA and 1 week later given EX-4 alone, with EX-(9-39 or nafadotride (D3 antagonist and BrdU. Seven days later, rats were challenged with apomorphine to evaluate circling. Extracellular DA was measured using striatal microdialysis and subsequently tissue DA measured. Tyrosine hydroxylase and BrdU were verified using immunohistochemistry. Apomorphine circling was reversed by EX-4 in lesioned rats, an effect reduced by EX-4, while both EX-(9-39 and NAF attenuated this. 6-OHDA decreased extracellular and tissue DA, both reversed by EX-4 but again attenuated by EX-(9-39 or NAF. Analysis of BrdU+ cells in the SVZ revealed increases in 6-OHDA-treated rats which were reversed by EX-4 and antagonised by either EX-(9-39 or NAF, while in the SN the opposite profile was seen.

  15. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment alters eicosanoid levels in several organs of the mouse in an aryl hydrocarbon receptor-dependent fashion

    International Nuclear Information System (INIS)

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many mammalian organs and tissues. These effects are mediated by the aryl hydrocarbon receptor (AHR). CYP1A1, CYP1A2 and CYP1B1 are upregulated by the liganded AHR. These (and other) cytochromes P450 can metabolize arachidonic acid into a variety of bioactive eicosanoids. Towards investigating a potential role of eicosanoids in TCDD toxicity, arachidonic acid, two other unsaturated long-chain fatty acids, and up to twenty-five eicosanoids were measured in five organs/tissues of male and female wild-type and Ahr null mice treated or untreated with TCDD. TCDD generally increased the levels of the four dihydroxyeicosatrienoic acids (DHETs) and (where measured) 5,6-epoxyeicosatrienoic acid and 18-, 19- and 20-hydroxyeicosatrienoic acids (HETEs) in the serum, liver, spleen and lungs, but not the heart, of both sexes, and increased the levels in the serum, liver and spleen of several metabolites that are usually considered products of lipoxygenase activity, but which may also be generated by cytochromes P450. TCDD also increased the levels of the esterified forms of these eicosanoids in the liver in parallel with the corresponding free forms. The levels of prostanoids were generally not affected by TCDD. The above changes did not occur in Ahr null mice, and are therefore mediated by the AHR. TCDD increased the mRNA levels of Cyp1a1, Cyp1a2, Cyp1b1 and the Pla2g12a form of phospholipase A2 to varying degrees in the different organs, and these increases correlated with some but not all the changes in eicosanoids levels in the organs, suggesting that other enzymes may also be involved. -- Highlights: ► TCDD treatment increases the levels of many eicosanoids in several mouse organs. ► Products of both the cytochrome P450 and classical lipoxygenase pathways are increased. ► These increases are dependent on the aryl hydrocarbon receptor. ► Cyp1a1, Cyp1a2 and Cyp1b1 appear to be responsible for much but not all of the increases.

  16. Dopamine D3 receptor-dependent changes in alpha6 GABAA subunit expression in striatum modulate anxiety-like behaviour: Responsiveness and tolerance to diazepam.

    Science.gov (United States)

    Leggio, Gian Marco; Torrisi, Sebastiano Alfio; Castorina, Alessandro; Platania, Chiara Bianca Maria; Impellizzeri, Agata Antonia Rita; Fidilio, Annamaria; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Salomone, Salvatore

    2015-09-01

    Increasing evidence indicates that central dopamine (DA) neurotransmission is involved in pathophysiology of anxiety, in particular the DA receptor subtype 3 (D3R). We previously reported that D3R null mice (D3R(-/-)) exhibit low baseline anxiety levels and that acutely administrated diazepam is more effective in D3R(-/-) than in wild type (WT) when tested in the elevated plus maze test (EPM). Here we tested the hypothesis that genetic deletion or pharmacological blockade of D3R affect GABAA subunit expression, which in turn modulates anxiety-like behaviour as well as responsiveness and tolerance to diazepam. D3R(-/-) mice exhibited tolerance to diazepam (0.5mg/kg, i.p.), assessed by EPM, as fast as after 3 day-treatment, performing similarly to untreated D3R(-/-) mice; conversely, WT exhibited tolerance to diazepam after a 14-21 day-treatment. Analysis of GABAA α6 subunit mRNA expression by qPCR in striatum showed that it was about 15-fold higher in D3R(-/-) than in WT. Diazepam treatment did not modify α6 expression in D3R(-/-), but progressively increased α6 expression in WT, to the level of untreated D3R(-/-) after 14-21 day-treatment. BDNF mRNA expression in striatum was remarkably (>10-fold) increased after 3 days of diazepam-treatment in both WT and D3R(-/-); such expression level, however, slowly declined below control levels, by 14-21 days. Following a 7 day-treatment with the selective D3R antagonist SB277011A, WT exhibited a fast tolerance to diazepam accompanied by a robust increase in α6 subunit expression. In conclusion, genetic deletion or pharmacological blockade of D3R accelerate the development of tolerance to repeated administrations of diazepam and increase α6 subunit expression, a GABAA subunit that has been linked to diazepam insensitivity. Modulation of GABAA receptor by DA transmission may be involved in the mechanisms of anxiety and, if occurring in humans, may have therapeutic relevance following repeated use of drugs targeting D3R. PMID:25482686

  17. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    Directory of Open Access Journals (Sweden)

    Chloë R McDonald

    2015-09-01

    Full Text Available The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

  18. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    Science.gov (United States)

    McDonald, Chloë R; Cahill, Lindsay S; Ho, Keith T; Yang, Jimmy; Kim, Hani; Silver, Karlee L; Ward, Peter A; Mount, Howard T; Liles, W Conrad; Sled, John G; Kain, Kevin C

    2015-09-01

    The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention. PMID:26402732

  19. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

    Science.gov (United States)

    Safari, Tahereh; Nematbakhsh, Mehdi; Evans, Roger G.; Denton, Kate M.

    2015-01-01

    Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7 ± 1.9% in estradiol-treated rats but only by 27.3 ± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen. PMID:26681937

  20. TRPM4-dependent post-synaptic depolarization is essential for the induction of NMDA receptor-dependent LTP in CA1 hippocampal neurons.

    Science.gov (United States)

    Menigoz, Aurélie; Ahmed, Tariq; Sabanov, Victor; Philippaert, Koenraad; Pinto, Silvia; Kerselaers, Sara; Segal, Andrei; Freichel, Marc; Voets, Thomas; Nilius, Bernd; Vennekens, Rudi; Balschun, Detlef

    2016-04-01

    TRPM4 is a calcium-activated but calcium-impermeable non-selective cation (CAN) channel. Previous studies have shown that TRPM4 is an important regulator of Ca(2+)-dependent changes in membrane potential in excitable and non-excitable cell types. However, its physiological significance in neurons of the central nervous system remained unclear. Here, we report that TRPM4 proteins form a CAN channel in CA1 neurons of the hippocampus and we show that TRPM4 is an essential co-activator of N-methyl-D-aspartate (NMDA) receptors (NMDAR) during the induction of long-term potentiation (LTP). Disrupting the Trpm4 gene in mice specifically eliminates NMDAR-dependent LTP, while basal synaptic transmission, short-term plasticity, and NMDAR-dependent long-term depression are unchanged. The induction of LTP in Trpm4 (-/-) neurons was rescued by facilitating NMDA receptor activation or post-synaptic membrane depolarization. Accordingly, we obtained normal LTP in Trpm4 (-/-) neurons in a pairing protocol, where post-synaptic depolarization was applied in parallel to pre-synaptic stimulation. Taken together, our data are consistent with a novel model of LTP induction in CA1 hippocampal neurons, in which TRPM4 is an essential player in a feed-forward loop that generates the post-synaptic membrane depolarization which is necessary to fully activate NMDA receptors during the induction of LTP but which is dispensable for the induction of long-term depression (LTD). These results have important implications for the understanding of the induction process of LTP and the development of nootropic medication. PMID:26631168

  1. Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways

    Directory of Open Access Journals (Sweden)

    Kummer Wolfgang

    2005-05-01

    Full Text Available Abstract Background In peripheral airways, acetylcholine induces contraction via activation of muscarinic M2-and M3-receptor subtypes (M2R and M3R. Cholinergic hypersensitivity is associated with chronic obstructive pulmonary disease and asthma, and therefore the identification of muscarinic signaling pathways are of great therapeutic interest. A pathway that has been shown to be activated via MR and to increase [Ca2+]i includes the activation of sphingosine kinases (SPHK and the generation of the bioactive sphingolipid sphingosine 1-phosphate (S1P. Whether the SPHK/S1P signaling pathway is integrated in the muscarinic control of peripheral airways is not known. Methods To address this issue, we studied precision cut lung slices derived from FVB and M2R-KO and M3R-KO mice. Results In peripheral airways of FVB, wild-type, and MR-deficient mice, SPHK1 was mainly localized to smooth muscle. Muscarine induced a constriction in all investigated mouse strains which was reduced by inhibition of SPHK using D, L-threo-dihydrosphingosine (DHS and N, N-dimethyl-sphingosine (DMS but not by N-acetylsphingosine (N-AcS, a structurally related agent that does not affect SPHK function. The initial phase of constriction was nearly absent in peripheral airways of M3R-KO mice when SPHK was inhibited by DHS and DMS but was unaffected in M2R-KO mice. Quantitative RT-PCR revealed that the disruption of the M2R and M3R genes had no significant effect on the expression levels of the SPHK1-isoform in peripheral airways. Conclusion These results demonstrate that the SPHK/S1P signaling pathway contributes to cholinergic constriction of murine peripheral airways. In addition, our data strongly suggest that SPHK is activated via the M2R. Given the important role of muscarinic mechanisms in pulmonary disease, these findings should be of considerable therapeutic relevance.

  2. A conserved aspartic acid is important for agonist (VUAA1 and odorant/tuning receptor-dependent activation of the insect odorant co-receptor (Orco.

    Directory of Open Access Journals (Sweden)

    Brijesh N Kumar

    Full Text Available Insect odorant receptors function as heteromeric odorant-gated cation channels comprising a conventional odorant-sensitive tuning receptor, and a conserved co-receptor (Orco. An Orco agonist, VUAA1, is able to activate both heteromeric and homomeric Orco-containing channels. Very little is known about specific residues in Orco that contribute to cation permeability and gating. We investigated the importance of two conserved Asp residues, one in each of transmembrane domains 5 and 7, for channel function by mutagenesis. Drosophila melanogaster Orco and its substitution mutants were expressed in HEK cells and VUAA1-stimulated channel activity was determined by Ca(2+ influx and whole-cell patch clamp electrophysiology. Substitution of D466 in transmembrane 7 with amino acids other than glutamic acid resulted in a substantial reduction in channel activity. The D466E Orco substitution mutant was ~2 times more sensitive to VUAA1. The permeability of the D466E Orco mutant to cations was unchanged relative to wild-type Orco. When D466E Orco is co-expressed with a conventional tuning odorant receptor, the heteromeric complex also shows increased sensitivity to an odorant. Thus, the effect of the D466E mutation is not specific to VUAA1 agonism or dependent on homomeric Orco assembly. We suggest the gain-of-activation characteristic of the D466E mutant identifies an amino acid that is likely to be important for activation of both heteromeric and homomeric insect odorant receptor channels.

  3. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

    OpenAIRE

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K.; Fiacco, Todd A.

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techn...

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

    International Nuclear Information System (INIS)

    Highlights: → We analyzed Phosphatidylinositol 5-phosphate kinase IIβ (PIPKIIβ) function in cancer. → PIPKIIβ is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. → PIPKIIβ suppresses cellular motility through E-cadherin induction in SW480 cells. → Nuclear PIP2 but not plasma membrane-localized PIP2 mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) has anti-cancer activity in several colon cancers. 1α,25(OH)2D3 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 (PIPKIIβ) but not PIPKIIα 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 (PLCδ1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLCδ1 PHD inhibited 1α,25(OH)2D3-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P2 production mediates E-cadherin expression through PIPKIIβ in a VDR-dependent manner. PIPKIIβ is also involved in the suppression of the cell motility induced by 1α,25(OH)2D3. These results indicate that PIPKIIβ-mediated PI(4,5)P2 signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

  5. Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1.

    Science.gov (United States)

    Lewis, George K; Finzi, Andrés; DeVico, Anthony L; Pazgier, Marzena

    2015-09-01

    The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus aggregation, are known. The interplay between virus neutralization and Fc-mediated effector function in protection against HIV-1 is complex and only partially understood. Passive immunization studies using potent broadly neutralizing antibodies (bnAbs) show that both neutralization and Fc-mediated effector function provides the widest dynamic range of protection; however, a vaccine to elicit these responses remains elusive. By contrast, active immunization studies in both humans and non-human primates using HIV-1 vaccine candidates suggest that weakly neutralizing or non-neutralizing antibodies can protect by Fc-mediated effector function, albeit with a much lower dynamic range seen for passive immunization with bnAbs. HIV-1 has evolved mechanisms to evade each type of antibody-mediated protection that must be countered by a successful AIDS vaccine. Overcoming the hurdles required to elicit bnAbs has become a major focus of HIV-1 vaccine development. Here, we discuss a less studied problem, the structural basis of protection (and its evasion) by antibodies that protect only by potent Fc-mediated effector function. PMID:26393642

  6. P2X receptor-dependent erythrocyte damage by α-hemolysin from Escherichia coli triggers phagocytosis by THP-1 cells

    DEFF Research Database (Denmark)

    Fagerberg, Steen Kåre; Skals, Marianne Gerberg; Leipziger, Jens Georg;

    2013-01-01

    found the HlyA to very potently trigger phagocytosis of erythrocytes by THP-1 cells. The HlyA-induced phagocytosis was prevented by inhibition of KCa3.1, which is known to reduce PS-exposure in human erythrocytes subjected to both ionomycin and HlyA. Moreover, we show that P2X receptor inhibition, which...

  7. CCAAT/enhancer-binding protein δ facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner

    OpenAIRE

    Duitman, JanWillem; Schouten, Marcel; Groot, Angelique P.; Borensztajn, Keren S.; Daalhuisen, Joost B.; Florquin, Sandrine; van der Poll, Tom; Spek, C Arnold

    2012-01-01

    CCAAT/enhancer-binding protein δ (C/EBPδ) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBPδ levels increase rapidly after a proinflammatory stimulus, and increasing C/EBPδ levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBPδ in host defense in community-acquired pneumococcal pneumonia. We show that C/EBPδ−/− mice are relatively resistant to pneumococcal pneumonia, as ind...

  8. Pregnenolone sulfate induces NMDA receptor dependent release of dopamIne from synaptIc termInals in the striatum

    OpenAIRE

    Whittaker, Matthew T.; Gibbs, Terrell T.; Farb, David H.

    2008-01-01

    Neuromodulators that alter the balance between lower-frequency glutamate-mediated excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABAA receptor mediated synaptic transmission. The enzymes necessary for PS synthesis and deg...

  9. Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease.

    Directory of Open Access Journals (Sweden)

    Gang Chen

    Full Text Available CD8+ T cells (Cytotoxic T cells, Tc are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD. However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg subsets, especially by modulating muscarinic acetylcholine receptors (MRs, has yet to be well elucidated.Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15, healthy smokers (n = 15 and COPD patients (n = 18 were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs.While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs.The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation.

  10. Fasciola hepatica tegumental antigens induce anergic-like T cells via dendritic cells in a mannose receptor-dependent manner.

