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Sample records for camp analog induce

  1. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway.

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    Judith A Enyeart

    Full Text Available Adrenal zona fasciculata (AZF cells express a cAMP-activated guanine nucleotide exchange protein (Epac2 that may function in ACTH-stimulated cortisol synthesis. Experiments were done to determine whether cAMP analogs that selectively activate Epacs could induce cortisol synthesis and the expression of genes coding for steroidogenic proteins in bovine AZF cells. Treatment of AZF cells with the Epac-selective cAMP analog (ESCA 8CPT-2'-OMe-cAMP induced large (>100 fold, concentration-dependent, delayed increases in cortisol synthesis and the expression of mRNAs coding for the steroid hydroxylases CYP11a1, CYP17, CYP21, and the steroid acute regulatory protein (StAR. However, a non-hydrolyzable analog of this ESCA, Sp-8CPT-2'-OMe-cAMP, failed to stimulate cortisol production even at concentrations that activated Rap1, a downstream effector of Epac2. Accordingly, putative metabolites of 8CPT-2'-OMe-cAMP, including 8CPT-2'-OMe-5'AMP, 8CPT-2'-OMe-adenosine, and 8CPT-adenine all induced cortisol synthesis and steroid hydroxylase mRNA expression with a temporal pattern, potency, and effectiveness similar to the parent compound. At concentrations that markedly stimulated cortisol production, none of these metabolites significantly activated cAMP-dependent protein kinase (PKA. These results show that one or more metabolites of the ESCA 8CPT-2'-OMe-cAMP induce cortico-steroidogenesis by activating a panel of genes that code for steroidogenic proteins. The remarkable increases in cortisol synthesis observed in this study appear to be mediated by a novel cAMP-, Epac- and PKA-independent signaling pathway.

  2. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

    Science.gov (United States)

    Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

    2016-01-01

    The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

  3. Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs.

    Science.gov (United States)

    Bellotti, Marta; Salis, Annalisa; Grozio, Alessia; Damonte, Gianluca; Vigliarolo, Tiziana; Galatini, Andrea; Zocchi, Elena; Benatti, Umberto; Millo, Enrico

    2015-01-01

    The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is also produced and released by several mammalian cell types, including human granulocytes, where it stimulates innate immune functions via an increase of the intracellular cAMP concentration ([cAMP]i). We synthesized several ABA analogs and evaluated the structure-activity relationship, by the systematical modification of selected regions of these analogs. The resulting molecules were tested for their ability to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modified configurations at C-2' and C-3' abrogated the ABA-induced increase of the [cAMP]i and also inhibited several pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly, these analogs could be suitable as novel putative anti-inflammatory compounds.

  4. Biochemical characterization and cellular imaging of a novel, membrane permeable fluorescent cAMP analog

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    Zaccolo Manuela

    2008-06-01

    Full Text Available Abstract Background A novel fluorescent cAMP analog (8-[Pharos-575]- adenosine-3', 5'-cyclic monophosphate was characterized with respect to its spectral properties, its ability to bind to and activate three main isoenzymes of the cAMP-dependent protein kinase (PKA-Iα, PKA-IIα, PKA-IIβ in vitro, its stability towards phosphodiesterase and its ability to permeate into cultured eukaryotic cells using resonance energy transfer based indicators, and conventional fluorescence imaging. Results The Pharos fluorophore is characterized by a Stokes shift of 42 nm with an absorption maximum at 575 nm and the emission peaking at 617 nm. The quantum yield is 30%. Incubation of the compound to RIIα and RIIβ subunits increases the amplitude of excitation and absorption maxima significantly; no major change was observed with RIα. In vitro binding of the compound to RIα subunit and activation of the PKA-Iα holoenzyme was essentially equivalent to cAMP; RII subunits bound the fluorescent analog up to ten times less efficiently, resulting in about two times reduced apparent activation constants of the holoenzymes compared to cAMP. The cellular uptake of the fluorescent analog was investigated by cAMP indicators. It was estimated that about 7 μM of the fluorescent cAMP analog is available to the indicator after one hour of incubation and that about 600 μM of the compound had to be added to intact cells to half-maximally dissociate a PKA type IIα sensor. Conclusion The novel analog combines good membrane permeability- comparable to 8-Br-cAMP – with superior spectral properties of a modern, red-shifted fluorophore. GFP-tagged regulatory subunits of PKA and the analog co-localized. Furthermore, it is a potent, PDE-resistant activator of PKA-I and -II, suitable for in vitro applications and spatial distribution evaluations in living cells.

  5. Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia.

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    Ocorr, K A; Walters, E T; Byrne, J H

    1985-04-01

    Bilateral clusters of sensory neurons in the pleural ganglia of Aplysia contain cells involved in a defensive tail withdrawal reflex. These cells exhibit heterosynaptic facilitation in response to noxious skin stimulation that can be mimicked by the application of serotonin. Recently it has been shown that this facilitation can be selectively amplified by the application of a classical conditioning procedure to individual sensory neurons. We now report that an analog of this classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. The enhancement is achieved within a single trial and appears to be localized to the sensory neurons. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative neuronal modifications and perhaps learning.

  6. Classical Analog of Electromagnetically Induced Transparency

    CERN Document Server

    Alzar, C L G; Nussenzveig, P

    2002-01-01

    We present a classical analog for Electromagnetically Induced Transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force we can reproduce the phenomenology observed in EIT. We describe a simple experiment performed with two linearly coupled RLC circuits which can be taught in an undergraduate laboratory class.

  7. Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury

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    Little, T. M.; Butler, B. D.

    1997-01-01

    Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

  8. cAMP Modulates Macrophage Development by Suppressing M-CSF-Induced MAPKs Activation

    Institute of Scientific and Technical Information of China (English)

    Ning Zhu; Jian Cui; Chunxia Qiao; Yan Li; Yuanfang Ma; Jiyan Zhang; Beifen Shen

    2008-01-01

    M-CSF is a key cytokine in macrophage development by inducing MAPKs activation, and cAMP can inhibit MAPKs activation induced by inflammatory stimuli. To explore the effects of cAMP on M-CSF-induced MAPKs activation and on macrophage development, the model of bone marrow-derived murine macrophages (BMMs) was used. The effects of cAMP on M-CSF-induced MAPKs activation were analyzed by Western blotting assay, and the effects of cAMP on CD14 and F4/80 expression during macrophage development were examined by FACS analysis.Macrophage morphology showed the successful establishment of the model of macrophage development. Western blotting assay revealed that M-CSF activated ERK, JNK and p38 in both mature and immature macrophages, and cAMP inhibited M-CSF-induced ERK, JNK and p38 activation in a time-dependent manner. FACS analysis revealed that macrophage development was impaired with cAMP pretreatment. In conclusion, cAMP modulates macrophage development by suppressing M-CSF-induced MAPKs activation.

  9. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

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    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  10. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes.

    Science.gov (United States)

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R

    2012-06-22

    Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

  11. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements.

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    Firth, J D; Ebert, B L; Ratcliffe, P J

    1995-09-08

    The oxygen-regulated control system responsible for the induction of erythropoietin (Epo) by hypoxia is present in most (if not all) cells and operates on other genes, including those involved in energy metabolism. To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, we have studied the 5' flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH). Deletional and mutational analysis of the function of mouse LDH-reporter fusion gene constructs in transient transfection assays defined three domains, between -41 and -84 base pairs upstream of the transcription initiation site, which were crucial for oxygen-regulated expression. The most important of these, although not capable of driving hypoxic induction in isolation, had the consensus of a hypoxia-inducible factor 1 (HIF-1) site, and cross-competed for the binding of HIF-1 with functionally active Epo and phosphoglycerate kinase-1 sequences. The second domain was positioned close to the HIF-1 site, in an analogous position to one of the critical regions in the Epo 3' hypoxic enhancer. The third domain had the motif of a cAMP response element (CRE). Activation of cAMP by forskolin had no effect on the level of LDH mRNA in normoxia, but produced a magnified response to hypoxia that was dependent upon the integrity of the CRE, indicating an interaction between inducible factors binding the HIF-1 and CRE sites.

  12. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes.

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    Abdel-Malek, Zalfa A; Ruwe, Andrew; Kavanagh-Starner, Renny; Kadekaro, Ana Luisa; Swope, Viki; Haskell-Luevano, Carrie; Koikov, Leonid; Knittel, James J

    2009-10-01

    One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.

  13. IL-4 induces cAMP and cGMP in human monocytic cells

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    B. Dugas

    1995-01-01

    Full Text Available Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min and cAMP (20 – 25 min in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1 IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2 cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.

  14. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S;

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determin...... an important role of these signalling molecules, the present study questions whether cAMP and cGMP in peripheral blood can be used for monitoring pathophysiological events in headache and migraine mechanisms.......Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...

  15. Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac.

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    Leech, Colin A; Dzhura, Igor; Chepurny, Oleg G; Schwede, Frank; Genieser, Hans-G; Holz, George G

    2010-01-01

    Clinical studies demonstrate that combined administration of sulfonylureas with exenatide can induce hypoglycemia in type 2 diabetic subjects. Whereas sulfonylureas inhibit ß-cell K(ATP) channels by binding to the sulfonylurea receptor-1 (SUR1), exenatide binds to the GLP-1 receptor, stimulates ß-cell cAMP production and activates both PKA and Epac. In this study, we hypothesized that the adverse in vivo interaction of sulfonylureas and exenatide to produce hypoglycemia might be explained by Epac-mediated facilitation of K(ATP) channel sulfonylurea sensitivity. We now report that the inhibitory action of a sulfonylurea (tolbutamide) at K(ATP) channels was facilitated by 2’-O-Me-cAMP, a selective activator of Epac. Thus, under conditions of excised patch recording, the dose-response relationship describing the inhibitory action of tolbutamide at human ß-cell or rat INS-1 cell K(ATP) channels was left-shifted in the presence of 2’-O-Me-cAMP, and this effect was abolished in INS-1 cells expressing a dominant-negative Epac2. Using an acetoxymethyl ester prodrug of an Epac-selective cAMP analog (8-pCP T-2’-O-Me-cAMP-AM), the synergistic interaction of an Epac activator and tolbutamide to depolarize INS-1 cells and to raise [Ca²(+)](i) was also measured. This effect of 8-pCP T-2’-O-Me-cAMP-AM correlated with its ability to stimulate phosphatidylinositol 4,5-bisphosphate hydrolysis that might contribute to the changes in K(ATP) channel sulfonylurea-sensitivity reported here. On the basis of such findings, we propose that the adverse interaction of sulfonylureas and exenatide to induce hypoglycemia involves at least in part, a functional interaction of these two compounds to close K(ATP) channels, to depolarize ß-cells and to promote insulin secretion.

  16. The cAMP signaling system inhibits the repair of {gamma}-ray-induced DNA damage by promoting Epac1-mediated proteasomal degradation of XRCC1 protein in human lung cancer cells

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    Cho, Eun-Ah [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr [Department of Biochemistry and Molecular Biology, Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer cAMP signaling system inhibits repair of {gamma}-ray-induced DNA damage. Black-Right-Pointing-Pointer cAMP signaling system inhibits DNA damage repair by decreasing XRCC1 expression. Black-Right-Pointing-Pointer cAMP signaling system decreases XRCC1 expression by promoting its proteasomal degradation. Black-Right-Pointing-Pointer The promotion of XRCC1 degradation by cAMP signaling system is mediated by Epac1. -- Abstract: Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on {gamma}-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (G{alpha}sQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of G{alpha}sQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after {gamma}-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2 Prime -O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2 Prime -O-Me-cAMP and restored XRCC1 protein level following {gamma}-ray irradiation. From

  17. Exchange factors directly activated by cAMP mediate melanocortin 4 receptor-induced gene expression

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    Glas, Evi; Mückter, Harald; Gudermann, Thomas; Breit, Andreas

    2016-01-01

    Gs protein-coupled receptors regulate many vital body functions by activation of cAMP response elements (CRE) via cAMP-dependent kinase A (PKA)-mediated phosphorylation of the CRE binding protein (CREB). Melanocortin 4 receptors (MC4R) are prototypical Gs-coupled receptors that orchestrate the hypothalamic control of food-intake and metabolism. Remarkably, the significance of PKA for MC4R-induced CRE-dependent transcription in hypothalamic cells has not been rigorously interrogated yet. In two hypothalamic cell lines, we observed that blocking PKA activity had only weak or no effects on reporter gene expression. In contrast, inhibitors of exchange factors directly activated by cAMP-1/2 (EPAC-1/2) mitigated MC4R-induced CRE reporter activation and mRNA induction of the CREB-dependent genes c-fos and thyrotropin-releasing hormone. Furthermore, we provide first evidence that extracellular-regulated kinases-1/2 (ERK-1/2) activated by EPACs and not PKA are the elusive CREB kinases responsible for MC4R-induced CREB/CRE activation in hypothalamic cells. Overall, these data emphasize the pivotal role of EPACs rather than PKA in hypothalamic gene expression elicited by a prototypical Gs-coupled receptor. PMID:27612207

  18. Effects of Multimedia and Schema Induced Analogical Reasoning on Science Learning

    Science.gov (United States)

    Zheng, R. Z.; Yang, W.; Garcia, D.; McCadden, E. P.

    2008-01-01

    The present study investigates the effects of multimedia and schema induced analogical reasoning on science learning. It involves 89 fourth grade elementary students in the north-east of the United States. Participants are randomly assigned into four conditions: (a) multimedia with analogy; (b) multimedia without analogy; (c) analogy without…

  19. Analogs of cyclic AMP as chemoattractants and inhibitors of Dictyostelium chemotaxis.

    Science.gov (United States)

    Van Haastert, P J; Jastorff, B; Pinas, J E; Konijn, T M

    1982-01-01

    Aggregative amoebae of Dictyostelium discoideum, D. mucoroides, D. purpureum, and D. rosarium react chemotactically to cyclic AMP (cAMP). We measured the chemotactic activity of 14 cAMP analogs and found that these four species have a similar sensitivity to chemical modifications of cAMP; this suggests that the cAMP receptor is identical in all of these species. Besides the induction of a chemotactic response, cAMP analogs also may delay or prevent cell aggregation. cAMP analogs like N1-O-cAMP, 2'-H-cAMP, and 5'NH-cAMP are chemotactically nearly as active as cAMP and induced no, or only a short, delay of cell aggregation. Other cAMP derivatives, such as 6-Cl-cPMP and 8-Br-cAMP, are chemotactically active only at high concentrations and delayed cell aggregation for several hours. Still other cAMP analogs, which do not induce a chemotactic reaction in D. mucoroides, D. purpureum, and D. rosarium, either prevented cell aggregation [cAMPS(S), cAMPS(R), and 3'-NH-cAMP[ or had no effect on cell aggregation [cAMPN(CH3)2(S) and cAMPN(CH3)2(R)]. cAMP analog 3'-NH-cAMP prevented cell aggregation by the inhibition of chemotaxis, whereas cell locomotion was not affected. Although we cannot provide a satisfactory explantation for these observations, our data suggest that occupation and activation of the cAMP receptors do not always induced a chemotactic response.

  20. Lidocaine-induced apoptosis of gingival fibroblasts: participation of cAMP and PKC activity.

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    Villarruel, Emmanuel Quinteros; Borda, Enri; Sterin-Borda, Leonor; Orman, Betina

    2011-08-01

    Local anaesthetics are drugs that prevent or relieve pain by interrupting nervous conduction and are the most commonly used drugs in dentistry. Their main targets of action are voltage-dependent Na+ channels. The Na+ channel is modulated by phosphorylation of two enzymes: PKA (protein kinase A) and PKC (protein kinase C). We studied the ability of lidocaine to modulate programmed cell death of human gingival fibroblasts and the mechanisms involved in this process. Lidocaine (10-5 to 10-7 M) stimulated apoptosis in primary cultures and the caspase-3 activity in a concentration-dependent manner. The stimulatory effect of lidocaine on apoptosis was attenuated in the presence of HA 1004 (PKA inhibitor) and stimulated by staurosporine and Go 6976 (PKC inhibitors). Lidocaine-induced apoptotic nuclei correlated positively with cAMP accumulation and negatively with PKC activity. These results show that lidocaine promotes apoptosis in human gingival fibroblasts at concentrations used for local anaesthesia. The mechanism involves PKA stimulation and PKC inhibition, which in turn stimulates caspase-3 and leads to programmed cell death.

  1. Hyperactivation of NF-κB via the MEK signaling is indispensable for the inhibitory effect of cAMP on DNA damage-induced cell death.

    Science.gov (United States)

    Kloster, Martine M; Naderi, Elin H; Carlsen, Harald; Blomhoff, Heidi K; Naderi, Soheil

    2011-04-21

    With cAMP signaling having a profound inhibitory effect on DNA damage-induced apoptosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, understanding how this signaling pathway affects the survival capacity of the cell has important implications for cancer therapy. We have recently shown that p53 is critical for the inhibitory effect of cAMP on genotoxic agents-mediated apoptosis in BCP-ALLs. Here, we show that elevation of cAMP levels in cells exposed to DNA damage enhances the nuclear translocation and DNA binding of NF-κB by accelerating the phosphorylation of IKKβ and thereby phosphorylation and degradation of IκBα. Furthermore, we show that the ability of cAMP to potentiate the ionizing radiation-induced activation of NF-κB requires the activity of MEK. Importantly, pharmacological or genetic ablation of NF-κB reversed the inhibitory effect of cAMP on DNA damage-induced apoptosis, demonstrating that, in addition to p53, cAMP relies on the activity of NF-κB to provide cells with a survival advantage in the face of DNA damage. Collectively, our results uncover a novel and important interaction between the cAMP and NF-κB pathways that may have implications for the targeted treatment of lymphoid malignancies, such as BCP-ALL, in which aberrant NF-κB activity functions as a driving force for treatment resistance.

  2. Panaxynol induces neurite outgrowth in PC12D cells via cAMP- and MAP kinase-dependent mechanisms.

    Science.gov (United States)

    Wang, Ze-Jian; Nie, Bao-Ming; Chen, Hong-Zhuan; Lu, Yang

    2006-01-05

    Panaxynol, a polyacetylene ((3R)-heptadeca-1,9-diene-4,6-diyn-3-ol; syn. falcarinol), was isolated from the lipophilic fractions of Panax notoginseng, a Chinese traditional medicinal plant. In the present study, we reported the neurotrophic effects of panaxynol on PC12D cells and mechanism involved in neurite outgrowth of the cells. Panaxynol could morphologically promote neurite outgrowth in PC12D cells, concentration-dependently reduce cell division and up-regulate molecular marker (MAP1B) expression in PC12D cells. Panaxynol induces the elevation of intracellular cAMP in PC12D cells. The neurite outgrowth in PC12D cells induced by panaxynol could be inhibited by the protein kinase A inhibitor RpcAMPS and by MAP kinase kinase 1/2 inhibitor U0126. These observations reveal that panaxynol could induce the differentiation of PC12D cells in a process similar to but distinct from that of NGF and the panaxynol's effects were via cAMP- and MAP kinase-dependent mechanisms.

  3. Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing

    Institute of Scientific and Technical Information of China (English)

    Nathalie Piazzon; Charlotte Maisonneuve; Isabelle Guilleret; Samuel Rotman; Daniel B. Constam

    2012-01-01

    Genetic defects in autosomal-dominant polycystic kidney disease (ADPKD) promote cystic growth of renal tubules,at least in part by stimulating the accumulation of cAMP.How renal cAMP levels are regulated is incompletely understood.We show that cAMP and the expression of its synthetic enzyme adenylate cyclase-6 (AC6) are up-regulated in cystic kidneys of Bicc1-/-knockout mice.Bicc1,a protein comprising three K homology (KH) domains and a sterile alpha motif (SAM),is expressed in proximal tubules.The KH domains independently bind AC6 mRNA and recruit the miR-125a from Dicer,whereas the SAM domain enables silencing by Argonaute and TNRC6A/GW182.Bicc1 similarly induces silencing of the protein kinase inhibitor PKlα by miR-27a.Thus,Bicc1 is needed on these target mRNAs for silencing by specific miRNAs.The repression of AC6 by Bicc1 might explain why cysts in ADPKD patients preferentially arise from distal tubules.

  4. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Zequn Jiang; Shasha Li; Yunyi Liu; Pengyi Deng; Jianguo Huang; Guangyuan He

    2011-01-01

    In this study,we confirmed that sesamin,an active lignan isolated from sesame seed and oil,is a novel skin-tanning compound.The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells.The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin.Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmiaassociated transcription factor (MITF).Sesamin could activate cAMP response element (CRE) binding protein (CREB),but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt.Moreover,sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway.Consistent with these results,sesamin-mediated increase of melanin synthesis was reduced significantly by H-89,a PKA inhibitor,but not by SB203580,a p38 MAPK inhibitor or by LY294002,a phosphatidylinositol-3-kinase (PI3K) inhibitor.Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89.These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase,which was,in turn,due to the activation of cAMP signaling.

  5. Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway.

    Science.gov (United States)

    Jiang, Zequn; Li, Shasha; Liu, Yunyi; Deng, Pengyi; Huang, Jianguo; He, Guangyuan

    2011-10-01

    In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling.

  6. [Hemophilia camps.

    Science.gov (United States)

    Juárez-Sierra, Julieta; Del Pilar Torres-Arreola, Laura; Marín-Palomares, Teresa; Dueñas-González, María Teresa; Monteros-Rincón, Martha Patricia; Osorio-Guzmán, Maricela

    2013-01-01

    We reported the experience of hemophilia camps which was accomplished with patients from hospitals of the Instituto Mexicano del Seguro Social. The aim was to prepare the families and patients regarding the disease treatment, in order to promote the self sufficiency and to know the impact of the program on the course of the disease. Surveys were applied about treatment items and personal opinions were collected. The results of the national hemophilia camp were: group of 56 patients, average 14 years, 2 % women, 51 % severe hemophilia and 43 % had hemophilic brothers. Benefits: patients increased their knowledge about earlier bleeding identification and the self-infusion method; they became aware on their responsibility in self care, timely treatment and duties at home. Hemophilia camps with patients are an option for attitude change before disease complications. Social network creation and the increase in self-sufficiency are other benefits.

  7. CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells.

    Science.gov (United States)

    Beauregard, Annie-Pier; Harquail, Jason; Lassalle-Claux, Grégoire; Belbraouet, Mehdi; Jean-Francois, Jacques; Touaibia, Mohamed; Robichaud, Gilles A

    2015-07-10

    Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53). With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations) in a more specific and targeted fashion.

  8. CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Annie-Pier Beauregard

    2015-07-01

    Full Text Available Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE, a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53. With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations in a more specific and targeted fashion.

  9. Piperine, a component of black pepper, decreases eugenol-induced cAMP and calcium levels in non-chemosensory 3T3-L1 cells.

    Science.gov (United States)

    Yoon, Yeo Cho; Kim, Sung-Hee; Kim, Min Jung; Yang, Hye Jeong; Rhyu, Mee-Ra; Park, Jae-Ho

    2015-01-01

    This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant-induced signal transduction in non-chemosensory cells. An ethanol extract of black pepper decreased eugenol-induced cAMP and calcium levels in preadipocyte 3T3-L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element-binding protein) was down-regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC-MS/MS. Pretreatment with piperine decreased eugenol-induced cAMP and calcium levels in 3T3-L1 cells. Piperine also decreased the phosphorylation of CREB, which is up-regulated by eugenol. These results suggest that piperine inhibits the eugenol-induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non-chemosensory cells.

  10. Feasibility of a Day-Camp Model of Modified Constraint-Induced Movement Therapy with and without Botulinum Toxin A Injection for Children with Hemiplegia

    Science.gov (United States)

    Eliasson, Ann-Christin; Shaw, Karin; Ponten, Eva; Boyd, Roslyn; Krumlinde-Sundholm, Lena

    2009-01-01

    The objective of the study was to investigate the feasibility of modified constraint-induced (CI) therapy provided in a 2-week day-camp model with and without intramuscular botulinum toxin type A (BoNT-A) injections for children with congenital cerebral palsy. Sixteen children with congenital hemiplegia, Manual Ability Classification System (MACS)…

  11. Hippocampal expression of synaptic structural proteins and phosphorylated cAMP response element-binding protein in a rat model of vascular dementia induced by chronic cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Zhiyong Li; Yali Wang; Qiuxia Zhang

    2012-01-01

    The present study established a rat model of vascular dementia induced by chronic cerebral hy-poperfusion through permanent ligation of bilateral common carotid arteries. At 60 days after mod-eling, escape latency and swimming path length during hidden-platform acquisition training in Morris water maze significantly increased in the model group. In addition, the number of accurate crossings over the original platform significantly decreased, hippocampal CA1 synaptophysin and growth-associated protein 43 expression significantly decreased, cAMP response element-binding protein expression remained unchanged, and phosphorylated cAMP response element-binding protein expression significantly decreased. Results suggested that abnormal expression of hippo-campal synaptic structural protein and cAMP response element-binding protein phosphorylation played a role in cognitive impairment following chronic cerebral hypoperfusion.

  12. Interaction between cAMP, volume‑regulated anion channels and the Na+‑HCO3‑‑cotransporter, NBCe1, in the regulation of nutrient‑ and hypotonicity‑induced insulin release from isolated rat pancreatic islets and tumoral insulin‑producing BRIN‑BD11 cells.

    Science.gov (United States)

    Bulur, Nurdan; Crutzen, Raphael; Malaisse, Willy J; Sener, Abdullah; Beauwens, Renaud; Golstein, Philippe

    2013-05-01

    Soluble adenylyl cyclase (sAC) has been hypothesized to play a role in insulin secretion. The present study aimed to investigate the interaction between adenosine 3',5'‑cyclic monophosphate (cAMP), volume‑regulated anion channels (VRACs) and the electrogenic sodium bicarbonate (Na+‑HCO3‑) cotransporter, NBCe1, in the regulation of nutrient‑ and hypotonicity‑induced insulin release from rat pancreatic islets and tumoral insulin‑producing BRIN‑BD11 cells. In the islets, 5‑nitro‑2‑(3‑phenylpropylamino)benzoic acid (NPPB) and 5‑chloro‑2‑hydroxy‑3‑(thiophene‑2‑carbonyl)indole‑1‑carboxamide (tenidap) reduced glucose‑stimulated insulin release, however, only NPPB suppressed the enhancing action of cAMP analogs upon such a release. Insulin output from the BRIN‑BD11 cells was stimulated by 2‑ketoisocaproate (KIC) or extracellular hypoosmolarity. cAMP analogs and 3‑isobutyl‑1‑methylxanthine increased the insulin output recorded in the isotonic medium to a greater relative extent than that in the hypotonic medium. The secretory response to KIC or hypotonicity was inhibited by NPPB or tenidap, which both also opposed the enhancing action of cAMP analogs. Inhibitors of mitogen‑activated protein (MAP) kinase decreased insulin output in isotonic and hypotonic media. The inhibitor of sAC, 2‑hydroxyestriol, caused only a modest inhibition of insulin release, whether in the isotonic or hypotonic medium, even when tested at a concentration of 100 µM. The omission of NaHCO3 markedly decreased the secretory response to KIC or extracellular hypotonicity. The omission of Na+ suppressed the secretory response to extracellular hypotonicity. The observations of the present study do not support the hypothesis of a major role for sAC in the regulation of insulin release.

  13. Transcriptional Regulation Induced by cAMP Elevation in Mouse Schwann Cells

    Directory of Open Access Journals (Sweden)

    Daniela Schmid

    2014-03-01

    Full Text Available In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1, whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix, underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

  14. Transcriptional regulation induced by cAMP elevation in mouse Schwann cells

    Directory of Open Access Journals (Sweden)

    Daniela Schmid

    2014-04-01

    Full Text Available In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1, whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix, underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

  15. cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

    Institute of Scientific and Technical Information of China (English)

    WEI; GUO; FENG; YI; BING; WANG; JIN; SONG; ZHANG; XING; YU; WANG; CHANG; LIN; LI; ZONG; LIANG; CHANG

    2002-01-01

    cAMP mediated signaling may play a suppressive role in immune response. We previously found thatthe cAMP-elevators (CTx and 8-Br-cAMP) inhibited IL-12, IL-la, IL-6 gene expression, but increasedthe transcriptional levels of IL-10 and IL-1Ra in LPS-treated murine peritoneal macrophages. The presentstudy examined a possible molecular mechanism involved in cAMP elevators-induced inhibition of IL-12 p40expression in response to LPS. Our data demonstrated that cAMP elevators downregulated IL-12 p40 mRNAexpression and IL-12 p70 production in murine peritoneal macrophages. Subsequent studies revealed thatcAMP-elevators blocked phosphorylation of p38 MAPK, but did not affect the activity of NF-κB bindingto IL-12 promoter (-136/-112). This is the first report that cAMP elevators inhibit LPS-induced IL-12production by a mechanism that is associated, at least in part, with p38-dependent inhibition by cAMPsignaling pathways.

  16. Antagonists of chemoattractants reveal separate receptors for cAMP, folic acid and pterin in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Wit, René J.W. de; Konijn, Theo M.

    1982-01-01

    Adenosine 3’,5’-monophosphate (cAMP), folic acid and pterin are chemoattractants in the cellular slime molds. The cAMP analog, 3’-amino-cAMP, inhibits a chemotactic reaction to cAMP at a concentration at which the analog is chemotactically inactive. The antagonistic effect of 3’-amino-cAMP on the ch

  17. Inhibitory effect of luteolin on the odorant-induced cAMP level in HEK293 cells expressing the olfactory receptor.

    Science.gov (United States)

    Yoon, Yeo Cho; Hwang, Jin-Teak; Sung, Mi-Jeong; Wang, Shuaiyu; Munkhtugs, Davaatseren; Rhyu, Mee-Ra; Park, Jae-Ho

    2012-01-01

    Luteolin is a flavonoid in many fruits and vegetables. Although luteolin has important biological functions, including antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities, little is known about the functions of luteolin in the olfactory system. Various odorants can be detected and distinguished by using several molecular processes, including the binding of odorants to odorant receptors, activation of adenylyl cyclase (AC), changes of cyclic adenosine monophosphate (cAMP) and Ca(2+) levels in olfactory sensory neurons, as well as changes in membrane potentials and the transmission of electric signals to the brain. Because AC-cAMP signal transduction plays a pivotal role in the olfactory system, we evaluated the effects of luteolin on the AC-cAMP pathway that had been stimulated by the odorant eugenol. We demonstrated that eugenol caused an upregulation of the cAMP level and the phosphorylation of phosphokinase A (PKA, a downstream target of cAMP) in human embryonic kidney 293 (HEK293) cells expressing the murine eugenol receptor. This upregulation significantly decreased in the presence of luteolin, suggesting that luteolin inhibited the odorant-induced production of cAMP and affected the downstream phosphorylation of PKA.

  18. Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

    Directory of Open Access Journals (Sweden)

    Ji Young Park

    2013-01-01

    Full Text Available A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6 to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release. Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK, and different mitogen-activated protein kinases (MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2 as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.

  19. Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking.

    NARCIS (Netherlands)

    Tamma, G.; Procino, G.; Mola, M.G.; Svelto, M.; Valenti, G.

    2008-01-01

    Annexin-2 is required for the apical transport in epithelial cells. In this study, we investigated the involvement of annexin-2 in cAMP-induced aquaporin-2 (AQP2) translocation to the apical membrane in renal cells. We found that the cAMP-elevating agent forskolin increased annexin-2 abundance in th

  20. Filling of Cloud-Induced Gaps for Land Use and Land Cover Classifications Around Refugee Camps

    Science.gov (United States)

    Braun, Andreas; Hagensieker, Ron; Hochschild, Volker

    2016-08-01

    Clouds cover is one of the main constraints in the field of optical remote sensing. Especially the use of multispectral imagery is affected by either fully obscured data or parts of the image which remain unusable. This study compares four algorithms for the filling of cloud induced gaps in classified land cover products based on Markov Random Fields (MRF), Random Forest (RF), Closest Spectral Fit (CSF) operators. They are tested on a classified image of Sentinel-2 where artificial clouds are filled by information derived from a scene of Sentinel-1. The approaches rely on different mathematical principles and therefore produced results varying in both pattern and quality. Overall accuracies for the filled areas range from 57 to 64 %. Best results are achieved by CSF, however some classes (e.g. sands and grassland) remain critical through all approaches.

  1. Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP

    Energy Technology Data Exchange (ETDEWEB)

    Sugita, Kazuya; Yamamura, Chiaki; Tabata, Ken-ichi [Laboratory of Pharmacoinformatics, Graduate School of Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); Fujita, Norihisa, E-mail: nori@ph.ritsumei.ac.jp [Laboratory of Pharmacoinformatics, Graduate School of Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); School of Pharmacy, Ristumeikan University, Kusatsu, Shiga 525-8577 (Japan)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Expression of GPR174 in CHO cells induces morphological changes and proliferation delay. Black-Right-Pointing-Pointer These are due to increase in intracellular cAMP concentration. Black-Right-Pointing-Pointer Lysophosphatidylserine was identified to stimulate GPR174 leading to activate ACase. Black-Right-Pointing-Pointer The potencies of fatty acid moiety on LysoPS were oleoyl Greater-Than-Or-Slanted-Equal-To stearoyl > palmitoyl. Black-Right-Pointing-Pointer We propose that GPR174 is a lysophosphatidylserine receptor. -- Abstract: We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delay of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of G{alpha}{sub s} protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with G{alpha}{sub s}, and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation.

  2. Signaling transcript profile of the asexual intraerythrocytic development cycle of Plasmodium falciparum induced by melatonin and cAMP

    Science.gov (United States)

    Rozanski, Andrei; Parreira, Kleber S.; Moraes, Miriam S.; Martins, David C.; Hashimoto, Ronaldo F.; Galante, Pedro A.F.; Garcia, Célia R.S.

    2016-01-01

    According to the World Health Organization (WHO), Plasmodium falciparum is the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP. Therefore, we performed RNA sequencing (RNA-Seq) analysis in P. falciparum erythrocytic stages (ring, trophozoite and schizont) treated with MEL and cAMP. To investigate the expression profile of P. falciparum genes regulated by MEL and cAMP, we performed RNA-Seq analysis in three P. falciparum strains (control, 3D7; protein kinase 7 knockout, PfPK7-; and PfPK7 complement, PfPK7C). In the 3D7 strain, 38 genes were differentially expressed upon MEL treatment; however, none of the genes in the trophozoite (T) stage PfPK7- knockout parasites were differentially expressed upon MEL treatment for 5 hours compared to untreated controls, suggesting that PfPK7 may be involved in the signaling leading to differential gene expression. Moreover, we found that MEL modified the mRNA expression of genes encoding membrane proteins, zinc ion-binding proteins and nucleic acid-binding proteins, which might influence numerous functions in the parasite. The RNA-Seq data following treatment with cAMP show that this molecule modulates different genes throughout the intraerythrocytic cycle, namely, 75, 101 and 141 genes, respectively, in the ring (R), T and schizont (S) stages. Our results highlight P. falciparum's perception of the external milieu through the signaling molecules MEL and cAMP, which are able to drive to changes in gene expression in the parasite. PMID:28050233

  3. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Science.gov (United States)

    Bacallao, Ketty; Monje, Paula V

    2015-01-01

    Isolated Schwann cells (SCs) respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1). To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP) and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC) agonists and antagonists revealed that selective transmembrane AC (tmAC) activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC), a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the uncoupling of signals

  4. Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

    Directory of Open Access Journals (Sweden)

    Ketty Bacallao

    Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

  5. A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma

    Science.gov (United States)

    Gendron, David R.; Lecours, Pascale B.; Lemay, Anne-Marie; Beaulieu, Marie-Josée; Huppé, Carole-Ann; Lee-Gosselin, Audrey; Flamand, Nicolas; Don, Anthony S.; Bissonnette, Élyse; Blanchet, Marie-Renée; Laplante, Mathieu; Bourgoin, Sylvain G.; Bossé, Ynuk; Marsolais, David

    2017-01-01

    In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs are primarily perceived as immune modulators with the ability to prevent experimental asthma, they also influence processes associated with tissue atrophy, supporting the hypothesis that they could interfere with mechanisms sustaining pre-established AHR. We thus assessed the ability of a sphingosine analog (AAL-R) to reverse AHR in a chronic model of asthma. We dissected the pharmacological mechanism of this class of agents using the non-phosphorylatable chiral isomer AAL-S and the pre-phosphorylated form of AAL-R (AFD-R) in vivo and in human ASM cells. We found that a therapeutic course of AAL-R reversed experimental AHR in the methacholine challenge test, which was not replicated by dexamethasone or the non-phosphorylatable isomer AAL-S. AAL-R efficiently interfered with ASM cell proliferation in vitro, supporting the concept that immunomodulation is not necessary to interfere with cellular mechanisms sustaining AHR. Moreover, the sphingosine-1-phosphate lyase inhibitor SM4 and the sphingosine-1-phosphate receptor antagonist VPC23019 failed to inhibit proliferation, indicating that intracellular accumulation of sphingosine-1-phosphate or interference with cell surface S1P1/S1P3 activation, are not sufficient to induce cytostasis. Potent AAL-R-induced cytostasis specifically related to its ability to induce intracellular AFD-R accumulation. Thus, a sphingosine analog that possesses the ability to be phosphorylated in situ interferes with cellular mechanisms that beget AHR.

  6. Flow-induced noise simulation using detached eddy simulation and the finite element acoustic analogy method

    Directory of Open Access Journals (Sweden)

    Kai Liu

    2016-06-01

    Full Text Available Signals in long-distance pipes are complex due to flow-induced noise generated in special structure, and the computation of these noise sources is difficult and time-consuming. To address this problem, a hybrid method based on computational fluid dynamics and Lighthill’s acoustic analogy theory is proposed to simulate flow-induced noise, with the results showing that the method is sufficient for noise predictions. The proposed method computes the turbulent flow field using detached eddy simulation and then calculates turbulence-generated sound using the finite element acoustic analogy method, which solves acoustic sources as volume sources. The velocity field obtained in the detached eddy simulation computation provides the sound source through interpolation between the computational fluid dynamics and acoustic meshes. The hybrid method is validated and assessed by comparing data from the cavity in pipe and large eddy simulation results. The peak value of flow-induced noise calculated at the monitor point is in good agreement with experimental data available in the literature.

  7. Slow-light plasmonic metamaterial based on dressed-state analog of electromagnetically-induced transparency

    CERN Document Server

    Raza, Søren

    2015-01-01

    We consider a simple configuration for realizing one-dimensional slow-light metamaterials with large bandwidth-delay products using stub-shaped Fabry-Perot resonators as building blocks. Each metaatom gives rise to large group indices due to a classical analog of the dressed-state picture of electromagnetically-induced transparency. By connecting up to eight metaatoms, we find bandwidth-delay products over unity and group indices approaching 100. Our approach is quite general and can be applied to any type of Fabry-Perot resonators and tuned to different operating wavelengths.

  8. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.

    Science.gov (United States)

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad

    2005-11-01

    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  9. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  10. Behavior of processionary males (Thaumetopoea pityocampa) induced by sex pheromone and analogs in a wind tunnel.

    Science.gov (United States)

    Quero, C; Camps, F; Guerrero, A

    1995-12-01

    The behavioral response of processionary males (Thaumetopoea pityocampa) to the natural pheromone (Z)-13-hexadecen-11-ynyl acetate (1) and structurally related analogs in a wind tunnel is presented. Stereomerically pureZ-1 and a mixture with theE isomer in 80:20 ratio elicited similar attraction responses at 1 µg and higher. The activity was dose-dependent, being optimum at 1 µg with 90% and 80% of males contacting with the source in the presence of theZ-1 andZ/E-1, respectively. 11-Hexadecynyl acetate (2) functioned as a pheromone mimic, being able to induce the complete mate-finding behavioral sequence, although its activity was much lower than that of the pheromone. (Z)-13-Hexadecen-11-ynyl alcohol (3) and, particularly, (Z)-13-hexadecen-11-ynal (4) were potent inhibitors of the upwind flight response in mixtures withZ-1 in 99:1, 95:5, and 91:9 ratios. (Z)-1,1,1-Trifluoro-16-nonadecen-14-yn-2-one (5) also inhibited the response of males to pheromone, particularly in the source contact behavior. Comparison with activity displayed by analogs in field tests is also reported.

  11. The scent of wolves: pyrazine analogs induce avoidance and vigilance behaviors in prey

    Directory of Open Access Journals (Sweden)

    Kazumi eOsada

    2015-10-01

    Full Text Available The common grey wolf (Canis lupus is an apex predator located at the top of the food chain in the Northern Hemisphere. It preys on rodents, rabbits, ungulates, and many other kinds of mammal. However, the behavioral evidence for, and the chemical basis of, the fear-inducing impact of wolf urine on prey are unclear. Recently, the pyrazine analogs 2, 6-dimethylpyrazine, 2, 3, 5-trimethylpyrazine and 3-ethyl-2, 5-dimethyl pyrazine were identified as kairomones in the urine of wolves. When mice were confronted with a mixture of purified pyrazine analogs, vigilance behaviors, including freezing and excitation of neurons at the accessory olfactory bulb, were markedly increased. Additionally, the odor of the pyrazine cocktail effectively suppressed the approach of deer to a feeding area, and for those close to the feeding area elicited fear-related behaviors such as the tail-flag, flight, and jump actions. In this review, we discuss the transfer of chemical information from wolf to prey through the novel kairomones identified in wolf urine and also compare the characteristics of wolf kairomones with other predator-produced kairomones that affect rodents.

  12. Observation of Fano resonance and classical analog of electromagnetically induced transparency in toroidal metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Han, Song; Yang, Helin [College of Physical Science and Technology, Central China Normal University, Wuhan (China); Cong, Lonqing; Singh, Ranjan [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore (Singapore); Centre for Disruptive Photonic Technologies, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore (Singapore); Gao, Fei [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore (Singapore)

    2016-05-15

    Toroidal multipoles have recently been explored in various scientific communities, ranging from atomic and molecular physics, electrodynamics, and solid-state physics to biology. Here we experimentally and numerically demonstrate a three-dimensional toroidal metamaterial where two different toroidal dipoles along orthogonal directions have been observed. The chosen toroidal metamaterial also simultaneously supports Fano resonance and the classical analog of electromagnetically induced transparency (EIT) phenomena in the transmission spectra that originate from the electric-toroidal dipole and electric-magnetic dipole destructive interference. The intriguing properties of the toroidal resonances may open up avenues for applications in toroidal moments generator, sensing and slow-light devices. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Analogy of electromagnetically induced transparency in plasmonic nanodisk with a square ring resonator

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xianping; Wei, Zhongchao, E-mail: wzc@scnu.edu.cn; Liu, Yuebo; Zhong, Nianfa; Tan, Xiaopei; Shi, Songsong; Liu, Hongzhan; Liang, Ruisheng

    2016-01-08

    We have demonstrated the analogy of electromagnetically induced transparency in plasmonic nanodisk with a square ring resonator. A reasonable analysis of the transmission feature based on the temporal coupled-mode theory is given and shows good agreement with the Finit-Difference Time-Domain simulation. The transparency window can be easily tuned by changing the geometrical parameters and the insulator filled in the resonator. The transmission of the resonator system is close to 80% and the full width at half maximum is less than 46 nm. The sensitivity of the structure is about 812 nm/RIU. These characteristics make the new system with potential to apply for optical storage, ultrafast plasmonic switch and slow-light devices.

  14. The melatonin agonist ramelteon induces duration-dependent clock gene expression through cAMP signaling in pancreatic INS-1 β-cells.

