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Sample records for multiple pro-apoptotic members

  1. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

    Rivera, Mariela; Ramos, Yanilda; Rodríguez-Valentín, Madeline; López-Acevedo, Sheila; Cubano, Luis A.; Zou, Jin; Zhang, Qiang; Wang, Guangdi

    2017-01-01

    Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses. PMID:28628644

  2. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells.

    Mariela Rivera

    Full Text Available Curcumin, an extract from the turmeric rhizome (Curcuma longa, is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12 and Poly (ADP-ribose polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

  3. Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells by NEO214, Perillyl Alcohol Conjugated to Rolipram.

    Chen, Thomas C; Chan, Nymph; Labib, Shirin; Yu, Jiali; Cho, Hee-Yeon; Hofman, Florence M; Schönthal, Axel H

    2018-01-17

    Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination. The cytotoxic mechanism of NEO214 involved severe ER stress and prolonged induction of CCAAT/enhancer-binding protein homologous protein (CHOP), a key pro-apoptotic component of the ER stress response. These effects were prevented by salubrinal, a pharmacologic inhibitor of ER stress, and by CHOP gene knockout. Conversely, combination of NEO214 with bortezomib, a drug in clinical use for patients with MM, resulted in synergistic enhancement of MM cell death. Combination with the adenylate cyclase stimulant forskolin did not enhance NEO214 impact, indicating that cyclic adenosine 3',5'-monophosphate (AMP) pathways might play a lesser role. Our study introduces the novel agent NEO214 as a potent inducer of ER stress with significant anti-MM activity in vitro. It should be further investigated as a potential MM therapy aimed at exploiting this tumor's distinct sensitivity to ER stress.

  4. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

    2011-03-04

    Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

  5. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Zeilstra, Jurrit; Joosten, Sander P.J.; Wensveen, Felix M.; Dessing, Mark C.; Schuetze, Denise M.; Eldering, Eric; Spaargaren, Marcel; Pals, Steven T.

    2011-01-01

    Research highlights: → Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. → Expression profiling of apoptosis-related genes in Apc Min/+ mice revealed the differential expression of pro-apoptotic Bok and Bax. → APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. → Blocking of β-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc Min/+ mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the

  6. Biochemical and biophysical investigations of the interaction between human glucokinase and pro-apoptotic BAD.

    Rexford, Alix; Zorio, Diego A R; Miller, Brian G

    2017-01-01

    The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD. Consistent with published reports, recombinant BAD displays high affinity for Bcl-xL (KD = 7 nM), and phosphorylation of BAD at S118, within the BH3 domain, abolishes this interaction. Unexpectedly, we do not detect association of recombinant, full-length BAD with recombinant human pancreatic GCK over a range of protein concentrations using various biochemical methods including size-exclusion chromatography, chemical cross-linking, analytical ultracentrifugation, and isothermal titration calorimetry. Furthermore, fluorescence polarization assays and isothermal titration calorimetry detect no direct interaction between GCK and BAD BH3 peptides. Kinetic characterization of GCK in the presence of high concentrations of recombinant BAD show modest (BAD BH3 peptides. These results raise questions as to the mechanism of action of stapled peptide analogs modeled after the BAD BH3 domain, which reportedly enhance the Vmax value of GCK and stimulate insulin release in BAD-deficient islets. Based on our results, we postulate that the BAD:GCK interaction, and any resultant regulatory effect(s) upon GCK activity, requires the participation of additional members of the mitochondrial complex.

  7. Baculovirus PTP2 functions as a pro-apoptotic protein

    Han, Yue; Houte, van Stineke; Oers, van Monique M.; Ros, Vera I.D.

    2018-01-01

    The family Baculoviridae encompasses a large number of invertebrate viruses, mainly infecting caterpillars of the order Lepidoptera. The baculovirus Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) induces physiological and behavioral changes in its host Spodoptera exigua, as well as