    Science.gov (United States)

    Aldridge, Allison; O'Neill, Sandra M

    2016-05-01

    FoxP3(+) Treg cells and anergic T cells are the two regulatory phenotypes of T-cell responses associated with helminth infection. Here, we examine the T-cell responses in mice during Fasciola hepatica infection, and to its tegumental coat antigens (FhTeg) that are shed from the fluke every 2-3 h. FhTeg comprises a rich source of glycoproteins, mainly oligomannose N-glycans that bind to mannose receptor. This study demonstrated a novel mechanism for the T-cell unresponsiveness observed during F. hepatica infection and after injection with FhTeg. Markers of T-cell anergy, such as GRAIL, EGR2, ICOS, and ITCH, are enhanced amongst CD4(+) T-cell populations during infection and following FhTeg injection. This is characterized by a lack of cytokine responses and reduced proliferative activity, which can be reversed with the addition of IL-2. FhTeg-activated dendritic cells (DCs) suppress T cells in vitro as measured by enhanced GRAIL and CTLA4 by RNA and suppressed cytokine expression in anti-CD3 stimulated CD4(+) T cells. FhTeg-treated DCs have enhanced MR expression, which is critical for DC-CD4(+) T-cell communication. Taken together, this study presents markers of anergy in a mouse model of F. hepatica infection, and improves our understanding of host-pathogen interactions and how helminths modulate host immunity. PMID:26931640

  11. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

    OpenAIRE

    Jacob Aude; Hartz Anika MS; Potin Sophie; Coumoul Xavier; Yousif Salah; Scherrmann Jean-Michel; Bauer Björn; Declèves Xavier

    2011-01-01

    Abstract Background AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels. Methods Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of A...

  12. Effect of benzophenone-1 and octylphenol on the regulation of epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in estrogen receptor expressing ovarian cancer cells.

    Science.gov (United States)

    Shin, Sam; Go, Ryeo-Eun; Kim, Cho-Won; Hwang, Kyung-A; Nam, Ki-Hoan; Choi, Kyung-Chul

    2016-07-01

    Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17β-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10(-6) M) and OP (10(-6) M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10(-9) M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells. PMID:27145024

  13. 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: zkouchi@toyaku.ac.jp [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)

    2011-05-20

    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.

  14. Personality Traits of Expert Teachers of Students with EBD: Clarifying a Teacher's X-Factor

    Science.gov (United States)

    Buttner, Svenja; Pijl, Sip Jan; Bijstra, Jan; Van den Bosch, Els

    2016-01-01

    Teaching students with emotional and behavioural difficulties (EBD) is a challenge for many teachers in inclusive education. Much research has been done to find out what differentiates expert teachers from their less skilled colleagues. Recent evidence points to personality as an underlying core factor influencing teacher performance. In this…

  15. Clarifying the importance of trust in organizations as a component of effective work relationships

    OpenAIRE

    Sousa-Lima, M.; Michel, J. W.; Caetano, A.

    2013-01-01

    Organizational trust is an important element of an organization's long-term success, as it is a central component of effective work relationships. This study examines the extent to which one's trust in the organization mediates the relationship between three drivers of social exchange relationships and three attitudinal outcomes. The results from a sample of 1,300 manufacturing employees revealed that trust in the organization partially mediated the relationship between perceived supervisor s...

  16. Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum

    Science.gov (United States)

    Tovar-Moll, Fernanda; Monteiro, Myriam; Andrade, Juliana; Bramati, Ivanei E.; Vianna-Barbosa, Rodrigo; Marins, Theo; Rodrigues, Erika; Dantas, Natalia; Behrens, Timothy E. J.; de Oliveira-Souza, Ricardo; Moll, Jorge; Lent, Roberto

    2014-01-01

    Why do humans born without the corpus callosum, the major interhemispheric commissure, lack the disconnection syndrome classically described in callosotomized patients? This paradox was discovered by Nobel laureate Roger Sperry in 1968, and has remained unsolved since then. To tackle the hypothesis that alternative neural pathways could explain this puzzle, we investigated patients with callosal dysgenesis using structural and functional neuroimaging, as well as neuropsychological assessments. We identified two anomalous white-matter tracts by deterministic and probabilistic tractography, and provide supporting resting-state functional neuroimaging and neuropsychological evidence for their functional role in preserved interhemispheric transfer of complex tactile information, such as object recognition. These compensatory pathways connect the homotopic posterior parietal cortical areas (Brodmann areas 39 and surroundings) via the posterior and anterior commissures. We propose that anomalous brain circuitry of callosal dysgenesis is determined by long-distance plasticity, a set of hardware changes occurring in the developing brain after pathological interference. So far unknown, these pathological changes somehow divert growing axons away from the dorsal midline, creating alternative tracts through the ventral forebrain and the dorsal midbrain midline, with partial compensatory effects to the interhemispheric transfer of cortical function. PMID:24821757

  17. No longer in suspense: Clarifying the Human Rights Jurisdiction of the SADC Tribunal

    OpenAIRE

    Moses R Phooko

    2015-01-01

    The Southern African Development Community Tribunal's (SADC Tribunal) decision in the matter of Mike Campbell (Pvt) Ltd v Republic of Zimbabwe 2008 SADCT 2 (28 November 2008) demonstrated its ability to utilise the principles contained in the Treaty of the Southern African Development Community when it ruled that it had the power and competency to adjudicate over a human rights case. The aforesaid decision was hailed by many scholars as a progressive judgment in the SADC region that would pro...

  18. Clarifying Observed Relationships Between Protective Behavioral Strategies and Alcohol Outcomes: The Importance of Response Options

    OpenAIRE

    Braitman, Abby L.; Henson, James M.; Carey, Kate B.

    2014-01-01

    Protective behavioral strategies (PBS), or harm-reduction behaviors that can potentially reduce alcohol consumption or associated problems, have been assessed in varied ways throughout the literature. Existing scales vary in focus (i.e., broad vs. narrow), and importantly, in response options (i.e., absolute frequency vs. contingent frequency). Absolute frequency conflates PBS use with number of drinking occasions, resulting in inconsistencies in the relationship between PBS use and alcohol o...

  19. Clarifying the Issues of Technology and Its Position in Theism

    OpenAIRE

    masomeh salari rad; Monireh Faridi khorshidi

    2013-01-01

    The question of technology, due to inability of a branch of knowledge to answer our contemporary important questions, is one of the interdisciplinary studies that was introduced since the second half of the 20th century to see the human world from a critical viewpoint. The issue appeared first in philosophy of technology as the issue of the relation between philosophy and technology. Martin Heidegger, the most important feature of contemporary philosophy distinguishes the philosophical delibe...

  20. Acid rain effects on aluminum mobilization clarified by inclusion of strong organic acids

    Science.gov (United States)

    Lawrence, G.B.; Sutherland, J.W.; Boylen, C.W.; Nierzwicki-Bauer, S. W.; Momen, B.; Baldigo, Barry P.; Simonin, H.A.

    2007-01-01

    Assessments of acidic deposition effects on aquatic ecosystems have often been hindered by complications from naturally occurring organic acidity. Measurements of pH and ANCG, the most commonly used indicators of chemical effects, can be substantially influenced by the presence of organic acids. Relationships between pH and inorganic Al, which is toxic to many forms of aquatic biota, are also altered by organic acids. However, when inorganic Al concentrations are plotted against ANC (the sum of Ca2+, Mg 2+, Na+, and K+, minus SO42-, NO3-, and Cl-), a distinct threshold for Al mobilization becomes apparent. If the concentration of strong organic anions is included as a negative component of ANC, the threshold occurs at an ANC value of approximately zero, the value expected from theoretical charge balance constraints. This adjusted ANC is termed the base-cation surplus. The threshold relationship between the base-cation surplus and Al was shown with data from approximately 200 streams in the Adirondack region of New York, during periods with low and high dissolved organic carbon concentrations, and for an additional stream from the Catskill region of New York. These results indicate that (1) strong organic anions can contribute to the mobilization of inorganic Al in combination with SO42- and NO 3-, and (2) the presence of inorganic Al in surface waters is an unambiguous indication of acidic deposition effects. ?? 2007 American Chemical Society.

  1. 77 FR 29935 - 2012 Technical Corrections, Clarifying and Other Amendments to the Greenhouse Gas Reporting Rule...

    Science.gov (United States)

    2012-05-21

    ... distribution facilities. 211 Extractors of crude petroleum and natural gas. 211112 Natural gas liquid... Reporting Tool EPA U.S. Environmental Protection Agency FR Federal Register GHG greenhouse gas GHGRP... October 30, 2009 (74 FR 56260, hereafter referred to as the ``2009 final rule'' or ``Part 98''). The...

  2. Applications of Structural Mass Spectrometry to Metabolomics: Clarifying Bond Specific Spectral Signatures with Isotope Edited Spectroscopy

    Science.gov (United States)

    Gorlova, Olga; Wolke, Conrad T.; Fournier, Joseph; Colvin, Sean; Johnson, Mark; Miller, Scott

    2015-06-01

    Comprehensive FTIR, MS/MS and NMR of pharmaceuticals are generally readily available but characterization of their metabolites has been an obstacle. Atorvastatin is a statin drug responsible for the maintenance of cholesterol in the body. Diovan is an angiostensin receptor antagonist used to treat high blood pressure and congestive heart failure. The field of metabolomics, however, is struggling to obtain the identity of their structures. We implement mass spectrometry with cryogenic ion spectroscopy to study gaseous ions of the desired metabolites which, in combination, not only identify the mass of the metabolite but also elucidate their structures through isotope-specific infrared spectroscopy.

  3. An Attempt to Clarify the Concept of Rational Suicide: A Commentary on Lokhandwala and Westefeld.

    Science.gov (United States)

    Werth, James L., Jr.

    1998-01-01

    Alternative perspectives are presented on the issue of rational suicide. An operational definition is provided; areas needing clarification are highlighted. The meta-issues are reviewed with regard to specific points raised by Lokhandwala and Westefeld. Concerns with research often cited to question the possibility of rational suicide are…

  4. 77 FR 51477 - 2012 Technical Corrections, Clarifying and Other Amendments to the Greenhouse Gas Reporting Rule...

    Science.gov (United States)

    2012-08-24

    ... is finalizing the amendments to both the centrifugal compressor and reciprocating compressor emission... finalizing a limited set of additional corrections for both the centrifugal and reciprocating compressor... reciprocating compressor (Equation W-27) for each of the mode-source combination in cubic feet. Similarly,...

  5. Clarifying Co-Rumination: Associations with Internalizing Symptoms and Romantic Involvement among Adolescent Girls

    Science.gov (United States)

    Starr, Lisa R.; Davila, Joanne

    2009-01-01

    Co-rumination, or excessive discussion of problems within friendships, has been associated with internalizing symptoms and is especially prevalent among adolescent girls. Eighty-three early adolescent girls participated in a prospective study further examining this construct. Co-rumination was positively correlated with depressive symptoms and…

  6. Swift Observations of Gamma-Ray Burst Pulse Shapes: GRB Pulse Spectral Evolution Clarified

    Science.gov (United States)

    Hakkila, Jon; Lien, Amy; Sakamoto, Takanori; Morris, David; Neff, James E.; Giblin, Timothy W.

    2015-12-01

    Isolated Swift gamma-ray burst (GRB) pulses, like their higher-energy BATSE counterparts, emit the bulk of their pulsed emission as a hard-to-soft component that can be fitted by the Norris et al. empirical pulse model. This signal is overlaid by a fainter, three-peaked signal that can be modeled by the residual fit of Hakkila & Preece: the two fits combine to reproduce GRB pulses with distinctive three-peaked shapes. The precursor peak appears on or before the pulse rise and is often the hardest component, the central peak is the brightest, and the decay peak converts exponentially decaying emission into a long, soft, power-law tail. Accounting for systematic instrumental differences, the general characteristics of the fitted pulses are remarkably similar. Isolated GRB pulses are dominated by hard-to-soft evolution; this is more pronounced for asymmetric pulses than for symmetric ones. Isolated GRB pulses can also exhibit intensity tracking behaviors that, when observed, are tied to the timing of the three peaks: pulses with the largest maximum hardnesses are hardest during the precursor, those with smaller maximum hardnesses are hardest during the central peak, and all pulses can re-harden during the central peak and/or during the decay peak. Since these behaviors are essentially seen in all isolated pulses, the distinction between “hard-to-soft and “intensity-tracking” pulses really no longer applies. Additionally, the triple-peaked nature of isolated GRB pulses seems to indicate that energy is injected on three separate occasions during the pulse duration: theoretical pulse models need to account for this.

  7. An attempt for clarifying some complications due to induced abortion by means of radioisotopes

    International Nuclear Information System (INIS)

    The possibility and degree of tissue and plasmic elements invasion and deportation during induced abortion depending on the operative method used are studied comparatively. To this end before the operation a lavage of the uterine cavity with technecium was performed. Ten minutes later blood radionuclide concentration was measured. A greater radionuclide blood concentration was observed after abortion made after the aspiration method than after abortion by the classical abrasive method. This indicates a greater invasion and deportation of tissue and plasmic elements from the embryo in the mother's blood circulation and is a substantial failure of the aspiration method which accounts for the more frequently occurring protracted menstruation disorders in such cases. (A.B.)

  8. [Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration].

    Science.gov (United States)

    Zhao, Jingke; Sun, Xiaodong

    2015-11-01

    Anti-VEGF therapy is currently one of the main treatments for neovascular age-related macular degeneration (nAMD). Clinically, patients under standardized anti-VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies. PMID:26850580

  9. American Psychologist Task Force Report: Clarifying Mission, Coverage, Communication, and Review Process.

    Science.gov (United States)

    Zimbardo, Philip G.

    2002-01-01

    An American Psychological Association task force reviewed the role and function of "American Psychologist," (AP) focusing on its coverage domain and issues related to its editorial review process. This report examines AP editorial domain, AP editorial instructions, AP editorship, communications within the AP editorial process, use of ad hoc action…

  10. Clarifying Slow Roll Inflation and the Quantum Corrections to the Observable Power Spectra

    CERN Document Server

    Boyanovsky, D; Sánchez, N G

    2006-01-01

    Slow-roll inflation can be studied as an effective field theory. The form of the inflaton potential consistent with the data is V(phi) = N M^4 w(phi/[sqrt{N} M_{Pl}]) where phi is the inflaton field, M is the inflation energy scale, and N ~ 50 the number of efolds. The dimensionless function w(chi) and field chi are O(1). This form of the potential encodes the slow-roll expansion as an expansion in 1/N.A The Hubble parameter, inflaton mass and non-linear couplings are of the see-saw form in terms of M/M_{Pl}. The quartic coupling is lambda~1/N (M/M_{Pl})^4. The smallness of the non-linear couplings is not a result of fine tuning but a natural consequence of the validity of the effective field theory and slow roll approximation. Quantum corrections to slow roll inflation are computed and turn to be an expansion in powers (H/M_{Pl})^2. The corrections to the inflaton effective potential and its equation of motion are computed, as well as the quantum corrections to the observable power spectra. The near scale in...

  11. Urgent Protection versus Chronic Need: Clarifying the Dual Mandate of Child Welfare Services across Canada

    Directory of Open Access Journals (Sweden)

    Nico Trocmé

    2014-08-01

    Full Text Available This study analyzed data from the 1998, 2003 and 2008 Canadian Incidence Study of reported child abuse and neglect (CIS and compared the profile of children who were reported for an urgent protection investigation versus any other investigation or assessment. As a proportion of all investigations, urgent protection cases have dropped from 28% of all investigations in 1998, to 19% in 2003, to 15% in 2008. Results from the CIS-2008 analysis revealed that 7% of cases involved neglect of a child under four, 4% of cases involved sexual abuse, 2% of cases involved physical abuse of a child under four and 1% of cases involved children who had sustained severe enough physical harm that medical treatment was required. The other 85% of cases of investigated maltreatment involved situations where concerns appear to focus less on immediate safety and more on the long-term effects of a range of family related problems. These findings underscore the importance of considering the dual mandate of child welfare mandates across Canada: intervening to assure the urgent protection and safety of the child versus intervening to promote the development and well-being of the child.