    Directory of Open Access Journals (Sweden)

    Keiji Nishiyama

    Full Text Available Prolonged exposure to melatonin improves glycemic control in animals. Although glucose metabolism is controlled by circadian clock genes, little is known about the role of melatonin signaling and its duration in the regulation of clock gene expression in pancreatic β-cells. Activation of MT1 and MT2 melatonin receptors inhibits cAMP signaling, which mediates clock gene expression. Therefore, this study investigated exposure duration-dependent alterations in cAMP element-binding protein (CREB phosphorylation and clock gene expression that occur during and after exposure to ramelteon, a selective melatonin agonist used to treat insomnia. In rat INS-1 cells, a pancreatic β-cell line endogenously expressing melatonin receptors, ramelteon persistently decreased CREB phosphorylation during the treatment period (2-14 h, whereas the subsequent washout induced an enhancement of forskolin-stimulated CREB phosphorylation in a duration- and concentration-dependent manner. This augmentation was blocked by forskolin or the melatonin receptor antagonist luzindole. Similarly, gene expression analyses of 7 clock genes revealed the duration dependency of the effects of ramelteon on Rev-erbα and Bmal1 expression through melatonin receptor-mediated cAMP signaling; longer exposure times (14 h resulted in greater increases in the expression and signaling of Rev-erbα, which is related to β-cell functions. Interestingly, this led to amplified oscillatory Rev-erbα and Bmal1 expression after agonist washout and forskolin stimulation. These results provide new insights into the duration-dependent effects of ramelteon on clock gene expression in INS-1 cells and may improve the understanding of its effect in vivo. The applicability of these results to pancreatic islets awaits further investigation.

  15. Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes to drug-induced diarrhea.

    Science.gov (United States)

    Moon, Changsuk; Zhang, Weiqiang; Ren, Aixia; Arora, Kavisha; Sinha, Chandrima; Yarlagadda, Sunitha; Woodrooffe, Koryse; Schuetz, John D; Valasani, Koteswara Rao; de Jonge, Hugo R; Shanmukhappa, Shiva Kumar; Shata, Mohamed Tarek M; Buddington, Randal K; Parthasarathi, Kaushik; Naren, Anjaparavanda P

    2015-05-01

    Diarrhea is one of the most common adverse side effects observed in ∼7% of individuals consuming Food and Drug Administration (FDA)-approved drugs. The mechanism of how these drugs alter fluid secretion in the gut and induce diarrhea is not clearly understood. Several drugs are either substrates or inhibitors of multidrug resistance protein 4 (MRP4), such as the anti-colon cancer drug irinotecan and an anti-retroviral used to treat HIV infection, 3'-azido-3'-deoxythymidine (AZT). These drugs activate cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluid secretion by inhibiting MRP4-mediated cAMP efflux. Binding of drugs to MRP4 augments the formation of MRP4-CFTR-containing macromolecular complexes that is mediated via scaffolding protein PDZK1. Importantly, HIV patients on AZT treatment demonstrate augmented MRP4-CFTR complex formation in the colon, which defines a novel paradigm of drug-induced diarrhea.

  16. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

    Science.gov (United States)

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

    2005-01-01

    Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  17. Lesbian camp: An unearthing.

    Science.gov (United States)

    Nielsen, Elly-Jean

    2016-01-01

    Camp-a sensibility, a style, and a form of artistic self-expression-is an elusive concept said to be in the eye of the beholder. To refute Susan Sontag's ( 1966 ) claims that camp is apolitical and not especially homosexual, a number of recent scholarly works have been geared toward revealing camp's fundamental gayness. With the odd footnote aside, lesbian camp has been collapsed into the category of gay male camp, if not eclipsed entirely. Despite the negligible efforts made to legitimize lesbian camp, there are numerous salient cultural examples one might draw on to illustrate, typify, and substantiate a lesbian camp sensibility. I lay the ground work for this scholarly exercise by outlining various definitions and critiques of camp, and by discussing its history and application to queer theory. Then, to unveil lesbian camp, three non-mutually exclusive categories are discussed: classic, erotic, and radical. By gathering various strands of inquiry, and various textual examples (e.g., photography, artistic performances, and literary tropes), this article attempts to reach a more inclusive and nuanced understanding of lesbian camp.

  18. Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum.

    Science.gov (United States)

    Gajate, C; Matos-da-Silva, M; Dakir, el-H; Fonteriz, R I; Alvarez, J; Mollinedo, F

    2012-05-24

    Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase- and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH(2)-terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 α-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER.

  19. Prophylactic Melatonin Attenuates Isoflurane-Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2 - cAMP Response Element Binding Signalling.

    Science.gov (United States)

    Liu, Yajie; Ni, Cheng; Li, Zhengqian; Yang, Ning; Zhou, Yang; Rong, Xiaoying; Qian, Min; Chui, Dehua; Guo, Xiangyang

    2017-03-01

    Melatonin exerts many physiological effects via melatonin receptors, among which the melatonin-2 receptor (MT2 ) plays a critical role in circadian rhythm disorders, Alzheimer's disease and other neurological disorders. A melatonin replacement strategy has been tested previously, and MT2 was a critical target during the process. cAMP response element binding (CREB) is an essential transcription factor for memory formation and could be involved in MT2 signalling. Therefore, the present study was designed to investigate the effects of prophylactic melatonin on inhaled anaesthetic isoflurane-induced cognitive impairment, and to determine whether the protective effects of melatonin are dependent on MT2 and downstream CREB signalling in the hippocampus of aged rats. The results showed that prophylactic melatonin attenuated isoflurane-induced decreases in plasma/hippocampal melatonin levels and cognitive impairment in aged rats. Furthermore, 4P-PDOT, a selective MT2 antagonist, blocked the protective effects of melatonin on isoflurane-induced decreases in both hippocampal MT2 expression and downstream CREB phosphorylation. And 4P-PDOT blocked the attenuation of melatonin on isoflurane-induced memory impairment. Collectively, the results suggest that the protective effects of prophylactic melatonin are dependent on hippocampal MT2 -CREB signalling, which could be a potential therapeutic target for anaesthetic-induced cognitive impairment.

  20. cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo.

    Science.gov (United States)

    Dragon, Stefanie; Offenhäuser, Nina; Baumann, Rosemarie

    2002-04-01

    During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5'-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548-551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870-R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol 202: 2787-2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052-3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188-R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787-2795, 1999; Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996). This leads via erythroid beta-adrenergic/adenosine A(2) receptor activation to a cAMP signal inducing several proteins in a transcription-dependent manner (Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon et al., Blood 91: 3052-3058, 1998; Glombitza S, Dragon S, Berghammer M, Pannermayr M, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R973-R981, 1996). To understand how the cAMP-dependent processes are initiated, we screened an erythroid cDNA library for cAMP-regulated genes. We detected three genes that were strongly upregulated (>5-fold) by cAMP in definitive and primitive red blood cells. They are homologous to the mammalian Tob, Ifr1, and Fos proteins. In addition, the genes are induced in the intact embryo during short-term hypoxia. Because the genes are regulators of proliferation and differentiation in other cell types, we suggest that cAMP

  1. Recreation Summer Camps 2016

    Data.gov (United States)

    Montgomery County of Maryland — List of all Camps (Register here:https://apm.activecommunities.com/montgomerycounty/Home) to include Aquatics, Basketball, Soccer, Special Interest, General Sports,...

  2. Registration Summer Camp 2016

    CERN Multimedia

    2016-01-01

    Reminder: registration for the CERN Staff Association Summer Camp is now open for children from 4 to 6 years old.   More information on the website: http://nurseryschool.web.cern.ch/. The summer camp is open to all children. The proposed cost is 480.-CHF/week, lunch included. The camp will be open weeks 27, 28, 29 and 30, from 8:30 a.m. to 5:30 p.m. For further questions, you are welcome to contact us by email at Summer.Camp@cern.ch. CERN Staff Association

  3. Assessing Climate Change Induced Turnover in Bird Communities Using Climatically Analogous Regions

    Directory of Open Access Journals (Sweden)

    Janine Sybertz

    2015-02-01

    Full Text Available It is crucial to define and quantify possible impacts of climate change on wildlife in order to be able to pre-adapt management strategies for nature conservation. Thus, it is necessary to assess which species might be affected by climatic changes, especially at the regional scale. We present a novel approach to estimate possible climate change induced turnovers in bird communities and apply this method to Lüneburg Heath, a region in northern Germany. By comparing species pools of future climatically analogous regions situated in France with the Lüneburg Heath species pool, we detected possible trends for alterations within the regional bird community in the course of climate change. These analyses showed that the majority of bird species in Lüneburg Heath will probably be able to tolerate the projected future climate conditions, but that bird species richness, in general, may decline. Species that might leave the community were often significantly associated with inland wetland habitats, but the proportion of inland wetlands within the regions had a significant influence on the magnitude of this effect. Our results suggest that conservation efforts in wetlands have to be strengthened in light of climate change because many species are, in principle, able to tolerate future climate conditions if sufficient habitat is available.

  4. Analogy of transistor function with modulating photonic band gap in electromagnetically induced grating.

    Science.gov (United States)

    Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng

    2015-09-09

    Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing.

  5. Novel 8-hydroxylquinoline analogs induce copper-dependent proteasome inhibition and cell death in human breast cancer cells.

    Science.gov (United States)

    Milacic, Vesna; Jiao, Peifu; Zhang, Bin; Yan, Bing; Dou, Q Ping

    2009-12-01

    An elevated level of copper (Cu), which is necessary for the growth and metastasis of tumor cells, has been found in many types of cancer, including breast, prostate, lung and brain. Although its molecular basis is unclear, this tumor-specific Cu elevation has been proposed to be a novel target for developing selective anti-cancer therapies. We previously reported that 8-hydroxylquinoline (8-OHQ) is able to form a Cu complex that inhibits the proteasome and induces apoptosis in cultured cancer cells. Toward the goal of discovering novel 8-OHQ analogs as potential anti-copper and anti-cancer drugs, in the current study we synthesized several 8-OHQ analogs and their copper complexes and evaluated their biological activities in human breast cancer cells. We report that when substitutions are made on the hydroxyl group of 8-OHQ, their copper mixtures have profound effects on the proteasome-inhibitory and apoptosis-inducing abilities in breast cancer MDA-MB-231 cells. In addition, the proteasome-inhibitory and apoptosis-inducing activities of 8-OHQ analog-copper mixtures are determined by both the polarity and position of the substituents. Finally, a synthetic complex of 8-OHQ analog-copper was able to inhibit the proteasome activity, induce cell death and suppress the growth selectively in breast cancer MDA-MB-231 cells, but not in normal immortalized human breast MCF-10A cells. Our results support the concept that human cancer cells and tissues, which contain an elevated copper level and are highly dependent on proteasome activity for their survival, should be sensitive to treatment with anti-copper drugs such as the novel 8-OHQ analogs described here.

  6. Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of prostaglandin EP2 receptors, cAMP, and pCREB.

    Science.gov (United States)

    Ahluwalia, Amrita; Baatar, Dolgor; Jones, Michael K; Tarnawski, Andrzej S

    2014-09-15

    Clinical studies indicate that prostaglandins of E class (PGEs) may promote healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways including cAMP and cAMP response element-binding protein (CREB), and their relation to VEGF and angiogenesis in the tissue injury healing process remain unknown, forming the rationale for this study. Using an esophageal ulcer model in rats, we demonstrated that esophageal mucosa expresses predominantly EP2 receptors and that esophageal ulceration triggers an increase in expression of the EP2 receptor, activation of CREB (the downstream target of the cAMP signaling), and enhanced VEGF gene expression. Treatment of rats with misoprostol, a PGE1 analog capable of activating EP receptors, enhanced phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and accelerated esophageal ulcer healing. In cultured human esophageal epithelial (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold), induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp-cAMP) blocked, these effects of misoprostol. These results indicate that the EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on angiogenesis essential for tissue injury healing via the induction of CREB activity and VEGF expression.

  7. Scrum Code Camps

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Pries-Heje, Lene; Dahlgaard, Bente

    2013-01-01

    is required. In this paper we present the design of such a new approach, the Scrum Code Camp, which can be used to assess agile team capability in a transparent and consistent way. A design science research approach is used to analyze properties of two instances of the Scrum Code Camp where seven agile teams...

  8. Orienteering in Camping.

    Science.gov (United States)

    Larson, Elston F.

    One of the recent developments in camping is "orienteering", a program using a map and compass. Orienteering can be dovetailed into an overall camping program and used to "point up" the entire program, or it can be confined to a single simple game. The arrangement depends on the situation. The minimum age of the participants should be about 9 or…

  9. Camp's "Disneyland" Effect.

    Science.gov (United States)

    Renville, Gary

    1999-01-01

    Describes the positive mental, physical, and social growth impacts that the camping experience had on the author, and urges camp program evaluation to plan and implement such changes. Sidebar lists steps of effective evaluation: program goals and objectives, goals of evaluation, implementation of evaluation, data analysis, and findings and…

  10. Friends' Discovery Camp

    Science.gov (United States)

    Seymour, Seth

    2008-01-01

    This article features Friends' Discovery Camp, a program that allows children with and without autism spectrum disorder to learn and play together. In Friends' Discovery Camp, campers take part in sensory-rich experiences, ranging from hands-on activities and performing arts to science experiments and stories teaching social skills. Now in its 7th…

  11. Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication in the human oral squamous carcinoma cell line SAS.

    Science.gov (United States)

    Chai, Hongbo; Hazawa, Masaharu; Hosokawa, Yoichiro; Igarashi, Jun; Suga, Hiroaki; Kashiwakura, Ikuo

    2012-01-01

    The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs was investigated on the human oral squamous carcinoma cell line SAS. One analog induced G2/M phase arrest at 5.3-10.6 µM and induced polyploidy at a higher dose (21.2 µM). Importantly, treatment of SAS cells with a combination of the AHL analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit clonogenic survival of SAS cells; however, its radiosensitizing effects were relative to not X-irradiation-induced apoptosis but mitotic failure following enhanced expression of Aurora A and B. These results suggest that the active AHL analog showed growth-suppressive and radiosensitizing effects, which involve polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell line.

  12. Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity and Induces Tumor Cell Death.

    Science.gov (United States)

    Bachmann, André S; Opoku-Ansah, John; Ibarra-Rivera, Tannya R; Yco, Lisette P; Ambadi, Sudhakar; Roberts, Christopher C; Chang, Chia-En A; Pirrung, Michael C

    2016-04-15

    Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested that TIR-199 covalently binds each of the three catalytic subunits (β1, β2, and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney tumor cell lines, with >250-fold higher anti-tumor activities than observed with the natural product syringolin A. In vivo studies in mice revealed a maximum tolerated dose of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer.

  13. Dibutyryl c-AMP as an inducer of sporidia formation: Biochemical and antigenic changes during morphological differentiation of Karnal bunt (Tilletia indica) pathogen in axenic culture

    Indian Academy of Sciences (India)

    Anil Kumar; Kaushlendra Tripathi; Manish Rana; Shalini Purwar; G K Garg

    2004-03-01

    Effect of dibutyryl adenosine 3′,5′-cyclic monophosphate (dbc-AMP), an analogue of c-AMP, was investigated on growth and morphological differentiation of Tilletia indica. Exponential growth was observed up to 21 days in both presence and absence of dbc-AMP; however, increasing concentration of dbc-AMP was deleterious to mycelial growth in liquid culture. A slow increase of mycelial biomass up to 21 days and decline at 30 days in the presence of 2.5 mM dbc-AMP was observed, therefore, this concentration was chosen in subsequent investigations. The inhibitory influence of dbc-AMP was further substantiated by decrease in soluble protein. The fungus on exposure to dbc-AMP experienced morphological differentiation from vegetative mycelial phase to sporogenous mycelial phase, and was induced to produce filiform sporidia. Use of quantitative ELISA further suggested that sporidia formation took more than 21 days in the presence of dbc-AMP. Variations of proteins during different stages of T. indica grown in the presence and absence of dbc-AMP suggested the expression of stage-specific proteins or differential expression of proteins induced by dbc-AMP. The changes in expression of cell surface antigens as evidenced from decrease and increase binding of anti-mycelial and anti-sporidial anti-bodies in dbc-AMP treated culture by ELISA was further interpreted on the basis of morphological differentiation from mycelial to sporidial phase.

  14. Sapacitabine, the prodrug of CNDAC, is a nucleoside analog with a unique action mechanism of inducing DNA strand breaks

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jun Liu; Billie Nowak; Ya-Qing Wang; William Plunkett

    2012-01-01

    Sapacitabine is an orally bioavailable prodrug of the nucleoside analog 2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC).Both the prodrug and active metabolite are in clinical trials for hematologic malignancies and/or solid tumors.CNDAC has a unique mechanism of action:after incorporation into DNA,it induces single-strand breaks (SSBs) that are converted into double-strand breaks (DSBs) when cells go through a second S phase.In our previous studies,we demonstrated that CNDAC-induced SSBs can be repaired by the transcription-coupled nucleotide excision repair pathway,whereas lethal DSBs are mainly repaired through homologous recombination.In the current work,we used clonogenic assays to compare the DNA damage repair mechanism of CNDAC with two other deoxycytidine analogs:cytarabine,which is used in hematologic malignacies,and gemcitabine,which shows activity in solid tumors.Deficiency in two Rad51 paralogs,Rad51D and XRCC3,greatly sensitized cells to CNDAC,but not to cytarabine or gemcitabine,indicating that homologous recombination is not a major mechanism for repairing damage caused by the latter two analogs.This study further suggests clinical activity and application of sapacitabine that is distinct from that of cytarabine or gemcitabine.

  15. Hitler's Death Camps.

    Science.gov (United States)

    Wieser, Paul

    1995-01-01

    Presents a high school lesson on Hitler's death camps and the widespread policy of brutality and oppression against European Jews. Includes student objectives, instructional procedures, and a chart listing the value of used clothing taken from the Jews. (CFR)

  16. CDC Disease Detective Camp

    Centers for Disease Control (CDC) Podcasts

    2010-08-02

    The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.  Created: 8/2/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/2/2010.

  17. Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB.

    Science.gov (United States)

    Lee, Jinwoo; Tong, Tiegang; Takemori, Hiroshi; Jefcoate, Colin

    2015-06-15

    In mouse steroidogenic cells the activation of cholesterol metabolism is mediated by steroidogenic acute regulatory protein (StAR). Here, we visualized a coordinated regulation of StAR transcription, splicing and post-transcriptional processing, which are synchronized by salt inducible kinase (SIK1) and CREB-regulated transcription coactivator (CRTC2). To detect primary RNA (pRNA), spliced primary RNA (Sp-RNA) and mRNA in single cells, we generated probe sets by using fluorescence in situ hybridization (FISH). These methods allowed us to address the nature of StAR gene expression and to visualize protein-nucleic acid interactions through direct detection. We show that SIK1 represses StAR expression in Y1 adrenal and MA10 testis cells through inhibition of processing mediated by CRTC2. Digital image analysis matches qPCR analyses of the total cell culture. Evidence is presented for spatially separate accumulation of StAR pRNA and Sp-RNA at the gene loci in the nucleus. These findings establish that cAMP, SIK and CRTC mediate StAR expression through activation of individual StAR gene loci.

  18. β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D

    NARCIS (Netherlands)

    Trian, Thomas; Burgess, Janette K; Niimi, Kyoko; Moir, Lyn M; Ge, Qi; Berger, Patrick; Liggett, Stephen B; Black, Judith L; Oliver, Brian G

    2011-01-01

    BACKGROUND AND OBJECTIVE: Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. OBJECTIVE:

  19. Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp transcription factors by targeting microRNAs

    Directory of Open Access Journals (Sweden)

    Gandhy Shruti U

    2012-11-01

    Full Text Available Abstract Background Curcumin inhibits growth of several cancer cell lines, and studies in this laboratory in bladder and pancreatic cancer cells show that curcumin downregulates specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and pro-oncogenic Sp-regulated genes. In this study, we investigated the anticancer activity of curcumin and several synthetic cyclohexanone and piperidine analogs in colon cancer cells. Methods The effects of curcumin and synthetic analogs on colon cancer cell proliferation and apoptosis were determined using standardized assays. The changes in Sp proteins and Sp-regulated gene products were analysed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a, miR-20a, miR-17-5p and ZBTB10 and ZBTB4 mRNA expression. Results The IC50 (half-maximal values for growth inhibition (24 hr of colon cancer cells by curcumin and synthetic cyclohexanone and piperidine analogs of curcumin varied from 10 μM for curcumin to 0.7 μM for the most active synthetic piperidine analog RL197, which was used along with curcumin as model agents in this study. Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis, and this was accompanied by downregulation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes including the epidermal growth factor receptor (EGFR, hepatocyte growth factor receptor (c-MET, survivin, bcl-2, cyclin D1 and NFκB (p65 and p50. Curcumin and RL197 also induced reactive oxygen species (ROS, and cotreatment with the antioxidant glutathione significantly attenuated curcumin- and RL197-induced growth inhibition and downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes. The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR-27a, miR-20a and miR-17-5p that regulate these repressors

  20. Analogs of Cyclic AMP as Chemoattractants and Inhibitors of Dictyostelium Chemotaxis

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Jastorff, Bernd; Pinas, Johan E.; Konijn, Theo M.

    1982-01-01

    Aggregative amoebae of Dictyostelium discoideum, D. mucoroides, D. purpureum, and D. rosarium react chemotactically to cyclic AMP (cAMP). We measured the chemotactic activity of 14 cAMP analogs and found that these four species have a similar sensitivity to chemical modifications of cAMP; this sugge

  1. Direct Light-up of cAMP Derivatives in Living Cells by Click Reactions

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2013-10-01

    Full Text Available 8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells.

  2. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio

    2014-01-01

    anticancer potency, but similar toxicity causing hypercalcemia. We focused on the effect of these compounds on the stimulation of expression of human cathelicidin antimicrobial peptide (CAMP) whose gene has a vitamin D response element in its promoter. Expression of CAMP mRNA and protein increased in a dose......-response fashion after exposure of acute myeloid leukemia (AML) cells to the Gemini analog, BXL-01-126, in vitro. A xenograft model of AML was developed using U937 AML cells injected into NSG-immunodeficient mice. Administration of vitamin D3 compounds to these mice resulted in substantial levels of CAMP...

  3. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells.

    Science.gov (United States)

    Yoon, Yeo Cho; Kim, Sung-Hee; Kim, Min Jung; Yang, Hye Jeong; Rhyu, Mee-Ra; Park, Jae-Ho

    2015-12-10

    Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca(2+) and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca(2+) and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca(2+) and cAMP levels and phosphorylation of CREB.

  4. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yeo Cho Yoon

    2015-12-01

    Full Text Available Limonin, one of the major components in dictamni radicis cortex (DRC, has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca2+ and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca2+ and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca2+ and cAMP levels and phosphorylation of CREB.

  5. Lunar Analog

    Science.gov (United States)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  6. Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP

    NARCIS (Netherlands)

    Kuiperij, H.B.; Horst, Armando van der; Raaijmakers, Judith; Weijzen, S.; Medema, R.H.; Bos, J.L.; Burgering, B.M.T.; Zwartkruis, G.J.T.

    2005-01-01

    cAMP is a potent inhibitor of cell proliferation in a variety of cell lines. Downregulation of cyclin D1 and upregulation of the cell cycle inhibitor p27Kip1 are two mechanisms by which cAMP may induce a G1-arrest. Here we show that cAMP inhibits proliferation of cells that constitutively express cy

  7. Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration.

    Science.gov (United States)

    Udina, E; Ladak, A; Furey, M; Brushart, T; Tyreman, N; Gordon, T

    2010-05-01

    The inhibitory growth environment of myelin and extracellular matrix proteoglycans in the central nervous system may be overcome by elevating neuronal cAMP or degrading inhibitory proteoglycans with chondroitinase ABC (ChABC). In this study, we asked whether similar mechanisms operate in peripheral nerve regeneration where effective Wallerian degeneration removes myelin and extracellular proteoglycans slowly. We repaired transected common peroneal (CP) nerve in rats and either elevated cAMP in the axotomized neurons by subcutaneous rolipram, a specific inhibitor of phosphodiesterase IV, and/or promoted degradation of proteoglycans in the distal nerve stump by local ChABC administration. Rolipram treatment significantly increased the number of motoneurons that regenerated axons across the repair site at 1 and 2 weeks, and increased the number of sensory neurons that regenerated axons across the repair site at 2 weeks. Local application of ChABC had a similar effect to rolipram treatment in promoting motor axon regeneration, the effect being no greater when rolipram and ChABC were administered simultaneously. We conclude that blocking inhibitors of axon regeneration by elevating cAMP or degrading proteoglycans in the distal nerve stump promotes peripheral axon regeneration after surgical repair of a transected nerve. It is likely that elevated cAMP is sufficient to encourage axon outgrowth despite the inhibitory growth environment such that simultaneous enzymatic proteoglycan degradation does not promote more axon regeneration than either elevated cAMP or proteoglycan degradation alone.

  8. Rehabilitating camp cities : community driven planning for urbanised refugee camps

    OpenAIRE

    Misselwitz, Philipp

    2009-01-01

    Focussing on Palestine refugee camps in the Near East, this dissertation aims to shed light on the potential relevance of urban planning to refugee camp environments worldwide. In particular, there is a focus on the role architects and urban planners can play in facilitating participatory planning processes as well as providing guidance and expertise in the development of a spatial vision for Camp Cities. Part I - The Urbanisation of Refugee Camps as a Global Challenge The first part o...

  9. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    Directory of Open Access Journals (Sweden)

    Neera Tewari-Singh

    Full Text Available Chemical warfare agent sulfur mustard (HD inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%, and activation of transcription factors NF-κB and AP-1 (complete reversal. Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  10. Gene Expression Patterns Define Key Transcriptional Events InCell-Cycle Regulation By cAMP And Protein Kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Zambon, Alexander C.; Zhang, Lingzhi; Minovitsky, Simon; Kanter, Joan R.; Prabhakar, Shyam; Salomonis, Nathan; Vranizan, Karen; Dubchak Inna,; Conklin, Bruce R.; Insel, Paul A.

    2005-06-01

    Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPTcAMP), a PKA-selective cAMP analog, alters the expression of approx equal to 4,500 of approx. equal to 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPTcAMP. Changes in mRNA and protein expression of several cell cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.

  11. The camp model for entrepreneurship teaching

    DEFF Research Database (Denmark)

    Bager, Torben

    2011-01-01

    Artiklen omhandler brugen af camps i entrepreneurship undervising - illustreret med danske camp eksempler Udgivelsesdato: online 31.03.2010......Artiklen omhandler brugen af camps i entrepreneurship undervising - illustreret med danske camp eksempler Udgivelsesdato: online 31.03.2010...

  12. Suppression of adipose lipolysis by long-chain fatty acid analogs.

    Science.gov (United States)

    Kalderon, Bella; Azazmeh, Narmen; Azulay, Nili; Vissler, Noam; Valitsky, Michael; Bar-Tana, Jacob

    2012-05-01

    Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA that is neither esterified into lipids nor β-oxidized, and therefore, it was exploited for suppressing agonist-induced lipolysis in analogy to natural LCFA. Mββ is shown here to suppress isoproterenol-induced lipolysis in the rat in vivo as well as in 3T3-L1 adipocytes. Inhibition of isoproterenol-induced lipolysis is due to decrease in isoproterenol-induced cAMP with concomitant inhibition of the phosphorylation of hormone-sensitive lipase and perilipin by protein kinase A. Suppression of cellular cAMP levels is accounted for by inhibition of the adenylate cyclase due to suppression of Raf1 expression by Mββ-activated AMPK. Suppression of Raf1 is further complemented by induction of components of the unfolded-protein-response by Mββ. Our findings imply genuine inhibition of agonist-induced adipose lipolysis by LCFA, independent of their β-oxidation or reesterification. Mββ suppression of agonist-induced lipolysis and cellular cAMP levels independent of the insulin transduction pathway may indicate that synthetic LCFA could serve as insulin mimetics in the lipolysis context under conditions of insulin resistance.

  13. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  14. Base Camp Design Simulation Training

    Science.gov (United States)

    2011-07-01

    The Army needs officers and noncommissioned officers with requisite base camp competencies. The Army’s Field Manual (FM) 3-34.400 defines a Base Camp...reason, we designed a 600-man base camp on VBS2TM from an AutoCAD diagram found on the Theater Construction Management System (version 3.2). Known

  15. Electrodynamic phenomena induced by a dark fluid: Analogs of pyromagnetic, piezoelectric, and striction effects

    CERN Document Server

    Balakin, Alexander B

    2014-01-01

    We establish a new model of coupling between a cosmic dark fluid and electrodynamic systems, based on an analogy with effects of electric and magnetic striction, piezo-electricity and piezo-magnetism, pyro-electricity and pyro-magnetism, which appear in classical electrodynamics of continuous media. Extended master equations for electromagnetic and gravitational fields are derived using Lagrange formalism. A cosmological application of the model is considered, and it is shown that a striction-type interaction between the dark energy (the main constituent of the dark fluid) and electrodynamic system provides the universe history to include the so-called unlighted epochs, during which electromagnetic waves can not propagate and thus can not scan the universe interior.

  16. Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: reduced synthesis or increased catabolism?

    Science.gov (United States)

    Sancesario, Giuseppe; Morrone, Luigi Antonio; D'Angelo, Vincenza; Castelli, Valentina; Ferrazzoli, Davide; Sica, Francesco; Martorana, Alessandro; Sorge, Roberto; Cavaliere, Federica; Bernardi, Giorgio; Giorgi, Mauro

    2014-12-01

    Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of levodopa/dopamine stimulated cAMP and cGMP levels, and/or with changes of their catabolism by phosphodiesterase activity in rats with experimental hemiparkinsonism. Microdialysis and tissue homogenates of the striatal tissues demonstrated that extracellular and intracellular cAMP/cGMP levels were lower in dyskinetic animals during the increasing phase of dyskinesias compared to eukinetic animals, but cAMP/cGMP levels increased in dyskinetic animals during the phase of decreasing and extinction of dyskinesias. Dyskinesias and the abnormal lowering of striatal cGMP and cAMP after levodopa were prevented by pretreatment with the multipotent drug amantadine, outlining the inverse relationship of cAMP/cGMP to dyskinesias. Moreover, dyskinetic animals showed higher striatal hydrolyzing cGMP-phosphodiesterase but not hydrolyzing cAMP-phosphodiesterase activity, suggesting that low cGMP but not cAMP levels could be due to increased catabolism. However, expressions of isozyme phosphodiesterase-1B and -10A highly and specifically located in the basal ganglia were not changed after levodopa in dyskinetic and eukinetic animals: accordingly, selective inhibitors of phosphodiesterase-1B and -10A were ineffective on levodopa dyskinesias. Therefore, the isozyme(s) expressing higher cGMP-phosphodiesterase activity in the striatum of dyskinetic animal should be determined. These observations suggest that dopamine-mediated processes of synthesis and/or degradation of cAMP/cGMP could be acutely impaired in levodopa dyskinesias, opening new ways to understanding physiopathology and treatment.

  17. Excessive grooming induced by somatostatin or its analog SMS 201-995

    NARCIS (Netherlands)

    Wimersma Greidanus, T.B. van; Maigret, C.; Krechting, B.

    1987-01-01

    Intracerebroventricular (i.c.v.) administration of somatostatin or SMS 201-995 induces excessive grooming behavior in rats. The grooming inducing effect of somatostatin is rather weak, as doses of 300 ng or less did not result in increased total grooming scores. In contrast a dose of 10 ng SMS 201-9

  18. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Neves-dos-Santos Sandra

    2010-01-01

    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  19. A new buprenorphine analogy, thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-liZHAO; Ze-huiGONG; Jian-huiLIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  20. A new buprenorphine analogy,thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-li ZHAO; Ze-hui GONG; Jian-hui LIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01).Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  1. The investigation of resveratrol and analogs as potential inducers of fetal hemoglobin.

    Science.gov (United States)

    Theodorou, Andria; Phylactides, Marios; Forti, Luca; Cramarossa, Maria Rita; Spyrou, Pantelis; Gambari, Roberto; Thein, Swee Lay; Kleanthous, Marina

    2016-05-01

    Βeta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone.

  2. Activation of cAMP Signaling Interferes with Stress-Induced p53 Accumulation in ALL-Derived Cells by Promoting the Interaction between p53 and HDM212

    OpenAIRE

    2011-01-01

    The tumor suppressor p53 provides an important barrier to the initiation and maintenance of cancers. As a consequence, p53 function must be inactivated for a tumor to develop. This is achieved by mutation in approximately 50% of cases and probably by functional inactivation in the remaining cases. We have previously shown that the second messenger cAMP can inhibit DNA damage-induced wild-type p53 accumulation in acute lymphoblastic leukemia cells, leading to a profound reduction of their apop...

  3. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Knop, Filip K; Ishøy, Pelle L;

    2012-01-01

    between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss...... are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes...... in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies...

  4. Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

    Science.gov (United States)

    Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

    2016-01-01

    Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3.

  5. Directed evolution of the Escherichia coli cAMP receptor protein at the cAMP pocket.

    Science.gov (United States)

    Gunasekara, Sanjiva M; Hicks, Matt N; Park, Jin; Brooks, Cory L; Serate, Jose; Saunders, Cameron V; Grover, Simranjeet K; Goto, Joy J; Lee, Jin-Won; Youn, Hwan

    2015-10-30

    The Escherichia coli cAMP receptor protein (CRP) requires cAMP binding to undergo a conformational change for DNA binding and transcriptional regulation. Two CRP residues, Thr(127) and Ser(128), are known to play important roles in cAMP binding through hydrogen bonding and in the cAMP-induced conformational change, but the connection between the two is not completely clear. Here, we simultaneously randomized the codons for these two residues and selected CRP mutants displaying high CRP activity in a cAMP-producing E. coli. Many different CRP mutants satisfied the screening condition for high CRP activity, including those that cannot form any hydrogen bonds with the incoming cAMP at the two positions. In vitro DNA-binding analysis confirmed that these selected CRP mutants indeed display high CRP activity in response to cAMP. These results indicate that the hydrogen bonding ability of the Thr(127) and Ser(128) residues is not critical for the cAMP-induced CRP activation. However, the hydrogen bonding ability of Thr(127) and Ser(128) was found to be important in attaining high cAMP affinity. Computational analysis revealed that most natural cAMP-sensing CRP homologs have Thr/Ser, Thr/Thr, or Thr/Asn at positions 127 and 128. All of these pairs are excellent hydrogen bonding partners and they do not elevate CRP activity in the absence of cAMP. Taken together, our analyses suggest that CRP evolved to have hydrogen bonding residues at the cAMP pocket residues 127 and 128 for performing dual functions: preserving high cAMP affinity and keeping CRP inactive in the absence of cAMP.

  6. Running Boot Camp

    CERN Document Server

    Toporek, Chuck

    2008-01-01

    When Steve Jobs jumped on stage at Macworld San Francisco 2006 and announced the new Intel-based Macs, the question wasn't if, but when someone would figure out a hack to get Windows XP running on these new "Mactels." Enter Boot Camp, a new system utility that helps you partition and install Windows XP on your Intel Mac. Boot Camp does all the heavy lifting for you. You won't need to open the Terminal and hack on system files or wave a chicken bone over your iMac to get XP running. This free program makes it easy for anyone to turn their Mac into a dual-boot Windows/OS X machine. Running Bo

  7. Dust Bowl migration as an analog for possible global warming-induced migration from Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Turner, M.H.; Longstreth, J.D.; Johnson, A.K.; Rosenberg, N.J.

    1994-06-01

    As a result of increases in CO{sub 2} and other radiatively important trace gases, scientists have predicted increases in mean worldwide temperatures of 2--5 degrees C over the next 50 to 100 years. Such temperature increases may result in climate modifications that would in turn be associated with increases in drought and desertification and could even change the patterns of the monsoons and tropical rains, which are important to agriculture throughout the world. They predicted that the rise in sea level caused by melting and thermal expansion of glaciers and polar icecaps could flood large population centers, destroying habitation and displacing populations. This will result in approximately 50 million ``environmental refugees`` worldwide, triple the number of today. The expected shifts in precipitation are also likely to result in (1) increased runoff contaminated with pesticides, salts, garbage, sewage, and eroded soil, and (2) drought also leading to increased soil erosion and salinization, as well as depletion of limited water resources. The total impact of global warming on agriculture and human habitation could considerably slow the economic development of some nations and would particularly affect agricultural production. Loss of homes, the inability to raise food, an increased prevalence of disease and worsened economic conditions may drive people to leave their homelands, seeking entry into countries which have more resources and greater resistance to the economic consequences of climatic change. This report looks at the possible environmental impacts and economic impacts of the greenhouse effect on Mexico while using the American Dust Bowl event as an analog.

  8. Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.

    Science.gov (United States)

    Kurosawa, Mie; Oda, Masataka; Domon, Hisanori; Saitoh, Issei; Hayasaki, Haruaki; Terao, Yutaka

    2016-02-01

    Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection.

  9. A Summer Camp

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    正This summer,I had some special days.I joined Dongzhou International Educational Exchange Summer Camp. First,I will tell you about our foreign teachers,they are Shrina and Rebecca. They are friendly and beautiful.They are students at Oxford University. We talked about many things:famous people,subjects in England,different jobs, our deal days,western star signs,what can we say in a restaurant and so on.

  10. Interprofessional Flight Camp.

    Science.gov (United States)

    Alfes, Celeste M; Rowe, Amanda S

    2016-01-01

    The Dorothy Ebersbach Academic Center for Flight Nursing in Cleveland, OH, holds an annual flight camp designed for master's degree nursing students in the acute care nurse practitioner program, subspecializing in flight nursing at the Frances Payne Bolton School of Nursing at Case Western Reserve University. The weeklong interprofessional training is also open to any health care provider working in an acute care setting and focuses on critical care updates, trauma, and emergency care within the critical care transport environment. This year, 29 graduate nursing students enrolled in a master's degree program from Puerto Rico attended. Although the emergency department in Puerto Rico sees and cares for trauma patients, there is no formal trauma training program. Furthermore, the country only has 1 rotor wing air medical transport service located at the Puerto Rico Medical Center in San Juan. Flight faculty and graduate teaching assistants spent approximately 9 months planning for their participation in our 13th annual flight camp. Students from Puerto Rico were extremely pleased with the learning experiences at camp and expressed particular interest in having more training time within the helicopter flight simulator.

  11. Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expression in CCRF-CEM lymphoblastic cells: evidence for the involvement of cAMP and p38 MAPK

    Directory of Open Access Journals (Sweden)

    M. Castro-caldas

    2003-01-01

    Full Text Available Aims: Annexin 1 (ANXA1, a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex, and the estrogen hormone, 17β-estradiol (E2β, induce the synthesis of ANXA1, by a mechanism independent of the activation of their nuclear receptors. Recently, it was reported that the gene coding for ANXA1 contains a cAMP-responsive element (CRE. In this work, we investigated whether Dex and E2β were able to induce the activation of CRE binding proteins (CREB in the CCRF-CEM cells. Moreover, we studied the intracellular signalling pathways involved in CREB activation and ANXA1 synthesis in response to Dex and E2β; namely, the role of cAMP and the p38 mitogen-activated protein kinase (MAPK.

  12. Hydrogen sulfide inhibits A2A adenosine receptor agonist induced β-amyloid production in SH-SY5Y neuroblastoma cells via a cAMP dependent pathway.

    Directory of Open Access Journals (Sweden)

    Bhushan Vijay Nagpure

    Full Text Available Alzheimer's disease (AD is the leading cause of senile dementia in today's society. Its debilitating symptoms are manifested by disturbances in many important brain functions, which are influenced by adenosine. Hence, adenosinergic system is considered as a potential therapeutic target in AD treatment. In the present study, we found that sodium hydrosulfide (NaHS, an H2S donor, 100 µM attenuated HENECA (a selective A2A receptor agonist, 10-200 nM induced β-amyloid (1-42 (Aβ42 production in SH-SY5Y cells. NaHS also interfered with HENECA-stimulated production and post-translational modification of amyloid precursor protein (APP by inhibiting its maturation. Measurement of the C-terminal APP fragments generated from its enzymatic cleavage by β-site amyloid precursor protein cleaving enzyme 1 (BACE1 showed that NaHS did not have any significant effect on β-secretase activity. However, the direct measurements of HENECA-elevated γ-secretase activity and mRNA expressions of presenilins suggested that the suppression of Aβ42 production in NaHS pretreated cells was mediated by inhibiting γ-secretase. NaHS induced reductions were accompanied by similar decreases in intracellular cAMP levels and phosphorylation of cAMP responsive element binding protein (CREB. NaHS significantly reduced the elevated cAMP and Aβ42 production caused by forskolin (an adenylyl cyclase, AC agonist alone or forskolin in combination with IBMX (a phosphodiesterase inhibitor, but had no effect on those caused by IBMX alone. Moreover, pretreatment with NaHS significantly attenuated HENECA-elevated AC activity and mRNA expressions of various AC isoforms. These data suggest that NaHS may preferentially suppress AC activity when it was stimulated. In conclusion, H2S attenuated HENECA induced Aβ42 production in SH-SY5Y neuroblastoma cells through inhibiting γ-secretase via a cAMP dependent pathway.

  13. Optical Analog to Electromagnetically Induced Transparency in Cascaded Ring-Resonator Systems

    Science.gov (United States)

    Wang, Yonghua; Zheng, Hua; Xue, Chenyang; Zhang, Wendong

    2016-01-01

    The analogue of electromagnetically induced transparency in optical methods has shown great potential in slow light and sensing applications. Here, we experimentally demonstrated a coupled resonator induced transparency system with three cascaded ring coupled resonators in a silicon chip. The structure was modeled by using the transfer matrix method. Influences of various parameters including coupling ratio of couplers, waveguide loss and additional loss of couplers on transmission characteristic and group index have been investigated theoretically and numerically in detail. The transmission character of the system was measured by the vertical grating coupling method. The enhanced quality factor reached 1.22 × 105. In addition, we further test the temperature performance of the device. The results provide a new method for the manipulation of light in highly integrated optical circuits and sensing applications. PMID:27463720

  14. Radio-deoxynucleoside Analogs used for Imaging tk Expression in a Transgenic Mouse Model of Induced Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Haibin Tian, Xincheng Lu, Hong Guo, David Corn, Joseph Molter, Bingcheng Wang, Guangbin Luo, Zhenghong Lee

    2012-01-01

    Full Text Available Purpose: A group of radiolabeled thymidine analogs were developed as radio-tracers for imaging herpes viral thymidine kinase (HSV1-tk or its variants used as reporter gene. A transgenic mouse model was created to express tk upon liver injury or naturally occurring hepatocellular carcinoma (HCC. The purpose of this study was to use this unique animal model for initial testing with radio-labeled thymidine analogs, mainly a pair of newly emerging nucleoside analogs, D-FMAU and L-FMAU.Methods: A transgeneic mouse model was created by putting a fused reporter gene system, firefly luciferase (luc and HSV1-tk, under the control of mouse alpha fetoprotein (Afp promoter. Initial multimodal imaging, which was consisted of bioluminescent imaging (BLI and planar gamma scintigraphy with [125I]-FIAU, was used for examining the model creation in the new born and liver injury in the adult mice. Carcinogen diethylnitrosamine (DEN was then administrated to induce HCC in these knock-in mice such that microPET imaging could be used to track the activity of Afp promoter during tumor development and progression by imaging tk expression first with [18F]-FHBG. Dynamic PET scans with D-[18F]-FMAU and L-[18F]-FMAU were then performed to evaluate this pair of relatively new tracers. Cells were derived from these liver tumors for uptake assays using H-3 labeled version of PET tracers.Results: The mouse model with dual reporters: HSV1-tk and luc placed under the transcriptional control of an endogenous Afp promoter was used for imaging studies. The expression of the Afp gene was highly specific in proliferative hepatocytes, in regenerative liver, and in developing fetal liver, and thus provided an excellent indicator for liver injury and cancer development in adult mice. Both D-FMAU and L-FMAU showed stable liver tumor uptake where the tk gene was expressed under the Afp promoter. The performance of this pair of tracers was slightly different in terms of signal

  15. Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages

    Directory of Open Access Journals (Sweden)

    Smith Milton

    2006-11-01

    Full Text Available Abstract Background 2-Chloroethyl ethyl sulphide (CEES is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD. Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. Results We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA or dichlorofluorescin diacetate (DCFH-DA. Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity Conclusion CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS

  16. Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation.