  8. The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma.

    Jolanta Kunert-Radek

    2004-03-01

    Full Text Available It is well established that disruption of apoptosis may lead to tumor initiation, progression or metastasis. It is also well documented that many anticancer drugs induce apoptosis. In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC and somatostatin analog octreotide (OCT were found to inhibit the growth of the estrogen-induced rat prolactinoma. Our previous investigations, applying the TUNEL method showed the involvement of the pro-apoptotic effect in the action of BC, and to a lesser degree, in the action of OCT. The aim of the present study was to investigate whether the pro-apoptotic action of these drugs involves the increased expression of Bax--a member of Bcl-2 protein family which is known to play an important role in the regulation of apoptosis. Male four-week Fisher 344 rats were used in the experiment. Capsules containing diethylstilboestrol (DES were implanted subcutaneously. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24, BC (3 mg/kg b.w./24 h or OCT and BC at the above doses for 10 days. Bax expression was detected by immunohistochemistry. Prolactin (PRL in blood serum was measured by radioimmunoassay (RIA. It has been found that both OCT and BC, alone or in combination, significantly reduce the tumor weight. Both OCT and BC suppressed PRL levels, but the inhibitory effect of BC was stronger than that of OCT. It has been found that the treatment with OCT and BC, alone or in combination, causes a significant increase in Bax expression in the rat prolactinoma cells. Our findings indicate that anti-tumoral action of bromocriptine and to some extent the action of octreotide in the experimental rat prolactinoma is connected with the induction of apoptosis and is associated with increased Bax expression.

  9. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation.

    Claudio Scafoglio

    Full Text Available Checkpoint kinase 2 (Chk2 is a major regulator of DNA damage response and can induce alternative cellular responses: cell cycle arrest and DNA repair or programmed cell death. Here, we report the identification of a new role of Chk2 in transcriptional regulation that also contributes to modulating the balance between survival and apoptosis following DNA damage. We found that Chk2 interacts with members of the NCoR/SMRT transcriptional co-regulator complexes and serves as a functional component of the repressor complex, being required for recruitment of SMRT on the promoter of pro-apoptotic genes upon DNA damage. Thus, the co-repressor SMRT exerts a critical protective action against genotoxic stress-induced caspase activation, repressing a functionally important cohort of pro-apoptotic genes. Amongst them, SMRT is responsible for basal repression of Wip1, a phosphatase that de-phosphorylates and inactivates Chk2, thus affecting a feedback loop responsible for licensing the correct timing of Chk2 activation and the proper execution of the DNA repair process.

  10. Pro-apoptotic signaling induced by Retinoic acid and dsRNA is under the control of Interferon Regulatory Factor-3 in breast cancer cells.

    Bernardo, Ana R; Cosgaya, José M; Aranda, Ana; Jiménez-Lara, Ana M

    2017-07-01

    Breast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic-polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells. IRF3 activation is mediated by a member of the pathogen recognition receptors, Toll-like receptor-3 (TLR3), since its depletion abrogates IRF3 activation by RA/poly(I:C) co-treatment. Besides induction of TRAIL, apoptosis induced by RA/poly(I:C) correlates with the increased expression of pro-apoptotic TRAIL receptors, TRAIL-R1/2, and the inhibition of the antagonistic receptors TRAIL-R3/4. IRF3 plays an important role in RA/poly(I:C)-induced apoptosis since IRF3 depletion suppresses caspase-8 and caspase-3 activation, TRAIL expression upregulation and apoptosis. Interestingly, RA/poly(I:C) combination synergizes to induce a bioactive autocrine/paracrine loop of type-I Interferons (IFNs) which is ultimately responsible for TRAIL and TRAIL-R1/2 expression upregulation, while inhibition of TRAIL-R3/4 expression is type-I IFN-independent. Our results highlight the importance of IRF3 and type-I IFNs signaling for the pro-apoptotic effects induced by RA and synthetic dsRNA in breast cancer cells.

  11. The pro-apoptotic action of the peptide hormone Neb-colloostatin on insect haemocytes.

    Czarniewska, E; Mrówczynska, L; Kuczer, M; Rosinski, G

    2012-12-15

    The gonadoinhibitory peptide hormone Neb-colloostatin was first isolated from ovaries of the flesh fly Neobellieria bullata. This 19-mer peptide is thought to be a cleaved product of a collagen-like precursor molecule that is formed during remodelling of the extracellular matrix. In this study, we report that upon injection of picomolar and nanomolar doses, this peptide exerts a pro-apoptotic action on haemocytes of Tenebrio molitor adults, as visualized by changes in morphology and viability. The F-actin cytoskeleton was found to aggregate into distinctive patches. This may be responsible for the observed inhibition of adhesion of haemocytes and for the stimulation of filopodia formation. However, Neb-colloostatin injection did not induce the formation of autophagic vacuoles. Our results suggest that physiological concentrations of Neb-colloostatin play an important role in controlling the quantity and activity of haemocytes in insect haemolymph. They also suggest that during periods in which Neb-colloostatin is released, this peptide may cause a weakening of the insects' immune system. This is the first report that exposure to a peptide hormone causes apoptosis in insect haemocytes.