  12. Evaluating for Public Value: Clarifying the Relationship Between Public Value and Program Evaluation

    Directory of Open Access Journals (Sweden)

    Scott A. Chazdon

    2014-06-01

    Full Text Available This article presents a framework that integrates the concept of public value, known primarily in public administration and public sector economics circles, with program evaluation. We identify four components of this Evaluating for Public Value (EPV framework. These are: (1 the “publicness” of the participant and the participant’s goals; (2 organizational credibility, which incorporates participant and stakeholder perceptions of the program, as well as the delivery organization; (3 program outcomes, with an emphasis on the value gained by program participants; and (4 broader impacts. The notion of measuring a program’s publicness is perhaps the most novel aspect of this framework. Extension professionals tend to think about who they are serving when they design programs, but often do not revisit these issues as part of program evaluation. This paper also provides guidance on strategies for measuring broader impacts, such as use of the community capitals framework or measurement of social capital creation.

  13. Evaluating for Public Value: Clarifying the Relationship Between Public Value and Program Evaluation

    OpenAIRE

    Scott A. Chazdon; Nathan Paine

    2014-01-01

    This article presents a framework that integrates the concept of public value, known primarily in public administration and public sector economics circles, with program evaluation. We identify four components of this Evaluating for Public Value (EPV) framework. These are: (1) the “publicness” of the participant and the participant’s goals; (2) organizational credibility, which incorporates participant and stakeholder perceptions of the program, as well as the delivery organization; (3) progr...

  14. Clarifying the Role of Defensive Reactivity Deficits in Psychopathy and Antisocial Personality Using Startle Reflex Methodology

    OpenAIRE

    Vaidyanathan, Uma; Hall, Jason R.; Patrick, Christopher J.; Bernat, Edward M.

    2011-01-01

    Prior research has demonstrated deficits in defensive reactivity (indexed by potentiation of the startle blink reflex) in psychopathic individuals. However, the basis of this association remains unclear, as diagnostic criteria for psychopathy encompass two distinct phenotypic components that may reflect differing neurobiological mechanisms – an affective-interpersonal component, and an antisocial deviance component. Likewise, the role of defensive response deficits in antisocial personality d...

  15. Simplified numerical model for clarifying scaling behavior in the intermediate dispersion regime in homogeneous porous media

    CERN Document Server

    van Milligen, B Ph

    2014-01-01

    The dispersion of solute in porous media shows a non-linear increase in the transition from diffusion to advection dominated dispersion as the flow velocity is raised. In the past, the behavior in this intermediate regime has been explained with a variety of models. {We present and use a simplified numerical model which does not contain any turbulence, Taylor dispersion, or fractality. With it, we show that the non-linearity in the intermediate regime nevertheless occurs. Furthermore,} we show that that the intermediate regime can be regarded as a phase transition between random, diffusive transport at low flow velocity and ordered transport controlled by the geometry of the pore space at high flow velocities. This phase transition explains the first-order behavior in the intermediate regime. A new quantifier, the ratio of the amount of solute in dominantly advective versus dominantly diffusive pore channels, plays the role of `order parameter' of this phase transition. Taylor dispersion, often invoked to exp...

  16. Urgent Protection versus Chronic Need: Clarifying the Dual Mandate of Child Welfare Services across Canada

    OpenAIRE

    Nico Trocmé; Alicia Kyte; Vandna Sinha; Barbara Fallon

    2014-01-01

    This study analyzed data from the 1998, 2003 and 2008 Canadian Incidence Study of reported child abuse and neglect (CIS) and compared the profile of children who were reported for an urgent protection investigation versus any other investigation or assessment. As a proportion of all investigations, urgent protection cases have dropped from 28% of all investigations in 1998, to 19% in 2003, to 15% in 2008. Results from the CIS-2008 analysis revealed that 7% of cases involved neglect of a child...

  17. Clarifying hierarchical age-period-cohort models: A rejoinder to Bell and Jones.

    Science.gov (United States)

    Reither, Eric N; Land, Kenneth C; Jeon, Sun Y; Powers, Daniel A; Masters, Ryan K; Zheng, Hui; Hardy, Melissa A; Keyes, Katherine M; Fu, Qiang; Hanson, Heidi A; Smith, Ken R; Utz, Rebecca L; Yang, Y Claire

    2015-11-01

    Previously, Reither et al. (2015) demonstrated that hierarchical age-period-cohort (HAPC) models perform well when basic assumptions are satisfied. To contest this finding, Bell and Jones (2015) invent a data generating process (DGP) that borrows age, period and cohort effects from different equations in Reither et al. (2015). When HAPC models applied to data simulated from this DGP fail to recover the patterning of APC effects, B&J reiterate their view that these models provide "misleading evidence dressed up as science." Despite such strong words, B&J show no curiosity about their own simulated data--and therefore once again misapply HAPC models to data that violate important assumptions. In this response, we illustrate how a careful analyst could have used simple descriptive plots and model selection statistics to verify that (a) period effects are not present in these data, and (b) age and cohort effects are conflated. By accounting for the characteristics of B&J's artificial data structure, we successfully recover the "true" DGP through an appropriately specified model. We conclude that B&Js main contribution to science is to remind analysts that APC models will fail in the presence of exact algebraic effects (i.e., effects with no random/stochastic components), and when collinear temporal dimensions are included without taking special care in the modeling process. The expanded list of coauthors on this commentary represents an emerging consensus among APC scholars that B&J's essential strategy--testing HAPC models with data simulated from contrived DGPs that violate important assumptions--is not a productive way to advance the discussion about innovative APC methods in epidemiology and the social sciences. PMID:26277370

  18. Causal networks clarify productivity-richness interrelations, bivariate plots do not

    Science.gov (United States)

    Grace, James B.; Adler, Peter B.; Harpole, W. Stanley; Borer, Elizabeth T.; Seabloom, Eric W.

    2014-01-01

    Perhaps no other pair of variables in ecology has generated as much discussion as species richness and ecosystem productivity, as illustrated by the reactions by Pierce (2013) and others to Adler et al.'s (2011) report that empirical patterns are weak and inconsistent. Adler et al. (2011) argued we need to move beyond a focus on simplistic bivariate relationships and test mechanistic, multivariate causal hypotheses. We feel the continuing debate over productivity–richness relationships (PRRs) provides a focused context for illustrating the fundamental difficulties of using bivariate relationships to gain scientific understanding.

  19. Clarifying assumptions to enhance our understanding and assessment of clinical reasoning.

    Science.gov (United States)

    Durning, Steven J; Artino, Anthony R; Schuwirth, Lambert; van der Vleuten, Cees

    2013-04-01

    Deciding on a diagnosis and treatment is essential to the practice of medicine. Developing competence in these clinical reasoning processes, commonly referred to as diagnostic and therapeutic reasoning, respectively, is required for physician success. Clinical reasoning has been a topic of research for several decades, and much has been learned. However, there still exists no clear consensus regarding what clinical reasoning entails, let alone how it might best be taught, how it should be assessed, and the research and practice implications therein.In this article, the authors first discuss two contrasting epistemological views of clinical reasoning and related conceptual frameworks. They then outline four different theoretical frameworks held by medical educators that the authors believe guide educators' views on the topic, knowingly or not. Within each theoretical framework, the authors begin with a definition of clinical reasoning (from that viewpoint) and then discuss learning, assessment, and research implications. The authors believe these epistemologies and four theoretical frameworks also apply to other concepts (or "competencies") in medical education.The authors also maintain that clinical reasoning encompasses the mental processes and behaviors that are shared (or evolve) between the patient, physician, and the environment (i.e., practice setting). Clinical reasoning thus incorporates components of all three factors (patient, physician, environment). The authors conclude by outlining practical implications and potential future areas for research. PMID:23425980

  20. Patient Empowerment and its neighbours: clarifying the boundaries and their mutual relationships.

    Science.gov (United States)

    Fumagalli, Lia Paola; Radaelli, Giovanni; Lettieri, Emanuele; Bertele', Paolo; Masella, Cristina

    2015-03-01

    Patients are increasingly encouraged to become active players in self-care and shared decision-making. Such attention has led to an explosion of terms - empowerment, engagement, enablement, participation, involvement, activation - each having multiple and overlapping meanings. The resulting ambiguity inhibits an effective use of existing evidence. This study addresses this problem by delivering an evidence-based concept mapping of these terms that delineates their boundaries and mutual relationships. We implemented a literature review of contributions associated to patient empowerment, activation, engagement, enablement, involvement, and participation. We implemented a keyword-based strategy collecting contributions published in PubMed database in the 1990-2013 timespan. A total of 286 articles were selected. The results identified three distinct interpretation of patient empowerment, either conceived as a process, an emergent state or as a participative behaviour. Most definitions recognize empowerment as the combination of ability, motivation and power opportunities. A concept mapping for patient empowerment, activation, enablement, engagement, involvement, and participation was then delineated. The concept map consists of two dimensions (nature and focus of concept) and marks distinctions and relationships between the concepts. The resulting concept map paves the way for a number of future research directions that can help improve our understanding of the antecedents and consequences of patient empowerment policies. PMID:25467286

  1. Clarifying anti-reflexivity: conservative opposition to impact science and scientific evidence

    Science.gov (United States)

    Dunlap, Riley E.

    2014-01-01

    The recent study reported by McCright et al (2013 Environ. Res. Lett. 8 044029) extends current research on conservatives’ distrust of science by distinguishing between public trust in production versus impact scientists (i.e. those whose work yields new technologies and marketable products versus those assessing the health and environmental impacts of such technologies and products). As expected, they find that conservatives are significantly less trustful of impact scientists but somewhat more trustful of production scientists. In the process they provide support for the Anti-Reflexivity Thesis, a perspective that attributes conservatives’ (and Republicans’) denial of anthropogenic climate change (ACC) and other environmental problems and attacks on climate/environmental science to their staunch commitment to protecting the current system of economic production. McCright et al’s innovative study deserves replication, and their approach should prove useful in accounting for divergent views of ACC. It is also important to keep in mind that anti-reflexivity is an institutional and structural issue, becoming more consequential when it is employed by political elites such as the George W Bush Administration in the US. Institutional anti-reflexivity is further illustrated by the widespread denial of ACC and a range of other problems among current Republican members of the US Congress.

  2. Clarifying the covariant formalism for the SZ effect due to relativistic non-thermal electrons

    OpenAIRE

    Boehm, Celine; Lavalle, Julien

    2008-01-01

    We derive the covariant formalism associated with the relativistic Sunyaev-Zel'dovich effect due to a non-thermal population of high energy electrons in clusters of galaxies. More precisely, we show that the formalism proposed by Wright in 1979, based on an empirical approach (and widely used in the literature) to compute the inverse Compton scattering of a population of relativistic electrons on CMB photons, can actually be re-interpreted as a Boltzmann-like equation, in the single scatterin...

  3. Visualization of nano risk research field to clarify domains year by year

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Yasuto; Hayashi, Takeshi; Miyaoi, Kenichi; Yamaguchi, Yukio [Department of Chemical System Engineering, Graduate School of Engineering, University of Tokyo (Japan)], E-mail: matsui@sogo.t.u-tokyo.ac.jp; Tomobe, Hironori; Kajikawa, Yuya; Matsushima, Katsumori [Innovation Policy Research Center, Institute of Engineering Innovation, University of Tokyo (Japan)

    2009-05-01

    With rising interest of nano technology R and D, nano risk researches have been greatly studied recently. They attract much attention since influence of nano products in the society is not well-known. Now the current state of nano risk research field is not fully investigated, and the object is overviewing this structure until 2008 and predicting the direction of next-coming studies. Nano risk 1611 papers were searched out with certain query and further refinement. And these papers were clustered by bibliometric method. The selected papers were clustered to seven parts and visually seen as aggregated blocks. Each cluster was labeled with proper name by analyzing in detail and the content of each cluster was classified with three terms, i.e. 'Material', 'Hazard' and 'Kinetics'. The biggest cluster was cluster no. 0 'atmospheric nanoparticles', and secondly cluster no. 1 'nanoparticles used in imaging', thirdly cluster no. 2 'toxicity of manufactured nano materials'. Furthermore, historical trend of the number of papers of each cluster was studied year by year. From the all results, short-term future predicting was performed by examining titles of papers or transition of the number of papers in each cluster and by watching the cluster position and gaps between clusters.

  4. Visualization of nano risk research field to clarify domains year by year

    International Nuclear Information System (INIS)

    With rising interest of nano technology R and D, nano risk researches have been greatly studied recently. They attract much attention since influence of nano products in the society is not well-known. Now the current state of nano risk research field is not fully investigated, and the object is overviewing this structure until 2008 and predicting the direction of next-coming studies. Nano risk 1611 papers were searched out with certain query and further refinement. And these papers were clustered by bibliometric method. The selected papers were clustered to seven parts and visually seen as aggregated blocks. Each cluster was labeled with proper name by analyzing in detail and the content of each cluster was classified with three terms, i.e. 'Material', 'Hazard' and 'Kinetics'. The biggest cluster was cluster no. 0 'atmospheric nanoparticles', and secondly cluster no. 1 'nanoparticles used in imaging', thirdly cluster no. 2 'toxicity of manufactured nano materials'. Furthermore, historical trend of the number of papers of each cluster was studied year by year. From the all results, short-term future predicting was performed by examining titles of papers or transition of the number of papers in each cluster and by watching the cluster position and gaps between clusters.

  5. Clarifying the anatomy of hearts with concordant ventriculo-arterial connections but abnormally related arterial trunks.

    Science.gov (United States)

    Gupta, Saurabh K; Ramakrishnan, Sivasubramanian; Gulati, Gurpreet S; Henry, G William; Spicer, Diane E; Backer, Carl L; Anderson, Robert H

    2016-01-01

    Hearts in which the arterial trunks arise from the morphologically appropriate ventricles, but in a parallel manner, rather than the usual spiralling arrangement, have long fascinated anatomists. These rare entities, for quite some time, were considered embryological impossibilities, but ongoing experience has shown that they can be found in various segmental combinations. Problems still exist about how best to describe them, as the different variants are often described with esoteric terms, such as anatomically corrected malposition or isolated ventricular inversion. In this review, based on our combined clinical and morphological experience, we demonstrate that the essential feature of all hearts described in this manner is a parallel arrangement of the arterial trunks as they exit from the ventricular mass. We show that the relationship of the arterial roots needs to be described in terms of the underlying ventricular topology, rather than according to the arrangement of the atrial chambers. We then discuss the importance of determining atrial arrangement on the basis of the morphology of the appendages, following the precepts as set out in the so-called "morphological method" and distinguished according to the extent of the pectinate muscles relative to the atrioventricular junctions as opposed to basing diagnosis on the venoatrial connections. We show that, when approached in this manner, the various combinations can be readily diagnosed in the clinical setting and described in straightforward way. PMID:26311213

  6. Divorce and Adult Psychological Well-Being: Clarifying the Role of Gender and Child Age

    Science.gov (United States)

    Williams, Kristi; Dunne-Bryant, Alexandra

    2006-01-01

    Substantial evidence indicates that marital dissolution has negative consequences for adult well-being. Because most research focuses on the average consequences of divorce, we know very little about factors that moderate this association. The present study tests the hypothesis that the effects of marital dissolution on adult well-being are…

  7. Beyond More Jews Doing Jewish: Clarifying the Goals of Informal Jewish Education

    Science.gov (United States)

    Reimer, Joseph

    2007-01-01

    Why has it been so difficult to define the goals of Jewish informal education? Often informal educators define their work in terms of the goals of Jewish socialization. Those terms have worked to attract funders' support, but also limited the educational creativity of this field. This article argues for a dual defining of goals: socialization and…

  8. No longer in suspense: Clarifying the Human Rights Jurisdiction of the SADC Tribunal

    Directory of Open Access Journals (Sweden)

    Moses R Phooko

    2015-12-01

    Full Text Available The Southern African Development Community Tribunal's (SADC Tribunal decision in the matter of Mike Campbell (Pvt Ltd v Republic of Zimbabwe 2008 SADCT 2 (28 November 2008 demonstrated its ability to utilise the principles contained in the Treaty of the Southern African Development Community when it ruled that it had the power and competency to adjudicate over a human rights case. The aforesaid decision was hailed by many scholars as a progressive judgment in the SADC region that would promote the rule of law and ensure that member states respected their treaty obligations in their own territories. Unfortunately, the same judgment resulted in the suspension of the SADC Tribunal in 2010 because it had purportedly acted beyond its mandate when it adjudicated over a case concerning a human rights dispute. This article investigates whether the SADC Tribunal had jurisdiction to deal with cases involving allegations of human rights violations. In addressing this question, this article will discuss the powers (implied and tacit of international organisations as understood within international law. In addition, the study will ascertain how the International Court of Justice and the International Criminal Tribunal for the former Yugoslavia have dealt with cases that involved disputes concerning a tribunal or an international organisation that was said to have acted beyond its mandate. The study will also make reference to the East African Court of Justice and the Economic Community of West African States Court of Justice as they have also dealt with implied powers when they were confronted with cases concerning human rights abuses. Certain decisions of the SADC Summit of Heads of States or Government (Summit and the Council of Ministers whose roles include the control of functions and/or overseeing the functioning of the SADC will also be referred to in this study.