    Science.gov (United States)

    Fatemi, Ahmad; Kazemi, Ahmad; Kashiri, Meysam; Safa, Majid

    2015-01-01

    Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin-mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation.

  17. Phosphorylation of β-actin by protein kinase C-delta in camptothecin analog-induced leukemic cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Shuang WANG; Ying ZHENG; Yun YU; Li XIA; Guo-qiang CHEN; Yong-zong YANG; Li-shun WANG

    2008-01-01

    Aim: This study was conducted to reveal new proteins involved in acute myeloid leukemia (AML) cell apoptosis. Methods: Using camptothecin analog NSC606985-induced leukemic U937 cell apoptosis as a model, this study performed a differen-tial proteomic analysis during apoptosis induction. The significantly modulated protein was underwent further investigation in the apoptotic process. Results: We found that β-actin protein presented two different spots on the two-dimen-sional electrophoresis (2-DE) map, which shared similar molecular weight and different pI. Those two spots demonstrated contrary changes (disappeared on the basic-end and increased on the acid-end spot) during apoptosis induction, although the total level of β-actin kept constant. This observation was further confirmed by immunoblot analysis on 2-DE gel. When NSC606985-treated cell iysate was incubated with alkaline phosphotase, β-actin on the basic-end spot was restored, indicating increased phosphorylation of β-actin during NSC606985-induced apoptosis. Moreover, the polymerization of actin also decreased after NSC606985 treatment. The increased β-actin phosphorylation and decreased ac-tin polymerization was antagonized by pre-treatment of rottlerin, a specific protein kinase C-delta (PKCδ) inhibitor. Conclusion: All these results indicate that β-actin was phosphorylated during apoptosis induction, which was mediated by acti-vated PKCδ.

  18. Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study).

    Science.gov (United States)

    Michałowicz, Jaromir; Mokra, Katarzyna; Bąk, Agata

    2015-10-01

    Few studies have addressed the cellular effects of bisphenol S (BPS) and bisphenol AF (BPAF) on cells, and no study has been conducted to analyze the mechanism of action of bisphenols in blood cells. In this study, the effect of bisphenol A (BPA), bisphenol F (BPF), BPS and BPAF on human peripheral blood mononuclear cells (PBMCs) was analyzed. It was shown that BPA, BPF and BPAF in particular, decreased cell viability, which was associated with depletion of intracellular ATP level and alterations in PBMCs size and granulation. Bisphenols enhanced ROS (including OH˙) formation, which led to damage to lipids and proteins in PBMCs. The most significant alterations in ROS level were induced by BPF, and particularly BPAF. Moreover, it was shown that BPAF most strongly provoked lipid peroxidation, while BPA and BPS caused the greatest damage to proteins. It may be concluded that BPA and its analogs were capable of inducing oxidative stress and damage in PBMCs in the concentrations ranging from 0.06 to 0.5 μM (0.02-0.1 μg/ml), which may be present in human blood as a result of environmental exposure. Although, most of bisphenols studied decreased cell viability, size and ATP level at higher concentrations, BPAF exhibited its cytotoxic potential at low concentrations ranging from 0.3 to 3 μM (0.1-1.0 μg/ml) that may correspond to concentrations in humans following occupational exposure.

  19. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  20. Registration Day-Camp 2016

    CERN Multimedia

    Nursery School

    2016-01-01

    Reminder Registration for the CERN Staff Association Day-camp are open for children from 4 to 6 years old More information on the website: http://nurseryschool.web.cern.ch/. The day-camp is open to all children. An inscription per week is proposed, cost 480.-CHF/week, lunch included The camp will be open weeks 27, 28, 29 and 30, from 8:30 am to 5:30 pm. For further questions, thanks you for contacting us by email at Summer.Camp@cern.ch.

  1. Tunable optical analog to electromagnetically induced transparency in graphene-ring resonators system

    Science.gov (United States)

    Wang, Yonghua; Xue, Chenyang; Zhang, Zengxing; Zheng, Hua; Zhang, Wendong; Yan, Shubin

    2016-12-01

    The analogue of electromagnetically induced transparency in optical ways has shown great potential in optical delay and quantum-information technology due to its flexible design and easy implementation. The chief drawback for these devices is the bad tunability. Here we demonstrate a tunable optical transparency system formed by graphene-silicon microrings which could control the transparent window by electro-optical means. The device consists of cascaded coupled ring resonators and a graphene/graphene capacitor which integrated on one of the rings. By tuning the Fermi level of the graphene sheets, we can modulate the round-trip ring loss so that the transparency window can be dynamically tuned. The results provide a new method for the manipulation and transmission of light in highly integrated optical circuits and quantum information storage devices.

  2. Analog electromagnetically induced transparency for circularly polarized wave using three dimensional chiral metamaterials

    CERN Document Server

    Lin, Hai; Han, Song; Liu, Yangjie; Yang, Helin

    2016-01-01

    In this paper, we theoretically and experimentally demonstrate a three dimensional metamaterial that can motivate electromagnetic induced transparency (EIT) by using circular polarized wave as stimulations. The unit cell consists of a pair of metallic strips printed on both sides of the printed circuit board (PCB), where a conductive cylinder junction is used to connect the metal strips by drilling a hole inside the substrate. When a right circularly polarized wave is incident, destructive interference is excited between meta-atoms of the 3D structure, the transmission spectrum demonstrates a sharp transparency window. A coupled oscillator model and an electrical equivalent circuit model are applied to quantitatively and qualitatively analyze the coupling mechanism in the EIT-like metamaterial. Analysis in detail shows the EIT window's amplitude and frequency are modulated by changing the degree of symmetry breaking. The proposed metamaterial may achieve potential applications in developing chiral slow light ...

  3. Genome-wide mutation avalanches induced in diploid yeast cells by a base analog or an APOBEC deaminase.

    Directory of Open Access Journals (Sweden)

    Artem G Lada

    Full Text Available Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.

  4. Summer Camp as Therapeutic Context: The Camp Logan Program.

    Science.gov (United States)

    McCammon, Susan; And Others

    These symposium papers describe various aspects of the Camp Logan, South Carolina, program, a therapeutic summer residential program for children, ages 8-14, who have significant behavior problems. The philosophy and advantages of the therapeutic camping model are discussed, e.g., structure during the summer, controlled though informal…

  5. Summer Camp, July 2016

    CERN Multimedia

    Staff Association

    2016-01-01

    During the month of July, the Staff Association’s Children’s Day-Care Centre and School EVEE held a summer camp for 4- to 6-year-olds. 24 children altogether joined in on the adventures. On the summer camp, the children got to “travel” to a different continent of the world every week. Day after day, they would pass through make-believe Customs upon arrival and get their passports stamped by a “customs officer”. For the first week, we went on a trip to Africa. In the spirit of the theme, the children got to do plenty of crafts and coloring, make their own little bindles and play various games. They even had the chance to visit the Museum of Ethnography in Geneva (MEG), learn to play the balafon and make musical instruments with Sterrenlab. For the second week, we set off to discover the Americas, exploring both the South and the North. Alongside different workshops (singing, dancing, storytelling, crafts), the children could enjoy several special ac...

  6. Fragmentation energetics for angiotensin II and its analogs from time- and energy-resolved surface-induced dissociation studies

    Science.gov (United States)

    Laskin, Julia; Bailey, Thomas H.; Futrell, Jean H.

    2004-05-01

    Surface-induced dissociation (SID) of four model peptides: DRVYIHPF, RVYIHPF, RVYIHAF, and RVYIHDF was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for SID experiments. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM based approach developed in our laboratory. Accurate dissociation parameters can be obtained from these experiments because collision-energy-resolved SID data are very sensitive to both the energetics and dynamics of dissociation. We found that transition from selective to non-selective fragmentation as ion kinetic energy is increased is associated with a substantial (ca. 0.5 eV) increase in the dissociation energy and a 3-4 orders of magnitude increase in the pre-exponential factor. Dissociation thresholds for angiotensin analogs derived from the experimental data are as follows: 1.62 eV for RVYIHAF and RVYIHPF, 1.14 eV for RVYIHDF and 1.13 eV for DRVYIHPF. Pre-exponential factors of 8.2×1011, 7.2×1012, 3.1×108, and 5.0×107 s-1 were obtained for RVYIHPF, RVYIHAF, RVYIHDF, and DRVYIHPF, respectively. Contribution from shattering to the total decomposition of the precursor ion increases for kinetically hindered fragmentation. The largest contribution is observed for a peptide ion that has the largest negative reaction entropy--DRVYIHPF.

  7. Mechanisms of Peptide Fragmentation from Time-and Energy-Resolved Surface-Induced Dissociation Studies: Dissociation of Angiotensin Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Laskin, Julia; Bailey, Thomas H.; Futrell, Jean H.

    2006-03-01

    Energetics and mechanism of dissociation of singly protonated angiotensin III (RVYIHPF) and its analogs RVYIFPF, RVYIYPF, RVYIHAF, and RVYIHDF was studied using surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for studying ion activation by collisions with surfaces. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM based approach developed in our laboratory. Fragmentation mechanisms were inferred from comparison of time- and energy-resolved fragmentation efficiency curves (TFECs) of different fragment ions followed by RRKM modeling of dissociation of angiotensin III into six major families of fragment ions. Detailed modeling demonstrated that dissociation of these peptides is dominated by loss of ammonia from the precursor ion and characterized by a high energy barrier of 1.6 eV. Loss of NH3 and subsequent rearrangement of the MH-NH3 ion results in proton mobilization and release of ca. 30 kcal/mol into internal excitation of the MH-NH3 ion. The resulting highly excited ion accesses a variety of non-specific dissociation pathways with very high rate constants. Fast fragmentation of excited MH-NH3 ion forms a variety of abundant bn-NH3 and an-NH3 fragment ions. Abundant XH and HX internal fragments are also formed, reflecting the stability of histidine-containing diketopiperazine structures.

  8. Mechanisms of peptide fragmentation from time- and energy-resolved surface-induced dissociation studies: Dissociation of angiotensin analogs

    Science.gov (United States)

    Laskin, Julia; Bailey, Thomas H.; Futrell, Jean H.

    2006-03-01

    Energetics and mechanism of dissociation of singly protonated angiotensin III (RVYIHPF) and its analogs RVYIFPF, RVYIYPF, RVYIHAF and RVYIHDF was studied using surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for studying ion activation by collisions with surfaces. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM-based approach developed in our laboratory. Fragmentation mechanisms were inferred from comparison of time- and energy-resolved fragmentation efficiency curves (TFECs) of different fragment ions followed by RRKM modeling of dissociation of angiotensin III into six major families of fragment ions. Detailed modeling demonstrated that dissociation of these peptides is dominated by loss of ammonia from the precursor ion and characterized by a high-energy barrier of 1.6 eV. Loss of NH3 and subsequent rearrangement of the MH+-NH3 ion results in proton mobilization and release of ca. 30 kcal/mol into internal excitation of the MH+-NH3 ion. The resulting highly excited ion accesses a variety of non-specific dissociation pathways with very high rate constants. Fast fragmentation of excited MH+-NH3 ion forms a variety of abundant bn-NH3 and an-NH3 fragment ions. Abundant XH and HX internal fragments are also formed, reflecting the stability of histidine-containing diketopiperazine structures.

  9. Kids Camping Takes the Challenge.

    Science.gov (United States)

    James, Vickie L.; Hohnbaum, Claudia

    2002-01-01

    A Wisconsin Girl Scout camp integrated The Healthy Kids Challenge into its program. The camp evaluated policies related to meals, snacks, physical activities, team building, and self-esteem. Staff inservice training resulted in healthier meals on the same budget and developed ownership of the program. Campers and families had opportunities to…

  10. Encountering Child Abuse at Camp.

    Science.gov (United States)

    Durall, John K.

    1997-01-01

    Defines child abuse, including the three categories: physical, sexual, and psychological. Presents characteristics and behaviors of each type of abuse, and long-term effects. Discusses how to handle abuse that occurs at camp, and the effects on the camp. Sidebars present abuse statistics, 15 activities that promote psychological wellness, and 8…

  11. Ca2+ influx through L-type Ca2+ channels and Ca2+-induced Ca2+ release regulate cAMP accumulation and Epac1-dependent ERK 1/2 activation in INS-1 cells.

    Science.gov (United States)

    Pratt, Evan P S; Salyer, Amy E; Guerra, Marcy L; Hockerman, Gregory H

    2016-01-05

    We previously reported that INS-1 cells expressing the intracellular II-III loop of the L-type Ca(2+) channel Cav1.2 (Cav1.2/II-III cells) are deficient in Ca(2+)-induced Ca(2+) release (CICR). Here we show that glucose-stimulated ERK 1/2 phosphorylation (GSEP) is slowed and reduced in Cav1.2/II-III cells compared to INS-1 cells. This parallels a decrease in glucose-stimulated cAMP accumulation (GS-cAMP) in Cav1.2/II-III cells. Influx of Ca(2+) via L-type Ca(2+) channels and CICR play roles in both GSEP and GS-cAMP in INS-1 cells since both are inhibited by nicardipine or ryanodine. Further, the Epac1-selective inhibitor CE3F4 abolishes glucose-stimulated ERK activation in INS-1 cells, as measured using the FRET-based sensor EKAR. The non-selective Epac antagonist ESI-09 but not the Epac2-selective antagonist ESI-05 nor the PKA antagonist Rp-cAMPs inhibits GSEP in both INS-1 and Cav1.2/II-III cells. We conclude that L-type Ca(2+) channel-dependent cAMP accumulation, that's amplified by CICR, activates Epac1 and drives GSEP in INS-1 cells.

  12. The effect of neuropeptides on vessel tone and cAMP production

    DEFF Research Database (Denmark)

    Yao, W; Sheikh, S P; Ottesen, B;

    1996-01-01

    The effect of VIP, PHM, PHV, PACAP-27, and PACAP-38 on vessel tone and cAMP production was investigated in rabbit ovarian arteries in vitro. The peptides (10(-7)M) induced a significant relaxation on NA-precontracted vessels and displayed similar potencies. The cAMP accumulation induced by PACAP-...

  13. Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination.

    Science.gov (United States)

    Vakilzadeh, Gelareh; Khodagholi, Fariba; Ghadiri, Tahereh; Darvishi, Marzieh; Ghaemi, Amir; Noorbakhsh, Farshid; Gorji, Ali; Sharifzadeh, Mohammad

    2015-08-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti-apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 μg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-κB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS.

  14. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

    Directory of Open Access Journals (Sweden)

    Irina S.-R. Waisertreiger

    2010-01-01

    Full Text Available Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP deoxynucleoside triphosphate and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of the ITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base-analog drugs. The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs.

  15. Cultured lymphocytes from alcoholic subjects have altered cAMP signal transduction.

    OpenAIRE

    Nagy, L E; Diamond, I; Gordon, A.

    1988-01-01

    Previous work has shown that freshly isolated lymphocytes from alcoholic subjects show significantly reduced basal and adenosine receptor-stimulated cAMP levels. This decrease could be due to ethanol-induced cellular adaptation or to a genetic difference in the regulation of cAMP signal transduction. Therefore, we cultured human lymphocytes in defined medium without ethanol for 7-8 days and then examined differences in receptor-dependent cAMP accumulation between lymphocytes from alcoholic an...

  16. Day Camp Manual: Administration. Book I.

    Science.gov (United States)

    Babcock, William

    The first book in a 5-book manual on day camping focuses on summer day camp administration. The book defines day camps as organized group experiences in outdoor living on a day-by-day basis and under trained leadership. It includes a philosophy of day camping, noting benefits to the campers. The book is divided into further chapters that describe…

  17. Slave Labor Camps of the Third Reich.

    Science.gov (United States)

    Stone, Adolf

    1983-01-01

    Describes the ground rules used by Nazi architects in choosing the sites for slave labor camps. While some, like Auschwitz, became extermination camps, others also produced armaments. One camp, Theresienstadt, became a "model" camp to show to reporters and Red Cross representatives. (CS)

  18. Comparison of work motivation in camp supervisors and camp counselors in Greek private camps

    Directory of Open Access Journals (Sweden)

    George Costa

    2008-06-01

    Full Text Available The purpose of this study was twofold. First, the study sought to better understand the work motivators that led camp supervisors and counselors to accept their job. Second, the study sought to better understand the ranking and rating of 20 work motivators from supervisors and camp counselors. Responders to the research questionnaire (n=121 were camp supervisory staff and counselors, age 15-55, working in seven private camps in Greece. Two instruments were used to collect data. The first instrument collected demographic data while the second instrument focused on ranking and rating 20 work motivators. The study suggested that Herzberg's theory (Motivator / Hygiene does not apply on a full scale. The results suggested that supervisory staff indicated good working conditions, meeting other people and carrying out personal growth are important. In addition, they don't like travel and don't consider working in a camp, as a stable job. The camp counselors want to have fun in their job and the opportunity to work with youth. They also don't consider working in a camp, as a stable job and they don't accept the responsibility in proportion to their position.

  19. Analog earthquakes

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, R.B. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  20. Registration Day-Camp 2016

    CERN Multimedia

    Nursery School

    2016-01-01

    Registration for the CERN SA Day-camp are open for children from 4 to 6 years old From March 14 to 25 for children already enrolled in CERN SA EVE and School From April 4 to 15 for the children of CERN members of the personnel (MP) From April 18 for other children More information on the website: http://nurseryschool.web.cern.ch/. The day-camp is open to all children. An inscription per week is proposed, cost 480.-CHF/week, lunch included The camp will be open weeks 27, 28, 29 and 30, from 8:30 am to 5:30 pm. For further questions, thanks you for contacting us by email at Summer.Camp@cern.ch.

  1. Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms.

    Science.gov (United States)

    Bogard, Amy S; Birg, Anna V; Ostrom, Rennolds S

    2014-04-01

    Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was induced by Fsk and select G protein-coupled receptor (GPCR) agonists, though IL-6 levels did not directly correlate with global cAMP levels. Treatment with PKA selective 6-Bnz-cAMP or Epac selective 8-CPT-2Me-cAMP cAMP analogs revealed a predominant role for PKA in cAMP-mediated induction of IL-6. IL-6 promoter mutations demonstrated that AP-1 and CRE transcription sites were required for Fsk to stimulate IL-6 expression. Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in BSMC via Epac and PKA and demonstrates that other AC isoforms are excluded from this pool.

  2. The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells

    OpenAIRE

    1986-01-01

    Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differentia...

  3. Coordinated induction of GST and MRP2 by cAMP in Caco-2 cells: Role of protein kinase A signaling pathway and toxicological relevance

    Energy Technology Data Exchange (ETDEWEB)

    Arana, Maite Rocío, E-mail: arana@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Tocchetti, Guillermo Nicolás, E-mail: gtocchetti@live.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Domizi, Pablo, E-mail: domizi@ibr-conicet.gov.ar [Instituto de Biología Molecular y Celular de Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Arias, Agostina, E-mail: agoarias@yahoo.com.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Rigalli, Juan Pablo, E-mail: jprigalli@gmail.com [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); Ruiz, María Laura, E-mail: ruiz@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 570, 2000 Rosario (Argentina); and others

    2015-09-01

    The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics. - Highlights: • cAMP positively modulates the expression and activity of GST and MRP2 in Caco-2 cells. • Such induction resulted in increased cytoprotection against chemical injury. • PKA

  4. The Popeye Domain Containing Genes and cAMP Signaling

    Directory of Open Access Journals (Sweden)

    Thomas Brand

    2014-05-01

    Full Text Available 3'-5'-cyclic adenosine monophosphate (cAMP is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs. Initially, it was thought that protein kinase A (PKA exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC and hyperpolarizing cyclic nucleotide-gated (HCN channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.

  5. Angiotensin-converting enzyme inhibition prevents myocardial infarction-induced increase in renal cortical cGMP and cAMP phosphodiesterase activities.

    Science.gov (United States)

    Clauss, François; Charloux, Anne; Piquard, François; Doutreleau, Stéphane; Talha, Samy; Zoll, Joffrey; Lugnier, Claire; Geny, Bernard

    2015-08-01

    We investigated whether myocardial infarction (MI) enhances renal phosphodiesterases (PDE) activities, investigating particularly the relative contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi) decreases such renal PDE hyperactivities. We also investigated whether ACEi might thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats treated with perindopril (ACEi) 1 month after coronary artery ligation. Circulating atrial natriuretic peptide (ANP), its second intracellular messenger cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined. Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1 pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs. 197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite increased ANP plasma level, ANP efficiency tended to be decreased in MI compared to SH rats. Perindopril restored PDE activities and tended to improve ANP efficiency in MI rats. One month after coronary ligation, perindopril treatment of MI rats prevents the increase in renal cortical PDE activities. This may contribute to increase renal ANP efficiency in MI rats.

  6. Hydromania: Summer Science Camp Curriculum.

    Energy Technology Data Exchange (ETDEWEB)

    Moura, Joan

    1995-07-01

    In 1992, Bonneville Power Administration (BPA) and the US Department of Energy (DOE) began a collaborative pilot project with the Portland Parks and Recreation Community Schools Program and others to provide summer science camps to children in Grades 4--6. Camps run two weeks in duration between late June and mid-August. Sessions are five days per week, from 9 a.m. to 3 p.m. In addition to hands-on science and math curriculum, at least three field trips are incorporated into the educational learning experience. The purpose of the BPA/DOE summer camps is to make available opportunities for fun, motivating experiences in science to students who otherwise would have difficulty accessing them. This includes inner city, minority, rural and low income students. Public law 101-510, which Congress passed in 1990, authorizes DOE facilities to establish collaborative inner-city and rural partnership programs in science and math. A primary goal of the BPA summer hands on science camps is to bring affordable science camp experiences to students where they live. It uses everyday materials to engage students` minds and to give them a sense that they have succeeded through a fun hands-on learning environment.

  7. Effect of Tiantai No.1(天泰1号) on β-Amyloid-induced Neurotoxicity and NF- к B and cAMP Responsive Element-binding Protein

    Institute of Scientific and Technical Information of China (English)

    WU Zheng-zhi; Andrew C. J. Huang; Jean de Vellis; LI Ying-hong

    2008-01-01

    To investigate the effect and molecular mechanism of Tiantai No.1 (天泰1号), a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by beta-element-binding protein (CREB) pathways using the gene transfection technique. Methods: B104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100, 150, or 200 μg/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptidel-40 (Aβ 1-40, 10 μmol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (A β 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 μg/m/and 150 μg/mL for 5 days or co-treated with Tiantai No.1 and A β 1-40 (5 μ mo/L) for 3 days after electroporation for the with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (Pinduced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF- к B and cAMP cellular signal pathways.

  8. "cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

    Directory of Open Access Journals (Sweden)

    Konstantinos Lefkimmiatis

    Full Text Available BACKGROUND: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP. METHODS/PRINCIPAL FINDINGS: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA. Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge" was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. CONCLUSIONS: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

  9. Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study).

    Science.gov (United States)

    Maćczak, Aneta; Cyrkler, Monika; Bukowska, Bożena; Michałowicz, Jaromir

    2016-04-15

    Bisphenols are important chemicals that are widely used in the manufacturing of polycarbonates, epoxy resin and thermal paper, and thus the exposure of humans to these substances has been noted. The purpose of this study was to assess eryptotic changes in human erythrocytes exposed (in vitro) to bisphenol A (BPA) and its selected analogs, i.e.,bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF). The erythrocytes were incubated with compounds studied at concentrations ranging from 1 to 250μg/mL for 4, 12 or 24h. The results showed that BPA and its analogs increased cytosolic calcium ions level with the strongest effect noted for BPAF. It has also been revealed that all bisphenols analyzed, and BPAF and BPF in particular increased phosphatidylserine translocation in red blood cells, which confirmed that they exhibited eryptotic potential in this cell type. Furthermore, it was shown that BPA and its analogs caused significant increase in calpain and caspase-3 activities, while the strongest effect was noted for BPAF. BPS, which is the main substituent of bisphenol A in polymers and thermal paper production exhibited similar eryptotic potential to BPA. Eryptotic changes in human erythrocytes were provoked by bisphenols at concentrations, which may influence the human body during occupational exposure or subacute poisoning with these compounds.

  10. The 2-oxoglutarate analog 3-oxoglutarate decreases normoxic hypoxia-inducible factor-1α in cancer cells, induces cell death, and reduces tumor xenograft growth

    Directory of Open Access Journals (Sweden)

    Koivunen P

    2016-03-01

    Full Text Available Peppi Koivunen,1 Stuart M Fell,2,3 Wenyun Lu,4 Joshua D Rabinowitz,4 Andrew L Kung,5,6 Susanne Schlisio,2,7 1Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland; 2Ludwig Institute for Cancer Research Ltd, Stockholm, Sweden; 3Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; 4Department of Chemistry and Integrative Genomics, Princeton University, Princeton, NJ, 5Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 6Department of Pediatrics, Columbia University Medical Center, New York, NY, USA; 7Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden Abstract: The cellular response to hypoxia is primarily regulated by the hypoxia-inducible factors (HIFs. HIF-1α is also a major mediator of tumor physiology, and its abundance is correlated with therapeutic resistance in a broad range of cancers. Accumulation of HIF-1α under hypoxia is mainly controlled by the oxygen-sensing HIF prolyl 4-hydroxylases (EGLNs, also known as PHDs. Here, we identified a high level of normoxic HIF-1α protein in various cancer cell lines. EGLNs require oxygen and 2-oxoglutarate for enzymatic activity. We tested the ability of several cell-permeable 2-oxoglutarate analogs to regulate the abundance of HIF-1α protein. We identified 3-oxoglutarate as a potent regulator of HIF-1α in normoxic conditions. In contrast to 2-oxoglutarate, 3-oxoglutarate decreased the abundance of HIF-1α protein in several cancer cell lines in normoxia and diminished HIF-1α levels independent of EGLN enzymatic activity. Furthermore, we observed that 3-oxoglutarate was detrimental to cancer cell survival. We show that esterified 3-oxoglutarate, in combination with the cancer chemotherapeutic drug vincristine, induces apoptosis and inhibits tumor growth in vitro and in vivo. Our data

  11. Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation.METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA.Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue,and the effect of the calcitriol analog on DCs was investigated.RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down-regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-γ and a significant increase in intereleukin (IL)-10 by MLN cells.Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSS colitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog.CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.

  12. Starting a Technology Camp for Children.

    Science.gov (United States)

    Litowitz, Len S.; Baylor, Steven C.

    1997-01-01

    Presents information for starting and maintaining a technology camp for students. Includes selecting topics, identifying participants, marketing, managing the camp, budgeting, and benefits to students and host institutions. (JOW)

  13. Eurasia Project—2007 Italian Camp Held

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>From July 14 to 29,the Eurasia Project—2007 Italian Camp was held at the Castle Fusano Country Club in Rome. 52 high school students from Germany,Poland,Italy and China participated in the summer camp.

  14. Mathematical problem solving by analogy.

    Science.gov (United States)

    Novick, L R; Holyoak, K J

    1991-05-01

    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

  15. Marketing Camp to Parents and Children.

    Science.gov (United States)

    Cony, Steven R.

    1995-01-01

    An effective camp marketing strategy should address both parents' and children's concerns that influence decisions about camp. Includes strategies for developing a targeted message through print media or video that addresses these concerns and persuades families to choose camp. Stresses the importance of following up with parents and children. (LP)

  16. Extension Sustainability Camp: Design, Implementation, and Evaluation

    Science.gov (United States)

    Brain, Roslynn; Upton, Sally; Tingey, Brett

    2015-01-01

    Sustainability Camps provide an opportunity for Extension educators to be in the forefront of sustainability outreach and to meet the growing demand for sustainability education. This article shares development, implementation, and evaluation of an Extension Sustainability Camp for youth, grades 4-6. Camp impact was measured via daily pre-and…

  17. Summer Science Camps Program (SSC).

    Science.gov (United States)

    National Science Foundation, Washington, DC. Directorate for Education and Human Resources.

    The Summer Science Camps (SSC) Program supports residential and commuter enrichment projects for seventh through ninth grade minority students who are underrepresented in science, engineering, and mathematics. Eligible organizations include school districts, museums, colleges, universities, and nonprofit youth-centered and/or community-based…

  18. The Emotional Benefits of Camping.

    Science.gov (United States)

    Johnson, Rebecca Cowan

    1991-01-01

    Regardless of participant background, age, or ethnic origin, camp can aid in the following key components of emotional maturity: open, positive and appropriate expression of feelings; self-acceptance; a sense of self; an awareness and acceptance of others and their feelings; the ability to develop relationships; and emotional stability. (LP)

  19. The NAO goes to camp

    NARCIS (Netherlands)

    Wigdor, N.; Fraaije, A.; Solms, L.; Greeff, J. de; Janssen, J.; Blanson Henkemans, O.A.

    2014-01-01

    ALIZ-E is a Europe-wide project focusing on long-term child-robot interaction, specifically as a means of educating diabetic children on their condition. This video showcases a recent field study at "SugarKidsClub", a camp devoted to helping 7-12 year-olds handle type-1 diabetes. A wide range of CRI

  20. Spatially uniform microflows induced by thermoviscous expansion along a traveling temperature wave: Analogies with electro-osmotic transport

    Science.gov (United States)

    Pal, Debashis; Chakraborty, Suman

    2012-07-01

    We discover that thermoviscous expansion along a traveling wave in a microfluidic channel may be capable of generating a spatially uniform flow profile in a time-averaged sense. We further delineate that the resultant complex flow characteristics, realized by virtue of an intricate interplay between thermal compression-expansion waves and temperature-dependent viscosity variations and controlled by an external heating, may be remarkably characterized by a unique thermal penetration depth scale (analogous to Debye length in electro-osmosis) and a velocity scale (analogous to the Helmholtz Smulochowski velocity in electro-osmosis) that in turn depends on the considerations of “thin” and “thick” microchannel limits, as dictated by the thermal penetration depth as compared to the lateral extent of the microfluidic channel. We show that, when the thermal penetration depth is small as compared to the channel height, a uniform velocity profile is generated in the channel in a time-averaged sense. The velocity scale characterizing this uniform flow may be represented by a function of the thermal diffusivity, volumetric expansion coefficient and thermal viscosity coefficient of the fluid, characteristic amplitude and speed of the thermal wave, as well as the channel height. Results from the present study are expected to provide valuable insights towards arresting hydrodynamic dispersion in microchannels by nonelectrochemical means, following a pH-independent route.

  1. The E92K melanocortin 1 receptor mutant induces cAMP production and arrestin recruitment but not ERK activity indicating biased constitutive signaling

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Mokrosinski, Jacek; Rosenkilde, Mette M

    2011-01-01

    The melanocortin 1 receptor (MC1R) constitutes a key regulator of melanism. Consequently, many naturally-occurring MC1R mutations are associated with a change in color. An example is the Glu-to-Lys substitution found at position II:20/2.60 in the top of transmembrane helix II which has been...... identified in melanic mice and several other species. This mutation induces a pronounced increase in MC1R constitutive activity suggesting a link between constitutive activity and melanism which is corroborated by the attenuation of a-melanocyte stimulating hormone (aMSH) induced activation. However......, the mechanism by which the mutation induces constitutive activity is currently not known....

  2. Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and cystic fibrosis transmembrane conductance regulator (CFTR) contributes to drug-induced diarrhea

    NARCIS (Netherlands)

    C. Moon (Changsuk); W. Zhang (Weiqiang); A. Ren (Aixia); K. Arora (Kavisha); C. Sinha (Chandrima); S. Yarlagadda (Sunitha); K. Woodrooffe (Koryse); J.D. Schuetz (John D.); K.R. Valasani (Koteswara Rao); H.R. de Jonge (Hugo); S.K. Shanmukhappa (Shiva Kumar); M.T.M. Shata (Mohamed Tarek M.); R.K. Buddington (Randal K.); K. Parthasarathi (Kaushik); A.P. Naren (Anjaparavanda P.)

    2015-01-01

    textabstractDiarrhea is one of the most common adverse side effects observed in ∼7% of individuals consuming Food and Drug Administration (FDA)-approved drugs. The mechanism of how these drugs alter fluid secretion in the gut and induce diarrhea is not clearly understood. Several drugs are either su

  3. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    Science.gov (United States)

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  4. The rapid immunosuppression in phytohemagglutinin-activated human T cells is inhibited by the proliferative Ca(2+) influx induced by progesterone and analogs.

    Science.gov (United States)

    Lin, Veronica Hui-Chen; Chen, Jiann-Jong; Liao, Chen-Chung; Lee, Shinn-Shing; Chien, Eileen Jea

    2016-07-01

    Progesterone, an endogenous immunomodulator, suppresses human T-cell activation during pregnancy. A sustained Ca(2 +) influx is an important signal for T-cell proliferation after crosslinking of T-cell receptor/CD3 complexes by anti-CD3 antibodies or phytohemagglutinin (PHA). Progesterone targets cell membrane sites inducing rapid responses including elevated intracellular free calcium concentration ([Ca(2+)]i) and suppressed T-cell PHA-activated proliferation. Interestingly, both PHA and progesterone induce [Ca(2+)]i elevation, but it remains unclear whether the PHA-induced Ca(2+) influx is affected by progesterone leading to T-cell immunosuppression. Primary T-cells were isolated from human peripheral blood and the quench effect on intracellular fura-2 fluorescence of Mn(2+) was used to explore the responses to Ca(2+) influx with cell proliferation being determined by MTT assay. PHA-stimulated Ca(2+) influx was dose-dependently suppressed by progesterone and its agonist R5020, which correlated with PHA-activated T-cell proliferation inhibition. A similar dose-dependent suppression effect on cellular Ca(2+) influx and proliferation occurred with the TRPC channel inhibitor BTP2 and selective TRPC3 channel inhibitor Pyr3. In addition, two progesterone analogs, Org OD 02-0 and 20α-hydroxyprogesterone (20α-OHP), also produced dose-dependent suppression of Ca(2+) influx, but had no effect on proliferation. Finally, inhibition of PHA-activated T-cell proliferation by progesterone is further suppressed by 20α-OHP, but not by Org OD 02-0. Overall, progesterone and R5020 are able to rapidly decrease PHA-stimulated sustained Ca(2+) influx, probably via blockade of TRPC3 channels, which suppresses T-cell proliferation. Taken together, the roles of progesterone and its analogs regarding the rapid response Ca(2+) influx need to be further explored in relation to cytokine secretion and proliferation in activated T-cells.

  5. Signal transduction in Dictyostelium fgd A mutants with a defective interaction between surface cAMP receptors and a GTP-binding regulatory protein [published erratum appears in J Cell Biol 1988 Dec;107(6 Pt 1):following 2463

    OpenAIRE

    1988-01-01

    Transmembrane signal transduction was investigated in four Dictyostelium discoideum mutants that belong to the fgd A complementation group. The results show the following. (a) Cell surface cAMP receptors are present in fgd A mutants, but cAMP does not induce any of the intracellular responses, including the activation of adenylate or guanylate cyclase and chemotaxis. (b) cAMP induces down- regulation and the covalent modification (presumably phosphorylation) of the cAMP receptor. (c) The inhi...

  6. Summer Camp July 2017 - Registration

    CERN Multimedia

    EVE et École

    2017-01-01

    The CERN Staff Association’s Summer Camp will be open for children from 4 to 6 years old during four weeks, from 3 to 28 July. Registration is offered on a weekly basis for 450 CHF, lunch included. This year, the various activities will revolve around the theme of the Four Elements. Registration opened on 20 March 2017 for children currently attending the EVE and School of the Association. It will be open from 3 April for children of CERN Members of Personnel, and starting from 24 April for all other children. The general conditions are available on the website of the EVE and School of CERN Staff Association: http://nurseryschool.web.cern.ch. For further questions, please contact us by email at Summer.Camp@cern.ch.

  7. Cytotoxicity Induced by a Redox-silent Analog of Tocotrienol in Human Mesothelioma H2452 Cell Line via Suppression of Cap-dependent Protein Translation.

    Science.gov (United States)

    Sato, Ayami; Ueno, Haruka; Takase, Akari; Ando, Akira; Sekine, Yuko; Yano, Tomohiro

    2016-04-01

    De novo synthesis of proteins is regulated by cap-dependent protein translation. Aberrant activation of the translation is a hallmark of many cancer types including malignant mesothelioma (MM). We previously reported that a redox-silent analog of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) induces potent cytotoxicity against human MM cells. However, the detailed mechanism of cytotoxicity of T3E remains unclear. In this study, we investigated if T3E induced potent cytotoxicity aganist MM cells. T3E reduced the formation of the cap-dependent translation complex and induced inactivation of oncogene from rat sarcoma virus (RAS). These events were associated with T3E cytotoxicity in MM cells. Furthermore, atorvastatin, an inhibitor of RAS function, had similar effects on MM cells. Moreover, 4EGI-1, a specific inhibitor of the cap-dependent translation complex, induced severe cytotoxicity in MM cells. Overall, T3E had a cytotoxic effect on MM cells via disruption of the activated cap-dependent translation complex through inactivation of RAS.

  8. Huijia School Summer Camp Program

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    As an open and international educational institution, Beijing Huijia Private School is located in Changping, a scenic district in Beijing's northern suburb. In order to strengthen international cultural exchanges, promote the study of Chinese language and the spread of Chinese culture, and make the world know more about China, Huijia School regularly organizes various summer camps for students of different ages every year. Until now, we have already successfully received more than 1,000 students from hom...

  9. Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.

    Science.gov (United States)

    Brooks, S C; Kazmer, S; Levin, A A; Yen, A

    1996-01-01

    The ability of subtypes of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) singly and in combination to elicit myeloid differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein dephosphorylation was determined in the human myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid (RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the above-mentioned three cellular responses. In contrast, simultaneous treatment with both an RAR-selective ligand (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three cellular processes. An RAR alpha-selective ligand used with an RXR-selective ligand generated the same responses as did all-trans RA or 9-cis RA, which affect both families of receptors, suggesting an important role for RAR alpha among RAR subtypes in eliciting cellular response. Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand. The coupling of the shift of RB to its hypophosphorylated form with G1/0 arrest and differentiation in response to ligands is consistent with a possible role of RB as a downstream target or effector of RAR alpha and RXR in combination.

  10. All-optical Mach-Zehnder interferometer switching based on the phase-shift multiplication effect of an analog on the electromagnetically induced transparency effect

    Science.gov (United States)

    Wang, Boyun; Xiong, Liangbin; Zeng, Qingdong; Chen, Zhihong; Lv, Hao; Ding, Yaoming; Du, Jun; Yu, Huaqing

    2016-06-01

    We theoretically and numerically investigate all-optical Mach-Zehnder interferometer switching based on the phase-shift multiplication effect of an all-optical analog on the electromagnetically induced transparency effect. The free-carrier plasma dispersion effect modulation method is applied to improve the tuning rate with a response time of picoseconds. All observed schemes are analyzed rigorously through finite-difference time-domain simulations and coupled-mode formalism. Compared with no phase-shift multiplication effect, the average pump power of all-optical switching required to yield the π-phase shift difference decreases by 55.1%, and the size of the modulation region is reduced by 50.1% when the average pump power reaches 60.8 mW. This work provides a new direction for low-power consumption and miniaturization of microstructure integration light-controlled switching devices in optical communication and quantum information processing.

  11. Effects of binary mixtures of inducers (toluene analogs) and of metals on bioluminescence induction of a recombinant bioreporter strain.

    Science.gov (United States)

    Kong, In Chul

    2014-10-13

    This paper investigated the effects of binary mixtures of bioluminescence inducers (toluene, xylene isomers, m-toluate) and of metals (Cu, Cd, As(III), As(V), and Cr) on bioluminescence activity of recombinant (Pm-lux) strain KG1206. Different responses and sensitivities were observed depending on the types and concentrations of mixtures of inducers or metals. In the case of inducer mixtures, antagonistic and synergistic modes of action were observed, whereas metal mixtures showed all three modes of action. Antagonistic mode of action was most common for mixtures of indirect inducers, which showed bioluminescence ranging from 29% to 62% of theoretically expected effects (P(E)). On the other hand, synergistic mode of action was observed for mixtures of direct and indirect inducers, which showed bioluminescence between 141% and 243% of P(E). In the case of binary metal mixtures, bioluminescence activities were ranged from 62% to 75% and 113% to 164% of P(E) for antagonistic and synergistic modes of action, respectively (p-values 0.0001-0.038). Therefore, mixture effects could not be generalized since they were dependent on both the types and concentrations of chemicals, suggesting that biomonitoring may constitute a better strategy by investigating types and concentrations of mixture pollutants at contaminated sites.

  12. Enantiomeric excesses induced in amino acids by ultraviolet circularly polarized light irradiation of extraterrestrial ice analogs: A possible source of asymmetry for prebiotic chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Modica, Paola; De Marcellus, Pierre; D' Hendecourt, Louis Le Sergeant [Univ. Paris-Sud, Institut d' Astrophysique Spatiale, UMR 8617, F-91405 Orsay (France); Meinert, Cornelia; Meierhenrich, Uwe J. [Univ. Nice Sophia Antipolis, Institut de Chimie de Nice, UMR 7272 CNRS, F-06108 Nice (France); Nahon, Laurent, E-mail: laurent.nahon@synchrotron-soleil.fr, E-mail: ldh@ias.u-psud.fr [Synchrotron SOLEIL, F-91192 Gif-sur-Yvette (France)

    2014-06-10

    The discovery of meteoritic amino acids with enantiomeric excesses of the L-form (ee {sub L}) has suggested that extraterrestrial organic materials may have contributed to prebiotic chemistry and directed the initial occurrence of the ee {sub L} that further led to homochirality of amino acids on Earth. A proposed mechanism for the origin of ee {sub L} in meteorites involves an asymmetric photochemistry of extraterrestrial ices by UV circularly polarized light (CPL). We have performed the asymmetric synthesis of amino acids on achiral extraterrestrial ice analogs by VUV CPL, investigating the chiral asymmetry transfer at two different evolutionary stages at which the analogs were irradiated (regular ices and/or organic residues) and at two different photon energies (6.6 and 10.2 eV). We identify 16 distinct amino acids and precisely measure the L-enantiomeric excesses using the enantioselective GC × GC-TOFMS technique in five of them: α-alanine, 2,3-diaminopropionic acid, 2-aminobutyric acid, valine, and norvaline, with values ranging from ee {sub L} = –0.20% ± 0.14% to ee {sub L} = –2.54% ± 0.28%. The sign of the induced ee {sub L} depends on the helicity and the energy of CPL, but not on the evolutionary stage of the samples, and is the same for all five considered amino acids. Our results support an astrophysical scenario in which the solar system was formed in a high-mass star-forming region where icy grains were irradiated during the protoplanetary phase by an external source of CPL of a given helicity and a dominant energy, inducing a stereo-specific photochemistry.