  9. Neurocognitive Functioning in Schizophrenia and Bipolar Disorder: Clarifying Concepts of Diagnostic Dichotomy vs. Continuum

    OpenAIRE

    Carissa Nadia Kuswanto; Min Yi eSum; Kang eSim

    2013-01-01

    The Kraepelinian dichotomy posits that patients with schizophrenia (SCZ) and bipolar disorder (BD) present as two separate psychotic entities such that they differ in terms of clinical severity including neurocognitive functioning. Our study aimed to specifically compare and contrast the level of neurocognitive functioning between SCZ and BD patients and identify predictors of their poor neurocognitive functioning. We hypothesized that patients with SCZ had a similar level of neurocognitive i...

  10. Neurocognitive functioning in schizophrenia and bipolar disorder: Clarifying concepts of diagnostic dichotomy versus continuum

    Directory of Open Access Journals (Sweden)

    Carissa Nadia Kuswanto

    2013-12-01

    Full Text Available The Kraepelinian dichotomy posits that patients with schizophrenia (SCZ and bipolar disorder (BD present as two separate psychotic entities such that they differ in terms of clinical severity including neurocognitive functioning. Our study aimed to specifically compare and contrast the level of neurocognitive functioning between SCZ and BD patients and identify predictors of their poor neurocognitive functioning. We hypothesized that patients with SCZ had a similar level of neurcognitive impairment compared with BD. Forty-nine healthy controls (HC, 72 SCZ and 42 BD patients who were matched for age, gender, and premorbid IQ were administered the Brief Assessment of Cognition battery (BAC. Severity of psychopathology and socio-occupational functioning were assessed for both patients groups. Both BD and SCZ groups demonstrated similar patterns of neurocognitive deficits across several domains (verbal memory, working memory, semantic fluency, processing speed compared with HC subjects. However, no significant difference was found in neurocognitive functioning between BD and SCZ patients, suggesting that both patient groups suffer the same degree of neurocognitive impairment. Patients with lower level of psychosocial functioning (F(1,112 = 2.661, p = 0.009 and older age (F(1,112 = -2.625, p = 0.010, not diagnosis or doses of psychotropic medications, predicted poorer overall neurocognitive functioning as measured by the lower BAC composite score. Our findings of comparable neurocognitive impairments between SCZ and BD affirm our hypothesis and support less the Kraepelinian concept of dichotomy but more of a continuum of psychotic spectrum conditions. This should urge clinicians to investigate further the underlying neural basis of these neurocognitive deficits, and be attentive to the associated socio-demographic and clinical profile in order to recognize and optimize early the management of the widespread neurocognitive deficits in patients with SCZ and BD.

  11. Ancient mitochondrial genomes clarify the evolutionary history of New Zealand's enigmatic acanthisittid wrens.

    Science.gov (United States)

    Mitchell, Kieren J; Wood, Jamie R; Llamas, Bastien; McLenachan, Patricia A; Kardailsky, Olga; Scofield, R Paul; Worthy, Trevor H; Cooper, Alan

    2016-09-01

    The New Zealand acanthisittid wrens are the sister-taxon to all other "perching birds" (Passeriformes) and - including recently extinct species - represent the most diverse endemic passerine family in New Zealand. Consequently, they are important for understanding both the early evolution of Passeriformes and the New Zealand biota. However, five of the seven species have become extinct since the arrival of humans in New Zealand, complicating evolutionary analyses. The results of morphological analyses have been largely equivocal, and no comprehensive genetic analysis of Acanthisittidae has been undertaken. We present novel mitochondrial genome sequences from four acanthisittid species (three extinct, one extant), allowing us to resolve the phylogeny and revise the taxonomy of acanthisittids. Reanalysis of morphological data in light of our genetic results confirms a close relationship between the extant rifleman (Acanthisitta chloris) and an extinct Miocene wren (Kuiornis indicator), making Kuiornis a useful calibration point for molecular dating of passerines. Our molecular dating analyses reveal that the stout-legged wrens (Pachyplichas) diverged relatively recently from a more gracile (Xenicus-like) ancestor. Further, our results suggest a possible Early Oligocene origin of the basal Lyall's wren (Traversia) lineage, which would imply that Acanthisittidae survived the Oligocene marine inundation of New Zealand and therefore that the inundation was not complete. PMID:27261250

  12. Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues

    Directory of Open Access Journals (Sweden)

    Janssens A Cecile JW

    2011-06-01

    Full Text Available Abstract Background As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics. Discussion This paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.' Summary Consideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility.

  13. Clarifying CLARITY: Quantitative Optimization of the Diffusion Based Delipidation Protocol for Genetically Labeled Tissue

    OpenAIRE

    Magliaro, Chiara; Callara, Alejandro L.; Mattei, Giorgio; Morcinelli, Marco; Viaggi, Cristina; Vaglini, Francesca; Ahluwalia, Arti

    2016-01-01

    Tissue clarification has been recently proposed to allow deep tissue imaging without light scattering. The clarification parameters are somewhat arbitrary and dependent on tissue type, source and dimension: every laboratory has its own protocol, but a quantitative approach to determine the optimum clearing time is still lacking. Since the use of transgenic mouse lines that express fluorescent proteins to visualize specific cell populations is widespread, a quantitative approach to determine t...

  14. Orthogonal Assays Clarify the Oxidative Biochemistry of Taxol P450 CYP725A4.

    Science.gov (United States)

    Biggs, Bradley Walters; Rouck, John Edward; Kambalyal, Amogh; Arnold, William; Lim, Chin Giaw; De Mey, Marjan; O'Neil-Johnson, Mark; Starks, Courtney M; Das, Aditi; Ajikumar, Parayil Kumaran

    2016-05-20

    Natural product metabolic engineering potentially offers sustainable and affordable access to numerous valuable molecules. However, challenges in characterizing and assembling complex biosynthetic pathways have prevented more rapid progress in this field. The anticancer agent Taxol represents an excellent case study. Assembly of a biosynthetic pathway for Taxol has long been stalled at its first functionalization, putatively an oxygenation performed by the cytochrome P450 CYP725A4, due to confounding characterizations. Here, through combined in vivo (Escherichia coli), in vitro (lipid nanodisc), and metabolite stability assays, we verify the presence and likely cause of this enzyme's inherent promiscuity. Thereby, we remove the possibility that promiscuity simply existed as an artifact of previous metabolic engineering approaches. Further, spontaneous rearrangement and the stabilizing effect of a hydrophobic overlay suggest a potential role for nonenzymatic chemistry in Taxol's biosynthesis. Taken together, this work confirms taxadiene-5α-ol as a primary enzymatic product of CYP725A4 and provides direction for future Taxol metabolic and protein engineering efforts. PMID:26930136

  15. Clarifying the Ambiguities between the Servicescape and Service Quality: A Field Study

    OpenAIRE

    Hooper, Daire; Coughlan, Joseph; Mullen, Michael R.

    2009-01-01

    Service quality is commonly described as a multi-dimensional concept under which a range of dimensions are subsumed. The number of these dimensions can vary widely with no consensus as to what should be considered as a service quality sub-construct. The American stream of thought has drawn heavily on Parasuraman (1991; 1985; 1988) and his colleagues’ SERVQUAL model which consists of five key dimensions. While replications of the dimensional structure have proven difficult (Babakus and Boller ...

  16. 76 FR 17135 - Clarifying Edits to Existing Special Controls Guidance Documents; Availability

    Science.gov (United States)

    2011-03-28

    ... Activity Monitors, 7. Pharmacy Compounding Systems, 8. Tissue Culture Media for Human ex vivo Tissue and Cell Culture Processing Applications, 9. Indwelling Blood Gas Analyzers, 10. Ingestible Telemetric..., Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry, 41. Implantable...

  17. Clarifying omics concepts, challenges, and opportunities for Prunus breeding in the postgenomic era.

    Science.gov (United States)

    Martínez-Gómez, Pedro; Sánchez-Pérez, Raquel; Rubio, Manuel

    2012-05-01

    The recent sequencing of the complete genome of the peach, together with the availability of new high-throughput genome, transcriptome, proteome, and metabolome analysis technologies, offers new possibilities for Prunus breeders in what has been described as the postgenomic era. In this context, new biological challenges and opportunities for the application of these technologies in the development of efficient marker-assisted selection strategies in Prunus breeding include genome resequencing using DNA-Seq, the study of RNA regulation at transcriptional and posttranscriptional levels using tilling microarray and RNA-Seq, protein and metabolite identification and annotation, and standardization of phenotype evaluation. Additional biological opportunities include the high level of synteny among Prunus genomes. Finally, the existence of biases presents another important biological challenge in attaining knowledge from these new high-throughput omics disciplines. On the other hand, from the philosophical point of view, we are facing a revolution in the use of new high-throughput analysis techniques that may mean a scientific paradigm shift in Prunus genetics and genomics theories. The evaluation of scientific progress is another important question in this postgenomic context. Finally, the incommensurability of omics theories in the new high-throughput analysis context presents an additional philosophical challenge. PMID:22394278

  18. New Developmental Evidence Clarifies the Evolution of Wrist Bones in the Dinosaur–Bird Transition

    Science.gov (United States)

    Botelho, João Francisco; Ossa-Fuentes, Luis; Soto-Acuña, Sergio; Smith-Paredes, Daniel; Nuñez-León, Daniel; Salinas-Saavedra, Miguel; Ruiz-Flores, Macarena; Vargas, Alexander O.

    2014-01-01

    From early dinosaurs with as many as nine wrist bones, modern birds evolved to develop only four ossifications. Their identity is uncertain, with different labels used in palaeontology and developmental biology. We examined embryos of several species and studied chicken embryos in detail through a new technique allowing whole-mount immunofluorescence of the embryonic cartilaginous skeleton. Beyond previous controversy, we establish that the proximal–anterior ossification develops from a composite radiale+intermedium cartilage, consistent with fusion of radiale and intermedium observed in some theropod dinosaurs. Despite previous claims that the development of the distal–anterior ossification does not support the dinosaur–bird link, we found its embryonic precursor shows two distinct regions of both collagen type II and collagen type IX expression, resembling the composite semilunate bone of bird-like dinosaurs (distal carpal 1+distal carpal 2). The distal–posterior ossification develops from a cartilage referred to as “element x,” but its position corresponds to distal carpal 3. The proximal–posterior ossification is perhaps most controversial: It is labelled as the ulnare in palaeontology, but we confirm the embryonic ulnare is lost during development. Re-examination of the fossil evidence reveals the ulnare was actually absent in bird-like dinosaurs. We confirm the proximal–posterior bone is a pisiform in terms of embryonic position and its development as a sesamoid associated to a tendon. However, the pisiform is absent in bird-like dinosaurs, which are known from several articulated specimens. The combined data provide compelling evidence of a remarkable evolutionary reversal: A large, ossified pisiform re-evolved in the lineage leading to birds, after a period in which it was either absent, nonossified, or very small, consistently escaping fossil preservation. The bird wrist provides a modern example of how developmental and paleontological data illuminate each other. Based on all available data, we introduce a new nomenclature for bird wrist ossifications. PMID:25268520

  19. Using the ICF to clarify team roles and demonstrate clinical reasoning in stroke rehabilitation

    OpenAIRE

    Tempest, S; McIntyre, A

    2006-01-01

    Purpose: The International Classification of Functioning, Disability and Health (ICF) is advocated as a tool to structure rehabilitation and a universal language to aid communication, within the multi-disciplinary team (MDT). The ICF may also facilitate clarification of team roles and clinical reasoning for intervention. This article aims to explore both factors in stroke rehabilitation. Method: Following a review of the literature, a summary was presented and discussed with...

  20. Young women's education and behavioural risk trajectories: clarifying their association with unintended-pregnancy resolution.

    Science.gov (United States)

    Gomez-Scott, Jessica; Cooney, Teresa M

    2014-06-01

    In the USA, most pregnancies occurring to teenage women are unplanned, making both the decisions regarding their resolution and the consequences of those decisions important topics of inquiry. Substantial debate surrounds the potential consequences for young women of either carrying an unintended pregnancy to term or voluntarily terminating it. The present study utilises data from The US National Longitudinal Study of Adolescent Health prospectively to examine the predictors of pregnancy resolution decisions in terms of young women's educational goals and their engagement in risk behaviours. Additionally, the long-term consequences of these decisions for education and risk-taking behaviours are identified. Results indicate that young women with strong educational goals have a greater likelihood of terminating an unintended pregnancy than those with low aspirations, and that pregnancy termination predicts higher educational attainment compared to motherhood. Risk behaviours did not predict pregnancy-resolution decisions, but young women who became mothers reported lower rates of subsequent substance use and fewer sexual partners post-pregnancy than those who terminated the pregnancy or who had never been pregnant. Motherhood appears to be a catalyst for lifestyle change among young women, limiting substance use and sexual partnering, in contrast to abortion, which appears to allow adolescents to continue risk-taking trajectories. PMID:24735279

  1. 78 FR 23578 - Clarifying Guidance, Waivers, and Alternative Requirements for Hurricane Sandy Grantees in...

    Science.gov (United States)

    2013-04-19

    ... communities in the disaster-impacted areas. Tourism in Sandy-impacted counties generates approximately $32.5... recovery in the most impacted and distressed areas declared a major disaster due to Hurricane Sandy (see 78... revitalization in the most impacted and distressed areas resulting from a major disaster declared pursuant to...

  2. Clarifying Cutting and Sewing Processes with Due Windows Using an Effective Ant Colony Optimization

    OpenAIRE

    Rong-Hwa Huang; Shun-Chi Yu

    2013-01-01

    The cutting and sewing process is a traditional flow shop scheduling problem in the real world. This two-stage flexible flow shop is often commonly associated with manufacturing in the fashion and textiles industry. Many investigations have demonstrated that the ant colony optimization (ACO) algorithm is effective and efficient for solving scheduling problems. This work applies a novel effective ant colony optimization (EACO) algorithm to solve two-stage flexible flow shop scheduling problems...

  3. 76 FR 40612 - Real Estate Settlement Procedures Act (RESPA): Technical Corrections and Clarifying Amendments

    Science.gov (United States)

    2011-07-11

    ... URBAN DEVELOPMENT 24 CFR Part 3500 RIN 2502-AH85 Real Estate Settlement Procedures Act (RESPA...., Washington, DC 20410. SUPPLEMENTARY INFORMATION: I. Background On November 17, 2008 (73 FR 68204), HUD... underwriting for borrowers who decide to proceed with a loan from that originator.'' (See 73 FR 68212,...