  13. Lipoxin A4 analog attenuates morphine antinociceptive tolerance, withdrawal-induced hyperalgesia, and glial reaction and cytokine expression in the spinal cord of rat.

    Science.gov (United States)

    Jin, H; Li, Y H; Xu, J S; Guo, G Q; Chen, D L; Bo, Y

    2012-04-19

    Spinal neuroinflammation has been shown to play an important role in the development of morphine tolerance and morphine withdrawal-induced hyperalgesia. Lipoxins are endogenous lipoxygenase-derived eicosanoids that can function as "braking signals" in inflammation. The present study investigated the effect of 5 (S), 6 (R)-lipoxin A4 methyl ester (LXA4ME), a stable synthetic analog of lipoxin A4, on the expression of antinociceptive tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced the development of hyperalgesia and the expression of spinal antinociceptive tolerance to morphine. However, LXA4ME treatment significantly attenuated the development of hyperalgesia and the expression of spinal antinociceptive tolerance to intrathecal morphine in both mechanical and thermal test. Moreover, the administration of LXA4ME during the induction of morphine tolerance inhibited the activation of microglia and astrocytes; reduced the expression of proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α); upregulated the expression of anti-inflammatory cytokines IL-10 and transforming growth factor-β1 (TGF-β1); and inhibited nuclear factor-kappa B (NF-κB) activation at the L5 lumbar spinal cord. These results suggest that treatment of LXA(4)ME provides a potential preventative or therapeutic approach for morphine tolerance and associated abnormal pain sensitivity.

  14. Contingency Base Camp Solid Waste Generation

    Science.gov (United States)

    2013-09-01

    wastes gener- ated at Army base camps. The data in this report were obtained from solid waste characterization surveys of base camps in Bosnia, Kosovo ...ER D C/ CE RL T R- 13 -1 7 Contingency Base Camp Solid Waste Generation Co ns tr uc tio n En gi ne er in g R es ea rc h La bo ra to...Contingency Base Camp Solid Waste Generation Stephen D. Cosper, H. Garth Anderson, Kurt Kinnevan, and Byung J. Kim Construction Engineering Research

  15. Modulation of the cAMP signaling pathway after traumatic brain injury

    OpenAIRE

    Atkins, Coleen M.; Oliva, Anthony A.; Alonso, Ofelia F.; Pearse, Damien D.; Bramlett, Helen M; Dietrich, W. Dalton

    2007-01-01

    Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream targ...

  16. PI3K/AKT and Mdm2 activation are associated with inhibitory effect of cAMP increasing agents on DNA damage-induced cell death in human pre-B NALM-6 cells.

    Science.gov (United States)

    Ghorbani, Arman; Jeddi-Tehrani, Mahmood; Saidpour, Atoosa; Safa, Majid; Bayat, Ahmad Ali; Zand, Hamid

    2015-01-15

    DNA damage response (DDR) consists of both proapoptotic and prosurvival signaling branches. Superiority of each signaling branch determines the outcome of DNA damage: death or allowing the repair. The present authors have previously shown that an increased intracellular level of cAMP disrupts p53-mediated apoptosis in human pre-B NALM-6 cells and inhibition of NF-κB prevents prosurvival effect of cAMP during DNA damage. AKT/PKB (protein kinase B) is a general mediator of survival signaling. AKT signaling inhibits p53-mediated transcription and apoptosis. The results of present study showed that cAMP disrupted DNA damage/p53-mediated apoptosis through AKT and subsequent NF-κB activation. These results suggested that AKT may be found as part of a complex with scaffolding proteins, beta-arrestins and PDE4D. cAMP disarticulated the complex through binding to PDE4D compartment. It seems that release of AKT protein potentiated DDR activated pro-survival AKT in NALM-6 cells. Taken together, the present data indicated that regulation of AKT signaling may determine the fate of cells exposed to genotoxic stress.

  17. Post-marathon wearing of Masai Barefoot Technology shoes facilitates recovery from race-induced fatigue: an evaluation utilizing a visual analog scale

    Directory of Open Access Journals (Sweden)

    Nakagawa K

    2014-12-01

    Full Text Available Kento Nakagawa, Takashi Obu, Kazuyuki KanosueFaculty of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan Purpose: To investigate the potential benefit of post-race wearing of unstable shoes (Masai Barefoot Technology [MBT] on recovery from marathon race–induced fatigue.Patients and methods: Forty-five runners who participated in a full marathon race were divided into three groups: 1 MBT shoes, 2 trail running shoes, and 3 control (CON. Participants ran a full marathon with their own running shoes, and then put on the assigned shoes immediately after the race. They continued to wear the assigned shoes for the ensuing 3 days. The CON group wore their usual shoes. Estimates of post-race fatigue were made by the participants on questionnaires that utilized a visual analog scale. Estimates were made just after the race, as well as for the next 3 days.Results: The subjective fatigue of the MBT group was lower than that of the CON (P<0.05 or trail running shoe groups (P<0.05 on day 3.Conclusion: MBT shoe intervention can promote recovery from the fatigue induced by running a full marathon.Keywords: footwear, VAS, full marathon

  18. Study of the photon-induced formation and subsequent desorption of CH3 OH and H2 CO in interstellar ice analogs

    CERN Document Server

    Martín-Doménech, R; Cruz-Díaz, G A

    2016-01-01

    Methanol and formaldehyde are two simple organic molecules that are ubiquitously detected in the interstellar medium. An origin in the solid phase and a subsequent nonthermal desorption into the gas phase is often invoked to explain their abundances in some of the environments where they are found. Experimental simulations under astrophysically relevant conditions have been carried out to find a suitable mechanism for that process. We explore the in situ formation and subsequent photon-induced desorption of these species, studying the UV photoprocessing of pure ethanol ice, and a more realistic binary H2O:CH4 ice analog. Ice samples deposited onto an infrared transparent window at 8 K were UV-irradiated using a microwave-discharged hydrogen flow lamp. Evidence of photochemical production of these two species and subsequent UV-photon-induced desorption into the gas phase were searched for by means of a Fourier transform infrared spectrometer and a quadrupole mass spectrometer, respectively. Formation of CH3OH ...

  19. Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.

    Science.gov (United States)

    Stocke, Nathanael A; Sethi, Pallavi; Jyoti, Amar; Chan, Ryan; Arnold, Susanne M; Hilt, J Zach; Upreti, Meenakshi

    2017-03-01

    Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.

  20. Cis-Lunar Base Camp

    Science.gov (United States)

    Merrill, Raymond G.; Goodliff, Kandyce E.; Mazanek, Daniel D.; Reeves, John D., Jr.

    2012-01-01

    Historically, when mounting expeditions into uncharted territories, explorers have established strategically positioned base camps to pre-position required equipment and consumables. These base camps are secure, safe positions from which expeditions can depart when conditions are favorable, at which technology and operations can be tested and validated, and facilitate timely access to more robust facilities in the event of an emergency. For human exploration missions into deep space, cis-lunar space is well suited to serve as such a base camp. The outer regions of cis-lunar space, such as the Earth-Moon Lagrange points, lie near the edge of Earth s gravity well, allowing equipment and consumables to be aggregated with easy access to deep space and to the lunar surface, as well as more distant destinations, such as near-Earth Asteroids (NEAs) and Mars and its moons. Several approaches to utilizing a cis-lunar base camp for sustainable human exploration, as well as some possible future applications are identified. The primary objective of the analysis presented in this paper is to identify options, show the macro trends, and provide information that can be used as a basis for more detailed mission development. Compared within are the high-level performance and cost of 15 preliminary cis-lunar exploration campaigns that establish the capability to conduct crewed missions of up to one year in duration, and then aggregate mass in cis-lunar space to facilitate an expedition from Cis-Lunar Base Camp. Launch vehicles, chemical propulsion stages, and electric propulsion stages are discussed and parametric sizing values are used to create architectures of in-space transportation elements that extend the existing in-space supply chain to cis-lunar space. The transportation options to cis-lunar space assessed vary in efficiency by almost 50%; from 0.16 to 0.68 kg of cargo in cis-lunar space for every kilogram of mass in Low Earth Orbit (LEO). For the 15 cases, 5-year campaign

  1. How to run a successful and educational basketball camp

    OpenAIRE

    Brooke LeMar; Joe Deutsch

    2015-01-01

    Camps are a great introduction to the sport of basketball for children. Universities and colleges usually offer different types of camps, typically during the summer months. Depending on the skill and maturity level of the player, basketball camps can serve a variety of purposes. Some popular types of camps include offensive skills, shooting, team, and youth camps. Regardless of the camp that is chosen, children need to have goals set for themselves before, during, and after to enhance the be...

  2. Mental health in Palestinian camps in Lebanon

    Directory of Open Access Journals (Sweden)

    Fabio Forgione

    2012-08-01

    Full Text Available Health agencies in refugee camps face the dual challenge of, firstly,convincing both camp populations and the international communitythat mental health disorders deserve treatment as much as any otherillness – and, secondly, building enough trust to encourage people toseek that treatment.

  3. Children with Cancer: Positive Benefits of Camp.

    Science.gov (United States)

    Winfree, Christy; Williams, Richard; Powell, Gwynn M.

    2002-01-01

    A relatively new method of helping pediatric cancer patients cope with their illness is specially designed summer camps. Camp helps children with cancer address psychological effects of the disease, bodily changes, and self-concept, and helps parents and siblings cope. Sidebars present resources and tips on incorporating children with cancer into…

  4. Why It's Good to Go to Camp

    Science.gov (United States)

    Howell, Matthew

    2008-01-01

    In the author's fourth year of undergraduate studies at the University of Waterloo he had the opportunity to explore the benefits attained by children attending a summer camp by way of an academic literature review. The author worked with Dr. Troy Glover who has been commissioned by a group of camping associations to perform a study on the…

  5. Accounting Boot Camp for College Juniors

    Science.gov (United States)

    Myring, Mark; Wrege, William; Van Alst, Lucinda

    2008-01-01

    We describe a day-long introduction to new accounting majors, which we call a boot camp. Boot camp it is an effort to make juniors more aware of their identity, career purposes and learning resources that are now parts of their world, much of which is not covered explicitly in the accounting curriculum. This paper provides an overview of the…

  6. Cyclic AMP induces IPC leukemia cell apoptosis via CRE-and CDK-dependent Bim transcription.

    Science.gov (United States)

    Huseby, S; Gausdal, G; Keen, T J; Kjærland, E; Krakstad, C; Myhren, L; Brønstad, K; Kunick, C; Schwede, F; Genieser, H-G; Kleppe, R; Døskeland, S O

    2011-12-08

    The IPC-81 cell line is derived from the transplantable BNML model of acute myelogenic leukemia (AML), known to be a reliable predictor of the clinical efficiency of antileukemic agents, like the first-line AML anthracycline drug daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to induce IPC cell death. The DNR-induced death differed from that induced by cAMP by (1) not involving Bim induction, (2) being abrogated by GSK3β inhibitors, (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23 and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the apoptosis induced by cAMP correlated tightly with Bim protein expression. It was abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis inhibitor. The forced expression of BimL killed IPC-81(WT) cells rapidly, Bcl2-overexpressing cells being partially resistant. The pivotal role of CREB and CDK activity for Bim transcription is unprecedented. It is also noteworthy that newly developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to induce IPC cell apoptosis. Our findings support the notion that AML cells may possess targetable death pathways not exploited by common anti-cancer agents.

  7. Opening of a summer camp at CERN

    CERN Multimedia

    Nursery School

    2015-01-01

    The Staff Association has the pleasure to announce the opening of a summer camp in l’EVE et Ecole de l’AP du CERN. With a capacity of 40 children, aged 4 to 6 years, it will be open from July 6 to 30. Registration Summer camp 2015 Registration for the CERN SA Summer camp for children aged 4 to 6 is open 16 to 30 April 2015 More information on the website: http://nurseryschool.web.cern.ch/ The Summer camp is open to all children of CERN Staff. An inscription per week is proposed, cost 480.-CHF/week, lunch included. The camp will be open weeks 28, 29, 30 and 31, from 8:30 am to 5:30 pm.

  8. Cyclic AMP (cAMP) confers drug resistance against DNA damaging agents via PKAIA in CML cells.

    Science.gov (United States)

    Xiao, Ling-Yi; Kan, Wai-Ming

    2017-01-05

    Cyclic adenosine monophosphate (cAMP) regulates many vital functions such as metabolism, proliferation, differentiation and death. Depending on cell types and stimulators, cAMP could either promote or attenuate cell death. cAMP signal can be transduced by protein kinase A (PKA) and/or exchange protein directly activated by cAMP (EPAC). In CML cells, cAMP may suppress their proliferation and enhance their differentiation. However, the role of cAMP on DNA damaging agent toxicity and the mechanism involved has not been studied. In this study, we studied the effect of cAMP on the sensitivity of CML cells to DNA damaging agents. We observed that forskolin (FSK) and dibutyryl-cAMP (DBcAMP) decreased cisplatin and etoposide-induced cell death in K562 cells. Moreover, PKA activator prevented K562 cells from DNA damaging agent-induced cell death while EPAC activator had no effect. Furthermore, we found that the PKA subtype, PKAIA, was involved in cAMP-attenuated resistance in K562 cells. Taken together, our results suggest that increased cAMP level confers CML cells to acquire a novel mechanism against DNA damaging agent toxicity via PKAIA. Thus, PKAIA inhibitor may be helpful in overcoming the resistance to DNA damaging agents in CML cells.

  9. Porcine induced pluripotent stem cells analogous to naïve and primed embryonic stem cells of the mouse.

    Science.gov (United States)

    Telugu, Bhanu Prakash V L; Ezashi, Toshihiko; Roberts, R Michael

    2010-01-01

    Authentic or naïve embryonic stem cells (ESC) have probably never been derived from the inner cell mass (ICM) of pig blastocysts, despite over 25 years of effort. Recently, several groups, including ours, have reported induced pluripotent stem cells (iPSC) from swine by reprogramming somatic cells with a combination of four factors, OCT4 (POU5F1)/SOX2/KLF4/c-MYC delivered by retroviral transduction. The porcine (p) iPSC resembled human (h) ESC and the mouse "Epiblast stem cells" (EpiSC) in their colony morphology and expression of pluripotent genes, and are likely dependent on FGF2/ACTIVIN/NODAL signaling, therefore representing a primed ESC state. These cells are likely to advance swine as a model in biomedical research, since grafts could potentially be matched to the animal that donated the cells for re-programming. The objective of the present work has been to develop naïve piPSC. Employing a combination of seven reprogramming factors assembled on episomal vectors, we successfully reprogrammed porcine embryonic fibroblasts on a modified LIF-medium supplemented with two kinase inhibitors; CHIR99021, which inhibits GSK-3beta, and PD0325901, a MEK inhibitor. The derived piPSC bear a striking resemblance to naïve mESC in colony morphology, are dependent on LIF to maintain an undifferentiated phenotype, and express markers consistent with pluripotency. They exhibit high telomerase activity, a short cell cycle interval, and a normal karyotype, and are able to generate teratomas. Currently, the competence of these lines for contributing to germ-line chimeras is being tested.

  10. Phosphodiesterase 2 negatively regulates adenosine-induced transcription of the tyrosine hydroxylase gene in PC12 rat pheochromocytoma cells.

    Science.gov (United States)

    Makuch, Edyta; Kuropatwa, Marianna; Kurowska, Ewa; Ciekot, Jaroslaw; Klopotowska, Dagmara; Matuszyk, Janusz

    2014-07-05

    Adenosine induces expression of the tyrosine hydroxylase (TH) gene in PC12 cells. However, it is suggested that atrial natriuretic peptide (ANP) inhibits expression of this gene. Using real-time PCR and luciferase reporter assays we found that ANP significantly decreases the adenosine-induced transcription of the TH gene. Results of measurements of cyclic nucleotide concentrations indicated that ANP-induced accumulation of cGMP inhibits the adenosine-induced increase in cAMP level. Using selective phosphodiesterase 2 (PDE2) inhibitors and a synthetic cGMP analog activating PDE2, we found that PDE2 is involved in coupling the ANP-triggered signal to the cAMP metabolism. We have established that ANP-induced elevated levels of cGMP as well as cGMP analog stimulate hydrolytic activity of PDE2, leading to inhibition of adenosine-induced transcription of the TH gene. We conclude that ANP mediates negative regulation of TH gene expression via stimulation of PDE2-dependent cAMP breakdown in PC12 cells.

  11. A model of the radiation-induced bystander effect based on an analogy with ferromagnets. Application to modelling tissue response in a uniform field

    Science.gov (United States)

    Vassiliev, O. N.

    2014-12-01

    We propose a model of the radiation-induced bystander effect based on an analogy with magnetic systems. The main benefit of this approach is that it allowed us to apply powerful methods of statistical mechanics. The model exploits the similarity between how spin-spin interactions result in correlations of spin states in ferromagnets, and how signalling from a damaged cell reduces chances of survival of neighbour cells, resulting in correlated cell states. At the root of the model is a classical Hamiltonian, similar to that of an Ising ferromagnet with long-range interactions. The formalism is developed in the framework of the Mean Field Theory. It is applied to modelling tissue response in a uniform radiation field. In this case the results are remarkably simple and at the same time nontrivial. They include cell survival curves, expressions for the tumour control probability and effects of fractionation. The model extends beyond of what is normally considered as bystander effects. It offers an insight into low-dose hypersensitivity and into mechanisms behind threshold doses for deterministic effects.

  12. Learning by Analogy: Discriminating between Potential Analogs

    Science.gov (United States)

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  13. NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage, Senescence and Apoptosis in Colorectal Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Aruna S Jaiswal

    Full Text Available Recently approved chemotherapeutic agents to treat colorectal cancer (CRC have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β activity. Temozolomide (TMZ, an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715. In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC50 of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients.

  14. Genetically-encoded yellow fluorescent cAMP indicator with an expanded dynamic range for dual-color imaging.

    Directory of Open Access Journals (Sweden)

    Haruki Odaka

    Full Text Available Cyclic AMP is a ubiquitous second messenger, which mediates many cellular responses mainly initiated by activation of cell surface receptors. Various Förster resonance energy transfer-based ratiometric cAMP indicators have been created for monitoring the spatial and temporal dynamics of cAMP at the single-cell level. However, single fluorescent protein-based cAMP indicators have been poorly developed, with improvement required for dynamic range and brightness. Based on our previous yellow fluorescent protein-based cAMP indicator, Flamindo, we developed an improved yellow fluorescent cAMP indicator named Flamindo2. Flamindo2 has a 2-fold expanded dynamic range and 8-fold increased brightness compared with Flamindo by optimization of linker peptides in the vicinity of the chromophore. We found that fluorescence intensity of Flamindo2 was decreased to 25% in response to cAMP. Live-cell cAMP imaging of the cytosol and nucleus in COS7 cells using Flamindo2 and nlsFlamindo2, respectively, showed that forskolin elevated cAMP levels in each compartment with different kinetics. Furthermore, dual-color imaging of cAMP and Ca2+ with Flamindo2 and a red fluorescent Ca2+ indicator, R-GECO, showed that cAMP and Ca2+ elevation were induced by noradrenaline in single HeLa cells. Our study shows that Flamindo2, which is feasible for multi-color imaging with other intracellular signaling molecules, is useful and is an alternative tool for live-cell imaging of intracellular cAMP dynamics.

  15. Genetically-Encoded Yellow Fluorescent cAMP Indicator with an Expanded Dynamic Range for Dual-Color Imaging

    Science.gov (United States)

    Odaka, Haruki; Arai, Satoshi; Inoue, Takafumi; Kitaguchi, Tetsuya

    2014-01-01

    Cyclic AMP is a ubiquitous second messenger, which mediates many cellular responses mainly initiated by activation of cell surface receptors. Various Förster resonance energy transfer-based ratiometric cAMP indicators have been created for monitoring the spatial and temporal dynamics of cAMP at the single-cell level. However, single fluorescent protein-based cAMP indicators have been poorly developed, with improvement required for dynamic range and brightness. Based on our previous yellow fluorescent protein-based cAMP indicator, Flamindo, we developed an improved yellow fluorescent cAMP indicator named Flamindo2. Flamindo2 has a 2-fold expanded dynamic range and 8-fold increased brightness compared with Flamindo by optimization of linker peptides in the vicinity of the chromophore. We found that fluorescence intensity of Flamindo2 was decreased to 25% in response to cAMP. Live-cell cAMP imaging of the cytosol and nucleus in COS7 cells using Flamindo2 and nlsFlamindo2, respectively, showed that forskolin elevated cAMP levels in each compartment with different kinetics. Furthermore, dual-color imaging of cAMP and Ca2+ with Flamindo2 and a red fluorescent Ca2+ indicator, R-GECO, showed that cAMP and Ca2+ elevation were induced by noradrenaline in single HeLa cells. Our study shows that Flamindo2, which is feasible for multi-color imaging with other intracellular signaling molecules, is useful and is an alternative tool for live-cell imaging of intracellular cAMP dynamics. PMID:24959857

  16. Generation solar case study : solar summer camp

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    This document presented a case study of the use of solar power at camp Tanamakoon in Ontario's Algonquin Park. It discussed camp facilities which include solar powered composting toilets and solar heated showers. Composting, recycling, and use of environmentally friendly products were also discussed. The camp also has a grid interactive solar electric system and a solar water heating system. The solar electric system provides backup power to critical loads such as safety lights and an emergency fridge and is also connected to the existing grid electricity system. Any excess energy from the solar system can be used by other kitchen appliances or, any other load anywhere in the camp. The main user of the solar heated water is a large automatic dishwasher which has as a built-in boost heater for those days when the solar heated water is insufficiently hot to sanitize dishes. It was concluded that while camp utility bills have been reduced by this investment in renewable energy technology, the primary objectives of the project were the protection of Tanamakoon's pristine Algonquin environment and the attraction and retention of clients for the camp by enhancing the camping experience. fig.

  17. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  18. Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon.

    Science.gov (United States)

    Warner, Douglas M; Levy, Stuart B

    2010-02-01

    Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the Escherichia coli transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of marA, either in an antibiotic-resistant marR mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the soxS gene from a plasmid, which decreased susceptibility to antibiotics, unexpectedly caused no decrease in CAMP susceptibility; instead it produced increased susceptibility to different CAMPs. Deletion or overexpression of rob had little effect on CAMP susceptibility. The marRAB operon was upregulated when E. coli was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human beta-defensin-1; however, this upregulation required Rob. Deletion of acrAB increased bacterial susceptibility to polymyxin B, LL-37 and human beta-defensin-1 peptides. Deletion of tolC yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human alpha-defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and acrAB deletion strains; however, it decreased susceptibility of tolC mutants. These findings demonstrate that CAMPs are both inducers of marA-mediated drug resistance through interaction with Rob and also substrates for efflux in E. coli. The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.

  19. Design and Development Issues for Educational Robotics Training Camps

    Science.gov (United States)

    Ucgul, Memet; Cagiltay, Kursat

    2014-01-01

    The aim of this study is to explore critical design issues for educational robotics training camps and to describe how these factors should be implemented in the development of such camps. For this purpose, two robotics training camps were organized for elementary school students. The first camp had 30 children attendees, and the second had 22. As…

  20. Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment.

    Directory of Open Access Journals (Sweden)

    Teruaki Nakatsuji

    Full Text Available BACKGROUND: In the progression of acne vulgaris, the disruption of follicular epithelia by an over-growth of Propionibacterium acnes (P. acnes permits the bacteria to spread and become in contact with various skin and immune cells. METHODOLOGY/PRINCIPAL FINDINGS: We have demonstrated in the present study that the Christie, Atkins, Munch-Peterson (CAMP factor of P. acnes is a secretory protein with co-hemolytic activity with sphingomyelinase that can confer cytotoxicity to HaCaT keratinocytes and RAW264.7 macrophages. The CAMP factor from bacteria and acid sphingomyelinase (ASMase from the host cells were simultaneously present in the culture supernatant only when the cells were co-cultured with P. acnes. Either anti-CAMP factor serum or desipramine, a selective ASMase inhibitor, significantly abrogated the P. acnes-induced cell death of HaCaT and RAW264.7 cells. Intradermal injection of ICR mouse ears with live P. acnes induced considerable ear inflammation, macrophage infiltration, and an increase in cellular soluble ASMase. Suppression of ASMase by systemic treatment with desipramine significantly reduced inflammatory reaction induced by intradermal injection with P. acnes, suggesting the contribution of host ASMase in P. acnes-induced inflammatory reaction in vivo. Vaccination of mice with CAMP factor elicited a protective immunity against P. acnes-induced ear inflammation, indicating the involvement of CAMP factor in P. acnes-induced inflammation. Most notably, suppression of both bacterial CAMP factor and host ASMase using vaccination and specific antibody injection, respectively, cooperatively alleviated P. acnes-induced inflammation. CONCLUSIONS/SIGNIFICANCE: These findings envision a novel infectious mechanism by which P. acnes CAMP factor may hijack host ASMase to amplify bacterial virulence to degrade and invade host cells. This work has identified both CAMP factor and ASMase as potential molecular targets for the development of drugs

  1. TLR-2 Recognizes Propionibacterium acnes CAMP Factor 1 from Highly Inflammatory Strains

    Science.gov (United States)

    Ollagnier, Guillaume; Désiré, Nathalie; Sayon, Sophie; Raingeaud, Jöel; Marcelin, Anne-Geneviève; Calvez, Vincent; Khammari, Amir; Batteux, Frédéric; Dréno, Brigitte; Dupin, Nicolas

    2016-01-01

    Background Propionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P. acnes triggers a strong immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P. acnes surface protein interacting with Toll-like receptors has been identified. P. acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes. Methodology and principal findings Far-western blotting identified two surface proteins, of 24.5- and 27.5-kDa in size, specifically recognized by TLR2. These proteins were characterized, by LC-MS/MS, as CAMP factor 1 devoid of its signal peptide sequence, as shown by N-terminal sequencing. Purified CAMP factor 1 induces CXCL8 production by activating the CXCL8 gene promoter, triggering the synthesis of CXCL8 mRNA. Antibodies against TLR2 significantly decreased the CXCL8 response. For the 27 P. acnes strains used in this study, CAMP1-TLR2 binding intensity was modulated and appeared to be strong in type IB and II strains, which produced large amounts of CXCL8, whereas most of the type IA1 and IA2 strains presented little or no CAMP1-TLR2 binding and low levels of CXCL8 production. The nucleotide sequence of CAMP factor displays a major polymorphism, defining two distinct genetic groups corresponding to CAMP factor 1 with 14 amino-acid changes from strains phylotyped II with moderate and high levels of CAMP1-TLR2 binding activity, and CAMP factor 1 containing 0, 1 or 2 amino-acid changes from strains phylotyped IA1, IA2, or IB presenting no, weak or moderate CAMP1-TLR2 binding. Conclusions Our findings indicate that CAMP factor 1 may contribute to P. acnes virulence, by amplifying the inflammation reaction through direct interaction with TLR2. PMID:27902761

  2. Regulation of cAMP Intracellular Levels in Human Platelets Stimulated by 2-Arachidonoylglycerol.

    Science.gov (United States)

    Signorello, Maria Grazia; Leoncini, Giuliana

    2016-05-01

    We demonstrated that in human platelets the endocannabinoid 2-arachidonoylglycerol (2-AG) decreased dose- and time-dependently cAMP intracellular levels. No effect on cAMP decrease induced by 2-AG was observed in the presence of the adenylate cyclase inhibitor SQ22536 as well in platelets pretreated with the thromboxane A2 receptor antagonist, SQ29548 or with aspirin, inhibitor of arachidonic acid metabolism through the cyclooxygenase pathway. An almost complete recovering of cAMP level was measured in platelets pretreated with the specific inhibitor of phosphodiesterase (PDE) 3A, milrinone. In platelets pretreated with LY294002 or MK2206, inhibitors of PI3K/AKT pathway, and with U73122, inhibitor of phospholipase C pathway, only a partial prevention was shown. cAMP intracellular level depends on synthesis by adenylate cyclase and hydrolysis by PDEs. In 2-AG-stimulated platelets adenylate cyclase activity seems to be unchanged. In contrast PDEs appear to be involved. In particular PDE3A was specifically activated, as milrinone reversed cAMP reduction by 2-AG. 2-AG enhanced PDE3A activity through its phosphorylation. The PI3K/AKT pathway and PKC participate to this PDE3A phosphorylation/activation mechanism as it was greatly inhibited by platelet pretreatment with LY294002, MK2206, U73122, or the PKC specific inhibitor GF109203X. Taken together these data suggest that 2-AG potentiates its power of platelet agonist reducing cAMP intracellular level.

  3. cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion.

    Science.gov (United States)

    Vitali, E; Cambiaghi, V; Spada, A; Tresoldi, A; Zerbi, A; Peverelli, E; Carnaghi, C; Mantovani, G; Lania, A G

    2015-12-10

    cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1. In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.

  4. 2012 USGS Lidar: Brooks Camp (AK)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The U.S. Geological Survey (USGS) had a requirement for high resolution Lidar needed for mapping the Brooks Camp region of Katmai National Park in Alaska....

  5. ESTCP Live Site Demonstrations Former Camp Beale

    Science.gov (United States)

    2012-03-01

    instrumentation package includes a real-time kinematic global positioning system ( RTK - GPS ) receiver for recording positional data and inertial measurement...RS232C ports. For the survey at Camp Beale, the RTK - GPS base station consisted of a Trimble R8 receiver and Trimble HPB450 external radio. CH2M...the former Camp Beale were selected by the ESTCP Program Office. Survey benchmarks for RTK - GPS base station locations had also been established by

  6. Los campings en España

    Directory of Open Access Journals (Sweden)

    Francisco Feo Parrondo

    2003-01-01

    Full Text Available Los campings son una de las variedades turísticas con más crecimiento en España en las últimas décadas: 52’76% el número de campings y 60’22% el de plazas que ofrecen entre 1980 y 2002. Aunque están presentes en todas las provincias, se ubican mayoritariamente en zonas costeras, superando en muchas localidades a los alojamientos hoteleros.

  7. 21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog.

    Science.gov (United States)

    Kelsen, Jens; Bartels, Lars Erik; Dige, Anders; Hvas, Christian Lodberg; Frings-Meuthen, Petra; Boehme, Gisela; Thomsen, Marianne Kragh; Fenger-Grøn, Morten; Dahlerup, Jens Frederik

    2012-08-01

    Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3 weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein-Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3) counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.

  8. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica

    2008-01-01

    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  9. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  10. Signal Transduction in Dictyostelium fgd A Mutants with a Defective Interaction between Surface cAMP Receptors and a GTP-binding Regulatory Protein

    NARCIS (Netherlands)

    Kesbeke, Fanja; Snaar-Jagalska, B. Ewa; Haastert, Peter J.M. van

    1988-01-01

    Transmembrane signal transduction was investigated in four Dictyostelium discoideum mutants that belong to the fgd A complementation group. The results show the following. (a) Cell surface cAMP receptors are present in fgd A mutants, but cAMP does not induce any of the intracellular responses, inclu

  11. Camp Sherman, Ohio: History of a World War I Training Camp

    Science.gov (United States)

    2015-12-01

    v Preface...85 Report Documentation Page ERDC/CERL TR-15-25 v Figures... Combed and Brushed on Camp Sherman Parade Ground for Photograph,” The Camp Sherman News, 5 November 1918, 5. ERDC/CERL TR-15-25 38 Figure 32

  12. Camping in the Disciplines: Assessing the Effect of Writing Camps on Graduate Student Writers

    Science.gov (United States)

    Busl, Gretchen; Donnelly, Kara Lee; Capdevielle, Matthew

    2015-01-01

    In the past ten years, an increasing number of universities have begun organizing writing "camps," or full-week immersion experiences, in an effort to address the increased need to support graduate student writing. Outside of anecdotes and testimonials, we have previously had very little data about these camps' success. This study,…

  13. cAMP-Induced Histones H3 Dephosphorylation Is Independent of PKA and MAP Kinase Activations and Correlates With mTOR Inactivation.

    Science.gov (United States)

    Rodriguez, Pedro; Rojas, Juan

    2016-03-01

    cAMP is a second messenger well documented to be involved in the phosphorylation of PKA, MAP kinase, and histone H3 (H3). Early, we reported that cAMP also induced H3 dephosphorylation in a variety of proliferating cell lines. Herein, it is shown that cAMP elicits a biphasic H3 dephosphorylation independent of PKA activation in cycling cells. H89, a potent inhibitor of PKA catalytic sub-unite, could not abolish this effect. Additionally, H89 induces a rapid and biphasic H3 serine 10 dephosphorylation, while a decline in the basal phosphorylation of CREB/ATF-1 is observed. Rp-cAMPS, an analog of cAMP and specific inhibitor of PKA, is unable to suppress cAMP-mediated H3 dephosphorylation, whereas Rp-cAMPS effectively blocks CREB/ATF-1 hyper-phosphorylation by cAMP and its inducers. Interestingly, cAMP exerts a rapid and profound H3 dephosphorylation at much lower concentration (50-fold lower, 0.125 mM) than the concentration required for maximal CREB/ATF-1 phosphorylation (5 mM). Much higher cAMP concentration is required to fully induce CREB/ATF-1 gain in phosphate (5 mM), which correlates with the inhibition of H3 dephosphorylation. Also, the dephosphorylation of H3 does not overlap at onset of MAP kinase phosphorylation pathways, p38 and ERK. Surprisingly, rapamycin (an mTOR inhibitor), cAMP, and its natural inducer isoproterenol, elicit identical dephosphorylation kinetics on both S6K1 ribosomal kinase (a downstream mTOR target) and H3. Finally, cAMP-induced H3 dephosphorylation is PP1/2-dependent. The results suggest that a pathway, requiring much lower cAMP concentration to that required for CREB/ATF-1 hyper-phosphorylation, is responsible for histone H3 dephosphorylation and may be linked to mTOR down regulation.

  14. Eviprostat Activates cAMP Signaling Pathway and Suppresses Bladder Smooth Muscle Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Masayuki Takeda

    2013-06-01

    Full Text Available Eviprostat is a popular phytotherapeutic agent for the treatment of lower urinary tract symptoms (LUTS. At present, the signaling mechanisms underlying its therapeutic effects are still poorly understood. Given that cAMP has been reported to suppress cell hyperplasia and hypertrophy in various pathological situations, we asked whether the effect of Eviprostat could be ascribed to the activation of the cAMP signaling pathway. In the study, exposure of cAMP response element (CRE-secreted alkaline phosphatase (SEAP (CRE-SEAP-reporter cells to Eviprostat elevated SEAP secretion, which was associated with an increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP and cAMP-response element-binding protein (CREB, as well as enhanced expression of CRE-regulated protein connexin43, indicating an activation of the cAMP signaling pathway. Consistent with these observations, Eviprostat-induced expression of Cx43 was abolished in the presence of adenylyl cyclase inhibitor SQ22536 or PKA inhibitor H89, whereas it was mimicked by adenylyl cyclase activator, forskolin. Further analysis demonstrated that Eviprostat significantly potentiated the effect of phosphodiesterase 3 (PDE3 inhibitor, but not that of PDE4 inhibitor, on CRE activation. Moreover, Eviprostat suppressed PDGF-induced activation of ERK and Akt and inhibited cell proliferation and hillock formation in both mesangial cells and bladder smooth muscle cells. Collectively, activation of the cAMP signaling pathway could be an important mechanism by which Eviprostat exerts its therapeutic effects for LUTS.

  15. The effect of hypoxia on PGE2-stimulated cAMP generation in HMEC-1.

    Science.gov (United States)

    Wiktorowska-Owczarek, Anna; Owczarek, Jacek

    2015-06-01

    Prostaglandin E2 (PGE2) is generated in various cells, including endothelial cells, and is responsible for various functions, such as vascular relaxation and angiogenesis. Effects of PGE2 are mediated via receptors EP1-EP4, among which EP2 and EP4 are coupled to Gs protein which activates adenylate cyclase (AC) and cAMP synthesis. The aim of this work was to study the ability of human microvascular endothelial cells (HMEC-1) to synthesize cAMP in the presence of PGE2, and to determine the effect of hypoxia on the PGE2- stimulated cAMP level. It was decided to evaluate the effect of PGE2 on the secretion of VEGF, an inducer of angiogenesis. In summary, our findings show that PGE2 induces cAMP production, but hypoxia may impair PGE2-stimulated activity of the AC-cAMP signaling pathway. These results suggest that the cardioprotective effect of PGE2/EP4/cAMP may be attenuated during ischemia. Furthermore, this study indicates that the pro-angiogenic effect of PGE2 is not associated with VEGF secretion in HMEC-1 cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  17. Analogy in CLAM

    OpenAIRE

    Melis, Erica

    1999-01-01

    CL A M is a proof planner, developed by the Dream group in Edinburgh,that mainly operates for inductive proofs. This paper addresses the questionhow an analogy model that I developed independently of CL A M can beapplied to CL A M and it presents analogy-driven proof plan construction as acontrol strategy of CL A M . This strategy is realized as a derivational analogythat includes the reformulation of proof plans. The analogical replay checkswhether the reformulated justifications of the sour...

  18. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  19. Analogies of Information Security

    OpenAIRE

    Sole, Amund Bauck

    2016-01-01

    In this thesis it will be tested wither analogies and metaphors would make it easier to teach the fundamental subjects of information security and hacking to people with no previous background in computer science and only basic computer skills. This will be done by conducting interview on people with no background in computer science to see what analogies work the best for different topics in information security. From the analogy getting the best response, a small game will be designed with ...

  20. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  1. Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: conformational selection highlights a new concept in allosteric inhibitor design.

    Science.gov (United States)

    Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W; Taylor, Susan S; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S

    2011-03-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound "B" and C-subunit-bound "H"-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through "induced fit" alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially "select" inactive conformations of target proteins by satisfying all "binding" constraints alone without inducing conformational changes necessary for activation.

  2. Evidences for involvement of endogenous cAMP in Arabidopsis defense responses to Verticillium toxins

    Institute of Scientific and Technical Information of China (English)

    Jing JIANG; Ling Wen FAN; Wei Hua WU

    2005-01-01

    Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades,there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical "wilt" symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway.Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endogenous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticilliumsecreted toxins by regulating the production of the known signal SA in plant defense pathway.

  3. Stimulation of adenylate cyclase in relation to dopamine-induced long-term enhancement (LTE) of muscarinic depolarization in the rabbit superior cervical ganglion.

    Science.gov (United States)

    Mochida, S; Kobayashi, H; Libet, B

    1987-02-01

    Dopamine (DA) induction of the long-term enhancement (LTE) of the slow muscarinic depolarizing response to methacholine (MCh), equivalent to the slow EPSP (S-EPSP), was previously found to be mimicked by exogenous cyclic AMP (cAMP) in the rabbit superior cervical ganglion (SCG). DA-induced LTE of the S-EPSP was shown to be depressed by some DA antagonists. We now show that DA (15 microM), its analog, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), and a D2 receptor antagonist, metoclopramide, each can induce both LTE of MCh depolarization and an increase in ganglionic cAMP. Conversely, antagonists of DA-induced LTE also depress DA-induced rises in cAMP; these antagonists include haloperidol (1 microM), both (+) and (-) enantiomers of butaclamol (0.7-7 microM), flupenthixol (1 microM), and (+)-R-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l (SCH-23390) (7 microM). The selective D2 antagonists sulpiride (10 microM) and domperidone (10 microM) affect neither DA action. Alpha-2 adrenergic agonists (alpha-methyl-norepinephrine and clonidine) produce no LTE; alpha-antagonist dihydroergotamine (35 microM) does not affect either DA action, although it can completely block the hyperpolarizing response to DA or other catecholamines. Beta-antagonist propranolol (5 microM) partially depresses DA-induced rises in cAMP but has no effect on the DA-induced LTE. (Butaclamol and propranolol in combination can completely block the cAMP rise induced by DA.) Beta-agonist isoproterenol can induce appreciable LTE of MCh depolarization, but this LTE is not depressed by propranolol (10 microM). Isoproterenol can elicit a substantial rise in cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. A specialized program for children with developmental disabilities within a "typical" overnight summer camp: Camp Ramah's Tikvah Program.

    Science.gov (United States)

    Blas, Howard I

    2007-10-01

    The Tikvah Program is an overnight camping program at Camp Ramah in New England that serves campers with a range of developmental disabilities. The program has evolved over its 37-year history and includes a camping program, vocational training program, and inclusion program. Select graduates are hired by the camp for summer employment. The Tikvah Program offers a model for serving campers with special needs within a larger "typical" summer camp. Although serving the needs of such campers offers unique challenges, the presence of such a program in a regular summer camp offers tremendous opportunities and benefits for campers with special needs and more typically developing campers.

  5. Ca2+ participates in α1B-adrenoceptor-mediated cAMP response in HEK293 cells

    Institute of Scientific and Technical Information of China (English)

    Yao SONG; Yun-fang LI; Er-dan DONG; Qi-de HAN; You-yi ZHANG

    2005-01-01

    Aim: To investigate the α1B-adrenoceptor (α1B-AR)-mediated cAMP response and underlying mechanisms in HEK293 cells. Methods: Full-length cDNA encoding α1B-AR was transfected into HEK293 cells using the calcium phosphate precipitation method, and α1B-AR expression and cAMP accumulation were determined by using the saturation radioligand binding assay and ion-exchange chromatography, respectively. Results: Under agonist stimulation, α1B-AR mediated cAMP synthesis in HEK293 cells, and blockade by PLC-PKC or tyrosine kinase did not reduce cAMP accumulation induced by NE. Pretreatment with pertussis toxin(PTX) had little effect on basal cAMP accumulation as well as norepinephrine(NE)-stimulated cAMP accumulation. In addition, pretreatment with cholera toxin(CTX) neither mimicked nor blocked the effect induced by NE. The extracellular Ca2+ chelator egtazic acid (EGTA), nonselective Ca2+ channel blocker CdC12 and calmodulin (CaM) inhibitor W-7 significantly reduced NE-induced cAMP accumulation from 1.59%±0.47% to 1.00%±0.31%, 0.78%±0.23%, and 0.90%±0.40%,respectively. Conclusion: By coupling with a PTX-insensitive G protein, α1B-AR promotes Ca2+ influx via receptor-dependent Ca2+ channels, then Ca2+ is linked to CaM to form a Ca2+-CaM complex, which stimulates adenylyl cyclase (AC),thereby increasing the cAMP production in HEK293 cell lines.

  6. Challenges in Using Analogies

    Science.gov (United States)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  7. Hydraulic Capacitor Analogy

    Science.gov (United States)

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  8. cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

    Directory of Open Access Journals (Sweden)

    Yijin Tao

    Full Text Available The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP. We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs. Form-deprived myopia (FDM was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

  9. Refugees in and out North Africa: a study of the Choucha refugee camp in Tunisia.

    Science.gov (United States)

    Dourgnon, Paul; Kassar, Hassène

    2014-08-01

    In recent years, North African (NA) countries ceased to be emigration-only countries and are now on the verge of becoming immigration as well as transit countries for economic migrants and refugees. Contextual as well as structural long-term factors are driving these changes. The ongoing crises in Africa and the Middle East are prompting strong outflows of refugees, which are likely to induce NA countries to share some common public policy and public health concerns with European countries in a near future. This article highlights some aspects of these changes, from the study of the consequences of the 2011 Libyan crisis in Tunisia. It addresses individual trajectories and health concerns of refugees in and out North Africa from a study of the Choucha camp in Tunisia. The camp opened to immigrants from Libya during the 2011 crisis and accommodated the bulk of the refugees flow to Tunisia until July 2012. The study includes a monographic approach and a qualitative survey in the Choucha camp refugees. We describe the crisis history and the health response with a focus on the camp. We then address refugees' trajectories, and health needs and concerns from the interviews we collected in the camp in April 2012.