  4. Guiding Principles of Hydrogenase Catalysis Instigated and Clarified by Protein Film Electrochemistry.

    Science.gov (United States)

    Armstrong, Fraser A; Evans, Rhiannon M; Hexter, Suzannah V; Murphy, Bonnie J; Roessler, Maxie M; Wulff, Philip

    2016-05-17

    Protein film electrochemistry (PFE) is providing cutting-edge insight into the chemical principles underpinning biological hydrogen. Attached to an electrode, many enzymes exhibit "reversible" electrocatalytic behavior, meaning that a catalyzed redox reaction appears reversible or quasi-reversible when viewed by cyclic voltammetry. This efficiency is most relevant for enzymes that are inspiring advances in renewable energy, such as hydrogen-activating and CO2-reducing enzymes. Exploiting the rich repertoire of available instrumental methods, PFE experiments yield both a general snapshot and fine detail, all from tiny samples of enzyme. The dynamic electrochemical investigations blaze new trails and add exquisite detail to the information gained from structural and spectroscopic studies. This Account describes recent investigations of hydrogenases carried out in Oxford, including ideas initiated with PFE and followed through with complementary techniques, all contributing to an eventual complete picture of fast and efficient H2 activation without Pt. By immobilization of an enzyme on an electrode, catalytic electron flow and the chemistry controlling it can be addressed at the touch of a button. The buried nature of the active site means that structures that have been determined by crystallography or spectroscopy are likely to be protected, retained, and fully relevant in a PFE experiment. An electrocatalysis model formulated for the PFE of immobilized enzymes predicts interesting behavior and gives insight into why some hydrogenases are H2 producers and others are H2 oxidizers. Immobilization also allows for easy addition and removal of inhibitors along with precise potential control, one interesting outcome being that formaldehyde forms a reversible complex with reduced [FeFe]-hydrogenases, thereby providing insight into the order of electron and proton transfers. Experiments on O2-tolerant [NiFe]-hydrogenases show that O2 behaves like a reversible inhibitor: it is also a substrate, and implicit in the description of some hydrogenases as "H2/O2 oxidoreductases" is the hypothesis that fast and efficient multielectron transfer is a key to O2 tolerance because it promotes complete reduction of O2 to harmless water. Not only is a novel [4Fe-3S] cluster (able to transfer two electrons consecutively) an important component, but connections to additional electron sources (other Fe-S clusters, an electrode, another quaternary structure unit, or the physiological membrane itself) ensure that H2 oxidation can be sustained in the presence of O2, as demonstrated with enzyme fuel cells able to operate on a H2/air mixture. Manipulating the H-H bond in the active site is the simplest proton-coupled electron-transfer reaction to be catalyzed by an enzyme. Unlike small molecular catalysts or the surfaces of materials, metalloenzymes are far better suited to engineering the all-important outer-coordination shell. Hence, recent successful site-directed mutagenesis of the conserved outer-shell "canopy" residues in a [NiFe]-hydrogenase opens up new opportunities for understanding the mechanism of H2 activation beyond the role of the inner coordination shell. PMID:27104487

  5. Oral history in the classroom: Clarifying the context through historical understanding.

    OpenAIRE

    Horn, Karen

    2014-01-01

    The focus of this paper is on the use of oral history in the classroom and it aims to suggest a method in which oral history recordings and transcriptions may be used to enhance historical understanding among learners by making historical context clear. Firstly, the paper gives background information on the historical research which was largely based on the oral testimony of World War Two veterans and former prisoners-of-war. This theme serves as an example theme for history ...

  6. Clarifying My World: Identity Work in the Context of Workplace Bullying

    Science.gov (United States)

    D'Cruz, Premilla; Noronha, Ernesto

    2012-01-01

    Based on a study rooted in van Manen's hermeneutic phenomenology, conducted with agents working in international facing call centers in Mumbai and Bangalore, India, this paper describes targets' identity work in the context of workplace bullying. Data were gathered through conversational interviews and were subject to sententious and selective…

  7. A critical review of clarifier modelling:State-of-the-art and engineering practices

    OpenAIRE

    Plósz, Benedek; Nopens, Ingmar; Rieger, Leiv; Griborio, Alonso; Clercq, Jeriffa De; Vanrolleghem, Peter A.; Daigger, Glen T.; Takacs, Imre; Wicks, Jim; Ekama, George A.

    2012-01-01

    This outline paper aims to provide a critical review of secondary settling tank (SST) modelling approaches used in current wastewater engineering and develop tools not yet applied in practice. We address the development of different tier models and experimental techniques in the field with a particular emphasis on works published since the reference work by Ekama et al. (1997). We give insight into the current engineering practice, identify how recent developments can be transferred to engine...

  8. Designing a Clarifier to Recover Wastewater Algae Biomass for Production of Biofuels

    OpenAIRE

    Martinez, Elizabeth

    2015-01-01

    The Logan Lagoons, Logan City’s Wastewater Treatment Facility ensures 15 million gallons of wastewater are cleaned and filtered each day. With the implementation of new and stricter wastewater effluent standards, the city of Logan now has to guarantee the phosphorous concentration in the effluent is also reduced. Algal biomass produced and harvested from the lagoons has been proven to affect the way nitrogen and phosphorous are removed, while having the potential to be converted to biofuels. ...

  9. The Princess Storyteller, Clara Clarifier, Quincy Questioner, and the Wizard: Reciprocal Teaching Adapted for Kindergarten Students

    Science.gov (United States)

    Myers, Pamela Ann

    2005-01-01

    In this study, the author adapted reciprocal teaching strategies for use with her kindergarten students. Using puppets to help model strategies, she implemented a series of lessons that showed students how to retell, ask questions, and predict what would happen in a story that was read aloud. The purpose was to provide students with comprehension…

  10. Study on liquid and deposit flow dynamics through Dorr type clarifier by radioactive tracers

    International Nuclear Information System (INIS)

    The methodics and results of researches on dynamics of liquid and deposit flow in biological sewage treatment have been presented. The 131I and 140La were used as tracers for liquid and deposits respectively. The application of amplitude analyser for radiometric measurement allowed to determine the residence time distribution in both phases in one experiment. The dynamic parameters of decanter eg. volumes of the zones with piston flow and perfect mixing and portion of dead volume were determined. (author)

  11. Clarifier et développer les caractéristiques de l'organisation civile

    OpenAIRE

    Patrice Meyer-Bisch

    2012-01-01

    The notion of civil society is blur, as it describes everything that is not from the State. Finding an operational definition that remains flexible enough to encompass the diversity of democratic cultures and forms of expressions is a challenge. This paper proposes to identify the characteristics of the general organization of civil society to better define civil society organizations (CSO). This clarification is essential to respect cultural diversity while analyzing strategies for democrati...

  12. From Votes to Dialogues: Clarifying the Role of Teachers' Voices in School Renewal

    Science.gov (United States)

    Allen, Lew

    2004-01-01

    Everyone agrees that teachers' voices should be heard in their schools. But what does that mean? And how can teachers' voices be used to improve student learning? In this article, the author offers insights from his experience with the League of Professional Schools. As a result of the teacher empowerment movement that began in the mid-1980s and…

  13. A clarified position for solanum lycopersicum var. cerasiforme in the evolutionary history of tomatoes (solanaceae

    Directory of Open Access Journals (Sweden)

    Causse Mathilde

    2008-12-01

    Full Text Available Abstract Background The natural phenotypic variability present in the germplasm of cultivated plants can be linked to molecular polymorphisms using association genetics. However it is necessary to consider the genetic structure of the germplasm used to avoid false association. The knowledge of genetic structure of plant populations can help in inferring plant evolutionary history. In this context, we genotyped 360 wild, feral and cultivated accessions with 20 simple sequence repeat markers and investigated the extent and structure of the genetic variation. The study focused on the red fruited tomato clade involved in the domestication of tomato and confirmed the admixture status of cherry tomatoes (Solanum lycopersicum var. cerasiforme. We used a nested sample strategy to set-up core collection maximizing the genetic diversity with a minimum of individuals. Results Molecular diversity was considerably lower in S. lycopersicum i.e. the domesticated form. Model-based analysis showed that the 144 S. lycopersicum var. cerasiforme accessions were structured into two groups: one close to the domesticated group and one resulting from the admixture of the S. lycopersicum and S. pimpinellifolium genomes. SSR genotyping also indicates that domesticated and wild tomatoes have evolved as a species complex with intensive level of hybridization. We compiled genotypic and phenotypic data to identify sub-samples of 8, 24, 32 and 64 cherry tomato accessions that captured most of the genetic and morphological diversity present in the entire S. lycopersicum var. cerasiforme collection. Conclusion The extent and structure of allelic variation is discussed in relation to historical events like domestication and modern selection. The potential use of the admixed group of S. lycopersicum var. cerasiforme for association genetics studies is also discussed. Nested core collections sampled to represent tomato diversity will be useful in diversity studies. Molecular and phenotypic variability of these core collections is defined. These collections are available for the scientific community and can be used as standardized panels for coordinating efforts on identifying novel interesting genes and on examining the domestication process in more detail.

  14. REPORT FROM THE STS NATIONAL DATABASE WORK FORCE: Clarifying the Definition of Operative Mortality

    OpenAIRE

    Overman, David M.; Jacobs, Jeffrey P.; Prager, Richard L.; Wright, Cameron D.; Clarke, David R.; Pasquali, Sara; O’Brien, Sean M.; Dokholyan, Rachel S.; Meehan, Paul; McDonald, Donna E.; Jacobs, Marshall L.; Mavroudis, Constantine; Shahian, David M.

    2013-01-01

    Several distinct definitions of postoperative death have been used in various quality reporting programs. Some have defined a postoperative mortality as a patient who expires while still in the hospital, while others have considered all deaths occurring within a predetermined, standardized time interval after surgery. While if continues to collect mortality data using both these individual definitions, the Society of Thoracic Surgeons (STS) believes that either alone may be inadequate. Accord...

  15. Ancient DNA reveals elephant birds and kiwi are sister taxa and clarifies ratite bird evolution.

    Science.gov (United States)

    Mitchell, Kieren J; Llamas, Bastien; Soubrier, Julien; Rawlence, Nicolas J; Worthy, Trevor H; Wood, Jamie; Lee, Michael S Y; Cooper, Alan

    2014-05-23

    The evolution of the ratite birds has been widely attributed to vicariant speciation, driven by the Cretaceous breakup of the supercontinent Gondwana. The early isolation of Africa and Madagascar implies that the ostrich and extinct Madagascan elephant birds (Aepyornithidae) should be the oldest ratite lineages. We sequenced the mitochondrial genomes of two elephant birds and performed phylogenetic analyses, which revealed that these birds are the closest relatives of the New Zealand kiwi and are distant from the basal ratite lineage of ostriches. This unexpected result strongly contradicts continental vicariance and instead supports flighted dispersal in all major ratite lineages. We suggest that convergence toward gigantism and flightlessness was facilitated by early Tertiary expansion into the diurnal herbivory niche after the extinction of the dinosaurs. PMID:24855267

  16. Evaluation of residual immunoreactivity in red and white wines clarified with gluten or gluten derivatives.

    Science.gov (United States)

    Cattaneo, A; Ballabio, C; Bertelli, A A E; Fiocchi, A; Galli, C L; Isoardi, P; Terracciano, L; Restani, P

    2003-01-01

    Gluten or hydrolyzed gluten could be a suitable alternative to animal proteins in the wine clarification process, but their residues could represent a risk for individuals suffering from coeliac disease or allergic to cereal proteins. The aim of this study was to investigate the presence of gluten in wines treated with gluten or its hydrolysate in the clarification process and to assess its antigenicity in commercial products. The presence of residual immunoreactive gluten was evaluated by electrophoresis (SDS-PAGE) and immunoblotting. Data obtained in several red and white wine samples showed that no residue was detectable in any of the red wines. In white wines, gluten reduced the protein content less completely, but most samples showed no immunoreactivity after the wine had been treated with gluten or its derivatives, either alone or combined with bentonite, silica gel or tannins. The use of gluten derivatives coupled with bentonite was the most effective method of removing immunoreactive protein in white wines. In conclusion, the use of gluten derivatives in wine clarification seems to exclude a risk for subjects susceptible to coeliac disease or gluten allergy. However, it is recommended that wine producers continuously monitor the clarification process in order to protect the most sensitive individuals. PMID:14518594

  17. Clarifying the Link between Parental Psychological Control and Adolescents' Depressive Symptoms: Reciprocal versus Unidirectional Models

    Science.gov (United States)

    Soenens, Bart; Luyckx, Koen; Vansteenkiste, Maarten; Duriez, Bart; Goossens, Luc

    2008-01-01

    Research has demonstrated consistent positive associations between perceived parental psychological control and adolescents' depressive symptoms, but the direction of influence remains unclear. Using a cross-lagged longitudinal design in two samples of late (Study 1, N = 396) and middle (Study 2, N = 724) adolescents, this study compared three…

  18. Gender and Condylar Differences in Distal Femur Morphometry Clarified by Automated Computer Analyses

    OpenAIRE

    Li, Kang; Langdale, Evan; Tashman, Scott; Harner, Christopher; Zhang, Xudong

    2011-01-01

    We elucidated the gender and condylar effects on distal femur morphology (DFM) while evaluating a newly developed computational framework that enables fully automated analyses of DFM in an objectively defined sagittal plane. Ninety high-resolution CT-acquired distal femur models from 51 males and 39 females were analyzed. The models were accurately characterized (mean least-squares fitting residual < 0.16 mm), and re-oriented to a unified sagittal plane; three morphometric measures were extra...

  19. Clarifying phylogenetic relationships and the evolutionary history of the bivalve order Arcida (Mollusca: Bivalvia: Pteriomorphia).

    Science.gov (United States)

    Combosch, David J; Giribet, Gonzalo

    2016-01-01

    The systematics of the bivalve order Arcida constitutes an unresolved conundrum in bivalve systematics. The current definition of Arcida encompasses two superfamilies: Limopsoidea, which includes the recent families Philobryidae and Limopsidae, and Arcoidea, which encompasses the families Arcidae, Cucullaeidae, Noetiidae, Glycymerididae and Parallelodontidae. This classification, however, is controversial particularly with respect to the position and taxonomic status of Glycymerididae. Previous molecular phylogenies were limited either by the use of only a single molecular marker or by including only a few limopsoid and glycymeridid taxa. The challenging nature of Arcida taxonomy and the controversial results of some of the previous studies, prompted us to use a broad range of taxa (55 species), three nuclear markers (18S rRNA, 28S rRNA and histone H3) and a wide range of algorithmic approaches. This broad but stringent approach led to a number of results that differ significantly from previous studies. We provide the first molecular evidence that supports the separation of Arcoidea from Limopsoidea, although the exact position of Glycymerididae remains unresolved, and the monophyly of Limopsoidea is algorithm-dependent. In addition, we present the first time-calibrated evolutionary tree of Arcida relationships, indicating a significant increase in the diversification of arcidan lineages at the beginning of the Cretaceous, around 140Ma. The monophyly of Arcida, which has been supported previously, was confirmed in all our analyses. Although relationships among families remain somehow unresolved we found support for the monophyly of most arcidan families, at least under some analytical conditions (i.e., Glycymerididae, Noetiidae, Philobryidae, and Limopsidae). However, Arcidae, and particularly Arcinae, remain a major source of inconsistency in the current system of Arcida classification and are in dire need of taxonomic revision. PMID:26427825

  20. 25 CFR 20.100 - What definitions clarify the meaning of the provisions of this part?