  10. Contingency Base Camp Operations and Management: Staffing and Organization

    Science.gov (United States)

    2013-09-17

    in a low-intensity conflict such as peacekeeping. The military devel- oped a number of enduring base camps such as Camp Bondsteel in Kosovo and Camp...works and engineering support All base camps require provision of potable water, waste water collection and treatment, solid waste collection and...IBCT (TF Red Bulls). Because the BCT also had responsibility for their International Security Assistance Force (ISAF) mission outside the wire

  11. Trainer Guide: Business and Finance Managerial. Camp Administration Series.

    Science.gov (United States)

    Farley, Elizabeth, Ed.

    Suggested ideas on conducting a managerial workshop for camp directors are offered in this trainer's guide. Workshops must be at least one full day of training (6 hours) on each topic to be counted toward the American Camping Association (ACA) Camp Director Certification Program. Suggested topics to be addressed are: (1) basic principles and…

  12. 14 CFR 91.1427 - CAMP: Manual requirements.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Manual requirements. 91.1427 Section... Operations Program Management § 91.1427 CAMP: Manual requirements. (a) Each program manager who maintains program aircraft under a CAMP must put in the operating manual the chart or description of the...

  13. Benefits of Residential and Nonresidential Youth Summer Camps.

    Science.gov (United States)

    Ross, David M.; Driver, B. L.

    1988-01-01

    Describes survey made as part of Youth Conservation Corps evaluation. Compares personal benefits of residential camping with benefits of nonresidential camps. Concludes residential participants benefited in different ways and to greater extent than nonresidential campers. Residential camping benefits measurable at least nine months after…

  14. Camp Health Aide Manual = Manual para trabajadores de salud.

    Science.gov (United States)

    Robinson, June Grube; And Others

    This bilingual manual serves as a textbook for migrant Camp Health Aides. Camp Health Aides are members of migrant labor camps enlisted to provide information about health and social services to migrant workers and their families. The manual is divided into 12 tabbed sections representing lessons. Teaching notes printed on contrasting paper…

  15. Summer Camp and Positive Youth Development: Program with Romanian Youth

    Science.gov (United States)

    Feenstra, Jennifer S.

    2015-01-01

    A variety of activities are used in camps to help promote positive youth development, improving social skills and self-esteem in campers. I expanded on previous camp research in this study to address the influence camps have on trust, belief in the honesty of others, empowerment, and care for others in youth in Eastern Europe. Since 1999, New…

  16. 22 CFR 62.30 - Camp counselors.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Camp counselors. 62.30 Section 62.30 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Specific Program... programs promote international understanding by improving American knowledge of foreign cultures...

  17. Conduct Disorders: Are Boot Camps Effective?

    Science.gov (United States)

    Jeter, LaVaughn V.

    2010-01-01

    Youth diagnosed with "conduct disorder" are often placed in programs using forced compliance and coercive control. One type of intervention used to treat conduct disorder is the boot camp. The basic idea is that disruptive behaviors can be corrected by strict behavioral regulation and an emphasis on skills training (Weis & Toolis 2009; Weis,…

  18. CS Radar Imaging via Adaptive CAMP

    NARCIS (Netherlands)

    Anitori, L.; Otten, M.P.G.; Hoogeboom, P.

    2012-01-01

    In this paper we present results on application of Compressive Sensing (CS) to high resolution radar imaging and pro- pose the adaptive Complex Approximate Message Passing (CAMP) algorithm for image reconstruction. CS provides a theoretical framework that guarantees, under certain assumptions, recon

  19. E. Coli: Preventing Outbreaks at Camp.

    Science.gov (United States)

    McKinney, Mary D.

    1996-01-01

    One strain of E. coli is not usually found in foods, but has been related to consumption of undercooked ground beef. Symptoms are stomach cramps and diarrhea, and 2-7% of infections lead to hemolytic uremic syndrome, which is life threatening. Camps can prevent outbreaks by avoiding uncooked meat on overnight campouts and requiring appropriate…

  20. 36 CFR 13.1402 - Camping.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Camping. 13.1402 Section 13.1402 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Klondike Gold Rush National Historical Park §...

  1. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  2. Cyclic adenosine 3'-5'-monophosphate (cAMP) exerts proliferative and anti-proliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac).

    Science.gov (United States)

    Vitali, E; Peverelli, E; Giardino, E; Locatelli, M; Lasio, G B; Beck-Peccoz, P; Spada, A; Lania, A G; Mantovani, G

    2014-03-05

    In the pituitary the activation of cyclic adenosine 3'-5'-monophosphate (cAMP) dependent pathways generates proliferative signals in somatotrophs, whereas in pituitary cells of other lineages its effect remains uncertain. Moreover, the specific role of the two main cAMP effectors, protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac), has not been defined. Aim of this study was to investigate the effect of cAMP on pituitary adenomatous cells proliferation and to identify PKA and Epac differential involvement. We found that cAMP increased DNA synthesis and cyclin D1 expression in somatotropinomas, whereas it reduced both parameters in prolactinomas and nonfunctioning adenomas, these effects being replicated in corresponding cell lines. Moreover, the divergent cAMP effects were mimicked by Epac and PKA analogs, which activated Rap1 and CREB, respectively. In conclusion, we demonstrated that cAMP exerted opposite effects on different pituitary cell types proliferation, these effects being mediated by both Epac and PKA.

  3. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

    Directory of Open Access Journals (Sweden)

    Xiaoying Li

    Full Text Available Our previous in vitro studies suggested that cyclic AMP (cAMP signaling prevents adriamycin (ADR and puromycin aminonucleoside (PAN-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA or exchange protein directly activated by cAMP (Epac pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator, PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  4. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

    Science.gov (United States)

    Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Chuang, Peter Y; He, John Cijiang; Gu, Leyi

    2014-01-01

    Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  5. Melanocortin 1 receptor mutations impact differentially on signalling to the cAMP and the ERK mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Herraiz, Cecilia; Jiménez-Cervantes, Celia; Zanna, Paola; García-Borrón, José C

    2009-10-06

    Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor expressed in melanocytes, is a major determinant of skin pigmentation, phototype and cancer risk. MC1R activates cAMP and mitogen-activated protein kinase ERK1/ERK2 signalling. When expressed in rat pheochromocytoma cell line cells, the R151C, R160W and D294H MC1R variants associated with melanoma and impaired cAMP signalling mediated ERK activation and ERK-dependent, agonist-induced neurite outgrowth comparable with wild-type. Dose-response curves for ERK activation and cAMP production indicated higher sensitivity of the ERK response. Thus, the melanoma-associated MC1R mutations impact differently on cAMP and ERK signalling, suggesting that cAMP is not responsible for functional coupling of MC1R to the ERK cascade.

  6. TV Analog Station Transmitters

    Data.gov (United States)

    Department of Homeland Security — This file is an extract from the Consolidated Database System (CDBS) licensed by the Media Bureau. It consists of Analog Television Stations (see Rule Part47 CFR...

  7. Analog multivariate counting analyzers

    CERN Document Server

    Nikitin, A V; Armstrong, T P

    2003-01-01

    Characterizing rates of occurrence of various features of a signal is of great importance in numerous types of physical measurements. Such signal features can be defined as certain discrete coincidence events, e.g. crossings of a signal with a given threshold, or occurrence of extrema of a certain amplitude. We describe measuring rates of such events by means of analog multivariate counting analyzers. Given a continuous scalar or multicomponent (vector) input signal, an analog counting analyzer outputs a continuous signal with the instantaneous magnitude equal to the rate of occurrence of certain coincidence events. The analog nature of the proposed analyzers allows us to reformulate many problems of the traditional counting measurements, and cast them in a form which is readily addressed by methods of differential calculus rather than by algebraic or logical means of digital signal processing. Analog counting analyzers can be easily implemented in discrete or integrated electronic circuits, do not suffer fro...

  8. Challenges in Analogical Reasoning

    CERN Document Server

    Lin, Shih-Yin

    2016-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  9. Synthesis of Paclitaxel Analogs

    OpenAIRE

    Xu, Zhibing

    2010-01-01

    Paclitaxel is one of the most successful anti-cancer drugs, particularly in the treatment of breast cancer and ovarian cancer. For the investigation of the interaction between paclitaxel and MD-2 protein, and development of new antagonists for lipopolysaccharide, several C10 A-nor-paclitaxel analogs have been synthesized and their biological activities have been evaluated. In order to reduce the myelosuppression effect of the paclitaxel, several C3â ² and C4 paclitaxel analogs have been synth...

  10. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  11. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  12. Summer camps for children with burn injuries: a literature review.

    Science.gov (United States)

    Maslow, Gary R; Lobato, Debra

    2010-01-01

    The first summer camps for children with burn injuries started over 25 years ago, and as of 2008, there were 60 camps worldwide. This review examines the literature on summer pediatric burn camps. The authors describe common characteristics of burn camp structure, activities, and staffing and then examine the scientific evidence regarding the effect of burn camp programs on campers and camp staff volunteers. A search of Pubmed and Psychinfo databases from 1970 to 2008 for articles related to pediatric burn summer camps identified 17 articles, of which 13 fit the inclusion criteria. Existing literature consists primarily of qualitative studies, suggesting that burn camp can decrease camper isolation, improve self-esteem, and promote coping and social skills. Studies examining volunteer staff at burn camp have consistently found that there are both personal and professional benefits. Quantitative studies of self-esteem have yielded equivocal results. No studies have examined safety or the effect of burn camp on medical or rehabilitation outcomes. For the past 25 years, pediatric summer camps for children with burn injuries have played an important rehabilitation role and provided a strong community that benefits both campers and staff. Future research using more rigorous research methods and examining a broader range of outcomes (eg, safety and medical/rehabilitation outcomes) is recommended.

  13. How to run a successful and educational basketball camp

    Directory of Open Access Journals (Sweden)

    Brooke LeMar

    2015-04-01

    Full Text Available Camps are a great introduction to the sport of basketball for children. Universities and colleges usually offer different types of camps, typically during the summer months. Depending on the skill and maturity level of the player, basketball camps can serve a variety of purposes. Some popular types of camps include offensive skills, shooting, team, and youth camps. Regardless of the camp that is chosen, children need to have goals set for themselves before, during, and after to enhance the benefits. Each camper should have the opportunity to grow and develop as a basketball player as well as an individual. Running a successful camp is not only rewarding for the coaches, but for the players and campers too, which ultimately leads to the campers choosing to come back every year.

  14. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  15. Cooperation between cAMP signalling and sulfonylurea in insulin secretion.

    Science.gov (United States)

    Shibasaki, T; Takahashi, T; Takahashi, H; Seino, S

    2014-09-01

    Although glucose is physiologically the most important regulator of insulin secretion, glucose-induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β-cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca²⁺ , and phospholipid-derived molecules by activating G protein-coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration-dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)-dependent and Epac2A-dependent mechanisms. Many of the proteins expressed in β-cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras-like small G protein Rap in a cAMP-dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β-cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin-related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes.

  16. Altered beta-adrenergic receptor-stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors.

    Science.gov (United States)

    Huang, H M; Gibson, G E

    1993-07-15

    An alteration in signal transduction systems in Alzheimer's disease would likely be of pathophysiological significance, because these steps are critical to normal brain function. Since dynamic processes are difficult to study in autopsied brain, the current studies utilized cultured skin fibroblasts. The beta-adrenergic-stimulated increase in cAMP was reduced approximately 80% in fibroblasts from Alzheimer's disease compared with age-matched controls. The deficit in Alzheimer fibroblasts in response to various adrenergic agonists paralleled their beta-adrenergic potency, and enhancement of cAMP accumulation by a non-adrenergic agonist, such as prostaglandin E1, was similar in Alzheimer and control fibroblasts. Diminished adenylate cyclase activity did not underlie these abnormalities, since direct stimulation of adenylate cyclase by forskolin elevated cAMP production equally in Alzheimer and control fibroblasts. Cholera toxin equally stimulated cAMP formation in Alzheimer and control fibroblasts. Moreover, cholera toxin partially reduced isoproterenol-induced cAMP deficit in Alzheimer fibroblasts. Pertussis toxin, on the other hand, did not alter the Alzheimer deficits. The results suggest either that the coupling of the GTP-binding protein(s) to the beta-adrenergic receptor is abnormal or that the sensitivity of receptor is altered with Alzheimer's disease. Further, any hypothesis about Alzheimer's disease must explain why a reduced beta-adrenergic-stimulated cAMP formation persists in tissue culture.

  17. Differential Effects of Temperature on cAMP-induced Excitation, Adaptation, and Deadaptation of Adenylate and Guanylate Cyclase in Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van

    1987-01-01

    Extracellular cAMP induces excitation of adenylate and guanylate cyclase in Dictyostelium discoideum. Continuous stimulation with cAMP leads to adaptation, while cells deadapt upon removal of the cAMP stimulus. Excitation of guanylate cyclase by cAMP has a lag time of ~1 s; excitation of adenylate c

  18. [Blockade of NMDA receptor enhances corticosterone-induced downregulation of brain-derived neurotrophic factor gene expression in the rat hippocampus through cAMP response element binding protein pathway].

    Science.gov (United States)

    Feng, Hao; Lu, Li-Min; Huang, Ying; Zhu, Yi-Chun; Yao, Tai

    2005-10-25

    High concentration of corticosterone leads to morphological and functional impairments in hippocampus, ranging from a reversible atrophy of pyramidal CA3 apical dendrites to the impairment of long-term potentiation (LTP) and hippocampus-dependent learning and memory. Glutamate and N-methyl-D-aspartate (NMDA) receptor play an important role in this effect. Because of the importance of brain-derived neurotrophic factor (BDNF) in the functions of the hippocampal neurons, alteration of the expression of BDNF is thought to be involved in the corticosterone effect on the hippocampus. To determine whether change in BDNF in the hippocampus is involved in the corticosterone effect, we injected corticosterone (2 mg/kg, s.c.) to Sprague-Dawley rats and measured the mRNA, proBDNF and mature BDNF protein levels in the hippocampus. We also measured the phosphorylation level of the transcription factor cAMP response element binding protein (CREB). Furthermore, we intraperitoneally injected NMDA receptor antagonist MK801 (0.1 mg/kg) 30 min before corticosterone administration to investigate whether and how MK801 affected the regulation of BDNF gene expression by corticosterone. Our results showed that 3 h after single s.c. injection of corticsterone, the expression of BDNF mRNA, proBDNF and mature BDNF protein decreased significantly (PBDNF gene expression in the rat hippocampus by corticosterone. We also found that either applying corticosterone or co-applying corticosterone with MK801 downregulated the phosphoration level of CREB, the latter (corticosterone plus MK801) being more effective (PBDNF gene expression in the rat hippocampus through CREB pathway and that blockade of NMDA receptor enhances this effect of corticosterone in reducing BDNF expression.

  19. Yoga camp in Ayurvedgrams of Chhattisgarh

    Directory of Open Access Journals (Sweden)

    Raghavendra Madhu

    2012-01-01

    Full Text Available The clinical and empirical health benefits of yoga and pranayam have been reiterated through research. Yoga is being adopted as a system to alleviate the burden of noncommunicable diseases (NCDs across the globe. The Directorate of AYUSH, Government of Chhattisgarh (DoA, GoCG conducts annual 5-day-yoga camp across 146 Ayurvedgrams in the State. The present article brings out the AYUSH initiatives the State is taking toward active ageing. A total of 71,096 people participated in the 5-day-yoga camp across the State. A mean participation of 5079 people over 5 days was reported across districts. Such statewide practices need to be promoted and appraised.

  20. Flaubert et Du Camp : quelques remarques

    Directory of Open Access Journals (Sweden)

    Michel Brix

    2016-12-01

    Full Text Available Les spécialistes de Flaubert ont fait de nombreux reproches à Maxime Du Camp et ne prêtent plus guère d’attention à ce qu’il a écrit. C’est une situation très regrettable, qui prive les lecteurs d’informations nombreuses, susceptibles d’éclairer les enjeux mais aussi les impasses et les contradictions du projet esthétique de Flaubert. Quelques cas significatifs sont évoqués dans le présent article, qui se penche plus particulièrement sur la ressemblance entre un passage du livre de Du Camp Le Nil (1854 et les lignes de L’Éducation sentimentale (1869 qui rapportent l’“apparition” de Mme Arnoux.

  1. Core Concepts: Orthopedic Intern Curriculum Boot Camp.

    Science.gov (United States)

    Seeley, Mark A; Kazarian, Erick; King, Brandon; Biermann, Janet S; Carpenter, James E; Caird, Michelle S; Irwin, Todd A

    2016-01-01

    Orthopedic surgical interns must gain a broad array of clinical skills in a short time. However, recent changes in health care have limited resident-patient exposures. With the reported success of simulation training in the surgical literature, the American Board of Orthopaedic Surgery (ABOS) and Residency Review Committee for Orthopaedic Surgery have required that surgical simulation training be a component of the intern curricula in orthopedic surgical residencies. This study examined the short-term effectiveness of an orthopedic "intern boot camp" covering 7 of 17 simulation training concept modules published by the ABOS. Eight orthopedic post-graduate year 1 (PGY-1) residents (study group) completed a structured 3-month curriculum and were compared with 7 post-graduate year 2 (PGY-2) residents (comparison group) who had just completed their orthopedic surgical internship. Seven core skills were assessed using both task-specific and global rating scales. The PGY-1 residents demonstrated a statistically significant improvement in all 7 modules with respect to their task-specific pre-test scores: sterile technique (P=.001), wound closure (P<.001), knot tying (P=.017), casting and splinting (P<.001), arthrocentesis (P=.01), basics of internal fixation (P<.001), and compartment syndrome evaluation (P=.004). After the camp, PGY-1 and -2 scores in task-specific measures were not significantly different. A 3-month simulation-based boot camp instituted early in orthopedic internship elevated a variety of clinical skills to levels exhibited by PGY-2 residents.

  2. Forskolin's effect on transient K current in nudibranch neurons is not reproduced by cAMP.

    Science.gov (United States)

    Coombs, J; Thompson, S

    1987-02-01

    Forskolin, a diterpene extracted from Coleus forskolii, stimulates the production of cAMP in a variety of cells and is potentially an important tool for studying the role of cAMP in the modulation of neuronal excitability. We studied the effects of forskolin on neurons of nudibranch molluscs and found that it caused characteristic, reversible changes in the amplitude and waveform of the transient K current, IA, and also activated an inward current similar to the cAMP-dependent inward current previously described in molluscan neurons. Forskolin altered the time course of IA activation and inactivation but did not affect the voltage dependence or the reversal potential of the current. IA normally inactivates exponentially, but in forskolin the time course of inactivation can be fit by the sum of 2 exponentials with an initial rate that is faster than the control and a final rate that is much slower. On depolarization in forskolin, IA begins to activate at the normal rate, but a slower component of activation is also seen. The changes in IA in the nudibranch cells were qualitatively different than the changes caused by forskolin in Aplysia bag cell neurons (Strong, 1984). Experiments were performed to determine whether these effects of forskolin require cAMP. Intracellular injection of cAMP, application of membrane-permeable analogs of cAMP, application of phosphodiesterase inhibitors, and intracellular injection of the active catalytic subunit of cAMP-dependent protein kinase did not affect the amplitude or waveform of IA. Also, the changes in IA that are caused by forskolin were not prevented or reversed by intracellular injection of an inhibitor of cAMP-dependent protein kinase. Cyclic AMP did, however, activate inward current at voltages near the resting potential. We conclude that the changes in IA and the activation of inward current represent separate affects of forskolin. The inward current appears to depend on an increase in intracellular cAMP, while the

  3. Digital and analog communication systems

    Science.gov (United States)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  4. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  5. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Zou, Xuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Cao, Ke; Xu, Jie; Yue, Tingting [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Dai, Fang; Zhou, Bo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou (China); Lu, Wuyuan [Center for Translational Medicine, FIST, Xi' an Jiaotong University, Xi' an (China); Feng, Zhihui, E-mail: zhfeng@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China); Liu, Jiankang, E-mail: j.liu@mail.xjtu.edu.cn [Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, FIST, Xi' an Jiaotong University, Xi' an (China)

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the

  6. Analogy, explanation, and proof.

    Science.gov (United States)

    Hummel, John E; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  7. Quantum Analog Computing

    Science.gov (United States)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  8. Are Scientific Analogies Metaphors?

    Science.gov (United States)

    1981-02-01

    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  9. Radioprotection of the rat parotid gland by cAMP

    Energy Technology Data Exchange (ETDEWEB)

    Sodicoff, M.; Conger, A.D.

    1983-10-01

    Most earlier studies showing a radioprotective effect by cAMP show only slight degrees of protection. The present study demonstrates a substantial protective effect (DMF, 1.63) of exogenously administered cAMP on the rat parotid gland and supports the mechanism suggested previously for protection afforded the parotid glands by the ..beta..-adrenergic agonist isoproterenol, which is known to elevate endogenous intracellular cAMP.

  10. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway.

    Science.gov (United States)

    He, Mingyuan; Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang; Shao, Chunlin

    2014-01-01

    Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in regulating the reciprocal bystander effects.

  11. Adventure Code Camp: Library Mobile Design in the Backcountry

    Directory of Open Access Journals (Sweden)

    David Ward

    2014-09-01

    Full Text Available This article presents a case study exploring the use of a student Coding Camp as a bottom-up mobile design process to generate library mobile apps. A code camp sources student programmer talent and ideas for designing software services and features.  This case study reviews process, outcomes, and next steps in mobile web app coding camps. It concludes by offering implications for services design beyond the local camp presented in this study. By understanding how patrons expect to integrate library services and resources into their use of mobile devices, librarians can better design the user experience for this environment.

  12. Stochastic noise and synchronisation during Dictyostelium aggregation make cAMP oscillations robust

    OpenAIRE

    Kim, J

    2007-01-01

    Author Summary The molecular network, which underlies the oscillations in the concentration of adenosine 3′, 5′-cyclic monophosphate (cAMP) during the aggregation phase of starvation-induced development in Dictyostelium discoideum, achieves remarkable levels of robust performance in the face of environmental variations and cellular heterogeneity. However, the reasons for this robustness remain poorly understood. Tools and concepts from the field of control engineering provide powerful methods...

  13. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xuenong; Wei, Han; Liu, Ziwei; Yuan, Qianying [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Wei, Anhua [Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Shi, Du; Yang, Xian [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Ruan, Jinlan, E-mail: jinlan8152@163.com [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China)

    2013-07-15

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death.

  14. Insulin analogs and cancer: A note of caution

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); A.J. Varewijck (Aimee)

    2014-01-01

    textabstractIn view of the lifelong exposure and large patient populations involved, insulin analogs with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogs may possibly induce the growth of pre-existing neoplasms. At p

  15. Camp Insurance 101: Understanding the Fundamentals of a Camp Insurance Program.

    Science.gov (United States)

    Garner, Ian

    2001-01-01

    This short course on insurance for camps discusses coverage, including the various types of liability, property, and other types of coverage; the difference between direct writers, brokers, agents, and captive agents; choosing an insurance company; and checking on the financial stability of recommended carriers. Three Web sites are given for…

  16. Staphylococcus pseudintermedius for CAMP-test.

    Science.gov (United States)

    Savini, Vincenzo; Paparella, Antonello; Serio, Annalisa; Marrollo, Roberta; Carretto, Edoardo; Fazii, Paolo

    2014-01-01

    CAMP test reliably detects Listeria monocytogenes (Lm) and Streptococcus agalactiae (group B streptococcus, GBS); it is traditionally performed streaking the tested isolate perpendicularly to Staphylococcus aureus (Sa), provided that reference Sa strains (that produce β-hemolysin) are used. In a zone of β-hemolysin activity, in fact, GBS and Lm form typical arrow-shaped hemolytic areas. While Sa production of the toxin is strain-dependent, however, that of Staphylococcus pseudintermedius (Sp), a pet-owner colonizer and an emerging human pathogen, is constitutive, then observed in all clinical isolates. Therefore, Sp may indeed represent a valid alternative to perform the assay.

  17. Berberine attenuates cAMP-induced lipolysis via reducing the inhibition of phosphodiesterase in 3T3-L1 adipocytes.

    Science.gov (United States)

    Zhou, Libin; Wang, Xiao; Yang, Ying; Wu, Ling; Li, Fengying; Zhang, Rong; Yuan, Guoyue; Wang, Ning; Chen, Mingdao; Ning, Guang

    2011-04-01

    Berberine, a hypoglycemic agent, has been shown to decrease plasma free fatty acids (FFAs) level in insulin-resistant rats. In the present study, we explored the mechanism responsible for the antilipolytic effect of berberine in 3T3-L1 adipocytes. It was shown that berberine attenuated lipolysis induced by catecholamines, cAMP-raising agents, and a hydrolyzable cAMP analog, but not by tumor necrosis factor α and a nonhydrolyzable cAMP analog. Unlike insulin, the inhibitory effect of berberine on lipolysis in response to isoproterenol was not abrogated by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but additive to that of PD98059, an extracellular signal-regulated kinase kinase inhibitor. Prior exposure of adipocytes to berberine decreased the intracellular cAMP production induced by isoproterenol, forskolin, and 3-isobutyl-1-methylxanthine (IBMX), along with hormone-sensitive lipase (HSL) Ser-563 and Ser-660 dephosphorylation, but had no effect on perilipin phosphorylation. Berberine stimulated HSL Ser-565 as well as adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. However, compound C, an AMPK inhibitor, did not reverse the regulatory effect of berberine on HSL Ser-563, Ser-660, and Ser-565 phosphorylation, nor the antilipolytic effect of berberine. Knockdown of AMPK using RNA interference also failed to restore berberine-suppressed lipolysis. cAMP-raising agents increased AMPK activity, which was not additive to that of berberine. Stimulation of adipocytes with berberine increased phosphodiesterase (PDE) 3B and PDE4 activity measured by hydrolysis of (3)[H]cAMP. These results suggest that berberine exerts an antilipolytic effect mainly by reducing the inhibition of PDE, leading to a decrease in cAMP and HSL phosphorylation independent of AMPK pathway.

  18. Partial correction of defective Cl(-) secretion in cystic fibrosis epithelial cells by an analog of squalamine.

    Science.gov (United States)

    Jiang, C; Lee, E R; Lane, M B; Xiao, Y F; Harris, D J; Cheng, S H

    2001-11-01

    Defective cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-mediated Cl(-) transport across the apical membrane of airway epithelial cells is implicated in the pathophysiology of CF lungs. A strategy to compensate for this loss is to augment Cl(-) transport through alternative pathways. We report here that partial correction of this defect could be attained through the incorporation of artificial anion channels into the CF cells. Introduction of GL-172, a synthetic analog of squalamine, into CFT1 cells increased cell membrane halide permeability. Furthermore, when a Cl(-) gradient was generated across polarized monolayers of primary human airway or Fischer rat thyroid cells in an Ussing chamber, addition of GL-172 caused an increase in the equivalent short-circuit current. The magnitude of this change in short-circuit current was ~30% of that attained when CFTR was maximally stimulated with cAMP agonists. Patch-clamp studies showed that addition of GL-172 to CFT1 cells also increased whole cell Cl(-) currents. These currents displayed a linear current-voltage relationship and no time dependence. Additionally, administration of GL-172 to the nasal epithelium of transgenic CF mice induced a hyperpolarization response to perfusion with a low-Cl(-) solution, indicating restoration of Cl(-) secretion. Together, these results demonstrate that in CF airway epithelial cells, administration of GL-172 is capable of partially correcting the defective Cl(-) secretion.

  19. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  20. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic whose truth was not even known prior to the existence of the explanation (proof. What do the cognitive operations underlying the (inductive inference that the milk is sour have in common with the (deductive proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence.

  1. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

    Directory of Open Access Journals (Sweden)

    Young Gregory S

    2010-06-01

    Full Text Available Abstract Background We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. Results FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3 and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures as determined by annexin V/propidium iodide staining and immunoblot analysis. FLLL32 treatment reduced expression of STAT3-target genes, induced caspase-dependent apoptosis, and reduced mitochondrial membrane potential. FLLL32 displayed specificity for STAT3 over other homologous STAT proteins. In contrast to other STAT3 pathway inhibitors (WP1066, JSI-124, Stattic, FLLL32 did not abrogate IFN-γ-induced pSTAT1 or downstream STAT1-mediated gene expression as determined by Real Time PCR. In addition, FLLL32 did not adversely affect the function or viability of immune cells from normal donors. In peripheral blood mononuclear cells (PBMCs, FLLL32 inhibited IL-6-induced pSTAT3 but did not reduce signaling in response to immunostimulatory cytokines (IFN-γ, IL 2. Treatment of PBMCs or natural killer (NK cells with FLLL32 also did not decrease viability or granzyme b and IFN-γ production when cultured with K562 targets as compared to vehicle (DMSO. Conclusions These data suggest that FLLL32 represents a lead compound that could serve as a platform for further optimization to develop improved STAT3 specific inhibitors for melanoma therapy.

  2. A Transiting Jupiter Analog

    CERN Document Server

    Kipping, David M; Henze, Chris; Teachey, Alex; Isaacson, Howard T; Petigura, Erik A; Marcy, Geoffrey W; Buchhave, Lars A; Chen, Jingjing; Bryson, Steve T; Sandford, Emily

    2016-01-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\\pm0.02)$ $R_{\\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric ...

  3. 3,3'-Diindolylmethane (DIM) and its ring-substituted halogenated analogs (ring-DIMs) induce differential mechanisms of survival and death in androgen-dependent and -independent prostate cancer cells.

    Science.gov (United States)

    Goldberg, Alexander A; Draz, Hossam; Montes-Grajales, Diana; Olivero-Verbél, Jesus; Safe, Stephen H; Sanderson, J Thomas

    2015-05-01

    We recently reported that novel ring-substituted analogs of 3,3'-diindolylmethane (ring-DIMs) induce apoptosis and necrosis in androgen-dependent and -independent prostate cancer cells. In this paper, we have focused on the mechanism(s) associated with ring-DIM-mediated cell death, and on identifying the specific intracellular target(s) of these compounds. The 4,4'- and 7,7'-dichloroDIMs and 4,4'- and 7,7'-dibromoDIMs induced the death of LNCaP, C42B and DU145 prostate cancer cells, but not that of immortalized normal human prostate epithelial (RWPE-1) cells. Ring-DIMs caused the early loss of mitochondrial membrane potential (MMP) and decreased mitochondrial ATP generation in prostate cancer cells. Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore, inhibited ring-DIM-mediated cell death, and salubrinal, an inhibitor of ER stress, inhibited cell death mediated only by 4,4'-dihaloDIMs. We found that although salubrinal did not inhibit the onset of ER stress, it prevented 4,4'-dibromoDIM mediated loss of MMP. Salubrinal potentiated cell death in response to 7,7'-dihaloDIMs and DIM, and this effect concurred with increased loss of MMP. Using in silico 3-D docking affinity analysis, we identified Ca2+/calmodulin-dependent kinase II (CaMKII) as a potential direct target for the most toxic ring-DIM, 4,4'-dibromoDIM. An inhibitor of CaMKII, KN93, but not its inactive analog KN92, abrogated cell death mediated by 4,4'-dibromoDIM. The ring-DIMs induced ER stress and autophagy, but these processes were not necessary for ring-DIM-mediated cell death. Inhibition of autophagy with bafilomycin A1, 3-methyladenine or by LC3B gene silencing sensitized LNCaP and C42B, but not ATG5-deficient DU145 cells to ring-DIM- and DIM-mediated cell death. We propose that autophagy induced by the ring-DIMs and DIM has a cytoprotective function in prostate cancer cells.

  4. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling

    2003-03-01

    Full Text Available Three forms of inductive generalization - statistical generalization, variation-based generalization and theory-carried generalization - are insufficient concerning case-to-case generalization, which is a form of analogical generalization. The quality of case-to-case generalization needs to be reinforced by setting up explicit analogical argumentation. To evaluate analogical argumentation six criteria are discussed. Good analogical reasoning is an indispensable support to forms of communicative generalization - receptive and responsive (participative generalization — as well as exemplary generalization.

  5. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  6. How to Respond to Problem Behavior in Camp.

    Science.gov (United States)

    Rotman, Charles B.

    1987-01-01

    Deals with types of behavior that cannot be allowed among staff or campers in the camp community--use of drugs or alcohol, personal abuse, crime, violence, and sexual activity. Urges camp directors to develop a written policy spelling out standards, expectations, and sanctions. Suggests staff orientation strategies. (JHZ)

  7. Socialization of Adolescents: Cultural Practices in Children's Summer Camp

    Science.gov (United States)

    Demakova, Irina D.; Valeeva, Roza A.; Shipova, Alina V.

    2016-01-01

    The article describes the relevant aspects of the adolescents' cultural practices in children's summer camp, taking into account their specific characteristics. The summer camp is considered as an educational formation and holistic socio-pedagogical body, designed to create conditions for the development of the person. The criteria for inclusion…

  8. Students Become Scientists at Science Skills Boot Camp | Poster

    Science.gov (United States)

    At the 2016 Science Skills Boot Camp (SSBC), a one-day training program designed for NIH summer interns with little or no prior research experience, students gathered to learn about basic research and laboratory skills. The boot camp provided a unique opportunity for interns to expand their knowledge of simple bench techniques, scientific papers, and ways to communicate their research.

  9. EduCamp Colombia: Social Networked Learning for Teacher Training

    Science.gov (United States)

    Fonseca, Diego Ernesto Leal

    2011-01-01

    This paper describes a learning experience called EduCamp, which was launched by the Ministry of Education of Colombia in 2007, based on emerging concepts such as e-Learning 2.0, connectivism, and personal learning environments. An EduCamp proposes an unstructured collective learning experience, which intends to make palpable the possibilities of…

  10. College and University Summer Camps: Creative Alternatives to Day Care.

    Science.gov (United States)

    Wever, Matthew F.

    1995-01-01

    The successful summer day camp program of Saint Louis University (Missouri) is described. Program rationale, philosophy, objectives, structure, staffing, activities, and benefits to the university community are discussed. A majority of the children served by the camp are the children, ages 6 to 12, of university employees. (MSE)

  11. Specialized Summer Camps: Provide Benefits for Children and Families Alike

    Science.gov (United States)

    Neff, John M.

    2009-01-01

    The arrival of summer signals a season of endless days of swimming, fishing, summer camps, and other outdoor activities. For children with chronic or terminal illnesses, it can be difficult to participate in many of these activities as well as challenging for parents to find summer camps that not only engage their children, but also offer the…

  12. Art Matters: The Creative Side of the Summer Camp Experience.

    Science.gov (United States)

    Foster, Eden

    2003-01-01

    In western North Carolina, 24 summer camps, business leaders, and a local community arts council collaborated on a project celebrating the visual and performing arts created by campers. Campers' art in every media was displayed in Hendersonville to highlight the benefits of summer camps to the community, including their economic, educational,…

  13. Vision, Leadership, and Change: The Case of Ramah Summer Camps

    Science.gov (United States)

    Reimer, Joseph

    2010-01-01

    In his retrospective essay, Seymour Fox (1997) identified "vision" as the essential element that shaped the Ramah camp system. I will take a critical look at Fox's main claims: (1) A particular model of vision was essential to the development of Camp Ramah; and (2) That model of vision should guide contemporary Jewish educators in creating Jewish…

  14. Residential Grief Camps: An Initial Phenomenological Study of Staff Perspectives

    Science.gov (United States)

    Brown, Tiffany B.; Kimball, Thomas G.

    2012-01-01

    Research has focused primarily on the impact of death on family functioning and the stages and tasks of grief, though little attention has been given to grief camps or the experiences of those who work there. This study explored the experiences of staff at a four-day overnight children's grief camp. Eight participants reported their experience of…

  15. Novel cAMP targets in cell proliferation

    NARCIS (Netherlands)

    Kuiperij, Hinke Bertha

    2004-01-01

    cAMP is a second messenger that plays a role in a wide variety of biological processes, one of which is the regulation of cell proliferation. Adenylate cyclases generate cAMP in the cell upon activation, followed by binding to and activation of its direct targets, PKA and Epac. PKA is a protein kina

  16. Creating a Healthy Camp Community: A Nurse's Role.

    Science.gov (United States)

    Lishner, Kris Miller; Bruya, Margaret Auld

    This book provides an organized, systematic overview of the basic aspects of health program management, nursing practice, and human relations issues in camp nursing. A foremost assumption is that health care in most camps needs improvement. Good health is dependent upon interventions involving social, environmental, and lifestyle factors that…

  17. Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells

    OpenAIRE

    Yeo Cho Yoon; Sung-Hee Kim; Min Jung Kim; Hye Jeong Yang; Mee-Ra Rhyu; Jae-Ho Park

    2015-01-01

    Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST p...

  18. TOWARDS A MATHEMATICAL THEORY OF ANALOGY

    OpenAIRE

    Haraguchi, Makoto

    1985-01-01

    This paper presents a mathematical theory of analogy, which should be a basis in developing analogical reasoning by a computer. The analogy is a partial identity between two sets of facts. In order to compare several analogies, we introduce an ordering of analogies, and we define two types of optimal analogies, maximal analogies and greatest ones. We show a condition under which the greatest analogy exists, and also present a top-down procedure to find the maximal analogies.

  19. Effect of cAMP on short-circuit current in isolated human ciliary body

    Institute of Scientific and Technical Information of China (English)

    WU Ren-yi; MA Ning; HU Qian-qian

    2013-01-01

    Background Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current,Isc) across the ciliary processes in pigs.The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change.Methods In an Ussing-type chamber system,the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed.The involvement of Cl-component in the bath solution was investigated.The effect of Cl-channel (10 μmol/L niflumic acid and 1 mmol/L 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)),K+ channel (10 mmol/L tetraethylammonium chloride (TEA)),or Na+ channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied.Results Dose-dependently,8-bromo-cAMP (10 nmol/L-30 μmol/L) or forskolin (10 nmol/L-3 μmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue.Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side.When the tissue was bathed in low Cl-solutions,the Isc increase was significantly inhibited.Finally,niflumic acid and DIDS,but not TEA or amiloride,significantly prevented the Isc increase induced by 8-bromo-cAMP.Conclusions cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes.Chloride is likely to be among the ions,the transportation of which across the tissue is triggered by cAMP,suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

  20. Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma

    Science.gov (United States)

    Friesen, Claudia; Hormann, Inis; Roscher, Mareike; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf; Debatin, Klaus-Michael; Miltner, Erich

    2014-01-01

    Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas’ resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells. PMID:24626197

  1. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Mingyuan [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Department of Radiation Oncology, China–Japan Union Hospital of Jilin University, Changchun 130033 (China); Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2014-05-15

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  2. Seizure Suppression by High Temperature via cAMP Modulation in Drosophila

    Science.gov (United States)

    Saras, Arunesh; Tanouye, Mark A.

    2016-01-01

    Bang-sensitive (BS) Drosophila mutants display characteristic seizure-like activity (SLA) and paralysis after mechanical shock . After high-frequency electrical stimulation (HFS) of the brain, they generate robust seizures at very low threshold voltage. Here we report an important phenomenon, which effectively suppresses SLA in BS mutants. High temperature causes seizure suppression in all BS mutants (parabss1, eas, sda) examined in this study. This effect is fully reversible and flies show complete recovery from BS paralysis once the temperature effect is nullified. High temperature induces an increase in seizure threshold after a brief pulse of heat shock (HS). By genetic screening, we identified the involvement of cAMP in the suppression of seizures by high temperature. We propose that HS induces adenylyl cyclase which in turn increases cAMP concentration which eventually suppresses seizures in mutant flies. In summary, we describe an unusual phenomenon, where high temperature can suppress SLA in flies by modulating cAMP concentration. PMID:27558668

  3. Theta-burst stimulation of hippocampal slices induces network-level calcium oscillations and activates analogous gene transcription to spatial learning.

    Directory of Open Access Journals (Sweden)

    Graham K Sheridan

    Full Text Available Over four decades ago, it was discovered that high-frequency stimulation of the dentate gyrus induces long-term potentiation (LTP of synaptic transmission. LTP is believed to underlie how we process and code external stimuli before converting it to salient information that we store as 'memories'. It has been shown that rats performing spatial learning tasks display theta-frequency (3-12 Hz hippocampal neural activity. Moreover, administering theta-burst stimulation (TBS to hippocampal slices can induce LTP. TBS triggers a sustained rise in intracellular calcium [Ca2+]i in neurons leading to new protein synthesis important for LTP maintenance. In this study, we measured TBS-induced [Ca2+]i oscillations in thousands of cells at increasing distances from the source of stimulation. Following TBS, a calcium wave propagates radially with an average speed of 5.2 µm/s and triggers multiple and regular [Ca2+]i oscillations in the hippocampus. Interestingly, the number and frequency of [Ca2+]i fluctuations post-TBS increased with respect to distance from the electrode. During the post-tetanic phase, 18% of cells exhibited 3 peaks in [Ca2+]i with a frequency of 17 mHz, whereas 2.3% of cells distributed further from the electrode displayed 8 [Ca2+]i oscillations at 33 mHz. We suggest that these observed [Ca2+]i oscillations could lead to activation of transcription factors involved in synaptic plasticity. In particular, the transcription factor, NF-κB, has been implicated in memory formation and is up-regulated after LTP induction. We measured increased activation of NF-κB 30 min post-TBS in CA1 pyramidal cells and also observed similar temporal up-regulation of NF-κB levels in CA1 neurons following water maze training in rats. Therefore, TBS of hippocampal slice cultures in vitro can mimic the cell type-specific up-regulations in activated NF-κB following spatial learning in vivo. This indicates that TBS may induce similar transcriptional changes to

  4. cGMP-PDE3-cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat.

    Science.gov (United States)

    Cai, Ying-Lan; Sun, Qian; Huang, Xu; Jiang, Jing-Zhi; Zhang, Mo-Han; Piao, Li-Hua; Jin, Zheng; Xu, Wen-Xie

    2013-01-10

    In the present study, we investigated the mechanism of C-type natriuretic peptide (CNP)-induced inhibitory effect on spontaneous contraction of gastric antral smooth muscle to clarify CNP-NPR-B/pGC-cGMP downstream signal transduction pathway using organ bath and ELISA methods in rat. CNP significantly reduced the amplitude of the spontaneous contraction and increased the contents of cGMP and cAMP in the gastric antral smooth muscle tissue. In the presence of IBMX, a non-selective phosphodiesterase (PDE) inhibitor, the inhibitory effect of CNP on spontaneous contraction was significantly suppressed; however, the production of cGMP but not cAMP was still increased by CNP. EHNA, a PDE2 inhibitor, did not affect both CNP-induced inhibition of the contraction and CNP-induced increase of cGMP and cAMP generations in gastric smooth muscle tissue, while milrinone, a PDE3 inhibitor, similar to IBMX, attenuated the CNP-induced inhibitory effect on spontaneous contraction and increased the content of cGMP but not cAMP. The results suggest that cGMP-PDE3-cAMP signal pathway is also involved in the CNP-induced inhibition of gastric motility in rat.

  5. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  6. Inhibin alpha gene expression in human trophoblasts is regulated by interactions between TFAP2 and cAMP signaling pathways.