    Science.gov (United States)

    2010-04-01

    ... person in the household that has primary responsibility and/or obligation for the financial support of... Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA). Tribal governing body means the... SERVICES FINANCIAL ASSISTANCE AND SOCIAL SERVICES PROGRAMS Definitions, Purpose and Policy § 20.100...

  1. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-01-01

    Full Text Available Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1 at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed.

  2. Clarifying the Consultant-Client Role Relationship through an Organizational Needs Model.

    Science.gov (United States)

    Tubbs, Stewart L.; Baird, John W.

    An organizational need hierarchy can be used by consultants as a model for diagnosing organizational problems, after which an intervention plan can be made. The need hierarchy, which approximates Abraham Maslow's individual need hierarchy, is composed of five ascending levels related to organizational needs in the areas of survival of the…

  3. Clarifying values, risk perceptions, and attitudes to resolve or avoid social conflicts in invasive species management.

    Science.gov (United States)

    Estévez, Rodrigo A; Anderson, Christopher B; Pizarro, J Cristobal; Burgman, Mark A

    2015-02-01

    Decision makers and researchers recognize the need to effectively confront the social dimensions and conflicts inherent to invasive species research and management. Yet, despite numerous contentious situations that have arisen, no systematic evaluation of the literature has examined the commonalities in the patterns and types of these emergent social issues. Using social and ecological keywords, we reviewed trends in the social dimensions of invasive species research and management and the sources and potential solutions to problems and conflicts that arise around invasive species. We integrated components of cognitive hierarchy theory and risk perceptions theory to provide a conceptual framework to identify, distinguish, and provide understanding of the driving factors underlying disputes associated with invasive species. In the ISI Web of Science database, we found 15,915 peer-reviewed publications on biological invasions, 124 of which included social dimensions of this phenomenon. Of these 124, 28 studies described specific contentious situations. Social approaches to biological invasions have emerged largely in the last decade and have focused on both environmental social sciences and resource management. Despite being distributed in a range of journals, these 124 articles were concentrated mostly in ecology and conservation-oriented outlets. We found that conflicts surrounding invasive species arose based largely on differences in value systems and to a lesser extent stakeholder and decision maker's risk perceptions. To confront or avoid such situations, we suggest integrating the plurality of environmental values into invasive species research and management via structured decision making techniques, which enhance effective risk communication that promotes trust and confidence between stakeholders and decision makers. PMID:25155068

  4. Autonomous Weapons and International Humanitarian Law: Advantages, Open Technical Questions and Legal Issues to be Clarified

    OpenAIRE

    Sassoli, Marco

    2014-01-01

    This contribution argues that autonomous weapon systems may have advantages from the perspective of ensuring better respect for international humanitarian law (IHL), if they are one day capable of perceiving the information necessary to comply with IHL, then to apply IHL to that information, and if it can be ensured that they will not do what humans who created them did not want them to do. In view of the author, targeting decisions do not imply subjective value judgements, a machine would be...

  5. A framework for clarifying the meaning of Triple Bottom-Line, Integrated, and Sustainability Assessment

    International Nuclear Information System (INIS)

    Terms such as Integrated Assessment and Sustainability Assessment are used to label 'new' approaches to impact assessment that are designed to direct planning and decision-making towards sustainable development (SD). Established assessment techniques, such as EIA and SEA, are also widely promoted as SD 'tools'. This paper presents the findings of a literature review undertaken to identify the features that are typically promoted for improving the SD-directedness of assessments. A framework is developed which reconciles the broad range of emerging approaches and tackles the inconsistent use of terminology. The framework comprises a three-dimensional space defined by the following axes: the comprehensiveness of the SD coverage; the degree of 'integration' of the techniques and themes; and the extent to which a strategic perspective is adopted. By applying the framework, assessment approaches can be positioned relative to one another, enabling comparison on the basis of substance rather than semantics

  6. N-dimensional animal energetic niches clarify behavioural options in a variable marine environment.

    Science.gov (United States)

    Wilson, Rory P; McMahon, Clive R; Quintana, Flavio; Frere, Esteban; Scolaro, Alejandro; Hays, Graeme C; Bradshaw, Corey J A

    2011-02-15

    Animals respond to environmental variation by exhibiting a number of different behaviours and/or rates of activity, which result in corresponding variation in energy expenditure. Successful animals generally maximize efficiency or rate of energy gain through foraging. Quantification of all features that modulate energy expenditure can theoretically be modelled as an animal energetic niche or power envelope; with total power being represented by the vertical axis and n-dimensional horizontal axes representing extents of processes that affect energy expenditure. Such an energetic niche could be used to assess the energetic consequences of animals adopting particular behaviours under various environmental conditions. This value of this approach was tested by constructing a simple mechanistic energetics model based on data collected from recording devices deployed on 41 free-living Magellanic penguins (Spheniscus magellanicus), foraging from four different colonies in Argentina and consequently catching four different types of prey. Energy expenditure was calculated as a function of total distance swum underwater (horizontal axis 1) and maximum depth reached (horizontal axis 2). The resultant power envelope was invariant, irrespective of colony location, but penguins from the different colonies tended to use different areas of the envelope. The different colony solutions appeared to represent particular behavioural options for exploiting the available prey and demonstrate how penguins respond to environmental circumstance (prey distribution), the energetic consequences that this has for them, and how this affects the balance of energy acquisition through foraging and expenditure strategy. PMID:21270314

  7. Education and parental involvement in decision-making about newborn screening: understanding goals to clarify content.

    Science.gov (United States)

    Potter, Beth K; Etchegary, Holly; Nicholls, Stuart G; Wilson, Brenda J; Craigie, Samantha M; Araia, Makda H

    2015-06-01

    A challenge in designing effective education for parents about newborn screening (NBS) has been uncertainty about appropriate content. Arguing that the goals of education may be usefully tied to parental decision-making, we sought to: (1) explore how different ways of implementing NBS differ in their approaches to parental engagement in decision-making; (2) map the potential goals of education onto these "implementation models"; and (3) consider the content that may be needed to support these goals. The resulting conceptual framework supports the availability of comprehensive information about NBS for parents, irrespective of the model of implementation. This is largely because we argue that meeting parental expectations and preferences for communication is an important goal regardless of whether or notparents are actively involved in making a decision. Our analysis supports a flexible approach, in which some educational messages are emphasized as important for all parents to understand while others are made available depending on parents' preferences. We have begun to define the content of NBS education for parents needed to support specific goals. Further research and discussion is important to determine the most appropriate strategies for delivering the tailored approach to education that emerged from our analysis. PMID:25403898

  8. Clarifying the Nature of the Brightest Submillimetre Sources via SMA Interferometry

    CERN Document Server

    Younger, J D; Peck, A B; Ivison, R J; Biggs, A D; Chapin, E L; Clements, D L; Dye, S; Greve, T R; Hughes, D H; Iono, D; Smail, I; Krips, M; Petitpas, G R; Wilner, D; Schael, A M; Wilson, C D

    2008-01-01

    We present high-resolution interferometric imaging of LH850.02, the brightest 850- and 1200-um submillimetre (submm) galaxy in the Lockman Hole, at 890um with the Submillimetre Array (SMA). Our high-resolution submm imaging detects LH850.02 at >6-sigma as a single compact (size <1 arcsec or <8 kpc) point source and yields its absolute position to ~0.2-arcsec accuracy. LH850.02 has two alternative radio counterparts within the SCUBA beam (LH850.02N & S), both of which are statistically very unlikely to be so close to the SCUBA source position by chance. However, the precise astrometry from the SMA shows that the submm emission arises entirely from LH850.02N, and is not associated with LH850.02S (by far the brighter of the two alternative identifications at 24-um). Fits to the optical-infrared multi-colour photometry of LH850.02N & S indicate that both lie at z~3.3, and are therefore likely to be physically associated. At these redshifts, the 24um-to-submm flux density ratios suggest that LH 850.0...

  9. Teaching statistics in the physics curriculum: Unifying and clarifying role of subjective probability

    OpenAIRE

    D'Agostini, G.

    1999-01-01

    Subjective probability is based on the intuitive idea that probability quantifies the degree of belief that an event will occur. A probability theory based on this idea represents the most general framework for handling uncertainty. A brief introduction to subjective probability and Bayesian inference is given, with comments on typical misconceptions which tend to discredit it and comparisons to other approaches.

  10. Teaching statistics in the physics curriculum Unifying and clarifying role of subjective probability

    CERN Document Server

    D'Agostini, Giulio

    1999-01-01

    Subjective probability is based on the intuitive idea that probability quantifies the degree of belief that an event will occur. A probability theory based on this idea represents the most general framework for handling uncertainty. A brief introduction to subjective probability and Bayesian inference is given, with comments on typical misconceptions which tend to discredit it and comparisons to other approaches.

  11. Use of Neuroimaging to Clarify How Human Brains Perform Mental Calculations

    Science.gov (United States)

    Ortiz, Enrique

    2010-01-01

    The purpose of this study was to analyze participants' levels of hemoglobin as they performed arithmetic mental calculations using Optical Topography (OT, helmet type brain-scanning system, also known as Functional Near-Infrared Spectroscopy or fNIRS). A central issue in cognitive neuroscience involves the study of how the human brain encodes and…

  12. Clarifying the generic limits of Talbotiella and Hymenostegia (Detarieae, Caesalpinioideae, Leguminosae)

    OpenAIRE

    Mackinder, B.; Wieringa, J. J.; Lunenburg, I.; Banks, H.

    2010-01-01

    The formal description of four species of Cameroonian forest legume trees new to science has been hampered by uncertainty as to whether their correct generic placement is within Hymenostegia Harms or Talbotiella Baker f. As there has been doubt as to whether these two genera differ from one another, an investigation was undertaken so that the new species could be correctly assigned to genus. Using morphological, molecular and pollen data, our study supports the recognition of Hymenostegia and...

  13. Teaching Philosophy Game - A Way to Clarify Values, Attitudes, and Preferences Related to Teaching

    DEFF Research Database (Denmark)

    Christiansen, Birgitte Lund; Hansen, Claus Thorp; Jensen, Lars Bogø

    and role as university teachers. During the gaming process, the participants get a chance to externalize their tacit knowledge through individual reflections and team-based discussions. This can be useful not only for individual clarification, but also for teams of teachers to develop common ground...... principles of teaching and learning. Although no award will be given and no winners will be appointed, all participants will potentially gain insight into their own and colleagues’ values, attitudes, and preferences related to teaching and learning. During this workshop, you will try out the game and engage...

  14. Clarifying the Public-Private Line: Legal and Policy Guidance for Catholic-Affiliated Charter Schools

    Science.gov (United States)

    Carr, Kari A.; Decker, Janet

    2015-01-01

    In the past 50 years, the share of students enrolled in U.S. Catholic schools has declined from approximately 12% to 3%. In reaction, many urban Catholic schools have closed and subsequently reopened as public charter schools in order to receive governmental funding and to increase enrollment. As public schools, these Catholic- affiliated charter…

  15. Toy-Mediated Distraction: Clarifying the Role of Distraction Agent and Preneedle Distress in Toddlers

    OpenAIRE

    Hillgrove-Stuart, Jessica; Pillai Riddell, Rebecca; Horton, Rachel; Greenberg, Saul

    2013-01-01

    BACKGROUND: Distraction has recently gained attention as a technique that may help reduce acute pain in infants and toddlers; however, results remain equivocal. It appears that these mixed results stem from a variety of methodological differences with regard to how distraction is implemented.OBJECTIVES: To offer more definitive conclusions regarding the efficacy and mechanisms of distraction for pain management during infancy. Specifically, the goal was to examine whether the agent of distrac...

  16. Teaching about Civil Disobedience: Clarifying a Recurring Theme in the Secondary Social Studies

    Science.gov (United States)

    Clark, J. Spencer; Vontz, Thomas S.; Barikmo, Kristoffer

    2008-01-01

    In this article, the authors offer social studies educators a way to deepen students' understanding of civil disobedience as a democratic and nonviolent means of instigating social change. The authors explore the concept of civil disobedience from a historical perspective and examine the justifications and ramifications of each historical example.…

  17. Swift Observations of Gamma-Ray Burst Pulse Shapes: GRB Pulse Spectral Evolution Clarified

    CERN Document Server

    Hakkila, Jon; Sakamoto, Takanori; Morris, David; Neff, James E; Giblin, Timothy W

    2015-01-01

    Isolated Swift gamma-ray burst (GRB) pulses, like their higher-energy BATSE counterparts, emit the bulk of their pulsed emission as a hard-to-soft component that can be fitted by the Norris et al. (2005) empirical pulse model. This signal is overlaid by a fainter, three-peaked signal that can be modeled by an empirical wave-like function (Hakkila and Preece, 2014): the two fits combine to reproduce GRB pulses with distinctive three-peaked shapes. The precursor peak appears on or before the pulse rise and is often the hardest component, the central peak is the brightest, and the decay peak converts exponentially decaying emission into a long, soft, power-law tail. Accounting for systematic instrumental differences, the general characteristics of the fitted pulses are remarkably similar. Isolated GRB pulses are dominated by hard-to-soft evolution; this is more pronounced for asymmetric pulses than for symmetric ones. Isolated GRB pulses can also exhibit intensity tracking behaviors that, when observed, are tied...

  18. Towards Clarifying the Role of O2 during the Phthalocyanine Synthesis.

    Science.gov (United States)

    Wang, Kang; Pan, Houhe; Jiang, Jianzhuang

    2015-12-01

    The role of O2 within the synthesis of phthalocyanines (Pcs) has remained unclear in the past century. Here, we demonstrate that O2 , in cooperation with the solvent n-pentanol, participates in the cyclic tetramerization of phthalonitriles over the half-sandwich complex template [Lu(Pc)(acac)] (acac=acetylacetonate) and terminates the reaction at the stage of uncyclized isoindole oligomeric derivatives rather than the phthalocyanine chromophores, resulting in the isolation of the heteroleptic (phthalocyaninato)(triisoindole-1-one) lutetium double-decker complexes [(Pc)Lu(TIO-I)] (TIO-I=3,4,7,8,11,12-sexi(2,6-diisopropylphenoxy)-15-[4,5-di(2,6-diisopropylphenoxy)-2-cyanobenzimidamido]triisoindole-1-one) and [(Pc)Lu(TIO-II)] (TIO-II=3,4,7,8,11,12-sexi(2,6-dimethylphenoxy)-15-[4,5-di(2,6-dimethylphenoxy)-2-cyanobenzimidamido]triisoindole-1-one) with the help of bulky substituents at the phthalonitrile periphery and an unsubstituted phthalocyanine ligand in the double-decker skeleton. Nevertheless, the cyclic tetramerization of the phthalonitriles was revealed to be sensitive to O2 with the reaction progression also depending on the oxygen concentration/content, leading to the O2 -senstive and -dependent nature for the isolation of phthalocyanine derivatives. PMID:26526528

  19. Employees and the Innovative Idea Contribution Process: Clarifying Individual and Contextual Characteristics

    OpenAIRE

    N. SERGEEVA

    2014-01-01

    Understanding how contextual and individual characteristics affect employee willingness to propose innovative ideas to an organization is an important, if understudied aspect of the innovation process. Based on an interactional perspective, widely used in creativity and innovation studies, this paper examines the influence of both contextual and individual characteristics on employee willingness to contribute innovative ideas to other organizational actors. Using a quasi-experimental approach...