    Science.gov (United States)

    Depoix, Christophe L; Debiève, Frédéric; Hubinont, Corinne

    2014-11-01

    Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expression was regulated by TFAP2A via association with an AP-2 site located upstream of this CRE. The aim of this study was to evaluate if the human INHA gene was also regulated by cAMP in trophoblasts, and to investigate the possible crosstalk between TFAP2 and cAMP signaling pathways in the regulation of INHA gene expression. Treatment with cAMP or forskolin increased INHA mRNA expression by 7- and 2-fold in primary cytotrophoblasts and choriocarcinoma-derived BeWo cells, respectively. Treatment with the protein kinase A inhibitor H-89 reduced forskolin-induced luciferase activity by ∼40% in BeWo cells transfected with an INHA promoter-driven luciferase reporter vector. TFAP2 overexpression increased basal luciferase activity, whereas the dominant repressor KCREB abolished it. Surprisingly, mutation of the CRE also eliminated the TFAP2-induced transcription, although TFAP2 overexpression was still able to increase forskolin-induced luciferase activity when the AP-2 binding site, but not the CRE site, was mutated. Thus, INHA gene expression is upregulated by cAMP via CRE in human trophoblasts, and TFAP2 regulates this expression by interacting with CRE.

  7. Changes in the expression of LIMP-2 during cerulein-induced pancreatitis in rats: Effect of inhibition of leukocyte infiltration, cAMP and MAPKs early on in its development.

    Science.gov (United States)

    García-Hernández, Violeta; Sarmiento, Nancy; Sánchez-Bernal, Carmen; Coveñas, Rafael; Hernández-Hernández, Angel; Calvo, José J; Sánchez-Yagüe, Jesús

    2016-03-01

    Lysosomal integral membrane protein-2 (LIMP-2) is an important protein in lysosomal biogenesis and function and also plays a role in the tissue inflammatory response. It is known that lysosomes play a central role in acute pancreatitis, with inflammatory cell infiltration triggering the disease early on. In this study we report increases in pancreatic LIMP-2 protein and mRNA levels as early events that occur during the development of cerulein (Cer)-induced acute pancreatitis (AP) in rats. GdCl3, a macrophage inhibitor, but not FK506, a T lymphocyte inhibitor, was able to reverse the increase in LIMP-2 expression after Cer treatment, although such reversion was abolished if the animals were depleted of neutrophils due to a vinblastine sulfate pre-treatment. Immunostaining revealed that the cellular source of LIMP-2 was mainly acinar cells. Additionally, pre-treatments with the MAPKs inhibitors SP600125 and PD98059, inhibitors of JNK and ERK½ activation, respectively, but not of rolipram, a type IV phosphodiesterase inhibitor, suppressed the increase in the expression of LIMP-2 after Cer administration. Together, these results indicate that neutrophils are able to drive a macrophage activation that would regulate the increase in LIMP-2 expression during the early phase of Cer-induced AP, with the stress kinases JNK and ERK½ also playing a coordinated role in the increase of LIMP-2 expression due to Cer.

  8. Superoxide dismutase analog (TEMPOL: 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) treatment restores erectile function in diabetes-induced impotence

    Science.gov (United States)

    Kawakami, Toshifumi; Urakami, Shinji; Hirata, Hiroshi; Tanaka, Yuichiro; Nakajima, Koichi; Enokida, Hideki; Shiina, Hiroaki; Ogishima, Tatsuya; Tokizane, Takashi; Kawamoto, Ken; Miura, Kazukiyo; Ishii, Nobuhisa; Dahiya, Rajvir

    2014-01-01

    We hypothesized that administration of the superoxide dismutase (SOD) mimetic Tempol (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine 1-oxyl) may reverse diabetes induced ED(erectile dysfunction). To test this hypothesis, ROS related genes (SOD1, SOD2, GPx1, CAT, NOS2, NOS3), erectile functional studies, and immunohistochemical analysis were performed in diabetic rats treated with or without Tempol. Thirty Sprague-Dawley (3–4 months old) rats were divided into 3 groups (n=10 each), 20 with diabetes (diabetic control and Tempol treatment) and 10 healthy controls. Twelve weeks after induction of diabetes by streptozotocin and Tempol treatment, all groups underwent in vivo cavernous nerve stimulation. Rat crura were harvested and expression of antioxidative defense enzymes examined by semi-quantitative RT-PCR. To confirm the RT-PCR results, we performed immunohistochemistry (IHC) for catalase (CAT) and iNOS (NOS2). Nitration of tyrosine groups in proteins was also examined by IHC. Mean intracavernous pressure in the diabetic group was significantly lower than in healthy controls (p<0.001) and was reversed by Tempol treatment (p<0.0108). NOS2 protein expression was significantly increased in diabetic animals compared to healthy controls and Tempol restored NOS2 protein level. Nitrotyrosine was also higher in diabetic animals and though Tempol treatment decreased its formation, it remained higher than that found in healthy controls. This study suggests that Tempol treatment increased erectile function through modulating oxidative stress related genes in diabetic rats. This is the first report about the relationship between diabetes induced erectile dysfunction and oxidative stress, and anti-oxidative therapy using the superoxide dismutase mimetic, Tempol to restore erectile function. PMID:19554009

  9. Albert Einstein, Analogizer Extraordinaire

    CERN Document Server

    CERN. Geneva

    2007-01-01

    Where does deep insight in physics come from? It is tempting to think that it comes from the purest and most precise of reasoning, following ironclad laws of thought that compel the clear mind completely rigidly. And yet the truth is quite otherwise. One finds, when one looks closely at any major discovery, that the greatest of physicists are, in some sense, the most crazily daring and irrational of all physicists. Albert Einstein exemplifies this thesis in spades. In this talk I will describe the key role, throughout Albert Einstein's fabulously creative life, played by wild guesses made by analogy lacking any basis whatsoever in pure reasoning. In particular, in this year of 2007, the centenary of 1907, I will describe how over the course of two years (1905 through 1907) of pondering, Einstein slowly came, via analogy, to understand the full, radical consequences of the equation that he had first discovered and published in 1905, arguably the most famous equation of all time: E = mc2.

  10. Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT, GABA and bone marrow cell supplementation

    Directory of Open Access Journals (Sweden)

    Romeo Chinthu

    2011-01-01

    Full Text Available Abstract Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P

  11. How to run a sports camp – legally speaking

    Directory of Open Access Journals (Sweden)

    Steven Monk

    2016-04-01

    Full Text Available Camps are a great way to keep kids active throughout the summer and to make money for the program sponsoring them. Planning is needed for a sports camp to be safe for both the camp personnel and the athletes, and to minimize legal negligence.  Having a risk management plan in place is important to insure that everyone is aware of the risks of participating. Background checks on camp personnel help ensure the camp leaders and coaches do not have a criminal background.  It is important to inspect the facilities/equipment to make sure they are safe to use.  Athletic trainers help with injuries that may occur with participation.  Supervisors make sure that everyone is accounted for and camp rules help the campers behave in an appropriate manner.  When planning activities, it is important to look at the skill level of the athletes. If all of these areas are covered, camps should be legally protected if an issue were to arise.

  12. Camp Sports Injuries: Analysis of Causes, Modes and Frequencies

    Directory of Open Access Journals (Sweden)

    Panagiota Papageorgiou

    2008-12-01

    Full Text Available The purpose of this study was the description of sports injuries sustained by campers at summer camps, aged 7-15 years. A sample of 8 camps from the Greek camp population participated in this sport injury surveillance study. Doctors and camp directors completed reports detailing the number of sports injuries events sustained and provided specific information about each event. During the period of the study, 337 sport injury reports were completed. A total of 237 (70.3% boys and 100 (29.7% girls reported having a sport injury. Age of campers sustaining a sport injury was 10-12 years old (60.8%. The frequency of sports injuries was highest during the first camp season. The leading causes of sports injuries in children’s were: falls, crushed by object, collision with other person and slips. Cut/scratch injuries were the most common diagnoses (38.9%. Football, basketball and volleyball were the most frequent sport activities for injuries. Reports based surveillance systems can be successfully used to conducts sport injury surveillance among children attending summer camps. Data collected via such systems can be used to calculate sports injury rates, to describe patterns of sport injury and to identify risk factors for camper – related sport injuries. The results provide necessary information to develop prevention interventions to decrease the number of youth whose camp experiences are negatively affected by sport injury.

  13. Interleukin-1 beta-induced nitric oxide production from isolated rat islets is modulated by D-glucose and 3-isobutyl-1-methyl xanthine

    DEFF Research Database (Denmark)

    Andersen, H U; Mauricio, D; Karlsen, Allan Ertman

    1996-01-01

    Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D-glucose-mediated modula......Interleukin-1 beta has been proposed to cause selective beta-cell destruction via the induction of nitric oxide synthesis. The cytotoxic effect of interleukin-1 beta is modulated by the concentration of D-glucose in the medium. The aim of this study was to investigate if D...... effects on acute insulin release was found at high (28 mmol/l) concentrations of D-glucose, and blocking nitrite production by the L-arginine analog aminoguanidine, which selectively inhibits the cytokine-inducible nitric oxide synthase, did not result in protection against the inhibitory action...... that could be reproduced by the cAMP analog dibutyryl cAMP. Addition of 3-isobutyl-1-methyl xanthine resulted in a threefold reduction in the mRNA level of interleukin-1 beta-induced inducible nitric oxide synthase. We conclude that interleukin-1 beta-induced islet nitric oxide synthesis is augmented by D...

  14. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity.

    Science.gov (United States)

    Tabbì, Giovanni; Magrì, Antonio; Giuffrida, Alessandro; Lanza, Valeria; Pappalardo, Giuseppe; Naletova, Irina; Nicoletti, Vincenzo Giuseppe; Attanasio, Francesco; Rizzarelli, Enrico

    2015-01-01

    Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity was observed in the presence of Semax by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a SHSY5Y neuroblastoma and RBE4 endothelial cell lines.

  15. Prostaglandin Analogous and Antioxidant Activity Mediated Gastroprotective Action of Tabernaemontana divaricata (L. R. Br. Flower Methanolic Extract against Chemically Induced Gastric Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Mohammed Safwan Ali Khan

    2013-01-01

    Full Text Available The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L. R. Br. flowers. T. divaricata flower methanolic extract (TDFME was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses—125, 250, and 500 mg/kg—orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization—high resolution mass spectral (ESI-HRMS analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.

  16. Transcriptome changes and cAMP oscillations in an archaeal cell cycle

    Directory of Open Access Journals (Sweden)

    Soppa Jörg

    2007-06-01

    Full Text Available Abstract Background The cell cycle of all organisms includes mass increase by a factor of two, replication of the genetic material, segregation of the genome to different parts of the cell, and cell division into two daughter cells. It is tightly regulated and typically includes cell cycle-specific oscillations of the levels of transcripts, proteins, protein modifications, and signaling molecules. Until now cell cycle-specific transcriptome changes have been described for four eukaryotic species ranging from yeast to human, but only for two prokaryotic species. Similarly, oscillations of small signaling molecules have been identified in very few eukaryotic species, but not in any prokaryote. Results A synchronization procedure for the archaeon Halobacterium salinarum was optimized, so that nearly 100% of all cells divide in a time interval that is 1/4th of the generation time of exponentially growing cells. The method was used to characterize cell cycle-dependent transcriptome changes using a genome-wide DNA microarray. The transcript levels of 87 genes were found to be cell cycle-regulated, corresponding to 3% of all genes. They could be clustered into seven groups with different transcript level profiles. Cluster-specific sequence motifs were detected around the start of the genes that are predicted to be involved in cell cycle-specific transcriptional regulation. Notably, many cell cycle genes that have oscillating transcript levels in eukaryotes are not regulated on the transcriptional level in H. salinarum. Synchronized cultures were also used to identify putative small signaling molecules. H. salinarum was found to contain a basal cAMP concentration of 200 μM, considerably higher than that of yeast. The cAMP concentration is shortly induced directly prior to and after cell division, and thus cAMP probably is an important signal for cell cycle progression. Conclusion The analysis of cell cycle-specific transcriptome changes of H. salinarum

  17. Imaging alterations of cardiomyocyte cAMP microdomains in disease

    Directory of Open Access Journals (Sweden)

    Alexander eFroese

    2015-08-01

    Full Text Available 3’,5’-cyclic adenosine monophosphate (cAMP is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed.

  18. Vorticity in analog gravity

    Science.gov (United States)

    Cropp, Bethan; Liberati, Stefano; Turcati, Rodrigo

    2016-06-01

    In the analog gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in curved space-time. This description is possible only when the fluid under consideration is barotropic, inviscid, and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric that depends algebrically on the local speed of sound, density, and the background flow velocity, the latter assumed to be vorticity-free. In this work we provide a straightforward extension in order to go beyond the irrotational constraint. Using a charged—relativistic and nonrelativistic—Bose-Einstein condensate as a physical system, we show that in the low-momentum limit and performing the eikonal approximation we can derive a d’Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on flow velocity in the presence of vorticity.

  19. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  20. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi

    2011-03-01

    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  1. Understanding a Spiritual Youth Camp as a Consciousness Raising Group: The Effects of a Subculture's Communication.

    Science.gov (United States)

    Schnell, Jim

    This paper defines a spiritual youth camp as a consciousness raising group. The camp, founded in 1956 as a community church camp, has been independent of any religious denomination since disassociating from the founding community church in 1986. Communication processes are described as they relate to primary aspects of the camp experience. Primary…

  2. Tying the Design of Your Camp Staff Training to the Delivery of Desired Youth Outcomes

    Science.gov (United States)

    Galloway, Robin; Bourdeau, Virginia; Arnold, Mary; Nott, Brooke D.

    2013-01-01

    As experience camp directors, we've seen the challenges faced by young camp counselors and inexperienced staff. Evaluations from staff at many camps motivated us to help our people be more effective with their campers. In response we created a comprehensive camp staff training. Lessons showed staff what we wanted them to do and say as they…

  3. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  4. Diatom acclimation to elevated CO2 via cAMP signalling and coordinated gene expression

    Science.gov (United States)

    Hennon, Gwenn M. M.; Ashworth, Justin; Groussman, Ryan D.; Berthiaume, Chris; Morales, Rhonda L.; Baliga, Nitin S.; Orellana, Mónica V.; Armbrust, E. V.

    2015-08-01

    Diatoms are responsible for ~40% of marine primary productivity, fuelling the oceanic carbon cycle and contributing to natural carbon sequestration in the deep ocean. Diatoms rely on energetically expensive carbon concentrating mechanisms (CCMs) to fix carbon efficiently at modern levels of CO2 (refs , , ). How diatoms may respond over the short and long term to rising atmospheric CO2 remains an open question. Here we use nitrate-limited chemostats to show that the model diatom Thalassiosira pseudonana rapidly responds to increasing CO2 by differentially expressing gene clusters that regulate transcription and chromosome folding, and subsequently reduces transcription of photosynthesis and respiration gene clusters under steady-state elevated CO2. These results suggest that exposure to elevated CO2 first causes a shift in regulation, and then a metabolic rearrangement. Genes in one CO2-responsive cluster included CCM and photorespiration genes that share a putative cAMP-responsive cis-regulatory sequence, implying these genes are co-regulated in response to CO2, with cAMP as an intermediate messenger. We verified cAMP-induced downregulation of CCM gene δ-CA3 in nutrient-replete diatom cultures by inhibiting the hydrolysis of cAMP. These results indicate an important role for cAMP in downregulating CCM and photorespiration genes under elevated CO2 and provide insights into mechanisms of diatom acclimation in response to climate change.

  5. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ionta, M. [Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas MG (Brazil); Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-05-25

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  6. H2S induces vasoconstriction of rat cerebral arteries via cAMP/adenylyl cyclase pathway.

    Science.gov (United States)

    Li, Sen; Ping, Na-Na; Cao, Lei; Mi, Yan-Ni; Cao, Yong-Xiao

    2015-12-15

    Hydrogen sulfide (H2S), traditionally known for its toxic effects, is now involved in regulating vascular tone. Here we investigated the vasoconstrictive effect of H2S on cerebral artery and the underlying mechanism. Sodium hydrosulfide (NaHS), a donor of H2S, concentration-dependently induced vasoconstriction on basilar artery, which was enhanced in the presence of isoprenaline, a β-adrenoceptor agonist or forskolin, an adenylyl cyclase activator. Administration of NaHS attenuated the vasorelaxant effects of isoprenaline or forskolin. Meanwhile, the NaHS-induced vasoconstriction was diminished in the presence of 8B-cAMP, an analog of cAMP, but was not affected by Bay K-8644, a selective L-type Ca(2+) channel agonist. These results could be explained by the revised effects of NaHS on isoprenaline-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. Additionally, NaHS-induced vasoconstriction was enhanced by removing the endothelium or in the presence of L-NAME, an inhibitor of nitric oxide synthase. L-NAME only partially attenuated the effect of NaHS which was given together with forskolin on the pre-contracted artery. In conclusion, H2S induces vasoconstriction of cerebral artery via, at least in part, cAMP/adenylyl cyclase pathway.

  7. [Analogies and analogy research in technical biology and bionics].

    Science.gov (United States)

    Nachtigall, Werner

    2010-01-01

    The procedural approaches of Technical Biology and Bionics are characterized, and analogy research is identified as their common basis. The actual creative aspect in bionical research lies in recognizing and exploiting technically oriented analogies underlying a specific biological prototype to indicate a specific technical application.

  8. New York Operation: Military Kids Afterschool Universe Cosmic Camps

    Science.gov (United States)

    Schaff, N.

    2010-08-01

    The Cornell Center for Radiophysics and Space Research education and public outreach program and the New York State Operation: Military Kids program partnered to plan four weekend "Cosmic Camps" for youth from military families using the NASA Afterschool Universe program.

  9. Nationalsozialistische Konzentrations- und Vernichtungslager National Socialist Concentration and Extermination Camps

    Directory of Open Access Journals (Sweden)

    Max Plassmann

    2000-11-01

    Full Text Available Das Buch stellt Organisationsformen, Zuständigkeiten und Politik hinter dem nationalsozialistischen Konzentrationslagersystem dar.This book presents organization, competences and policies underlying the system of National Socialist concentration camps.

  10. Building a Successful Middle School Outreach Effort: Microscopy Camp

    Science.gov (United States)

    Penn, Lee R.; Flynn, Leslie; Johnson, Page

    2007-01-01

    Microscopy Camp program is designed to introduce acceptable representations of crystalline particles and their atomic structure to twelve-year-old middle school students at a developmental and educational stage.

  11. 14 CFR 91.1413 - CAMP: Responsibility for airworthiness.

    Science.gov (United States)

    2010-01-01

    ..., including airframes, aircraft engines, propellers, rotors, appliances, and parts. (2) Maintaining its..., including airframes, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under... Ownership Operations Program Management § 91.1413 CAMP: Responsibility for airworthiness. (a) For...

  12. A summer day camp approach to adolescent weight loss.

    Science.gov (United States)

    Southam, M A; Kirkley, B G; Murchison, A; Berkowitz, R I

    1984-01-01

    Twenty-five overweight adolescents completed a summer weight loss day camp program on the Stanford University campus. All participants attended camp four days per week for four hours to learn and practice eating and exercise skills conducive to weight loss. Parents met weekly to discuss the program content and to explore their role in their adolescent's weight management. At posttreatment, reductions were achieved in weight, percent overweight, and skinfold, with greater changes observed for the eight-week group than for the four-week group. Improvements were also evident in participants' self-reported habits and knowledge of weight management concepts. Parent and participant assessment of the camp experience was very positive. The results of the summer weight loss day camp suggest that an intensive program of eating and exercise habit instruction, practice, and monitoring, which allows the participants to remain in the home setting, may provide benefits not found in other more traditional approaches to adolescent weight loss.

  13. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN

    2015-10-01

    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  14. 14 CFR 91.1423 - CAMP: Maintenance organization.

    Science.gov (United States)

    2010-01-01

    ... Operations Program Management § 91.1423 CAMP: Maintenance organization. (a) Each program manager who... maintenance, or alterations, must organize the performance of those functions so as to separate the...

  15. The Physics of Quidditch Summer Camp: An Interdisciplinary Approach

    Science.gov (United States)

    Hammer, Donna; Uher, Tim

    The University of Maryland Physics Department has developed an innovative summer camp program that takes an interdisciplinary approach to engaging and teaching physics. The Physics of Quidditch Camp uniquely sits at the intersection of physics, sports, and literature, utilizing the real-life sport of quidditch adapted from the Harry Potter novels to stimulate critical thinking about real laws of physics and leaps of imagination, while actively engaging students in learning the sport and discussing the literature. Throughout the camp, middle school participants become immersed in fun physics experiments and exciting physical activities, which aim to build and enhance skills in problem-solving, analytical thinking, and teamwork. This camp has pioneered new ways of teaching physics to pre-college students, successfully engaged middle school students in learning physics, and grown a large demand for such activities.

  16. Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

    Science.gov (United States)

    Devasena, T; Rajasekaran, K N; Gunasekaran, G; Viswanathan, P; Menon, Venugopal P

    2003-02-01

    1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ

  17. Science and technology camp for girls. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    This document reports on the success of Pacific University`s camp held during the summers of 1992 and 1993; ultimate goal of this summer day camp was to increase the number of women in technical and scientific fields. Some experimentation was done with the age groups (7th and 8th grade girls). The curriculum was biology, chemistry, physics, and mathematics/computer science. Laboratory work and field trips were emphasized, along with socialization.

  18. The Effect of a Nature Camp on Children’s Conceptions of Nature

    OpenAIRE

    Esra Yardimci; Gulsen Leblebicioglu

    2012-01-01

    In this study, a nature camp which provides authentic learning opportunities for children was conducted. Twenty-four 4th and 5th graders (9 girls, 15 boys) participated to the camp. The camp program started with observations in the forest nearby. More focused observations were also made. Children discussed their observations with their friends and scientists. A questionnaire was applied at the beginning and end of the camp. The results showed that the nature camp program was effective in exte...

  19. Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

    Directory of Open Access Journals (Sweden)

    Shihui Wang

    Full Text Available The molecular interactions between pancreatic lipase (PL and four tea polyphenols (EGCG analogs, like (--epigallocatechin gallate (EGCG, (--gallocatechin gallate (GCG, (--epicatechin gallate (ECG, and (--epigallocatechin (EC, were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.

  20. Novel Analog For Muscle Deconditioning

    Science.gov (United States)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd. Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Ploutz-Snyder, Robert; Bloomberg, Jacob

    2011-01-01

    Existing models (such as bed rest) of muscle deconditioning are cumbersome and expensive. We propose a new model utilizing a weighted suit to manipulate strength, power, or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre-and postflightastronaut performance data for the same tasks. Splineregression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/BW of 79 J/kg, isokineticknee extension (KE)/BW of 6 Nm/kg, and KE torque/BW of 1.9 Nm/kg.Conclusions: Laboratory manipulation of relative strength has promise as an appropriate analog for spaceflight-induced loss of muscle function, for predicting occupational task performance and establishing operationally relevant strength thresholds.

  1. Multiple facets of cAMP signalling and physiological impact : cAMP compartmentalization in the lung

    NARCIS (Netherlands)

    Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

    2012-01-01

    Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelli

  2. Conjecturing via Reconceived Classical Analogy

    Science.gov (United States)

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  3. Musik som analogi og metafor

    DEFF Research Database (Denmark)

    2014-01-01

    Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser......Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser...

  4. Natural analog studies: Licensing perspective

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, J.W. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    This report describes the licensing perspective of the term {open_quotes}natural analog studies{close_quotes} as used in CFR Part 60. It describes the misunderstandings related to its definition which has become evident during discussions at the U.S Nuclear Regulatory Commission meetings and tries to clarify the appropriate applications of natural analog studies to aspects of repository site characterization.

  5. Inhibition of a plant virus infection by analogs of melittin.

    Science.gov (United States)

    Marcos, J F; Beachy, R N; Houghten, R A; Blondelle, S E; Pérez-Payá, E

    1995-01-01

    An approach that enables identification of specific synthetic peptide inhibitors of plant viral infection is reported. Synthetic analogs of melittin that have sequence and structural similarities to an essential domain of tobacco mosaic virus coat protein were found to possess highly specific antiviral activity. This approach involves modification of residues located at positions analogous to those that are critical for virus assembly. The degree of inhibition found correlates well with sequence similarities between the viral capsid protein and the melittin analogs studied as well as with the induced conformational changes that result upon interaction of the peptides and ribonucleic acid. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8618922

  6. Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes.

    Science.gov (United States)

    Plée-Gautier, E; Grober, J; Duplus, E; Langin, D; Forest, C

    1996-09-15

    Hormone-sensitive lipase (HSL) catalyses the rate-limiting step in adipocyte lipolysis. Short-term hormonal regulation of HSL activity is well characterized, whereas little is known about the control of HSL gene expression. We have measured HSL mRNA content of 3T3-F442A and BFC-1 adipocytes in response to the cAMP analogue 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP) and to the phorbol ester phorbol 12-myristate 13-acetate (PMA) by Northern blot, using a specific mouse cDNA fragment. Treatment of the cells for 12 or 6 h with, respectively, 0.5 mM 8-CPT-cAMP or 1 microM PMA produced a maximal decrease of about 60% in HSL mRNA. These effects were unaffected by the protein-synthesis inhibitor anisomycin, suggesting that cAMP and PMA actions were direct. The reduction in HSL mRNA was accompanied by a reduction in HSL total activity. The intracellular routes that cAMP and PMA follow for inducing such an effect seemed clearly independent. (i) After desensitization of the protein kinase C regulation pathway by a 24 h treatment of the cells with 1 microM PMA, PMA action was abolished whereas cAMP was still fully active. (ii) Treatment with saturating concentrations of both agents produced an additive effect. (iii) The synthetic glucocorticoid dexamethasone had no proper effect on HSL gene expression but potentiated cAMP action without affecting PMA action. cAMP inhibitory action on HSL is unexpected. Indeed, the second messenger of catecholamines is the main activator of HSL by phosphorylation. We envision that a long-term cAMP treatment of adipocytes induces a counter-regulatory process that reduces HSL content and, ultimately, limits fatty acid depletion from stored triacylglycerols.

  7. Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells.

    Science.gov (United States)

    Damdindorj, Boldbaatar; Dezaki, Katsuya; Kurashina, Tomoyuki; Sone, Hideyuki; Rita, Rauza; Kakei, Masafumi; Yada, Toshihiko

    2012-07-30

    We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca(2+)](i) increases in single β-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca(2+)](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca(2+)](i) and insulin release in islet β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.

  8. Revisiting cAMP signaling in the carotid body

    Directory of Open Access Journals (Sweden)

    Ana Rita eNunes

    2014-10-01

    Full Text Available Chronic carotid body (CB activation is now recognized as being essential in the development of hypertension and promoting insulin resistance; thus, it is imperative to characterize the chemotransduction mechanisms of this organ in order to modulate its activity and improve patient outcomes. For several years, and although controversial, cyclic adenosine monophosphate (cAMP was considered an important player in initiating the activation of the CB. However, its relevance was partially displaced in the 90s by the emerging role of the mitochondria and molecules such as AMP-activated protein kinase (AMPK and O2-sensitive K+ channels. Neurotransmitters/neuromodulators binding to metabotropic receptors are essential to chemotransmission in the CB, and cAMP is central to this process. cAMP also contributes to raise intracellular Ca2+ levels, and is intimately related to the cellular energetic status (AMP/ATP ratio. Furthermore, cAMP signaling is a target of multiple current pharmacological agents used in clinical practice. This review provides an outline on 1 the classical view of the cAMP-signaling pathway in the CB that originally supported its role in the O2/CO2 sensing mechanism, 2 present recent evidence on CB cAMP neuromodulation and 3 discuss how CB activity is affected by current clinical therapies that modify cAMP-signaling, namely dopaminergic drugs, caffeine (modulation of A2A/A2B receptors and roflumilast (PDE4 inhibitors. cAMP is key to any process that involves metabotropic receptors and the intracellular pathways involved in CB disease states are likely to involve this classical second messenger. Research examining the potential modification of cAMP levels and/or interactions with molecules associated with CB hyperactivity is currently in its beginning and this review will open doors for future explorations.

  9. Emergency Medicine Residency Boot Camp Curriculum: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Ataya, Ramsey

    2015-03-01

    Full Text Available Introduction: Establishing a boot camp curriculum is pertinent for emergency medicine (EM residents in order to develop proficiency in a large scope of procedures and leadership skills.  In this article, we describe our program’s EM boot camp curriculum as well as measure the confidence levels of resident physicians through a pre- and post-boot camp survey. Methods: We designed a one-month boot camp curriculum with the intention of improving the confidence, procedural performance, leadership, communication and resource management of EM interns. Our curriculum consisted of 12 hours of initial training and culminated in a two-day boot camp. The initial day consisted of clinical skill training and the second day included code drill scenarios followed by interprofessional debriefing.   Results: Twelve EM interns entered residency with an overall confidence score of 3.2 (1-5 scale across all surveyed skills. Interns reported the highest pre-survey confidence scores in suturing (4.3 and genitourinary exams (3.9. The lowest pre-survey confidence score was in thoracostomy (2.4. Following the capstone experience, overall confidence scores increased to 4.0. Confidence increased the most in defibrillation and thoracostomy. Additionally, all interns reported post-survey confidence scores of at least 3.0 in all skills, representing an internal anchor of “moderately confident/need guidance at times to perform procedure.” Conclusion: At the completion of the boot camp curriculum, EM interns had improvement in self-reported confidence across all surveyed skills and procedures. The described EM boot camp curriculum was effective, feasible and provided a foundation to our trainees during their first month of residency. [West J Emerg Med. 2015;16(2:356–361.

  10. Distributed Episodic and Analogical Reasoning (DEAR)

    Science.gov (United States)

    2010-04-01

    ends analysis Carbonell 1983 Modeling of Analogy Making Structure Mapping Theory (SMT) Gentner 1984 Agent based approach to analogy making...Mapping Engine (SME) Forbus 1990 Learning by analogy with larger domains Prodigy/Analogy Veloso and Carbonell 1991 Analogical Retrieval Engine MAC/FAC

  11. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  12. Students' Perceptions of the Long-Term Impact of Attending a "CSI Science Camp"

    Science.gov (United States)

    Yanowitz, Karen L.

    2016-07-01

    A science summer camp is a popular type of informal science experience for youth. While there is no one model of a science camp, these experiences typically allow for more focused and in-depth exploration of different science domains and are usually hands-on and participatory. The goal of this research was to examine the impact of a short science camp program approximately 1 year after students attended the camp. Overall, the results revealed that attending a 2-day forensic science camp had a positive and continuing influence on the participants. Students' science self-efficacy increased immediately after attending the camp and remained higher than pre-camp levels approximately 1 year later. Students were able to articulate why they believed the camp had a long-term impact on their lives. Furthermore, participants attributed a higher level of engaging in additional informal STEM-related activities during the academic year as a result of attending the camp.

  13. Students' Perceptions of the Long-Term Impact of Attending a "CSI Science Camp"

    Science.gov (United States)

    Yanowitz, Karen L.

    2016-12-01

    A science summer camp is a popular type of informal science experience for youth. While there is no one model of a science camp, these experiences typically allow for more focused and in-depth exploration of different science domains and are usually hands-on and participatory. The goal of this research was to examine the impact of a short science camp program approximately 1 year after students attended the camp. Overall, the results revealed that attending a 2-day forensic science camp had a positive and continuing influence on the participants. Students' science self-efficacy increased immediately after attending the camp and remained higher than pre-camp levels approximately 1 year later. Students were able to articulate why they believed the camp had a long-term impact on their lives. Furthermore, participants attributed a higher level of engaging in additional informal STEM-related activities during the academic year as a result of attending the camp.

  14. Pleiotropic effects of cAMP on germination, antibiotic biosynthesis and morphological development in Streptomyces coelicolor.

    Science.gov (United States)

    Süsstrunk, U; Pidoux, J; Taubert, S; Ullmann, A; Thompson, C J

    1998-10-01

    In wild-type Streptomyces coelicolor MT1110 cultures, cyclic adenosine 3',5' monophosphate (cAMP) was synthesized throughout the developmental programme with peaks of accumulation both during germination and later when aerial mycelium and actinorhodin were being produced. Construction and characterization of an adenylate cyclase disruption mutant (BZ1) demonstrated that cAMP facilitated these developmental processes. Although pulse-labelling experiments showed that a similar germination process was initiated in BZ1 and MT1110, germ-tube emergence was severely delayed in BZ1 and never occurred in more than 85% of the spores. Studies of growth and development on solid glucose minimal medium (SMMS, buffered or unbuffered) showed that MT1110 and BZ1 produced acid during the first rapid growth phase, which generated substrate mycelium. Thereafter, on unbuffered SMMS, only MT1110 resumed growth and produced aerial mycelium by switching to an alternative metabolism that neutralized its medium, probably by reincorporating and metabolizing extracellular acids. BZ1 was not able to neutralize its medium or produce aerial mycelium on unbuffered SMMS; these defects were suppressed by high concentrations (>1 mM) of cAMP during early growth or on buffered medium. Other developmental mutants (bldA, bldB, bldC, bldD, bldG) also irreversibly acidified this medium. However, these bald mutants were not suppressed by exogenous cAMP or neutralizing buffer. BZ1 also differentiated when it was cultured in close proximity to MT1110, a property observed in cross-feeding experiments between bald mutants and commonly thought to reflect diffusion of a discrete positively acting signalling molecule. In this case, MT1110 generated a more neutral pH environment that allowed BZ1 to reinitiate growth and form aerial mycelium. The fact that actinorhodin synthesis could be induced by concentrations of cAMP (< 20 microM) found in the medium of MT1110 cultures, suggested that it may serve as a

  15. Modulation of phenotype and function of human CD4+CD25+ T regulatory lymphocytes mediated by cAMP elevating agents

    Directory of Open Access Journals (Sweden)

    Antonella Riccomi

    2016-09-01

    Full Text Available We have shown that Cholera Toxin (CT and other cyclic AMP (cAMP elevating agents induce up-regulation of the inhibitory molecule CTLA-4 in human resting CD4+ T lymphocytes, which following the treatment acquired suppressive functions. In this study, we evaluated the effect of cAMP elevating agents on human CD4+CD25+ T cells, which include the T regulatory (Treg cells that play a pivotal role in the maintenance of immunological tolerance. We found that cAMP elevating agents induce up-regulation of CTLA-4 in CD4+CD25- and further enhance its expression in CD4+CD25+ T cells. We observed an increase of two isoforms of mRNA coding for the membrane and the soluble CTLA-4 molecules, suggesting that the regulation of CTLA-4 expression by cAMP is at the transcriptional level. In addition, we found that the increase of cAMP in CD4+CD25+ T cells converts the CD4+CD25+Foxp3- T cells in CD4+CD25+Foxp3+ T cells, whereas the increase of cAMP in CD4+CD25- T cells did not up-regulate Foxp3 in the absence of activation stimuli. To investigate the function of these cells, we performed an in vitro suppression assay by culturing CD4+CD25+ T cells untreated or pre-treated with CT with anti-CD3 mAbs-stimulated autologous PBMC. We found that CT enhances the inhibitory function of CD4+CD25+ T cells, CD4+ and CD8+ T cell proliferation and IFNγ production are strongly inhibited by CD4+CD25+ T cells pre-treated with cAMP elevating agents. Furthermore, we found that CD4+CD25+ T lymphocytes pre-treated with cAMP elevating agents induce the up-regulation of CD80 and CD86 co-stimulatory molecules on immature dendritic cells (DCs in the absence of antigenic stimulation, however without leading to full DC maturation. These data show that the increase of intracellular cAMP modulates the phenotype and function of human CD4+CD25+ T cells.

  16. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  17. Sulfonimidamide analogs of oncolytic sulfonylureas.

    Science.gov (United States)

    Toth, J E; Grindey, G B; Ehlhardt, W J; Ray, J E; Boder, G B; Bewley, J R; Klingerman, K K; Gates, S B; Rinzel, S M; Schultz, R M; Weir, L C; Worzalla, J F

    1997-03-14

    A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.

  18. Advances in Pediatric Cardiology Boot Camp: Boot Camp Training Promotes Fellowship Readiness and Enables Retention of Knowledge.

    Science.gov (United States)

    Ceresnak, Scott R; Axelrod, David M; Sacks, Loren D; Motonaga, Kara S; Johnson, Emily R; Krawczeski, Catherine D

    2017-03-01

    We previously demonstrated that a pediatric cardiology boot camp can improve knowledge acquisition and decrease anxiety for trainees. We sought to determine if boot camp participants entered fellowship with a knowledge advantage over fellows who did not attend and if there was moderate-term retention of that knowledge. A 2-day training program was provided for incoming pediatric cardiology fellows from eight fellowship programs in April 2016. Hands-on, immersive experiences and simulations were provided in all major areas of pediatric cardiology. Knowledge-based examinations were completed by each participant prior to boot camp (PRE), immediately post-training (POST), and prior to the start of fellowship in June 2016 (F/U). A control group of fellows who did not attend boot camp also completed an examination prior to fellowship (CTRL). Comparisons of scores were made for individual participants and between participants and controls. A total of 16 participants and 16 control subjects were included. Baseline exam scores were similar between participants and controls (PRE 47 ± 11% vs. CTRL 52 ± 10%; p = 0.22). Participants' knowledge improved with boot camp training (PRE 47 ± 11% vs. POST 70 ± 8%; p < 0.001) and there was excellent moderate-term retention of the information taught at boot camp (PRE 47 ± 11% vs. F/U 71 ± 8%; p < 0.001). Testing done at the beginning of fellowship demonstrated significantly better scores in participants versus controls (F/U 71 ± 8% vs. CTRL 52 ± 10%; p < 0.001). Boot camp participants demonstrated a significant improvement in basic cardiology knowledge after the training program and had excellent moderate-term retention of that knowledge. Participants began fellowship with a larger fund of knowledge than those fellows who did not attend.

  19. Evaluating the Effectiveness of the General Surgery Intern Boot Camp.

    Science.gov (United States)

    Schoolfield, Clint S; Samra, Navdeep; Kim, Roger H; Shi, Runhua; Zhang, Wayne W; Tan, Tze-Woei

    2016-03-01

    The aim of our study is to evaluate the effectiveness of newly implemented general surgery intern boot camp. A 2-day didactic and skills-based intern boot camp was implemented before the start of clinical duties. Participants who did not attend all boot camp activities and had prior postgraduate training were excluded. A survey utilizing a 5-point Likert scale scoring system was used to assess the participants' confidence to perform intern-level tasks before and after the boot camp. Subgroup analyses were performed comparing changes in confidence among graduates from home institution versus others and general surgery versus other subspecialties. In the analysis, 21 participants over two years were included. Among them, 7 were graduates from home institution (4 general surgery, 3 subspecialty) and 14 were from other institutions (6 general surgery and 8 subspecialty). There were significant increases in overall confidence levels (pre = 2.79 vs post = 3.43, P surgery (2.78 vs 3.46, P = 0.001) and other specialties (2.74 vs 3.34, P surgery intern boot camp before the start of official rotation is effective in improving confidence level in performing level-appropriate tasks of the incoming new interns.

  20. Analog CMOS contrastive Hebbian networks

    Science.gov (United States)

    Schneider, Christian; Card, Howard

    1992-09-01

    CMOS VLSI circuits implementing an analog neural network with on-chip contrastive Hebbian learning and capacitive synaptic weight storage have been designed and fabricated. Weights are refreshed by periodic repetition of the training data. To evaluate circuit performance in a medium-sized system, these circuits were used to build a 132 synapse neural network. An adaptive neural system, such as the one described in this paper, can compensate for imperfections in the components from which it is constructed, and thus it is possible to build this type of system using simple, silicon area-efficient analog circuits. Because these analog VLSI circuits are far more compact than their digital counterparts, analog VLSI neural network implementations are potentially more efficient than digital ones.

  1. Solving a problem by analogy

    Science.gov (United States)

    Easton, Don

    1999-03-01

    This note is a description of a student solution to a problem. I found the solution exciting because it exemplifies the kind of solution by analogy that Feynman describes in The Feynman Lectures on Physics.

  2. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  3. Analog electronic neural network circuits

    Energy Technology Data Exchange (ETDEWEB)

    Graf, H.P.; Jackel, L.D. (AT and T Bell Labs., Holmdel, NJ (USA))

    1989-07-01

    The large interconnectivity and moderate precision required in neural network models present new opportunities for analog computing. This paper discusses analog circuits for a variety of problems such as pattern matching, optimization, and learning. Most of the circuits build so far are relatively small, exploratory designs. The most mature circuits are those for template matching. Chips performing this function are now being applied to pattern recognition problems.

  4. PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression.

    Science.gov (United States)

    Desch, Michael; Schubert, Thomas; Schreiber, Andrea; Mayer, Sandra; Friedrich, Björn; Artunc, Ferruh; Todorov, Vladimir T

    2010-11-01

    The second messenger cAMP plays an important role in the regulation of renin gene expression. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is known to stimulate renin gene transcription acting through PPARγ-binding sequences in renin promoter. We show now that activation of PPARγ by unsaturated fatty acids or thiazolidinediones drastically augments the cAMP-dependent increase of renin mRNA in the human renin-producing cell line Calu-6. The underlying mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3). AC6Pal3 bound PPARγ and mediated trans-activation by PPARγ agonist. AC6 knockdown decreased basal renin mRNA level and attenuated the maximal PPARγ-dependent stimulation of the cAMP-induced renin gene expression. AC6Pal3 decoy oligonucleotide abrogated the PPARγ-dependent potentiation of cAMP-induced renin gene expression. Treatment of mice with PPARγ agonist increased AC6 mRNA kidney levels. Our data suggest that in addition to its direct effect on renin gene transcription, PPARγ "sensitizes" renin gene to cAMP via trans-activation of AC6 gene. AC6 has been identified as PPARγ target gene with a functional Pal3 sequence.

  5. Stress and glucocorticoids impair memory retrieval via β2-adrenergic, Gi/o-coupled suppression of cAMP signaling.

    Science.gov (United States)

    Schutsky, Keith; Ouyang, Ming; Castelino, Christina B; Zhang, Lei; Thomas, Steven A

    2011-10-05

    Acute stress impairs the retrieval of hippocampus-dependent memory, and this effect is mimicked by exogenous administration of stress-responsive glucocorticoid hormones. It has been proposed that glucocorticoids affect memory by promoting the release and/or blocking the reuptake of norepinephrine (NE), a stress-responsive neurotransmitter. It has also been proposed that this enhanced NE signaling impairs memory retrieval by stimulating β(1)-adrenergic receptors and elevating levels of cAMP. In contrast, other evidence indicates that NE, β(1), and cAMP signaling is transiently required for the retrieval of hippocampus-dependent memory. To resolve this discrepancy, wild-type rats and mice with and without gene-targeted mutations were stressed or treated with glucocorticoids and/or adrenergic receptor drugs before testing memory for inhibitory avoidance or fear conditioning. Here we report that glucocorticoids do not require NE to impair retrieval. However, stress- and glucocorticoid-induced impairments of retrieval depend on the activation of β(2) (but not β(1))-adrenergic receptors. Offering an explanation for the opposing functions of these two receptors, the impairing effects of stress, glucocorticoids and β(2) agonists on retrieval are blocked by pertussis toxin, which inactivates signaling by G(i/o)-coupled receptors. In hippocampal slices, β(2) signaling decreases cAMP levels and greatly reduces the increase in cAMP mediated by β(1) signaling. Finally, augmenting cAMP signaling in the hippocampus prevents the impairment of retrieval by systemic β(2) agonists or glucocorticoids. These results demonstrate that the β(2) receptor can be a critical effector of acute stress, and that β(1) and β(2) receptors can have quite distinct roles in CNS signaling and cognition.

  6. Intracellular cAMP signaling by soluble adenylyl cyclase.

    Science.gov (United States)

    Tresguerres, Martin; Levin, Lonny R; Buck, Jochen

    2011-06-01

    Soluble adenylyl cyclase (sAC) is a recently identified source of the ubiquitous second messenger cyclic adenosine 3',5' monophosphate (cAMP). sAC is distinct from the more widely studied source of cAMP, the transmembrane adenylyl cyclases (tmACs); its activity is uniquely regulated by bicarbonate anions, and it is distributed throughout the cytoplasm and in cellular organelles. Due to its unique localization and regulation, sAC has various functions in a variety of physiological systems that are distinct from tmACs. In this review, we detail the known functions of sAC, and we reassess commonly held views of cAMP signaling inside cells.

  7. Investigation of Sylvatic Typhus at a Wilderness Camp

    Centers for Disease Control (CDC) Podcasts

    2009-06-30

    In this podcast, Dr. Greg Dasch discusses an outbreak of four cases of sylvatic typhus that occurred at a wilderness camp in Pennsylvania. Sylvatic typhus is very rare in the United States, with only 41 cases since it was discovered in the United States in 1975. Lab work at CDC and the discovery that all four camp counselors who became ill had slept in the same bunk at the camp between 2004 and 2006 ultimately led to confirmation that flying squirrels living in the wall of the cabin were to blame for the illnesses.  Created: 6/30/2009 by Emerging Infectious Diseases.   Date Released: 6/30/2009.

  8. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

    Science.gov (United States)

    Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M

    2015-01-01

    Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.

  9. Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure

    DEFF Research Database (Denmark)

    Torp, M; Brønd, L; Hadrup, N;

    2007-01-01

    receptor type-1 (AT(1)) blockade with losartan. AIM: In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT(1) receptor blockade on this system. METHOD: CHF was induced by ligation of the left anterior descending coronary...

  10. Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation

    DEFF Research Database (Denmark)

    Karsdal, Morten Asser; Sumer, Eren Ufuk; Wulf, Helle

    2007-01-01

    was assessed by 1) quantification of C-terminal crosslinking telopeptide of type II collagen fragments (CTX-II), 2) matrix metalloproteinase (MMP)-mediated aggrecan degradation by (342)FFGV- G2 assay, 3) aggrecanase-mediated degradation by (374)ARGS-G2 assay, 4) release of sulfated glycosaminoglycans (s......-dependently inhibited by forskolin and IBMX. The highest concentration of IBMX lowered cytokine-induced release of sGAG by 72%. CONCLUSION: Levels of cAMP in chondrocytes play a key role in controlling catabolic activity. Increased cAMP levels in chondrocytes inhibited MMP expression and activity and consequently...

  11. Analog approach to mixed analog-digital circuit simulation

    Science.gov (United States)

    Ogrodzki, Jan

    2013-10-01

    Logic simulation of digital circuits is a well explored research area. Most up-to-date CAD tools for digital circuits simulation use an event driven, selective trace algorithm and Hardware Description Languages (HDL), e.g. the VHDL. This techniques enable simulation of mixed circuits, as well, where an analog part is connected to the digital one through D/A and A/D converters. The event-driven mixed simulation applies a unified, digital-circuits dedicated method to both digital and analog subsystems. In recent years HDL techniques have been also applied to mixed domains, as e.g. in the VHDL-AMS. This paper presents an approach dual to the event-driven one, where an analog part together with a digital one and with converters is treated as the analog subsystem and is simulated by means of circuit simulation techniques. In our problem an analog solver used yields some numerical problems caused by nonlinearities of digital elements. Efficient methods for overriding these difficulties have been proposed.

  12. Rebuilding Jewish identities in Displaced Persons Camps in Germany

    Directory of Open Access Journals (Sweden)

    Françoise Ouzan

    2007-10-01

    Full Text Available In the summer 1945, Displaced Persons camps in Germany epitomized a place of contrasts and paradoxes. DPs still languished behind barbed wires after the Allied armies had liberated the concentration camps. The military had assumed that practically all of the Displaced Persons would be sent to their countries of origin. In the spring and summer 1945, 65 000 DPs were sent back home every day and almost six million were repatriated in September 1945. Accurate statistics are impossible, yet, acco...

  13. Science Camp - lystigt eller lærerigt

    DEFF Research Database (Denmark)

    Ahrenkiel, Linda; Albrechtsen, Thomas S. R.

    2013-01-01

    I oplægget vil vi undersøge fænomenet Science Camps nærmere ved at fortælle om dets historiske udvikling og ikke mindst lægge op til en diskussion af en definition. Derudover vil vi præsentere en case, hvor der med udgangspunkt i et aktuelt ph.d.-projekt er blevet undersøgt, hvad deltagerne får ud...... af at deltage i en science camp: Kan man både vække begejstring og medvirke til læring?...

  14. "Camping up" self-esteem in children with hemophilia.

    Science.gov (United States)

    Thomas, D; Gaslin, T C

    2001-01-01

    Children with hemophilia have often been viewed at greater risk for altered self-esteem than their healthy counterparts. Our article shares the positive effects of the camp experience on children with hemophilia and subsequent enhancement of self-esteem. Interaction and support in the camp environment provide an opportunity for these children to gain independence and "prove" their self-worth and ability. Previous literature has provided a variety of findings on the relationship between chronic illness, such as hemophilia, and self-esteem alterations. We identify many opportunities for future education and research to provide quality nursing support to this unique population.

  15. EduCamp Colombia: Social Networked Learning for Teacher Training

    Directory of Open Access Journals (Sweden)

    Diego Ernesto Leal Fonseca

    2011-03-01

    Full Text Available This paper describes a learning experience called EduCamp, which was launched by the Ministry of Education of Colombia in 2007, based on emerging concepts such as e-Learning 2.0, connectivism, and personal learning environments. An EduCamp proposes an unstructured collective learning experience, which intends to make palpable the possibilities of social software tools in learning and interaction processes while demonstrating face-to-face organizational forms that reflect social networked learning ideas. The experience opens new perspectives for the design of technology training workshops and for the development of lifelong learning experiences.

  16. Science Skills Boot Camp Gets Interns Ready for Research | Poster

    Science.gov (United States)

    By Ashley DeVine, Staff Writer Summer interns learned how to read a scientific paper, present a poster, maintain a laboratory notebook, and much more, at the Science Skills Boot Camp in June. “It was a great experience, and it was a great opportunity to meet some of the other interns also working on the campus,” said Alyssa Klein, a Werner H. Kirsten student intern in the Cellular Immunology Group, Laboratory of Molecular Immunoregulation. “The boot camp covered many topics essential to being a good scientist and science researcher.”

  17. Camp as a Teaching Method in Health Education

    DEFF Research Database (Denmark)

    Ringby, Betina

    methodology and theories/methods put INTO action. The camp method encourages a student-participatory and an inter-professionally approach required to think out-of-the-box. Teachers were offered the possibility to be mentor/coach for students. ‘Effectuation’, the ‘PUSH model’ and the ‘Entrepreneurial...... education to support students in gaining innovative and entrepreneurial skills. Participants A total of 33 physiotherapist students each participated in one of three CAMPS of 48, 24 or 12 hours in an elective module named “Sport, innovation and entrepreneurship”. Methods The project was based on case...

  18. Promoting independence in adolescent paraplegics: a 2-week "camping" experience.

    Science.gov (United States)

    Bodzioch, J; Roach, J W; Schkade, J

    1986-01-01

    In the summer of 1982, Texas Scottish Rite Hospital (Dallas, TX, U.S.A.) sponsored a camp for paraplegic adolescents. Six patients, three boys and three girls 14-17 years of age, participated in a 2-week program that was designed to improve their self-esteem, independence, and eventual employability. In their pre- and postcamp psychological evaluations, the campers demonstrated improvement in social skills and self-concept testing as compared with the scores of a matched control group, although this improvement did not reach statistical significance. We believe the camp was immensely successful, an opinion that was shared by both the campers and their parents.

  19. Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells.

    Science.gov (United States)

    Salinthone, Sonemany; Schillace, Robynn V; Marracci, Gail H; Bourdette, Dennis N; Carr, Daniel W

    2008-08-13

    The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNgamma secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway.

  20. L-pGlu-(2-propyl)-L-His-L-ProNH₂ attenuates 4-aminopyridine-induced epileptiform activity and sodium current: a possible action of new thyrotropin-releasing hormone analog for its anticonvulsant potential.

    Science.gov (United States)

    Sah, N; Rajput, S K; Singh, J N; Meena, C L; Jain, R; Sikdar, S K; Sharma, S S

    2011-12-29

    L-PGlu-(2-propyl)-L-His-L-ProNH₂ (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg⁺²-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg⁺² (2.10±0.47 Hz) as compared with nACSF (0.12±0.08 Hz). A significant decrease in mean firing frequency (0.61±0.22 Hz), mean frequency of epileptiform events (0.03±0.02 Hz vs. 0.22±0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54±1.21 Hz vs. 8.16±0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246±19 mV ms⁻¹ vs. 297±18 mV ms⁻¹ of 4-AP+0 Mg) and increase (1.332±0.018 ms vs. 1.292±0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 μM) depressed sodium current (15±0.5%, 50±2.6%, and 75±0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly.

  1. Seafloor Science and Remotely Operated Vehicle (SSROV) Day Camp: A Week-Long, Hands-On STEM Summer Camp

    Science.gov (United States)

    Wheat, C. G.; Fournier, T.; Monahan, K.; Paul, C.

    2015-12-01

    RETINA (Robotic Exploration Technologies IN Astrobiology) has developed a program geared towards stimulating our youth with innovative and relevant hands-on learning modules under a STEM umbrella. Given the breadth of potential science and engineering topics that excite children, the RETINA Program focuses on interactive participation in the design and development of simple robotic and sensor systems, providing a range of challenges to engage students through project-based learning (PBL). Thus, young students experience scientific discovery through the use and understanding of technology. This groundwork serves as the foundation for SSROV Camp, a week-long, summer day camp for 6th-8th grade students. The camp is centered on the sensors and platforms that guide seafloor exploration and discovery and builds upon the notion that transformative discoveries in the deep sea result from either sampling new environments or making new measurements with sensors adapted to this extreme environment. These technical and scientific needs are folded into the curriculum. Each of the first four days of the camp includes four team-based, hands-on technical challenges, communication among peer groups, and competition. The fifth day includes additional activities, culminating in camper-led presentations to describe a planned mission based on a given geologic setting. Presentations include hypotheses, operational requirements and expected data products. SSROV Camp was initiated last summer for three sessions, two in Monterey, CA and one in Oxford, MS. Campers from both regions grasped key elements of the program, based on written responses to questions before and after the camp. On average, 32% of the pre-test questions were answered correctly compared with 80% of the post-test questions. Additional confirmation of gains in campers' knowledge, skills, and critical thinking on environmental issues and engineering problems were apparent during the "jeopardy" competition, nightly homework

  2. All-optical analog comparator

    Science.gov (United States)

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  3. The freshman camp report of Computer & Information Engineering(Educationai Development Symposiums)

    OpenAIRE

    粂野, 文洋; Fumihiro, Kumeno

    2016-01-01

    In 2015 and 2016, the freshman camp of Computer & Information Engineering was conducted at Kinugawa Park Hotels, Nikko National Park. We successfully carried out the both camps in almost the same program and schedule. Based on this experience, the basic outline of our camp and the process for preparation and execution has been definite. In this report, we explain the basic outline and what we have done in each phase of the camp: plan, preparation, execution and finalizing. We also analyze the...

  4. Streptococcus pyogenes streptolysin O as a cause of false-positive CAMP reactions.

    OpenAIRE

    Tapsall, J W; Phillips, E A

    1984-01-01

    The synergistic hemolysis of sheep erythrocytes in the CAMP reaction by the sequential action of staphylococcal beta-lysin and the CAMP factor of group B streptococci is the only known function of this extracellular product of group B streptococci. The reaction forms the basis of the CAMP test used to identify group B streptococci because the CAMP factor is believed to be restricted to this group of organisms. However, on occasion other streptococci, notably group A streptococci, may produce ...

  5. The gravitational analog of Faraday's induction law

    Science.gov (United States)

    Zile, Daniel; Overduin, James

    2015-04-01

    Michael Faraday, the discoverer of electromagnetic induction, was convinced that there must also be a gravitational analog of this law, and he carried out drop-tower experiments in 1849 to look for the electric current induced in a coil by changes in gravitational flux through the coil. This work, now little remembered, was in some ways the first investigation of what we would now call a unified-field theory. We revisit Faraday's experiments in the light of current knowledge and ask what might be learned if they were to be performed today. We then review the gravitational analog for Faraday's law that arises within the vector (or gravito-electromagnetic) approximation to Einstein's theory of general relativity in the weak-field, low-velocity limit. This law relates spinning masses and induced ``mass currents'' rather than spinning charges and electric currents, but is otherwise remarkably similar to its electromagnetic counterpart. The predicted effects are completely unobservable in everyday settings like those envisioned by Faraday, but are thought to be relevant in astrophysical contexts like the accretion disks around collapsed stars, thus bearing out Faraday's remarkable intuition. Undergraduate student.

  6. Test Wiseness and Analogy Test Performance

    Science.gov (United States)

    Moore, James C.

    1971-01-01

    Subjects received self instruction on how to approach analogy questions. Instruction was directed toward knowledge of the general format of analogy questions in standarized tests and the 15 types of relationships commonly asked for in analogy questions. An analogies post-test showed a significant effect for the group. (Author)

  7. Hack City Summer: Computer Camps Can Bring a Vacation of Keyboard Delights.

    Science.gov (United States)

    Shell, Ellen Ruppel

    1983-01-01

    Activities at a summer computer camp (Camp Atari held at East Stroudsburg State College PA) are described. The curriculum, using logic, systematic analysis, and other fundamental programing skills, teaches students to interact effectively and creatively with computers. Sources for finding a computer camp are included. (JN)

  8. Culture Camp, Ethnic Identity, and Adoption Socialization for Korean Adoptees: A Pretest and Posttest Study

    Science.gov (United States)

    Baden, Amanda L.

    2015-01-01

    This study explores the impact of racial-ethnic socialization on adopted South Korean children and adolescents who attended a sleepaway Korean culture camp for one week. This camp provided racial-ethnic socialization experiences via exposure to camp counselors, staff, and teachers who were Korean Americans, Korean nationals, and Korean adult…

  9. The accidental city : violence, economy and humanitarianism in Kakuma refugee camp Kenya

    NARCIS (Netherlands)

    Jansen, B.J.

    2011-01-01

    In this research I examine social ordering processes in Kakuma refugee camp in Kenya. I view the camp as an accidental city, by which I challenge the image of the camp as a temporary and artificial waiting space or a protracted refugee crisis per se. The reference to the city is both metaphorical

  10. A Multidisciplinary Science Summer Camp for Students with Emphasis on Environmental and Analytical Chemistry

    Science.gov (United States)

    Schwarz, Gunnar; Frenzel, Wolfgang; Richter, Wolfgang M.; Ta¨uscher, Lothar; Kubsch, Georg

    2016-01-01

    This paper presents the course of events of a five-day summer camp on environmental chemistry with high emphasis on chemical analysis. The annual camp was optional and open for students of all disciplines and levels. The duration of the summer camp was five and a half days in the Feldberg Lake District in northeast Germany (federal state of…

  11. 77 FR 56174 - Proposed Establishment of Class D and Class E Airspace; Camp Guernsey, WY

    Science.gov (United States)

    2012-09-12

    ... 14 CFR Part 71 Proposed Establishment of Class D and Class E Airspace; Camp Guernsey, WY AGENCY... action proposes to establish Class D airspace and Class E airspace at Camp Guernsey Airport, Camp... holidays. An informal docket may also be examined during normal business hours at the Northwest...

  12. Reflections on Refugee Students' Major Perceptions of Education in Kakuma Refugee Camp, Kenya

    Science.gov (United States)

    Mareng, Chuei D.

    2010-01-01

    This reflective study explores refugee students' perceptions of the educational approach used in Kakuma Refugee Camp in Kenya. The study focuses on my personal reflections as a teacher and a student in this camp, and as a refugee. My goal of writing this narrative is to reflect fully on the refugee students' life in a camp and then contribute to…

  13. History Matters: Children's Art Education inside the Japanese American Internment Camp

    Science.gov (United States)

    Wenger, Gina Mumma

    2012-01-01

    What did art education look like within the confines of the Japanese American Internment Camp classrooms? Did the art education in the camps reflect the same curriculum that was being taught outside the camps and what other factors may have played a part in the students' experience? I propose that there were at least three significant…

  14. What Do Children Most Enjoy about Summer Soccer Camp? Gender and Group Perceptions

    Science.gov (United States)

    Jones, Rhys

    2005-01-01

    One hundred children attending a summer soccer camp in NE Ohio provided written data on what they most enjoyed about the camp. Findings indicated that, overall, they ranked "soccer games and skills" and "camp related activities" as the two leading major categories. In terms of gender group analysis (females = 49; males = 51)…

  15. 78 FR 55671 - Hospital Care and Medical Services for Camp Lejeune Veterans

    Science.gov (United States)

    2013-09-11

    ... the residences and workplaces, in addition to other water systems on Camp Lejeune, have tested... substances while at Camp Lejeune. U.S. Marine Corps Base Camp Lejeune includes base housing, training sites..., 2015. We believe that 2 years would provide veterans sufficient time to learn about the new status...

  16. Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway

    DEFF Research Database (Denmark)

    Guo, Chunxiao; Rosoha, Elena; Lowry, Malcolm B;

    2013-01-01

    and PUFAs would induce expression of known VDR target genes in cells. In this study, we tested whether these compounds regulated two important VDR target genes - human cathelicidin antimicrobial peptide (CAMP) and 1,25-dihydroxyvitamin D(3) 24-hydroxylase (CYP24A1) - in human monocytic cell line U937, colon...... cancer cell line HT-29 and keratinocyte cell line HaCaT. We demonstrated that PUFAs failed to induce CAMP or CYP24A1 mRNA expression in all three cell lines, but curcumin up-regulated CAMP mRNA and protein levels in U937 cells. Curcumin treatment induced CAMP promoter activity from a luciferase reporter...

  17. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  18. Elevated cAMP increases aquaporin-3 plasma membrane diffusion

    DEFF Research Database (Denmark)

    Marlar, Saw; Christensen, Eva Arnspang; Koffman, Jennifer Skaarup

    2014-01-01

    .05)]. Immunoelectron microscopy showed no obvious difference in AQP3-EGFP expression levels or localization in the plasma membrane upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased cAMP, which may correspond to basolateral adaptations in response to the increased apical water readsorption...

  19. Phun Physics 4 Phemales: Physics Camp for High School Girls

    Science.gov (United States)

    Kwon, Chuhee; Gu, Jiyeong; Henriquez, Laura

    2014-03-01

    The department of Physics and Astronomy with the department of Science Education at California State University, Long Beach hosted summer program of ``Phun Physics 4 Phemales (PP4P)'' during summer 2012 and summer 2013 with the support from APS public outreach program. PP4P summer camp was hosted along with a two-week summer science camp, Young Scientists Camp, which has been institutionalized for the last 14 years since 1999. More than 2,500 3rd -8th grade students and 250 teachers have participated in the program. PP4P program provided the tools and support that female high school students need to pursue careers in physics and/or science, technology, engineering and math (STEM) field. This girls-only camp created connections among the girls and built confidence. In addition PP4P program introduced students to key principles in physics by a hands-on lab environment and demonstrated the real-world social impact of physics. In summer 2012, high school girls worked on physics experimental project on electronics and in summer 2013 they worked on the mechanics. I would share our experience in this program and the impact on the female high school students. This work was supported by 2012 Public Outreach and Informing the Public Grants from American Physical Society.

  20. Addressing Nature Deficit Disorder through Primitive Camping Experiences

    Science.gov (United States)

    Allen, Kevin; Varner, Keegan; Sallee, Jeff

    2011-01-01

    Today's youth suffer from Nature Deficit Disorder, a condition that has been connected to ADHD, shortage of creativity, and general lack of knowledge about the outdoors. A team of educators and specialists are addressing this issue with primitive camping. County educators were trained using experiential learning and train-the-trainer techniques.…

  1. Credit-based livelihood interventions in a Zambian refugee camp

    Directory of Open Access Journals (Sweden)

    Jane Travis

    2004-05-01

    Full Text Available Establishing community credit facilities has become an important developmental tool for building livelihood strategies. In the refugee camps where the British NGO Christian Outreach Relief andDevelopment (CORD has worked, programmes have provided credit in the form of cash, agricultural inputs or livestock.

  2. Snakes Have Feelings, Too: Elements of a Camp Snake Program.

    Science.gov (United States)

    Allen, Robert Ross

    2001-01-01

    A camp snake program can help campers overcome their fear of snakes, and people cannot truly enjoy nature when they carry a phobia about any one part of it. It can also help overcome prejudice by teaching truth and respect, instilling compassion, and helping campers develop empathy. Advice on catching, handling, identifying, keeping, and feeding…

  3. A Pediatric Cardiology Fellowship Boot Camp improves trainee confidence.

    Science.gov (United States)

    Allan, Catherine K; Tannous, Paul; DeWitt, Elizabeth; Farias, Michael; Mansfield, Laura; Ronai, Christina; Schidlow, David; Sanders, Stephen P; Lock, James E; Newburger, Jane W; Brown, David W

    2016-12-01

    Introduction New paediatric cardiology trainees are required to rapidly assimilate knowledge and gain clinical skills to which they have limited or no exposure during residency. The Pediatric Cardiology Fellowship Boot Camp (PCBC) at Boston Children's Hospital was designed to provide incoming fellows with an intensive exposure to congenital cardiac pathology and a broad overview of major areas of paediatric cardiology practice.

  4. The Career Camp: An Early, Early Career Guidance Program.

    Science.gov (United States)

    Wright, Sue Edmonds

    1995-01-01

    Describes Marshall University's summer camp where young people participate in activities that help prepare them for important career choices they will need to make when entering college. Benefits for the university include: recruitment, enhanced community partnerships, better informed incoming freshman, and publicity for the career center. (JBJ)

  5. Camping Burner-Based Flame Emission Spectrometer for Classroom Demonstrations

    Science.gov (United States)

    Ne´el, Bastien; Crespo, Gasto´n A.; Perret, Didier; Cherubini, Thomas; Bakker, Eric

    2014-01-01

    A flame emission spectrometer was built in-house for the purpose of introducing this analytical technique to students at the high school level. The aqueous sample is sprayed through a homemade nebulizer into the air inlet of a consumer-grade propane camping burner. The resulting flame is analyzed by a commercial array spectrometer for the visible…

  6. Novel H1N1 Flu and Camp

    Centers for Disease Control (CDC) Podcasts

    2009-06-30

    This podcast gives tips to stay healthy and help prevent infection with novel H1N1 flu if your child or someone you know is going to camp.  Created: 6/30/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 6/30/2009.

  7. Archaeology and Memory. Former WWII Camps in Europe

    NARCIS (Netherlands)

    Laarse, van der R.; Ooijen, van I.M.A.

    The archaeology of 20th-century war, terror and conflict is a growing field of research. The archaeological research of ‘terrorscapes’ often overlaps with personal and collective memories. Besides memory, the heritage of the camps has been dominated in the last decades by historical research. What t

  8. Menselijk gedrag bij de evacuatie van een camping

    NARCIS (Netherlands)

    Kerstholt, J.H.; Groenewegen-Ter Morsche, K.; Johannink, R.; Getz-Smeenk, A.F.

    2010-01-01

    In geval van onbeheersbare natuurbranden zal er een beroep moeten worden gedaan op de zelfredzaamheid van burgers. De resultaten van een ontruiming van een camping laten zien dat vele deelnemers niet reageerden op rook en brandgeur en dat ze slechts in actie kwamen nadat z|j door een personeelslid v

  9. Academic Boot Camp for the Writing of Psychology Research Reports

    Science.gov (United States)

    Skues, Jason L.; Wise, Lisa

    2014-01-01

    Herein, we describe the implementation of, and responses to, a structured writing workshop in the form of an academic boot camp. Participants were 42 undergraduate psychology students from a medium-sized Australian university who were completing their major assignment for the semester. A majority of the students expressed satisfaction with the…

  10. Chinese Students’ Winter Camp Tour of the U. S.

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>At the invitation of Brigham Young University (BYU)-Hawaii of the U. S., a 26-member middle school student winter camp delegation, organized and sent by the CPAFFC, made a study tour of the U. S. with the theme of enhancing friendship between the

  11. Graying America Presents Golden Opportunities for Camp Directors.

    Science.gov (United States)

    Cosky, Alicia C.

    1989-01-01

    Discusses quality-of-life issues for ever-increasing population of American elderly, emphasizing value of recreation. Offers organized camping as way of exposing older adults to enjoyable physical activities. Cites evidence supporting beneficial effects of regular exercise for elderly, beginning at any age. (TES)

  12. Camp stability predicts patterns of hunter-gatherer cooperation.

    Science.gov (United States)

    Smith, Daniel; Dyble, Mark; Thompson, James; Major, Katie; Page, Abigail E; Chaudhary, Nikhil; Salali, Gul Deniz; Vinicius, Lucio; Migliano, Andrea Bamberg; Mace, Ruth

    2016-07-01

    Humans regularly cooperate with non-kin, which has been theorized to require reciprocity between repeatedly interacting and trusting individuals. However, the role of repeated interactions has not previously been demonstrated in explaining real-world patterns of hunter-gatherer cooperation. Here we explore cooperation among the Agta, a population of Filipino hunter-gatherers, using data from both actual resource transfers and two experimental games across multiple camps. Patterns of cooperation vary greatly between camps and depend on socio-ecological context. Stable camps (with fewer changes in membership over time) were associated with greater reciprocal sharing, indicating that an increased likelihood of future interactions facilitates reciprocity. This is the first study reporting an association between reciprocal cooperation and hunter-gatherer band stability. Under conditions of low camp stability individuals still acquire resources from others, but do so via demand sharing (taking from others), rather than based on reciprocal considerations. Hunter-gatherer cooperation may either be characterized as reciprocity or demand sharing depending on socio-ecological conditions.

  13. All-optical analog comparator

    OpenAIRE

    Pu Li; Xiaogang Yi; Xianglian Liu; Dongliang Zhao; Yongpeng Zhao; Yuncai Wang

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical device...

  14. Using Science Camps to Develop Understandings about Scientific Inquiry--Taiwanese Students in a U.S. Summer Science Camp

    Science.gov (United States)

    Antink-Meyer, Allison; Bartos, Stephen; Lederman, Judith S.; Lederman, Norman G.

    2016-01-01

    Recent years have witnessed a dramatic rise in the number of middle and high school students from Asian countries participating in U.S.-based summer experiences (Perlez & Gao, 2013). Although summer science camps have been shown to improve students' attitudes and interests related to science and science learning (Bhattacharyya, Mead &…

  15. Mathematical Analogy and Metaphorical Insight

    Science.gov (United States)

    Zwicky, Jan

    2010-01-01

    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  16. Geometrical Analogies in Mathematics Lessons

    Science.gov (United States)

    Eid, Wolfram

    2007-01-01

    A typical form of thinking to approach problem solutions humanly is thinking in analogous structures. Therefore school, especially mathematical lessons should help to form and to develop corresponding heuristic abilities of the pupils. In the contribution, a summary of possibilities of mathematics lessons regarding this shall particularly be…

  17. Schema Training in Analogical Reasoning.

    Science.gov (United States)

    Robins, Shani; Mayer, Richard E.

    1993-01-01

    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)

  18. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  19. Analog Input Data Acquisition Software

    Science.gov (United States)

    Arens, Ellen

    2009-01-01

    DAQ Master Software allows users to easily set up a system to monitor up to five analog input channels and save the data after acquisition. This program was written in LabVIEW 8.0, and requires the LabVIEW runtime engine 8.0 to run the executable.

  20. International Alligator Rivers Analog Project

    Energy Technology Data Exchange (ETDEWEB)

    Bichard, G.F.

    1988-01-01

    The Australian Nuclear Science and Technology Organization (ANSTO), the Japan Atomic Energy Research Institute, the Swedish Nuclear Power Inspectorate, the U.K. Department of the Environment, the US Nuclear Regulatory Commission (NRC), and the Power Reactor and Nuclear Fuel Development Corporation of Japan are participating under the aegis of the Nuclear Energy Agency in the International Alligator Rivers Analog Project. The project has a duration of 3 yr, starting in 1988. The project has grown out of a research program on uranium ore bodies as analogs of high-level waste (HLW) repositories undertaken by ANSTO supported by the NRC. A primary objective of the project is to develop an approach to radionuclide transport model validation that may be used by the participants to support assessments of the safety of radioactive waste repositories. The approach involves integrating mathematical and physical modeling with hydrological and geochemical field and laboratory investigations of the analog site. The Koongarra uranium ore body has been chosen as the analog site because it has a secondary ore body that has formed over the past million years as a result of leaching by groundwater flowing through fractures in the primary ore body.

  1. Novel cAMP signalling paradigms: therapeutic implications for airway disease

    OpenAIRE

    Billington, Charlotte K; Hall, Ian P

    2012-01-01

    Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP to PKA to biological effect. After a brief description of this canonical cAMP signalling pathway, a snapshot is provided of the novel paradigms of cAMP signalling. As in the airwa...

  2. Inactivation of Multidrug Resistance Proteins Disrupts Both Cellular Extrusion and Intracellular Degradation of cAMP

    OpenAIRE

    Xie, Moses; Rich, Thomas C.; Scheitrum, Colleen; Conti, Marco; Richter, Wito

    2011-01-01

    In addition to xenobiotics and several other endogenous metabolites, multidrug-resistance proteins (MRPs) extrude the second-messenger cAMP from various cells. Pharmacological and/or genetic inactivation of MRPs has been shown to augment intracellular cAMP signaling, an effect assumed to be a direct consequence of the blockade of cAMP extrusion. Here we provide evidence that the augmented intracellular cAMP levels are not due exclusively to the prevention of cAMP efflux because MRP inactivati...

  3. Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

    Directory of Open Access Journals (Sweden)

    Martina Schmidt

    2012-11-01

    Full Text Available Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD. Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myofibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP superfamily and IQ motif containing GTPase activating protein (IQGAPs. In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target.

  4. [Medicine in the concentration camps of the Third Reich].

    Science.gov (United States)

    Shasha, Shaul M

    2005-04-01

    Between 1942 and 1944 millions of prisoners were subjected to forced labor in concentration camps throughout the Third Reich, all the while being the victims of a systematic and "scientific" extermination policy. Though the policy was directed mainly against Jews, it was implemented against other "inferior races" as well. The prisoners, stripped of all rights, experienced constant humiliation, uncertain survival and terror. The harsh living condition, characterized by crowding, absent sanitation and poor personal hygiene led to considerable morbidity, mainly due to injuries, infectious diseases and famine, and to high mortality rates. Medical care in the camps was the responsibility of the S.S. Each camp had a chief S.S. physician accompanied by a number of assistants and orderlies. There was also a parallel system of "prisoner-physicians." There was a chief prisoner-physician in every camp, and each block was assigned a "block doctor" who was responsible for sanitation, the removal of corpses, setting up the sick- call and authorizing sick leave. Work teams were accompanied by "mobile doctors" (Streckenpfleger), who dispensed first aid for work injuries. Prisoner-physicians were also charged with disinfecting the blocks and maintaining hygienic conditions in the camp. Every camp had one or more blocks, called "Reviers", that were used for treatment and hospitalization. In the larger camps a number of blocks were designated to function as a sort of hospital (Krankenbau). At times one camp out of a group of camps would be set aside as quarantine, primarily for patients with infectious diseases. Officially, the "Revier" was the responsibility of an S.S. physicians', assisted by a chief prisoner-physician, his assistants and, at times, nurses. But in actuality the Reviers were managed by prisoners (Capos) who did not have medical training but were authorized to make decisions in medical matters such as operations and, on occasion, even performed them. The Reviers

  5. Preliminary Study on the Relationship between cAMP Level and gsp Expression in Cultured Human Pituitary Somatotrophinomas

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA)-dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC)-dependent GH-releasing peptide (GHRP-6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP-6 exerted significant stimulatory effect on cAMP production by 2 gsp-positive tumors and no effect on the gsp-negative tumors. GHRP-6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP-6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross-talk between the two intracellular signal transduction pathways in pituitary cells.

  6. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  7. Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.

    Science.gov (United States)

    Kumar, Naveen; Gupta, Sonal; Dabral, Surbhi; Singh, Shailja; Sehrawat, Seema

    2017-02-16

    Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP-EPAC1-AKAP9 direction to the development of additional biotherapeutics for breast cancer.

  8. Holism and nonseparability by analogy

    Science.gov (United States)

    Arageorgis, Aristidis

    2013-08-01

    This paper explores the issues of holism and nonseparability in relativistic quantum field theory (QFT) by focusing on an analog of the typical model featuring in many discussions of holism and nonseparability in nonrelativistic quantum mechanics. It is argued that the quantum field theoretic model does exhibit holism in a metaphysical sense and that there are plausible grounds to view QFT holistic in an epistemological sense. However, the complexities arising from the fact that quantum fields have infinite degrees of freedom prohibit the exploitation of the elaborated analogy toward demonstrating that the QFT model exhibits the kind of state nonseparability familiar from ordinary quantum mechanics. Still, it is argued that the QFT model does satisfy a rather weak epistemological criterion for state nonseparability.

  9. Synaptic dynamics in analog VLSI.

    Science.gov (United States)

    Bartolozzi, Chiara; Indiveri, Giacomo

    2007-10-01

    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties.

  10. Mechanical Analogies of Fractional Elements

    Institute of Scientific and Technical Information of China (English)

    HU Kai-Xin; ZHU Ke-Qin

    2009-01-01

    A Fractional element model describes a special kind of viscoelastic material.Its stress is proportional to the fractional-order derivative of strain. Physically the mechanical analogies of fractional elements can be represented by spring-dashpot fractal networks. We introduce a constitutive operator in the constitutive equations of viscoelastic materials.To derive constitutive operators for spring-dashpot fractal networks, we use Heaviside operational calculus, which provides explicit answers not otherwise obtainable simply.Then the series-parallel formulas for the constitutive operator are derived. Using these formulas, a constitutive equation of fractional element with 1/2-order derivative is obtained.Finally we find the way to derive the constitutive equations with other fractional-order derivatives and their mechanical analogies.

  11. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel

    2017-01-01

    This textbook is appropriate for use in graduate-level curricula in analog-to-digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters. It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation. This book presents an overview of the state of the art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, third edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 22-nm technology and the need for a more statistical approach to accuracy. Pedagogical enhancements to this edition include additional, new exercises, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate. Considerable background information and practical tips, from designing a PCB, to lay-o...

  12. From camp to kitsch: A queer eye on console fandom

    Directory of Open Access Journals (Sweden)

    Rob Gallagher

    2014-03-01

    Full Text Available Offering a queer perspective on video game fandom, this article considers the factors that fostered a subculture of Western devotees of Japanese video games in the 1990s. Focused on readers of the English publication Sega Saturn Magazine, it shows how, for these players, Japanese games became the basis of a collective identity founded on precisely the kinds of perverse over-attachment, projective identification and hermeneutic ingenuity that Eve Kosofsky Sedgwick identifies with camp. Citing this subculture as an example of how fans transform the texts they put to use, the article also addresses its implications for our understanding of fandom today, at a time when the proliferation of quantitative analysis techniques is transforming the production and consumption of games. Such techniques, I argue, threaten to compromise the contingency and ambiguity on which camp thrives, instead fostering the kinds of cynical calculation Sedgwick associates with kitsch.

  13. Low Power CMOS Analog Multiplier

    Directory of Open Access Journals (Sweden)

    Shipra Sachan

    2015-12-01

    Full Text Available In this paper Low power low voltage CMOS analog multiplier circuit is proposed. It is based on flipped voltage follower. It consists of four voltage adders and a multiplier core. The circuit is analyzed and designed in 0.18um CMOS process model and simulation results have shown that, under single 0.9V supply voltage, and it consumes only 31.8µW quiescent power and 110MHZ bandwidth.

  14. Collaborative Tools Used to Organize a Library Camp Unconference

    OpenAIRE

    Crossett, Laura; Kraus, Joseph; Lawson, Steve

    2009-01-01

    From July to October, 2008, Laura Crossett, Joseph Kraus and Steve Lawson organized the Library Camp of the West (http://librarycampwest.pbwiki.com/). This was an unconference that took place on October 10, 2008 at the University of Denver. The authors used many technology tools to organize the event, such as email, wikis, blogs, two tools from Google, the Doodle scheduling Website, Flickr and more. This article will explain how they used those tools to prepare for the unconference.

  15. CORRECTIVE SURGERY IN CONGENITAL TALIPES EQUINOVARUS DEFORMITY: A CAMP APPROACH

    Directory of Open Access Journals (Sweden)

    Antony R.

    2015-09-01

    Full Text Available The study was intended to assess the results of soft tissue release and bony corrective surgery in patients of moderate to severe deformed rigid club foot (CTEV and neglected clubfoot (CTEV at free disabled surgical camps at Chhattisgarh state . MATERIAL AND METHODS : In our study 50 patients were included with 70% male and 30% female with 4 - 16 years of age grou p and 70% unilateral and 30% bilateral foot involvement. Patients were admitted and operated in different free disabled surgical camps at Chhattisgarh state over the period of 36 months (1 may 2004 to 30 th April 2007. Improvement in functional ability and locomotion of all operated patients were assessed by physical and clinical examination. RESULTS : All patients who were operated in our study showed significant improvement in functional ability and locomotion after surgery. All patients were maintaining f unctional ability at follow up duration of 12 months (1 year. 75% patients were walking normally, 10% cases were walking with internal rotation of leg and 5% cases were walking with midtarsal varus foot with AFO with medial bar support. CONCLUSION : Our st udy showed and established that excellent results can be obtained in congenital talipes equinovarus (CTEV patients by soft tissue release with bony corrective surgery. The team work of devoted surgeons, paramedical and rehabilitation staff in whole durati on of camps to achieve the goal. With an aim to help more number of CTEV cases by surgery, our team has started doing surgeries in small institutions, and organize charity camps to help poor patients and mankind even in small clinics

  16. Camp Pendleton Saves 91% in Parking Lot Lighting

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-01-01

    Case study describes how Camp Pendleton Marine Corps Base replaced high-pressure sodium (HPS) fixtures in one parking lot with high-efficiency induction fixtures for 91% savings in energy use and $5,700 in cost savings annually. This parking lot is estimated to have a simple payback of 2.9 years. Sitewide up-grades yielded annual savings of 1 million kWh.

  17. ESTCP Live Site Demonstrations Former Camp Beale, Marysville, CA

    Science.gov (United States)

    2011-08-23

    31  Figure 10-1 – Management and Staffing Wiring Diagram . ...........................................................32  Tables Table...the completion of the demonstration. The schedule of field testing activities is provided in Figure 5-1 as a Gantt chart. Activity Name 5 12 19...Management and Staffing Wiring Diagram . 32 33 11.0 REFERENCES 1. “ESTCP Munitions Response, Live Site Demonstrations, former Camp Beale, CA

  18. Building Energy Audit Report for Camp Smith, HI

    Energy Technology Data Exchange (ETDEWEB)

    Chvala, William D.; De La Rosa, Marcus I.; Brown, Daryl R.; Dixon, Douglas R.

    2010-09-30

    A detailed energy assessment was performed by a team of engineers from Pacific Northwest National Laboratory (PNNL) under contract to the Department of Energy/Federal Energy Management program (FEMP). The effort used the Facility Energy Decision System (FEDS) model to determine how energy is consumed at Camp Smith, identify the most cost-effective energy retrofit measures, and calculate the potential energy and cost savings. This report documents the results of that assessment.

  19. Tidal Marsh Vegetation of China Camp, San Pablo Bay, California

    OpenAIRE

    Baye, Peter R.

    2012-01-01

    China Camp (Marin County, California) preserves extensive relict stands of salt marsh vegetation developed on a prehistoric salt marsh platform with a complex sinuous tidal creek network. The low salt marsh along tidal creeks supports extensive native stands of Pacific cordgrass (Spartina foliosa). The outer salt marsh accreted following hydraulic gold mining sedimentation. It consists of a wave-scarped pickleweed-dominated (Sarcocornia pacifica) high salt marsh terrace with a broad fringing ...

  20. Smart and Green Energy (SAGE) for Base Camps Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Engels, Matthias; Boyd, Paul A.; Koehler, Theresa M.; Goel, Supriya; Sisk, Daniel R.; Hatley, Darrel D.; Mendon, Vrushali V.; Hail, John C.

    2014-02-11

    The U.S. Army Logistics Innovation Agency’s (LIA’s) Smart and Green Energy (SAGE) for Base Camps project was to investigate how base camps’ fuel consumption can be reduced by 30% to 60% using commercial off-the-shelf (COTS) technologies for power generation, renewables, and energy efficient building systems. Field tests and calibrated energy models successfully demonstrated that the fuel reductions are achievable.

  1. Flame Retardant Applications in Camping Tents and Potential Exposure

    OpenAIRE

    Keller, Alexander S.; Raju, Nikhilesh P.; Webster, Thomas F.; Stapleton, Heather M.

    2014-01-01

    Concern has mounted over health effects caused by exposure to flame retardant additives used in consumer products. Significant research efforts have focused particularly on exposure to polybrominated diphenyl ethers (PBDEs) used in furniture and electronic applications. However, little attention has focused on applications in textiles, particularly textiles meeting a flammability standard known as CPAI-84. In this study, we investigated flame retardant applications in camping tents that met C...

  2. A global analog of Cheshire charge

    CERN Document Server

    McGraw, P

    1994-01-01

    It is shown that a model with a spontaneously broken global symmetry can support defects analogous to Alice strings, and a process analogous to Cheshire charge exchange can take place. A possible realization in superfluid He-3 is pointed out.