  20. Identification of a membrane-bound prepore species clarifies the lytic mechanism of actinoporins

    CERN Document Server

    Morante, Koldo; Gil-Cartón, David; Redondo-Morata, Lorena; Sot, Jesús; Scheuring, Simon; Valle, Mikel; González-Mañas, Juan Manuel; Tsumoto, Kouhei; Caaveiro, Jose M M

    2016-01-01

    Pore-forming toxins (PFT) are cytolytic proteins belonging to the molecular warfare apparatus of living organisms. The assembly of the functional transmembrane pore requires several intermediate steps ranging from a water-soluble monomeric species to the multimeric ensemble inserted in the cell membrane. The non-lytic oligomeric intermediate known as prepore plays an essential role in the mechanism of insertion of the class of $\\beta$-PFT. However, in the class of $\\alpha$-PFT like the actinoporins produced by sea anemones, evidence of membrane-bound prepores is still lacking. We have employed single-particle cryo-electron microscopy (cryo-EM) and atomic force microscopy (AFM) to identify, for the first time, a prepore species of the actinoporin fragaceatoxin C (FraC) bound to lipid vesicles. The size of the prepore coincides that of the functional pore, except for the transmembrane region, which is absent in the prepore. Biochemical assays indicated that, in the prepore species, the N-terminus is not inserte...

  1. Net Generation at Social Software: Challenging Assumptions, Clarifying Relationships and Raising Implications for Learning

    Science.gov (United States)

    Valtonen, Teemu; Dillon, Patrick; Hacklin, Stina; Vaisanen, Pertti

    2010-01-01

    This paper takes as its starting point assumptions about use of information and communication technology (ICT) by people born after 1983, the so called net generation. The focus of the paper is on social networking. A questionnaire survey was carried out with 1070 students from schools in Eastern Finland. Data are presented on students' ICT-skills…

  2. Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy.

    Science.gov (United States)

    Casarejos, Maria J; Perucho, Juan; Gomez, Ana; Muñoz, Maria P; Fernandez-Estevez, Marian; Sagredo, Onintza; Fernandez Ruiz, Javier; Guzman, Manuel; de Yebenes, Justo Garcia; Mena, Maria A

    2013-01-01

    Cannabinoids are neuroprotective in models of neurodegenerative dementias. Their effects are mostly mediated through CB1 and CB2 receptor-dependent modulation of excitotoxicity, inflammation, oxidative stress, and other processes. We tested the effects of Sativex®, a mixture of Δ9-tetrahydrocannabinol and cannabidiol, acting on both CB1 and CB2 receptors, in parkin-null, human tau overexpressing (PK-/-/TauVLW) mice, a model of complex frontotemporal dementia, parkinsonism, and lower motor neuron disease. The animals received Sativex®, 4.63 mg/kg, ip, daily, for one month, at six months of age, at the onset of the clinical symptoms. We evaluated the effects of Sativex® on behavior, dopamine neurotransmission, glial activation, redox state, mitochondrial activity, and deposition of abnormal proteins. PK-/-/TauVLW mice developed the neurological deficits, but those treated with Sativex® showed less abnormal behaviors related to stress, less auto and hetero-aggression, and less stereotypy. Sativex® significantly reduced the intraneuronal, MAO-related free radicals produced during dopamine metabolism in the limbic system. Sativex® also decreased gliosis in cortex and hippocampus, increased the ratio reduced/oxidized glutathione in the limbic system, reduced the levels of iNOS, and increased those of complex IV in the cerebral cortex. With regard to tau and amyloid pathology, Sativex® reduced the deposition of both in the hippocampus and cerebral cortex of PK-/-/TauVLW mice and increased autophagy. Sativex®, even after a short administration in animals with present behavioral and pathological abnormalities, improves the phenotype, the oxidative stress, and the deposition of proteins in PK-/-/TauVLW mice, a model of complex neurodegenerative disorders. PMID:23478312

  3. Analyses of 32 Loci Clarify Phylogenetic Relationships among Trypanosoma cruzi Lineages and Support a Single Hybridization prior to Human Contact

    OpenAIRE

    Flores-López, Carlos A.; Machado, Carlos A.

    2011-01-01

    Background The genetic diversity of Trypanosoma cruzi, the etiological agent of Chagas disease, has been traditionally divided in two major groups, T. cruzi I and II, corresponding to discrete typing units TcI and TcII-VI under a recently proposed nomenclature. The two major groups of T. cruzi seem to differ in important biological characteristics, and are thus thought to represent a natural division relevant for epidemiological studies and development of prophylaxis. To understand the potent...

  4. Cholesterolosis as a clinical entity which has not been clarified completely by review of the literature and our experience

    OpenAIRE

    ÖZBAĞI, Tuna; ÇAKAR, Kenan Sami; MALKOÇ, Gültekin; TUNÇ, Bilge

    2006-01-01

    Background/aim: Cholesterolosis of the human gallbladder has long been considered as a histomorphological entity. Although its etiology has not been fully understood, recognition of cholesterolosis by the pathologist is easy. Recently it has been questioned whether it is a clinical as well as a histomorphological entity, and it has been reported that it could cause symptoms. Materials and methods: In the Pathology Department of SSK Gazi Hospital, we examined 118 cholecystectomy specimen...

  5. [Case of gallbladder cancer in which the surface structure of gallbladder was clarified using the endoscopic double contrast cholecystography].

    Science.gov (United States)

    Miyata, Hideki; Sato, Kazuhiro; Iwao, Toshiyasu; Yoshida, Koji; Usio, Jun; Sato, Masashi; Ishino, Atsushi; Nagata, Yuki; Kawase, Tomoya; Nomura, Yoshikatsu; Morimoto, Seiko; Takamori, Shigeru; Ajioka, Yoichi

    2009-05-01

    A 75-year-old woman was admitted to our hospital with a gallbladder tumor by detected ultrasonography (US). On endoscopic ultrasonography (EUS), and abdominal CT, we diagnosed the Is+IIa+IIb-like ss lesion invasive gallbladder cancer, but endoscopic double contrast cholecystography suggested IIa+IIb-like ss invasive gallbladder cancer because the lesion had the same granular membrane a other cancer membrane and cholecystectomy was carried out. The pathologic diagnosis was IIa+IIb-like ss invasive gallbladder cancer. PMID:19420873

  6. Does Students' Machismo Fit in School? Clarifying the Implications of Traditional Gender Role Ideology for School Belonging

    Science.gov (United States)

    Huyge, Ellen; Van Maele, Dimitri; Van Houtte, Mieke

    2015-01-01

    How much students feel at home in school predicts academic outcomes. In view of the gender achievement gap, it is worth examining the gendered pattern of this school belonging. Studies on school belonging, however, have barely acknowledged possible obstructive effects of traditional gender role attitudes of individual students and student…

  7. Can Creativity Be Measured? An Attempt to Clarify the Notion of Creativity and General Directions for Future Research

    Science.gov (United States)

    Piffer, Davide

    2012-01-01

    The goal of this investigation is to demonstrate that much of the confusion regarding the measurement of creativity is caused by the insufficient clarity of its definition and to provide suggestions for an improved assessment and new possible tools of investigation (e.g. interviews). It is shown that three dimensions of creativity (novelty,…

  8. Introducing personality tests to clarify engineering student self-perception and demystify recruitment procedures: quantitative and qualitative results

    OpenAIRE

    ROUVRAIS, Siegfried; Chelin, Nathalie

    2012-01-01

    It is often said that Generation Y students have little professional ideal, uncertainty and indecision dominating their professional future appraisal. Engineering program designers are now faced with such new student generations. They certainly must trust students to finally find their own way, but they must also give them a sense of responsibility so as to enable them to take care of their career, as soon as possible and at best, in accordance with their genuine wishes. In 2007, Telecom Bret...

  9. An example of how barcodes can clarify cryptic species: the case of the calanoid copepod Mastigodiaptomus albuquerquensis (Herrick.

    Directory of Open Access Journals (Sweden)

    Martha Angélica Gutiérrez-Aguirre

    Full Text Available BACKGROUND: The freshwater calanoid Mastigodiaptomus is a genus with high richness in the Americas and is composed of nine species, seven recorded in Mexico and four that are apparently endemic to small areas. Mastigodiaptomus albuquerquensis is a common, widely distributed species ranging from the southern USA to Central America. This species can be easily identified by a notable butterfly-like sclerotization on the basis of the right fifth leg of males. Nevertheless, morphological differences observed among populations throughout this species distributional range have led to the description of several related species or subspecies, such as M. albuquerquensis patzcuarensis from Lake Pátzcuaro in the Central Plateau of Mexico. METHODS: Genetic results based on barcodes, morphology based on scanning electron and light microscopy images, and morphometric analyses were used to describe cryptic species within the M. albuquerquensis complex. RESULTS: The morphological analyses coincided partially with the genetic markers, suggesting the existence of at least two sibling species: M. albuquerquensis s. str. and M. patzcuarensis. A third species was genetically separated but was morphologically indistinguishable from the M. patzcuarensis group. CONCLUSIONS: Hidden diversity has been a major problem in establishing real patterns of species distribution and genetic acquisition from megadiverse hotspots such as Mexico, where the Nearctic and the Neotropical regions of the Americas meet. Barcodes can help taxonomists to reveal and formally name these new species. Here, we describe two of three potential species highlighted by the use of barcodes: M. albuquerquensis s. str. in the northern semi-desert and M. patzcuarensis on the Central Plateau at more than 2000 m above sea level.

  10. An Example of How Barcodes Can Clarify Cryptic Species: The Case of the Calanoid Copepod Mastigodiaptomus albuquerquensis (Herrick)

    OpenAIRE

    Martha Angélica Gutiérrez-Aguirre; Adrián Cervantes-Martínez; Manuel Elías-Gutiérrez

    2014-01-01

    BACKGROUND: The freshwater calanoid Mastigodiaptomus is a genus with high richness in the Americas and is composed of nine species, seven recorded in Mexico and four that are apparently endemic to small areas. Mastigodiaptomus albuquerquensis is a common, widely distributed species ranging from the southern USA to Central America. This species can be easily identified by a notable butterfly-like sclerotization on the basis of the right fifth leg of males. Nevertheless, morphological differenc...

  11. Towards clarifying what distinguishes cyanobacteria able to resurrect after desiccation from those that cannot: The photosynthetic aspect.

    Science.gov (United States)

    Raanan, Hagai; Oren, Nadav; Treves, Haim; Keren, Nir; Ohad, Itzhak; Berkowicz, Simon M; Hagemann, Martin; Koch, Moriz; Shotland, Yoram; Kaplan, Aaron

    2016-06-01

    Organisms inhabiting biological soil crusts (BSCs) are able to cope with extreme environmental conditions including daily hydration/dehydration cycles, high irradiance and extreme temperatures. The photosynthetic machinery, potentially the main source of damaging reactive oxygen species during cessation of CO(2) fixation in desiccating cells, must be protected to avoid sustained photodamage. We compared certain photosynthetic parameters and the response to excess light of BCS-inhabiting, desiccation-tolerant cyanobacteria Leptolyngbya ohadii and Nostoc reinholdii with those observed in the "model" organisms Nostoc sp. PCC 7120, able to resurrect after mild desiccation, and Synechococcus elongatus PCC 7942 and Synechocystis sp. PCC 6803 that are unable to recover from dehydration. Desiccation-tolerant strains exhibited a transient decline in the photosynthetic rate at light intensities corresponding to the inflection point in the PI curve relating the O(2) evolution rate to light intensity. They also exhibited a faster and larger loss of variable fluorescence and profoundly faster Q(A)(-) re-oxidation rates after exposure to high illumination. Finally, a smaller difference was found in the temperature of maximal thermoluminescence signal in the absence or presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) than observed in "model" cyanobacteria. These parameters indicate specific functional differences of photosystem II (PSII) between desiccation tolerant and sensitive cyanobacteria. We propose that exposure to excess irradiation activates a non-radiative electron recombination route inside PSII that minimizes formation of damaging singlet oxygen in the desiccation-tolerant cyanobacteria and thereby reduces photodamage. PMID:26896589

  12. Comparative phylogeography clarifies the complexity and problems of continental distribution that drove A. R. Wallace to favor islands.

    Science.gov (United States)

    Riddle, Brett R

    2016-07-19

    Deciphering the geographic context of diversification and distributional dynamics in continental biotas has long been an interest of biogeographers, ecologists, and evolutionary biologists. Thirty years ago, the approach now known as comparative phylogeography was introduced in a landmark study of a continental biota. Here, I use a set of 455 studies to explore the current scope of continental comparative phylogeography, including geographic, conceptual, temporal, ecological, and genomic attributes. Geographically, studies are more frequent in the northern hemisphere, but the south is catching up. Most studies focus on a Quaternary timeframe, but the Neogene is well represented. As such, explanations for geographic structure and history include geological and climatic events in Earth history, and responses include vicariance, dispersal, and range contraction-expansion into and out of refugia. Focal taxa are biased toward terrestrial or semiterrestrial vertebrates, although plants and invertebrates are well represented in some regions. The use of various kinds of nuclear DNA markers is increasing, as are multiple locus studies, but use of organelle DNA is not decreasing. Species distribution models are not yet widely incorporated into studies. In the future, continental comparative phylogeographers will continue to contribute to erosion of the simple vicariance vs. dispersal paradigm, including exposure of the widespread nature of temporal pseudocongruence and its implications for models of diversification; provide new templates for addressing a variety of ecological and evolutionary traits; and develop closer working relationships with earth scientists and biologists in a variety of disciplines. PMID:27432953

  13. Clarifying the paradigm for the ethics of donation and transplantation: Was 'dead' really so clear before organ donation?

    OpenAIRE

    Shemie Sam D

    2007-01-01

    Abstract Recent commentaries by Verheijde et al, Evans and Potts suggesting that donation after cardiac death practices routinely violate the dead donor rule are based on flawed presumptions. Cell biology, cardiopulmonary resuscitation, critical care life support technologies, donation and transplantation continue to inform concepts of life and death. The impact of oxygen deprivation to cells, organs and the brain is discussed in relation to death as a biological transition. In the face of ad...

  14. Formative and shared assessment in higher education. Clarifying concepts and proposing interventions from the formative and shared assessment network

    OpenAIRE

    Víctor Manuel López Pastor

    2012-01-01

    The purpose of this paper is threefold: (a)-making an introduction to the formative and shared assessment at Higher Education teaching and tracing its connections within the process of convergence towards the Higher Education European Area (HEEA), (b) - establishing a conceptual clarification of the different terms that are currently used in the literature in relation to the formative assessment and student participation in assessment, (c)- making a brief introduction to the proposal of Forma...

  15. Sequencing of 15,622 gene-bearing BACs clarifies the gene-dense regions of the barley genome

    Science.gov (United States)

    Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework....

  16. Clarifying the learning experiences of healthcare professionals with in situ and off-site simulation-based medical education

    DEFF Research Database (Denmark)

    Sørensen, Jette Led; Navne, Laura Emdal; Martin, Helle Max;

    2015-01-01

    -five healthcare professionals (obstetricians, midwives, auxiliary nurses, anaesthesiologists, a nurse anaesthetist and operating theatre nurse) participated in four focus groups and were recruited due to their exposure to either ISS or OSS in multidisciplinary obstetric emergencies in a randomised trial. SETTING......OBJECTIVE: To examine how the setting in in situ simulation (ISS) and off-site simulation (OSS) in simulation-based medical education affects the perceptions and learning experience of healthcare professionals. DESIGN: Qualitative study using focus groups and content analysis. PARTICIPANTS: Twenty...... independent of the ISS or OSS setting. Several positive and negative factors in simulation were identified, but these had no relation to the simulation setting. Participants from ISS and OSS generated a better understanding of and collaboration with the various health professionals. They also provided...

  17. mtDNA from hair and nail clarifies the genetic relationship of the 15th century Qilakitsoq Inuit mummies

    DEFF Research Database (Denmark)

    Gilbert, M Thomas P; Djurhuus, Durita; Melchior, Linea;

    2007-01-01

    typing, and incomplete STR results led researchers to conclude that the eight mummies formed two distinct family groups: A grandmother (I/5), two daughters (I/3, I/4), and their two children (I/1, I/2) in one grave, and two sisters (II/6, II/8) and a daughter (II/7) of one of them in the other. Using mtDNA...... from hair and nail, we have reanalyzed the mummies. The results allowed the unambiguous assignment of each of the mummies to one of three mtDNA haplogroups: A2b (I/5); A2a (I/2, I/3, II/6, II/8); A2a-311 (I/1, I/4, II/7), excluded some of the previous relations, and pointed to new ones. I/5 is not the...