  3. Exchange Protein Directly Activated by cAMP (epac) : A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

    NARCIS (Netherlands)

    Schmidt, Martina; Dekker, Frank J.; Maarsingh, Harm

    2013-01-01

    Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and g

  4. What Do Students Gain from a Week at Science Camp? Youth Perceptions and the Design of an Immersive, Research-Oriented Astronomy Camp

    Science.gov (United States)

    Fields, Deborah Anne

    2009-01-01

    This study explored American high school students' perceptions of the benefits of a summer astronomy camp, emphasizing a full cycle of the research process and how the organization of the camp contributed to those perceptions. Semi-structured interviews with students and staff were used to elicit the specific benefits that campers perceived from…

  5. The Effect of a Disability Camp Program on Attitudes towards the Inclusion of Children with Disabilities in a Summer Sport and Leisure Activity Camp

    Science.gov (United States)

    Papaioannou, Christina; Evaggelinou, Christina

    2014-01-01

    The aim of the present study was to examine the impact of a specific Disability Camp Program (DCP) in the attitudes of children without disabilities toward the inclusion of children with disabilities in a summer sport and leisure activity camp. Three hundred eighty-seven campers without disabilities participated in the study and were divided into…

  6. Developing Social Skills of Summer Campers with Autism Spectrum Disorder: A Case Study of Camps on TRACKS Implementation in an Inclusive Day-Camp Setting

    Science.gov (United States)

    Maich, Kimberly; Hall, Carmen L.; van Rhijn, Tricia Marie; Quinlan, Laurie

    2015-01-01

    This research provides preliminary results of an exploratory case study conducted of the Camps on TRACKS program in an inclusive, municipal day-camp program in southwestern Ontario, Canada. Positive changes are demonstrated in the social skills of nine day campers with an autism spectrum disorder (ASD) who participated in the program. In this…

  7. Outbreak of chickenpox in a refugee camp of northern Thailand

    Directory of Open Access Journals (Sweden)

    Camélique Olivier

    2010-02-01

    Full Text Available Abstract Although chickenpox is a generally mild, self-limited illness of children, it can cause fatal disease in adults. Accumulating reports from tropical countries showed a high prevalence of seronegativity among the adults, implying that varicella diseases could become a heavy burden in tropical countries. However, in the situation of humanitarian emergencies in tropical areas, chickenpox has largely been ignored as a serious communicable disease, due to lack of data regarding varicella mortality and hospital admissions in such a context. This is the first report describing an outbreak of chickenpox in a refugee camp of tropical region. In 2008, we experienced a varicella outbreak in ethnic Lao Hmong refugee camp in Phetchabun Province, northern Thailand. The attack rate was 4.0% (309/7,815 and this caused 3 hospitalizations including one who developed severe varicella pneumonia with respiratory failure. All hospitalizations were exclusively seen in adults, and the proportion of patients ≥15 years old was 13.6% (42/309. Because less exposure to varicella-zoster virus due to low population density has previously been suggested to be one of the reasons behind higher prevalence of susceptible adults in tropics, the influx of displaced people from rural areas to a densely populated asylum might result in many severe adult cases once a varicella outbreak occurs. Control interventions such as vaccination should be considered even in refugee camp, if the confluence of the risk factors present in this situation.

  8. Investigating visual analogies for visual insight problems

    OpenAIRE

    Corina Sas; Eric Luchian; Linden Ball

    2010-01-01

    Much research has focused on the impact of analogies in insight problem solving, but less work has investigated how the visual analogies for insight are actually constructed. Thus, it appears that in the search for their facilitative impact on the incubation effect, the understanding of what makes good visual analogies has somehow been lost. This paper presents preliminary work of constructing a set of 6 visual analogies and evaluating their impact on solving the visual problem of eight coins...

  9. Biological roles of cAMP: variations on a theme in the different kingdoms of life.

    Science.gov (United States)

    Gancedo, Juana M

    2013-08-01

    Cyclic AMP (cAMP) plays a key regulatory role in most types of cells; however, the pathways controlled by cAMP may present important differences between organisms and between tissues within a specific organism. Changes in cAMP levels are caused by multiple triggers, most affecting adenylyl cyclases, the enzymes that synthesize cAMP. Adenylyl cyclases form a large and diverse family including soluble forms and others with one or more transmembrane domains. Regulatory mechanisms for the soluble adenylyl cyclases involve either interaction with diverse proteins, as happens in Escherichia coli or yeasts, or with calcium or bicarbonate ions, as occurs in mammalian cells. The transmembrane cyclases can be regulated by a variety of proteins, among which the α subunit and the βγ complex from G proteins coupled to membrane receptors are prominent. cAMP levels also are controlled by the activity of phosphodiesterases, enzymes that hydrolyze cAMP. Phosphodiesterases can be regulated by cAMP, cGMP or calcium-calmodulin or by phosphorylation by different protein kinases. Regulation through cAMP depends on its binding to diverse proteins, its proximal targets, this in turn causing changes in a variety of distal targets. Specifically, binding of cAMP to regulatory subunits of cAMP-dependent protein kinases (PKAs) affects the activity of substrates of PKA, binding to exchange proteins directly activated by cAMP (Epac) regulates small GTPases, binding to transcription factors such as the cAMP receptor protein (CRP) or the virulence factor regulator (Vfr) modifies the rate of transcription of certain genes, while cAMP binding to ion channels modulates their activity directly. Further studies on cAMP signalling will have important implications, not only for advancing fundamental knowledge but also for identifying targets for the development of new therapeutic agents.

  10. Three-dimensional measurement of cAMP gradients using hyperspectral confocal microscopy

    Science.gov (United States)

    Rich, Thomas C.; Annamdevula, Naga; Britain, Andrea L.; Mayes, Samuel; Favreau, Peter F.; Leavesley, Silas J.

    2016-03-01

    Cyclic AMP (cAMP) is a ubiquitous second messenger known to differentially regulate many cellular functions over a wide range of timescales. Several lines of evidence have suggested that the distribution of cAMP within cells is not uniform, and that cAMP compartmentalization is largely responsible for signaling specificity within the cAMP signaling pathway. However, to date, no studies have experimentally measured three dimensional (3D) cAMP distributions within cells. Here we use both 2D and 3D hyperspectral microscopy to visualize cAMP gradients in endothelial cells from the pulmonary microvasculature (PMVECs). cAMP levels were measured using a FRETbased cAMP sensor comprised of a cAMP binding domain from EPAC sandwiched between FRET donors and acceptors -- Turquoise and Venus fluorescent proteins. Data were acquired using either a Nikon A1R spectral confocal microscope or custom spectral microscopy system. Analysis of hyperspectral image stacks from a single confocal slice or from summed images of all slices (2D analysis) indicated little or no cAMP gradients were formed within PMVECs under basal conditions or following agonist treatment. However, analysis of hyperspectral image stacks from 3D cellular geometries (z stacks) demonstrate marked cAMP gradients from the apical to basolateral membrane of PMVECs. These results strongly suggest that 2D imaging studies of cAMP compartmentalization -- whether epifluorescence or confocal microscopy -- may lead to erroneous conclusions about the existence of cAMP gradients, and that 3D studies are required to assess mechanisms of signaling specificity.

  11. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    Science.gov (United States)

    Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen; Docken, Steffen S; Lewis, Timothy J; McCulloch, Andrew D; Harvey, Robert D; Clancy, Colleen E

    2016-07-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  12. Chlorella intake attenuates reduced salivary SIgA secretion in kendo training camp participants

    Directory of Open Access Journals (Sweden)

    Otsuki Takeshi

    2012-12-01

    Full Text Available Abstract Background The green alga Chlorella contains high levels of proteins, vitamins, and minerals. We previously reported that a chlorella-derived multicomponent supplement increased the secretion rate of salivary secretory immunoglobulin A (SIgA in humans. Here, we investigated whether intake of this chlorella-derived supplement attenuated the reduced salivary SIgA secretion rate during a kendo training camp. Methods Ten female kendo athletes participated in inter-university 6-day spring and 4-day summer camps. They were randomized into two groups; one took placebo tablets during the spring camp and chlorella tablets during the summer camp, while the other took chlorella tablets during the spring camp and placebo tablets during the summer camp. Subjects took these tablets starting 4 weeks before the camp until post-camp saliva sampling. Salivary SIgA concentrations were measured by ELISA. Results All subjects participated in nearly all training programs, and body-mass changes and subjective physical well-being scores during the camps were comparable between the groups. However, salivary SIgA secretion rate changes were different between these groups. Salivary SIgA secretion rates decreased during the camp in the placebo group (before vs. second, middle, and final day of camp, and after the camp: 146 ± 89 vs. 87 ± 56, 70 ± 45, 94 ± 58, and 116 ± 71 μg/min, whereas no such decreases were observed in the chlorella group (121 ± 53 vs. 113 ± 68, 98 ± 69,115 ± 80, and 128 ± 59 μg/min. Conclusion Our results suggest that a use of a chlorella-derived dietary supplement attenuates reduced salivary SIgA secretion during a training camp for a competitive sport.

  13. Hegel, Analogy, and Extraterrestrial Life

    Science.gov (United States)

    Ross, Joseph T.

    Georg Wilhelm Friedrich Hegel rejected the possibility of life outside of the Earth, according to several scholars of extraterrestrial life. Their position is that the solar system and specifically the planet Earth is the unique place in the cosmos where life, intelligence, and rationality can be. The present study offers a very different interpretation of Hegel's statements about the place of life on Earth by suggesting that, although Hegel did not believe that there were other solar systems where rationality is present, he did in fact suggest that planets in general, not the Earth exclusively, have life and possibly also intelligent inhabitants. Analogical syllogisms are superficial, according to Hegel, insofar as they try to conclude that there is life on the Moon even though there is no evidence of water or air on that body. Similar analogical arguments for life on the Sun made by Johann Elert Bode and William Herschel were considered by Hegel to be equally superficial. Analogical arguments were also used by astronomers and philosophers to suggest that life could be found on other planets in our solar system. Hegel offers no critique of analogical arguments for life on other planets, and in fact Hegel believed that life would be found on other planets. Planets, after all, have meteorological processes and therefore are "living" according to his philosophical account, unlike the Moon, Sun, and comets. Whereas William Herschel was already finding great similarities between the Sun and the stars and had extended these similarities to the property of having planets or being themselves inhabitable worlds, Hegel rejected this analogy. The Sun and stars have some properties in common, but for Hegel one cannot conclude from these similarities to the necessity that stars have planets. Hegel's arguments against the presence of life in the solar system were not directed against other planets, but rather against the Sun and Moon, both of which he said have a different

  14. Analogical Reasoning: A Review of the Literature.

    Science.gov (United States)

    Dawis, Rene V.; Siojo, Luis T.

    The mathematical and philosophical origins of "analogy" are described and their influence on the thinking of intelligence theorists is traced. Theories of intelligence and cognition bearing on analogical reasoning are examined, specifically those of Spearman, Thorndike, Guilford and Piaget. The analogy test item is shown to be a paradigm…

  15. Reasoning by Analogy in Constructing Mathematical Ideas.

    Science.gov (United States)

    English, Lyn D.

    A powerful way of understanding something new is by analogy with something already known. An analogy is defined as a mapping from one structure, which is already known (the base or source), to another structure that is to be inferred or discovered (the target). The research community has given considerable attention to analogical reasoning in the…

  16. Camping with the Stars: Queer Perfomativity, Pop Intertextuality, and Camp in the Pop Art of Lady Gaga

    Directory of Open Access Journals (Sweden)

    Horn, Katrin

    2010-01-01

    Full Text Available The article is concerned with the possibility of employing countercultural and subversive strategies in U.S. mainstream media. The concept in question is camp, historically rooted in gay subculture, as performed by pop artist Lady Gaga. She is presented as challenging gender as well as aesthetic norms in her performances via the employment of camp—thus opening her public persona to queer readings.

  17. Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

    Directory of Open Access Journals (Sweden)

    Xun Wan

    Full Text Available The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac, as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

  18. Methoxychlor and its metabolite HPTE inhibit cAMP production and expression of estrogen receptors α and β in the rat granulosa cell in vitro.

    Science.gov (United States)

    Harvey, Craig N; Chen, Joseph C; Bagnell, Carol A; Uzumcu, Mehmet

    2015-01-01

    The major metabolite of the estrogenic pesticide methoxychlor (MXC) HPTE is a stronger ESR1 agonist than MXC and acts also as an ESR2 antagonist. In granulosa cells (GCs), FSH stimulates estradiol via the second messenger cAMP. HPTE inhibits estradiol biosynthesis, and this effect is greater in FSH-treated GCs than in cAMP-treated GCs. Therefore; we examined the effect of MXC/HPTE on FSH-stimulated cAMP production in cultured GCs. To test involvement of ESR-signaling, we used the ESR1 and ESR2 antagonist ICI 182,780, ESR2 selective antagonist PHTPP, and ESR2 selective agonist DPN. ESR1 and ESR2 mRNA and protein levels were quantified. Both HPTE and MXC inhibited the FSH-induced cAMP production. ICI 182,780 and PHTPP mimicked the inhibitory action of HPTE. MXC/HPTE reduced FSH-stimulated Esr2 mRNA and protein to basal levels. MXC/HPTE also inhibited FSH-stimulated Esr1. The greater inhibition on FSH-stimulated GCs is likely due to reduced cAMP level that involves ESR-signaling, through ESR2.

  19. Hydrogen sulfide-mediated stimulation of mitochondrial electron transport involves inhibition of the mitochondrial phosphodiesterase 2A, elevation of cAMP and activation of protein kinase A.

    Science.gov (United States)

    Módis, Katalin; Panopoulos, Panagiotis; Coletta, Ciro; Papapetropoulos, Andreas; Szabo, Csaba

    2013-11-01

    Although hydrogen sulfide (H₂S) is generally known as a mitochondrial poison, recent studies show that lower concentrations of H₂S play a physiological role in the stimulation of mitochondrial electron transport and cellular bioenergetics. This effect involves electron donation at Complex II. Other lines of recent studies demonstrated that one of the biological actions of H₂S involves inhibition of cAMP and cGMP phosphodiesterases (PDEs). Given the emerging functional role of the mitochondrial isoform of cAMP PDE (PDE2A) in the regulation of mitochondrial function the current study investigated whether cAMP-dependent mechanisms participate in the stimulatory effect of NaHS on mitochondrial function. In isolated rat liver mitochondria, partial digestion studies localized PDE2A into the mitochondrial matrix. NaHS exerted a concentration-dependent inhibitory effect on recombinant PDE2A enzyme in vitro. Moreover, NaHS induced an elevation of cAMP levels when added to isolated mitochondria and stimulated the mitochondrial electron transport. The latter effect was inhibited by Rp-cAMP, an inhibitor of the cAMP-dependent protein kinase (PKA). The current findings suggest that the direct electron donating effect of NaHS is amplified by an intramitochondrial cAMP system, which may involve the inhibition of PDE2A and subsequent, cAMP-mediated stimulation of PKA.

  20. 眼前节内眼模拟手术诱发血眼屏障破坏的大鼠动物模型%Rat model of blood-ocular barrier breakdown induced by anterior segment intraocular analogic surgery

    Institute of Scientific and Technical Information of China (English)

    谢茂松; 郑永征; 徐国兴

    2012-01-01

    目的 建立眼前节内眼模拟手术诱发血眼屏障破坏的大鼠动物模型.方法 清洁级健康成年雄性Sprague-Dawley大鼠150只,随机分为对照组和模型组,每组75只.按1 ml/kg的剂量腹腔注射盐酸氯胺酮-盐酸甲苯噻嗪混合液麻醉大鼠.磷酸盐缓冲液灌注袋连接三通管.三通管一端连接24G静脉留置针,手术显微镜下在3点时钟位从角巩缘前透明角膜30°斜行穿刺入前房,退出针头,留置套管;另一端连接24G静脉留置针套管,与测压计相连测量大鼠眼压.大鼠眼压波动于0~12 mm Hg(1 mm Hg=0.133 kPa)之间,波动30次/min,重复60次.采用氧氟沙星滴眼液滴眼.建模后第1、2、3、5、7天,采用免疫组织化学法检测大鼠白蛋白;定量检测大鼠房水、视网膜中伊凡思蓝(EB)浓度.结果 免疫组织化学染色结果显示,建模后第1、2、3、5、7天对照组白蛋白阳性染色均局限于虹膜和视网膜血管内,脉络膜弥漫性着色.建模后第1天,模型组白蛋白阳性染色主要位于虹膜和视网膜神经层血管周围;建模后第2、3天,阳性染色扩散到虹膜和视网膜全层;建模后第5、7天,阳性染色主要局限于虹膜和视网膜血管内.模型组房水中EB浓度在建模后第1、2、3、5天,均较对照组高(t=25.781,37.433,25.150,19.171;P<0.01);建模后第7天,与对照组接近(t=1.303,P=0.209).模型组视网膜EB浓度在建模后第1、2、3天,均较对照组高(t=11.997,14.622,23.014;P<0.01);建模后第5、7天,与对照组接近(t=2.027,0.756; P=0.058,0.459).结论 通过模拟眼前节内眼手术损伤因素,可建立内眼手术诱发的血眼屏障破坏的大鼠动物模型.%Objective To establish a rat model of blood ocular barrier breakdown induced by anterior segment intraocular analogic surgery. Methods One hundred and fifty healthy adult male rats were randomly divided into control group and model group,75 rats in each group.The rats were

  1. CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Ying-Lan Cai

    2015-01-01

    Full Text Available Our previous studies have shown that CNP-NPR-B/pGC-cGMP is upregulated in the diabetic rats. The present study was designed to determine whether the upregulation of CNP-NPR-B/pGC-cGMP signal pathway affects cGMP-PDE3-cAMP signal pathway in diabetic gastric smooth muscle. The gastric smooth muscle motility was observed by using isometric measurement. PDEs expressions in diabetic gastric smooth muscle tissue were observed by using immunohistochemistry, Western blotting, and RT-PCR methods. The results demonstrated that the inhibitory effect of CNP on the spontaneous contraction of gastric antral circular smooth muscle was potentiated in STZ-induced diabetic rat. CNP-induced increase of cGMP and cAMP was much higher in diabetic gastric smooth muscle tissue than in controls. The expression of PDE3 is downregulated while the levels of gene expression of PDE1, PDE2, PDE4, and PDE5 were not altered in the diabetic gastric smooth muscle tissue. The results suggest that the sensitivity of gastric smooth muscle to CNP is potentiated via activation of CNP-pGC-cGMP-PDE3-cAMP signal pathway in STZ-induced diabetic rats, which may be associated with diabetes-induced gastric motility disorder.

  2. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  3. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  4. Barriers and Facilitators for Generalizing Cycling Skills Learned at Camp to Home.

    Science.gov (United States)

    Temple, Viviene A; Purves, P Lynn; Misovic, Robyn; Lewis, Coral J; DeBoer, Carrie

    2016-01-01

    Many children with disabling conditions do not acquire the skills to successfully ride a 2-wheeled bicycle. The aim was to describe cycling patterns before and after an innovative learn-to-ride bike camp and factors that facilitate or hinder the generalization of skills developed at camp to home. Parents and children participated in semistructured interviews 3-4 mo postcamp. Transcripts were examined deductively for participation and contextual influences using a template of codes approach. None of the children were successfully riding a 2-wheeled bicycle before camp. Two patterns of participation were evident from narrative descriptions of postcamp riding: "riders" and "not there yet." Major facilitating factors were the camp itself, the interaction between the camp and the health service, and continued parent involvement. The program transferred well to home for children who were riding independently on the last day of camp. Ongoing support is needed for children "not there yet."

  5. cAMP biosensors applied in molecular pharmacological studies of G protein-coupled receptors

    DEFF Research Database (Denmark)

    Mathiesen, Jesper Mosolff; Vedel, Line; Bräuner-Osborne, Hans

    2013-01-01

    end-point assays for quantifying GPCR-mediated changes in intracellular cAMP levels exist. More recently, fluorescence resonance energy transfer (FRET)-based cAMP biosensors that can quantify intracellular cAMP levels in real time have been developed. These FRET-based cAMP biosensors have been used...... primarily in single cell FRET microscopy to monitor and visualize changes in cAMP upon GPCR activation. Here, a similar cAMP biosensor with a more efficient mCerulean/mCitrine FRET pair is described for use in the 384-well plate format. After cloning and expression in HEK293 cells, the biosensor...... is characterized in the 384-well plate format and used for measuring the signaling of the G(s)-coupled ß(2)-adrenergic receptor. The procedures described may be applied for other FRET-based biosensors in terms of characterization and conversion to the 384-well plate format....

  6. How Women Work: The Symbolic and Material Reproduction of Migrant Labor Camps in United States Agribusiness

    Directory of Open Access Journals (Sweden)

    Robert CARLEY

    2011-05-01

    Full Text Available This article analyzes gender exploitation in Mexican and Central American migrant farm worker camps in the U.S through small group interactions. We describe how gender exploitation and oppression is transmitted through the social fabric of the camp. We argue that the camp produces an endogenous system of social interaction, which maintains uneven gender relationships. Our data is based on observations of twenty-five women and girls in three labor camps in North Carolina. Research was conducted over a period of six weeks. We found that women who served as the primary bearers of patrimonial authority best maintained the camp community. We conclude that women who successfully reproduce the authority structure gain social status in the camps and are more likely to stay.

  7. The Effect of a Nature Camp on Children’s Conceptions of Nature

    Directory of Open Access Journals (Sweden)

    Esra Yardimci

    2012-01-01

    Full Text Available In this study, a nature camp which provides authentic learning opportunities for children was conducted. Twenty-four 4th and 5th graders (9 girls, 15 boys participated to the camp. The camp program started with observations in the forest nearby. More focused observations were also made. Children discussed their observations with their friends and scientists. A questionnaire was applied at the beginning and end of the camp. The results showed that the nature camp program was effective in extending the children’s conception of the nature by including both living and non-living things. Most of them started the camp with a conception of the nature which consisted of only living things whereas only four children left with this conception at the end. Biological aspects of the nature also increased. Children generally stated that living or non-living things exist or live together at the nature, but relationships between them were noticed by fewer children.

  8. Receptor-mediated stimulation of lipid signalling pathways in CHO cells elicits the rapid transient induction of the PDE1B isoform of Ca2+/calmodulin-stimulated cAMP phosphodiesterase.

    Science.gov (United States)

    Spence, S; Rena, G; Sullivan, M; Erdogan, S; Houslay, M D

    1997-01-01

    Chinese hamster ovary cells (CHO cells) do not exhibit any Ca2+/calmodulin-stimulated cAMP phosphodiesterase (PDE1) activity. Challenge of CHO cells with agonists for endogenous P2-purinoceptors, lysophosphatidic acid receptors and thrombin receptors caused a similar rapid transient induction of PDE1 activity in each instance. This was also evident on noradrenaline challenge of a cloned CHO cell line transfected so as to overexpress alpha 1B-adrenoceptors. This novel PDE1 activity appeared within about 15 min of exposure to ligands, rose to a maximum value within 30 min to 1 h and then rapidly decreased. In each case, the expression of novel PDE1 activity was blocked by the transcriptional inhibitor actinomycin D. Challenge with insulin of either native CHO cells or a CHO cell line transfected so as to overexpress the human insulin receptor failed to induce PDE1 activity. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1C isoform, did not amplify any fragment from RNA preparations of CHO cells expressing PDE1 activity, although they did so from the human thyroid carcinoma FTC133 cell line. Reverse transcriptase-PCR analyses, using degenerate primers able to detect the PDE1A and PDE1B isoforms, successfully amplified a fragment of the predicted size from RNA preparations of both CHO cells expressing PDE1 activity and human Jurkat T-cells. Sequencing of the PCR products, generated using the PDE1A/B primers, yielded a novel sequence which, by analogy with sequences reported for bovine and murine PDE1B forms, suggests that the PDE1 species induced in CHO cells through protein kinase C activation and that expressed in Jurkat T-cells are PDE1B forms.

  9. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  10. College of Agriculture and Life Sciences will host ExxonMobil Bernard Harris Summer Science Camp

    OpenAIRE

    Greiner, Lori A.

    2007-01-01

    Virginia Tech has been chosen as a site for a 2007 ExxonMobil Bernard Harris Summer Science Camp on June 18-30. The Virginia Tech camp will be one of 20 hosted by universities across the country. The two-week residential camp offers an innovative program that enhances middle school students' knowledge of science, technology, engineering, and mathematics (STEM) while encouraging students to stay in school and fostering leadership and citizenship.

  11. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

    Science.gov (United States)

    Zippin, Jonathan H.; Farrell, Jeanne; Huron, David; Kamenetsky, Margarita; Hess, Kenneth C.; Fischman, Donald A.; Levin, Lonny R.; Buck, Jochen

    2004-01-01

    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation. PMID:14769862

  12. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

    OpenAIRE

    2004-01-01

    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation.

  13. The effectiveness of an American science camp for Taiwanese high school students

    Science.gov (United States)

    Kuo, Pi-Chu

    The purposes of this study were: (1) to evaluate the effectiveness of an American science camp for Taiwanese high school students in terms of student attitudes toward science; (2) to understand the factors that affect student attitudes toward science in the American science camp. Qualitative and quantitative data were collected and analyzed to answer my research questions: (1) How did the influence of the abroad science camp differ from the local one in terms of student attitudes toward science? (2) How did gender, grade level, and personality affect student attitudes toward science in the abroad science camp? An Attitudes toward Science Inventory was used in this study to measure student attitudes. The results of factor analysis suggested that the attitudes measured in this study include five common factors: science as school subjects (SC), science in society (SS), value of science (VS), science in laboratory (SL), and nature of science (NS). Significant improvements were found in SS, VS, and NS after the experiences of the abroad science camp. In the local science camp, only NS was non-significant comparing before and after the camp. The results from the comparisons between the two science camps show that different program designs have different impacts on student attitudes toward science. Furthermore, whether the science camps are designed based on learning theory or not, and regardless of how much time the campers spend in science-related activities during science camps, science camps can motivate students' interests in learning science. The results of mixed-design ANOVA for gender, grade level, and personality suggest that most of these personal factors did not significantly affect student attitudes. However, extraversion/introversion and sensing/intuition had impacts on the persuasibility of the abroad science camp.

  14. Transfer Between Analogies: How Solving One Analogy Problem Helps to Solve Another

    OpenAIRE

    Keane, Mark T.

    1995-01-01

    This paper deals with transfer between analogies; with what people acquire from one analogy problem-solving episode that can be re-applied to a subsequent analogy, problem-solving episode. This issue must be resolved if we are to understand the nature of expertise and the appropriate use of analogy in education. There are two main explanations of what subjects acquire from an analogy problem-solving episode. The schema-induction hypothesis maintains that subjects acquire an abs...

  15. USE OF MODIFIED CAMP TEST FOR PRELIMINARY NONSEROLOGIC IDENTIFICATION OF VIBRIO CHOLERAE IN STOOL SPECIMENS

    Directory of Open Access Journals (Sweden)

    Murad Lesmana

    2012-09-01

    Full Text Available Suatu modifikasi uji CAMP digunakan bersama dengan reaksi biokimiawi untuk identifikasi Vibrio cholerae pada sampel klinis. Dari 579 usap dubur penderita diare, 92 (16% memberikan hasil isolasi V. cholerae 01 biotipe El Tor dan 34 (6% V. cholerae non-01. Semua isolat V. cholerae 01 El Tor menunjukkan reaksi CAMP positif kuat dengan gambaran hemolisis sinergistik lengkap berbentuk sosis; sedangkan V. cholerae non-01 memberikan reaksi CAMP yang sempit dengan pola hemolisis menyerupai bulan sabit. Hasil uji CAMP yang dilakukan bersama dengan reaksi biokimiawi sesuai dengan metode biakan konvensional yang menyertakan tes aglutinasi dengan antiserum V. cholerae 01 untuk mengidentifikasi V. cholerae.

  16. cAMP diffusion in Dictyostelium discoideum: A Green's function method

    Science.gov (United States)

    Calovi, Daniel S.; Brunnet, Leonardo G.; de Almeida, Rita M. C.

    2010-07-01

    A Green’s function method is developed to approach the spatiotemporal equations describing the cAMP production in Dictyostelium discoideum, markedly reducing numerical calculations times: cAMP concentrations and gradients are calculated just at the amoeba locations. A single set of parameters is capable of reproducing the different observed behaviors, from cAMP synchronization, spiral waves and reaction-diffusion patterns to streaming and mound formation. After aggregation, the emergence of a circular motion of amoebas, breaking the radial cAMP field symmetry, is observed.

  17. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  18. RESULTS OF PROPHYLACTIC VACCINATION AGAINST PNEUMONIA AT CAMP WHEELER.

    Science.gov (United States)

    Cecil, R L; Vaughan, H F

    1919-05-01

    1. 13,460 men, or about 80 per cent of the entire camp strength, were vaccinated against pneumonia with pneumococcus lipovaccine. 2. The dosage employed in all cases was 1 cc. of the lipovaccine containing approximately 10 billion each of Pneumococcus Types I, II, and III. 3. Both the local and general reactions produced by the vaccine were usually mild. Only 0.7 per cent of those who received the vaccine were sufficiently affected to need hospital care. None of these was seriously ill, and a majority of them returned to duty on the 2nd or 3rd day after admission. 4. Most of the troops inoculated were under observation for 2 or 3 months after vaccination. During this period there were 32 cases of Pneumococcus Type I, II, and III pneumonia among the vaccinated four-fifths of camp, and 42 cases of pneumonia of these types among the unvaccinated one-fifth of camp. If, however, all cases of pneumonia that developed within 1 week after vaccination are excluded from the vaccinated group, there remain only 8 cases of pneumonia produced by fixed types, and these were all secondary to severe attacks of influenza. This exclusion is justified by the fact that protective bodies do not begin to appear in the serum until the 8th day after injection of pneumococcus lipovaccine. 5. There is no evidence whatever that pneumococcus vaccine predisposes the individual even temporarily toward either pneumococcus or streptococcus pneumonia. 6. The weekly incidence rate for pneumonia (all types) among the vaccinated troops was conspicuously lower than that for the unvaccinated troops. 7. The pneumonia incidence rate per 1,000 men during the period of the experiment was twice as high for unvaccinated recruits as for vaccinated recruits, and nearly seven times as high for unvaccinated seasoned men as for vaccinated seasoned men. 8. Influenza causes a marked reduction in resistance to pneumonia even among vaccinated men. Of the 155 cases of pneumonia (all types) developing 1 week or more

  19. MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D3 in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kun-Chun Chiang

    2012-01-01

    Full Text Available Hormone antagonist therapy for estrogen receptor positive (ER+ breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1α,25-dihydroxyvitamin D3 [1α,25(OH2D3] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH2D3 analog, 19-nor-2α-(3-hydroxypropyl-1α,25-dihydroxyvitamin D3 (MART-10, on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH2D3 in inhibiting cell growth in a dose- and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G0/G1 phase as compared to 1α,25(OH2D3, possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH2D3 in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted.

  20. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

    Science.gov (United States)

    Narayanan, R.; Smith, C. L.; Weigel, N. L.

    2002-01-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

  1. Classification of MEC with the ALLTEM at Camp Stanley, Texas

    Science.gov (United States)

    Asch, T.; Moulton, C.; Smith, D.V.

    2011-01-01

    The ALLTEM is a multi-axis electromagnetic induction system designed for unexploded ordnance UXO applications. It uses a continuous triangle-wave excitation and provides good late-time signal-to-noise ratio SNR especially for ferrous targets. Multi-axis transmitter Tx and receiver Rx systems such as ALLTEM provide a richer data set from which to invert for the target parameters required to distinguish between clutter and UXO. Inversions of field data acquired between 2006 and 2010 over the Army's UXO Standardized Test sites at the Yuma Proving Ground YPG in Arizona and at the Aberdeen Proving Ground APG in Maryland have produced reasonable and generally repeatable results for many UXO items buried at different orientations and depths. In February-March 2011 ALLTEM data was acquired at two locations on the Camp Stanley Storage Activity CSSA just north of San Antonio, Texas. Camp Stanley is used to store munitions as well as test, fire, and overhaul munitions components. Site B-20 is an open burn/open detonation OBOD area and Site B-27 consists of narrow trenches blasted into limestone containing buried range and munitions debris and possibly MEC. The processing, analysis, and classification techniques developed at the controlled environments of YPG and APG have been applied to these two "live" sites at Camp Stanley. ALLTEM data analysis includes both classical numerical inversion of data from each anomaly and clustering of the raw data by means of a self-organizing map SOM via generalized neural network algorithms. Final classification consists of an integration of both the numerical and SOM results. ?? 2011 Society of Exploration Geophysicists.

  2. Camp Upshur, Marine Corps Base Quantico, VA Architectural Survey

    Science.gov (United States)

    2009-08-01

    ERDC/CERL SR-09-11 viii Unit Conversion Factors Multiply By To Obtain acres 4,046.873 square meters degrees Fahrenheit (F-32)/1.8 degrees Celsius...Office 1952 No 451 26109 Chapel 1952 No 461 26110 Administrative Office 1952 No 473 26111 Administrative Office 1952 No 483 26112 Storage A/G...Floor Tile Replacement-Camp Upshur, Building 26110, floor plan, March 1962 ERDC/CERL SR-09-11 451 B ui ld in g 26 11 0 HISTORIC PHOTOGRAPHS

  3. The Camp Edwards Experiment in Battalion Level Consolidated Field Feeding

    Science.gov (United States)

    1975-12-01

    Cucumbers 6 - 1.0 1 Apple Juices 8 42 8.5 NATIONAL GUARD CAMP EDWARDS MENU REVISED BY NARADCOM & 101ST EWG 7 J"{JLY -1975 Rl 88 MENU I - SATURDAY 9...August 1975 Dinner Cheeseburgers/Hamburgers (~32) Catsup - Mustard Pickle Relish Lyonnaise Potatoes {Q-54) Buttered Cor~ (Q-G-3) Lettuce and... Pickle Relish O’Brien Potatoes (Q-54) Buttered Green Beans (Q-G-1) Lettuce and Tomato Salad (M-33) Sliced Onion French Dressing (M-58) Hamburger

  4. Effect of a bispidinone analog on mitochondria‑mediated apoptosis in HeLa cells.

    Science.gov (United States)

    Yi, Myeongjin; Parthiban, Paramasivam; Hwang, Jiyoung; Zhang, Xin; Jeong, Hyunjin; Park, Dong Ho; Kim, Dong-Kyoo

    2014-01-01

    The present study was carried out to investigate the effect of 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one (bispidinone) analogs on the in vitro growth of human cervical carcinoma (HeLa) cells. A series of 11 bispidinone analogs was synthesized with substituents, e.g., fluoro/methyl/ethyl/isopropyl/thiomethyl/methoxy groups, at various positions. These compounds were synthesized to identify which substituent and position induced the strongest cytotoxic effect in cancer cells. Among these synthetics, analog 9, which contains methoxy groups, had the most significant cytotoxic effect on HeLa cells, and its IC50 value was less than 13 µM. A WST-8 assay also showed that analog 9 inhibited the proliferation of HeLa cells. By using DNA content analysis, we found that analog 9 induced sub-G1 and G1 phase arrest in a time-dependent manner. A [3H]-thymidine incorporation assay suggested that analog 9 inhibited DNA replication in HeLa cells. On performing light microscopy, morphological changes such as cellular shrinkage and disruption, which are apoptotic features, were observed in HeLa cells. Annexin V/propidium iodide double staining and rhodamine-123 staining showed that analog 9 induced apoptosis and disrupted the intracellular mitochondrial membrane potential in HeLa cells. The western blot analysis results suggested that analog 9 induced mitochondria-mediated apoptosis. In addition, we have shown that analog 9 may play a role in the Fas signaling apoptotic pathway.

  5. Genetically-encoded tools for cAMP probing and modulation in living systems.

    Directory of Open Access Journals (Sweden)

    Valeriy M Paramonov

    2015-09-01

    Full Text Available Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP is one of the principal second messengers downstream of a manifold of signal transduction pathways, including the ones triggered by G protein-coupled receptors. Not surprisingly, biochemical assays for cAMP have been instrumental for basic research and drug discovery for decades, providing insights into cellular physiology and guiding pharmaceutical industry. However, despite impressive track record, the majority of conventional biochemical tools for cAMP probing share the same fundamental shortcoming - all the measurements require sample disruption for cAMP liberation. This common bottleneck, together with inherently low spatial resolution of measurements (as cAMP is typically analyzed in lysates of thousands of cells, underpin the ensuing limitations of the conventional cAMP assays: 1 genuine kinetic measurements of cAMP levels over time in a single given sample are unfeasible; 2 inability to obtain precise information on cAMP spatial distribution and transfer at subcellular levels, let alone the attempts to pinpoint dynamic interactions of cAMP and its effectors. At the same time, tremendous progress in synthetic biology over the recent years culminated in drastic refinement of our toolbox, allowing us not only to bypass the limitations of conventional assays, but to put intracellular cAMP life-span under tight control – something, that seemed scarcely attainable before. In this review article we discuss the main classes of modern genetically-encoded tools tailored for cAMP probing and modulation in living systems. We examine the capabilities and weaknesses of these different tools in the context of their operational characteristics and applicability to various experimental set-ups involving living cells, providing the guidance for rational selection of the best tools for particular needs.

  6. Analog computing by Brewster effect.

    Science.gov (United States)

    Youssefi, Amir; Zangeneh-Nejad, Farzad; Abdollahramezani, Sajjad; Khavasi, Amin

    2016-08-01

    Optical computing has emerged as a promising candidate for real-time and parallel continuous data processing. Motivated by recent progresses in metamaterial-based analog computing [Science343, 160 (2014)SCIEAS0036-807510.1126/science.1242818], we theoretically investigate the realization of two-dimensional complex mathematical operations using rotated configurations, recently reported in [Opt. Lett.39, 1278 (2014)OPLEDP0146-959210.1364/OL.39.001278]. Breaking the reflection symmetry, such configurations could realize both even and odd Green's functions associated with spatial operators. Based on such an appealing theory and by using the Brewster effect, we demonstrate realization of a first-order differentiator. Such an efficient wave-based computation method not only circumvents the major potential drawbacks of metamaterials, but also offers the most compact possible device compared to conventional bulky lens-based optical signal and data processors.

  7. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  8. Design and Analysis of Reconfigurable Analog System

    Science.gov (United States)

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  9. Rapid Assessment of Seismic Vulnerability in Palestinian Refugee Camps

    Science.gov (United States)

    Al-Dabbeek, Jalal N.; El-Kelani, Radwan J.

    Studies of historical and recorded earthquakes in Palestine demonstrate that damaging earthquakes are occurring frequently along the Dead Sea Transform: Earthquake of 11 July 1927 (ML 6.2), Earthquake of 11 February 2004 (ML 5.2). In order to reduce seismic vulnerability of buildings, losses in lives, properties and infrastructures, an attempt was made to estimate the percentage of damage degrees and losses at selected refugee camps: Al Ama`ri, Balata and Dhaishe. Assessing the vulnerability classes of building structures was carried out according to the European Macro-Seismic Scale 1998 (EMS-98) and the Fedral Emergency Management Agency (FEMA). The rapid assessment results showed that very heavy structural and non structural damages will occur in the common buildings of the investigated Refugee Camps (many buildings will suffer from damages grades 4 and 5). Bad quality of buildings in terms of design and construction, lack of uniformity, absence of spaces between the building and the limited width of roads will definitely increase the seismic vulnerability under the influence of moderate-strong (M 6-7) earthquakes in the future.

  10. Photovoltaic Technology of Electricity Generation for Desert Camping

    Directory of Open Access Journals (Sweden)

    Shafiqur Rehman

    2005-01-01

    Full Text Available This study presents a case study on the utilization of global solar radiation data on horizontal surface to perform economical feasibility of using Photovoltaic (PV panels with battery backup to meet a small load for a camping site in Saudi Arabia. The analysis considers three scenarios with daily average energy demands of: (i full load, (ii 75% load and (iii half load with annual peak load of 3.84, 3.06 and 2.27 kW, respectively. Each of these loads is further studied economically to investigate the effect of battery storage for 1 to 5 days. The study also compares the cost of electricity generation in $/kWh from PV system and diesel generating systems. The lower mean temperature (~20°C and high intensity of radiation (~ 6.3 kWh m2/day in Abha make it a promising site for the usage of PV systems for desert camping. Analysis of the data indicates that the battery storage capacity cost plays an important role in the overall cost of the PV system. The economical indicators suggest that larger PV systems be preferred over the smaller ones with minimal storage option. The energy generation cost analysis indicated that the diesel generating cost was found to be 29, 56 and 116% higher than the PV system for full, 75% and half load systems, respectively.

  11. Robust hyperchaotic synchronization via analog transmission line

    Science.gov (United States)

    Sadoudi, S.; Tanougast, C.

    2016-02-01

    In this paper, a novel experimental chaotic synchronization technique via analog transmission is discussed. We demonstrate through Field-Programmable Gate Array (FPGA) implementation design the robust synchronization of two embedded hyperchaotic Lorenz generators interconnected with an analog transmission line. The basic idea of this work consists in combining a numerical generation of chaos and transmitting it with an analog signal. The numerical chaos allows to overcome the callback parameter mismatch problem and the analog transmission offers robust data security. As application, this technique can be applied to all families of chaotic systems including time-delayed chaotic systems.

  12. Fermilab accelerator control system: Analog monitoring facilities

    Energy Technology Data Exchange (ETDEWEB)

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system.

  13. The Efficacy of Family Camp Experience for Families Who Have Children with Visual Impairments. Research Report

    Science.gov (United States)

    Day, Janice Neibaur; Kleinschmidt, Julia

    2005-01-01

    This study was designed to address the paucity of research on the efficacy of camps for children with visual impairments and their families. The study evaluated the performance of a two-day camp for families with young visually impaired children at the Utah Schools for the Deaf and the Blind whose program was based on perceived family needs and…

  14. A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning

    Science.gov (United States)

    Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2007-01-01

    Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

  15. Offering a Forensic Science Camp to Introduce and Engage High School Students in Interdisciplinary Science Topics

    Science.gov (United States)

    Ahrenkiel, Linda; Worm-Leonhard, Martin

    2014-01-01

    In this article, we present details of a one-week interdisciplinary science camp for high school students in Denmark, "Criminal Camp". We describe the use of forensic science and simulated crimes as a common foundation for teaching the theory and practice of concepts in chemistry, physics, and medicine or biology. The main goal of the…

  16. The Representation and Appropriation of Indigenous Cultures at Ontario Summer Camps.

    Science.gov (United States)

    Hamilton, Ty

    2003-01-01

    Interviews with directors at five Ontario summer camps found that three camps exposed children to stereotypes of Indigenous peoples and to cultural appropriation. This is inconsistent with goals of educating campers about and showing respect for Indigenous cultures. Given the current issues of land-claims and Aboriginal rights, non-Indigenous…

  17. Alaska Native Elders' Contribution to Education: The Fairbanks AISES Science Camp.

    Science.gov (United States)

    Bradley, Claudette; Reyes, Maria Elena

    The Fairbanks American Indian Science and Engineering Society (AISES) Science Camp was designed for Alaska Native middle school students from 11 school districts. The camp enables students to learn from Native Elders while completing hands-on science projects; stimulates interest and confidence in mathematics, science, and engineering among Alaska…

  18. Hands-on Summer Camp to Attract K-12 Students to Engineering Fields

    Science.gov (United States)

    Yilmaz, Muhittin; Ren, Jianhong; Custer, Sheryl; Coleman, Joyce

    2010-01-01

    This paper explains the organization and execution of a summer engineering outreach camp designed to attract and motivate high school students as well as increase their awareness of various engineering fields. The camp curriculum included hands-on, competitive design-oriented engineering projects from several disciplines: the electrical,…

  19. Adventure, Wilderness, Outward Bound, Therapeutic Camping, Experiental Learning, Ropes Courses & Games.

    Science.gov (United States)

    Gillis, H. Lee

    Focusing on the therapeutic aspects of camping experiences for delinquent and psychologically disturbed youth, this 382-item bibliography lists books, journal articles, theses, dissertations, and unpublished reports written from 1928 to 1983 on adventure education, wilderness experience, Outward Bound, therapeutic camping, experiential learning,…

  20. A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval

    NARCIS (Netherlands)

    Isiegas, Carolina; McDonough, Conor; Huang, Ted; Havekes, Robbert; Fabian, Sara; Wu, Long-Jun; Xu, Hui; Zhao, Ming-Gao; Kim, Jae-Ick; Lee, Yong-Seok; Lee, Hye-Ryeon; Ko, Hyoung-Gon; Lee, Nuribalhae; Choi, Sun-Lim; Lee, Jeong-Sik; Son, Hyeon; Zhuo, Min; Kaang, Bong-Kiun; Abel, Ted

    2008-01-01

    Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. However, the potential of the cAMP signaling pathway as a target for memory enhancement remains unclear because of contradictory findings from pharmacolog