  18. 75 FR 31334 - Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's “Required Use...

    Science.gov (United States)

    2010-06-03

    ... agencies, the real estate and mortgage industry, and federal, state, and local consumer protection and... URBAN DEVELOPMENT 24 CFR Part 3500 RIN 2502-A178 Real Estate Settlement Procedures Act (RESPA... system of referrals by those in a position to refer settlement business (such as builders, real...

  19. Clarifying the Effects of Human Resource Diversity Management Practices on Organizational Citizenship Behavior: The Mediating Role of Diversity Receptiveness

    Directory of Open Access Journals (Sweden)

    Ahmad Nizan Mat Noor

    2014-06-01

    Full Text Available The aim of this study is to scrutinize the impact of employees’ perceptions of their organization’s human resource diversity management (HRDM practices on their organizational citizenship behavior (OCB level. The influence of diversity receptiveness as a mediator in the proposed relationship is also examined. Survey data were gathered from operational employees attached to large hotel in Malaysia. 430 usable questionnaires were used in statistical analyses. The results indicated that the hypothesized linkage between HRDM practices and diversity receptiveness as well as between HRDM practices and OCB were partially supported. The mediating role of diversity receptiveness in the relationship was also partially supported. Implications and limitations of the findings are specified. Finally, directions for future research are suggested.

  20. Towards Using Transformative Education as a Benchmark for Clarifying Differences and Similarities between Environmental Education and Education for Sustainable Development

    Science.gov (United States)

    Pavlova, Margarita

    2013-01-01

    The UN Decade of Education for Sustainable Development (DESD) charges educators with a key role in developing and "securing sustainable life chances, aspirations and futures for young people". Environmental Education (EE) and ESD share a vision of quality education and a society that lives in balance with Earth's carrying capacity,…

  1. 76 FR 71294 - Prions; Proposed Amendment To Clarify Product Performance Data for Products With Prion-Related...

    Science.gov (United States)

    2011-11-17

    ... types of prions are commonly designated by the type of diseases they produce, such as PrP\\Sc\\ (prions associated with scrapie) and PrP\\BSE\\ (prions associated with bovine spongiform encephalopathy--mad cow disease). In the disease process, prions (such as PrP\\sc\\) recruit normal prion proteins (PrP\\c\\)...

  2. 蜂蜜酒澄清机理研究%Study on Mechanism of Clarifying Honey Wine

    Institute of Scientific and Technical Information of China (English)

    王淼

    2005-01-01

    用魔芋精粉作为蜂蜜酒的澄清剂,其作用明显优于其他的澄清剂.魔芋精粉在溶液中形成网状结构,蛋白质分子和杂质被吸附在网膜上,从而使蜂蜜酒得到澄清.

  3. Lipid Exchange Mechanism of the Cholesteryl Ester Transfer Protein Clarified by Atomistic and Coarse-grained Simulations

    DEFF Research Database (Denmark)

    Koivuniemi, A.; Vuorela, T.; Kovanen, P. T.; Vattulainen, I.; Hyvonen, M. T.

    2012-01-01

    change of helix X of CETP to an open state, in which we found the accessibility of cholesteryl esters to the C-terminal tunnel opening of CETP to increase. Furthermore, in the absence of helix X, cholesteryl esters rapidly diffused into CETP through the C-terminal opening. The results provide compelling...... through its charged and tryptophan residues. Upon binding, CETP rapidly (in about 10 ns) induced the formation of a small hydrophobic patch to the phospholipid surface of the droplet, opening a route from the core of the lipid droplet to the binding pocket of CETP. This was followed by a conformational...... evidence that helix X acts as a lid which conducts lipid exchange by alternating the open and closed states. The findings have potential for the design of novel molecular agents to inhibit the activity of CETP....

  4. The Time Value of Carbon and Carbon Storage: Clarifying the terms and the policy implications of the debate

    OpenAIRE

    Marshall, Liz; Kelly, Alexia

    2010-01-01

    The question of whether there is any value to the temporary storage of carbon is fundamental to climate policy design across a number of arenas, including physical carbon discounting in greenhouse gas accounting, the relative value of temporary carbon offsets, and the value of other carbon mitigation efforts that are known to be impermanent, including deferred deforestation. Quantifying the value of temporary carbon storage depends on a number of assumptions about how the incremental impact (...

  5. Novel storage technologies for raw and clarified syrup biomass feedstocks from sweet sorghum (Sorghum bicolor L. Moench)

    Science.gov (United States)

    Attention is currently focused on developing sustainable supply chains of sugar feedstocks for new, flexible biorefineries. Fundamental processing needs identified by industry for the large-scale manufacture of biofuels and bioproducts from sweet sorghum (Sorghum bicolor L. Moench) include stabiliz...

  6. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes

    OpenAIRE

    Hughes, Jennifer F.; Skaletsky, Helen; Page, David C.

    2012-01-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the...

  7. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes.

    Science.gov (United States)

    Hughes, Jennifer F; Skaletsky, Helen; Page, David C

    2012-12-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the Y chromosome about 38 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage. Editor's suggested further reading in BioEssays Should Y stay or should Y go: The evolution of non-recombining sex chromosomes Abstract. PMID:23055411

  8. In-situ biodiesel production from a municipal waste water clarifier effluent stream / Gert Cornelius van Tonder

    OpenAIRE

    Van Tonder, Gert Cornelius

    2014-01-01

    This study investigated In situ biodiesel production with supercritical methanol. A micro-algae based feedstock was used and obtained from a local water treatment plant situated just outside of Bethal, South Africa (S 26° 29’ 19.362” E 29° 27’ 11.552”). The wet feedstock was used as harvested with only the excess moisture being removed. Characterisation of the feedstock showed that a wide variety of macro-algae, micro-algae, cyanobacteria and bacterial species were present in the feedstock...

  9. DNA barcode of Parodontidae species from the La Plata river basin - applying new data to clarify taxonomic problems

    Directory of Open Access Journals (Sweden)

    Elisangela Bellafronte

    2013-09-01

    Full Text Available In the past years, DNA barcoding has emerged as a quick, accurate and efficient tool to identify species. Considering the difficulty in identifying some Parodontidae species from the La Plata basin and the absence of molecular data for the group, we aimed to test the effectiveness of DNA barcoding and discuss the importance of using different approaches to solve taxonomic problems. Eight species were analyzed with partial sequences of Cytochrome c oxidase I. The mean intraspecific K2P genetic distance was 0.04% compared to 4.2% for mean interspecific K2P genetic distance. The analyses of distance showed two pairs of species with K2P genetic divergence lower than 2%, but enough to separate these species. Apareiodon sp. and A. ibitiensis, considered as the same species by some authors, showed 4.2% genetic divergence, reinforcing their are different species. Samples of A. affinis from the Uruguay and Paraguay rivers presented 0.3% genetic divergence, indicating a close relationship between them. However, these samples diverged 6.1% from the samples of the upper Paraná River, indicating that the latter represents a potentially new species. The results showed the effectiveness of the DNA barcoding method in identifying the analyzed species, which, together with the morphological and cytogenetic available data, help species identification.

  10. Sequencing of 15622 gene-bearing BACs clarifies the gene-dense regions of the barley genome

    Czech Academy of Sciences Publication Activity Database

    Munoz-Amatriain, M.; Lonardi, S.; Luo, M.C.; Madishetty, K.; Svensson, J.T.; Moscou, M. J.; Wanamaker, S.; Kudrna, D.; Zheng, J.; Šimková, Hana; Doležel, Jaroslav; Grimwood, J.; Mammadov, J.; Close, T.J.

    2015-01-01

    Roč. 84, č. 1 (2015), s. 216-227. ISSN 0960-7412 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Barley * Hordeum vulgare L * BAC sequencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.972, year: 2014

  11. To thine own self be true? Clarifying the effects of identity discrepancies on psychological distress and emotions.

    Science.gov (United States)

    Kalkhoff, Will; Marcussen, Kristen; Serpe, Richard T

    2016-07-01

    After many years of research across disciplines, it remains unclear whether people are more motivated to seek appraisals that accurately match self-views (self-verification) or are as favorable as possible (self-enhancement). Within sociology, mixed findings in identity theory have fueled the debate. A problem here is that a commonly employed statistical approach does not take into account the direction of a discrepancy between how we see ourselves and how we think others see us in terms of a given identity, yet doing so is critical for determining which self-motive is at play. We offer a test of three competing models of identity processes, including a new "mixed motivations" model where self-verification and self-enhancement operate simultaneously. We compare the models using the conventional statistical approach versus response surface analysis. The latter method allows us to determine whether identity discrepancies involving over-evaluation are as distressing as those involving under-evaluation. We use nationally representative data and compare results across four different identities and multiple outcomes. The two statistical approaches lead to the same conclusions more often than not and mostly support identity theory and its assumption that people seek self-verification. However, response surface tests reveal patterns that are mistaken as evidence of self-verification by conventional procedures, especially for the spouse identity. We also find that identity discrepancies have different effects on distress and self-conscious emotions (guilt and shame). Our findings have implications not only for research on self and identity across disciplines, but also for many other areas of research that incorporate these concepts and/or use difference scores as explanatory variables. PMID:27194649

  12. Relational and Overt Aggression in Childhood and Adolescence: Clarifying Mean-Level Gender Differences and Associations with Peer Acceptance

    Science.gov (United States)

    Smith, Rhiannon L.; Rose, Amanda J.; Schwartz-Mette, Rebecca A.

    2010-01-01

    Research on relational aggression has drawn attention to how girls may be likely to aggress, but the role of gender is not fully understood. There are opposing views regarding whether relational aggression is most common among girls. Current findings demonstrate that when gender differences in relational aggression are assessed with peer…

  13. Defining the value of community benefits. Analyzing the kinds of goods society produces clarifies hospitals' charity care contribution.

    Science.gov (United States)

    Sanders, S M

    1992-01-01

    Community benefits occur when a hospital bears all or part of the relatively unquantifiable costs of promoting, sponsoring, or engaging in religious, educational, scientific, or health-related activities designed to improve community health. By the very nature of their health-related activities, not-for-profit hospitals make extensive and varied contributions to community benefit. When a hospital free clinic inoculates a child for measles, the community as a whole benefits because the inoculation reduces the chance that measles will spread. Not-for-profit hospitals also provide many goods that are "undersupplied" by the for-profit private sector or the public sector, such as research, trauma centers used disproportionately by self-pay patients, and advocacy to rid the community of health hazards. Moreover, a number of factors impose a legal and normative obligation on not-for-profit hospitals to engage in activities that benefit the community. These include Internal Revenue Service rules governing tax exemption, hospitals' fiduciary responsibilities to philanthropic donors, their obligations as "institutional actors" in their communities, and their mission to reach out to the poor and underserved. PMID:10119536

  14. Clarifying Parent Involvement and Family-School Partnership Intervention Research: A Preliminary Synthesis. CYFS Working Paper No. 2012-4

    Science.gov (United States)

    Sheridan, Susan M.; Kim, Elizabeth Moorman; Coutts, Michael J.; Sjuts, Tara M.; Holmes, Shannon R.; Ransom, Kelly A.; Garbacz, S. Andrew

    2012-01-01

    Interactions and experiences within home and school systems, uniquely and together, form the foundation for developmental trajectories throughout students' educational careers. As a lifelong resource, families represent the first essential system and source of support for the learning and development of children and adolescents. When parents are…

  15. Clarifying the paradigm on radiator effects and safety management: unscear report on attribution on effects and inference of risks

    International Nuclear Information System (INIS)

    The aim of this paper is to describe a relatively recent international agreement on the widely debated concepts of: (i) attributing effects to low dose radiation exposure situations that have occurred in the past and, (ii) inferring radiation risk to situations that are planned to occur in the future. An important global consensus has been recently achieved on these fundamental issues at the level of the highest international intergovernmental body: the General Assembly of the United Nations. The General Assembly has welcomed with appreciation a scientific report on attributing health effects to radiation exposure and inferring risks that had been prepared the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) following a formal request by the General Assembly.

  16. Comparative genetics: a lens through which to clarify the genomes, the transmission history, and the reproductive biology of Trichinella spp.

    Science.gov (United States)

    Progress in studying the biology of Trichinella spp. was greatly advanced with the publication and analysis of the draft genome sequence of T. spiralis. Those data provide a basis for constructing testable hypothesis concerning parasite physiology, immunology, and genetics. They also provide tools...

  17. New approaches to clarify antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves.

    Science.gov (United States)

    da Silva, Jucélia Barbosa; Temponi, Vanessa dos Santos; Fernandes, Felipe Valente; de Assis Dias Alves, Geórgia; de Matos, Dalyara Mendonça; Gasparetto, Carolina Miranda; Ribeiro, Antônia; de Pinho, José de Jesus R G; Alves, Maria Silvana; de Sousa, Orlando Vieira

    2011-01-01

    The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved. PMID:22272116

  18. New Approaches to Clarify Antinociceptive and Anti-Inflammatory Effects of the Ethanol Extract from Vernonia condensata Leaves

    Directory of Open Access Journals (Sweden)

    Orlando Vieira de Sousa

    2011-12-01

    Full Text Available The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00, 200 (42.00 ± 2.98 and 400 mg/kg (39.00 ± 4.00. In formalin tests, a significant reduction in the licking time (p < 0.01 was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44 and 31.15% (400 mg/kg = 48.00 ± 4.37. The doses of 100 (43.37 ± 5.15, 200 (34.62 ± 4.16 and 400 mg/kg (28.37 ± 3.98 inhibited (p < 0.001 the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001 at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved.

  19. Clarifying the chemical state of additives in membranes for polymer electrolyte fuel cells by X-ray absorption fine structure

    Science.gov (United States)

    Tanuma, Toshihiro; Itoh, Takanori

    2016-02-01

    Cerium and manganese compounds are used in the membrane for polymer electrolyte fuel cells (PEFCs) as radical scavengers to mitigate chemical degradation of the membrane. The chemical states of cerium and manganese in the membrane were investigated using a fluorescence X-ray absorption fine structure (XAFS) technique. Membrane electrode assemblies (MEAs) were subjected to open circuit voltage (OCV) condition, under which hydroxyl radicals attack the membrane; a shift in absorption energy in X-ray absorption near edge structure (XANES) spectra was compared between Ce- and Mn-containing membranes before and after OCV testing. In the case of the Ce-containing MEA, there was no significant difference in XANES spectra before and after OCV testing, whereas in the case of the Mn-containing MEA, there was an obvious shift in XANES absorption energy after OCV testing, indicating that Mn atoms with higher valence state than 2+ exist in the membrane after OCV testing. This can be attributed to the difference in the rate of reduction; the reaction of Ce4+ with ·OOH is much faster than that of Mn3+ with ·OOH, leaving some of the Mn atoms with higher valence state. It was confirmed that cerium and manganese redox couples reduced the attack from radicals, mitigating membrane degradation.

  20. DICER1 syndrome ? clarifying the diagnosis, clinical features and management implications of a pleiotropic tumor predisposition syndrome

    OpenAIRE

    2011-01-01

    Abstract Background: Constitutional DICER1 mutations were recently reported to cause familial pleuropulmonary blastoma (PPB). We sought to investigate the contribution and phenotypic spectrum of constitutional and somatic DICER1 mutations to cancer. Methods and Results: We sequenced DICER1 in constitutional DNA from 823 unrelated individuals with a variety of tumors and in 781 cancer cell lines. We identified constitutional DICER1 mutations in 19 families including 11/14 wi...