  12. Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

    Takehara Tadamichi

    2006-03-01

    Full Text Available Abstract Background Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. Results We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2–12 h, P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24–36 h the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp suggested a role of some or all these proteases in myriad aspects of bacteria-gingival interaction. Conclusion The pathology of the gingival fibroblast in P. gingivalis infection is affected by a temporal shift from cellular survival response to apoptosis, regulated by a number of anti- and pro-apoptotic molecules. The gingipain group of proteases affects bacteria-host interactions and may directly promote apoptosis by intracellular proteolytic activation of caspase-3.

  13. Intrinsic, pro-apoptotic effects of IGFBP-3 on breast cancer cells are reversible: Involvement of PKA, Rho and ceramide.

    Claire M Perks

    2011-05-01

    Full Text Available We established previously that IGFBP-3 could exert positive or negative effects on cell function depending upon the extracellular matrix composition and by interacting with integrin signalling. To elicit its pro-apoptotic effects IGFBP-3 bound to caveolin-1 and the beta 1 integrin receptor and increased their association culminating in MAPK activation. Disruption of these complexes or blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP-3. In this study we have examined the signalling pathway between integrin receptor binding and MAPK activation that mediates the intrinsic, pro-apoptotic actions of IGFBP-3. We found on inhibiting protein kinase A(PKA, Rho associated kinase (ROCK and ceramide, the accentuating effects of IGFBP-3 on apoptotic triggers were reversed, such that IGFBP-3 then conferred cell survival. We established that IGFBP-3 activated Rho, the upstream regulator of ROCK and that beta1 integrin and PKA were upstream of Rho activation, whereas the involvement of ceramide was downstream. The beta 1 integrin, PKA, Rho and ceramide were all upstream of MAPK activation. These data highlight key components involved in the pro-apoptotic effects of IGFBP-3 and that inhibiting them leads to a reversal in the action of IGFBP-3.

  14. Inhibition of Hepatocarcinogenesis by ArtinM via Anti-proliferative and Pro-apoptotic Mechanisms.

    Braz, Mariana M; Roque-Barreira, Maria Cristina; Ramalho, Fernando S; Oliveira, Carlos A; Augusto, Marlei J; Ramalho, Leandra N Z

    ArtinM is a d-mannose-binding lectin found in the seeds of Artocarpus heterophyllus (jackfruit) that interacts with N-glycans, that is associated with receptors on the surface of phagocytic cells and induces the production of inflammatory mediators. Some of them are especially important because they may be required for antitumor immune response. This study aimed to evaluate the effect of ArtinM on hepatocellular preneoplastic foci. Wistar rats received 50 mg/kg of diethyl-nitrosamine (DEN) intraperitoneal weekly for 12 weeks. From the 14th week, the treated animals received 50 μg/kg of ArtinM subcutaneous every 2 weeks until the 18th week, whereas control animals were injected with vehicle alone. Preneoplastic-related factors were estimated using histological, western blotting and RT-PCR analysis. In comparison to the groups exposed to DEN, the ArtinM-treated rats showed diminution of preneoplastic foci, decreased expression of proliferating cell nuclear antigen (PCNA), increased number of nuclear p21 and p27 stained cells, augmented number of apoptotic cells, increased expression of p53, p42/44 MAPK and p21 proteins, reduced cyclin D1 (CCND1) protein levels and increased expression of TNFα and IFNγ genes. No difference was observed in interleukin 12 (IL12) protein levels. These findings indicate that ArtinM may provide protection against hepatocarcinogenesis as a result of the induction of cell-cycle blockage and pro-apoptotic mechanisms. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

    Xu, Ying; Gao, Cheng-Cheng; Pan, Zhen-Guo; Zhou, Chuan-Wen

    2018-02-12

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment. Copyright © 2018. Published by Elsevier Inc.

  16. EFP1 is an ER stress-induced glycoprotein which interacts with the pro-apoptotic protein Par-4

    Sarah Appel

    2009-05-01

    Full Text Available Sarah Appel1,2,6, Susanne Vetterkind1,2,6, Ansgar Koplin1,3, Barbara Maertens1,4, Meike Boosen1,5, Ute Preuss11The Institute of Genetics, University of Bonn, Bonn, Germany; 2Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, MA, USA; 3Center for Molecular Biology Heidelberg (ZMBH, Heidelberg, Germany; 4Institute of Biochemistry II, University of Cologne, Cologne, Germany; 5Institute of Pharmacology and Toxicology, University Hospital of Johann Wolfgang Goethe-University Frankfurt am Main, Frankfurt am Main, Germany; 6These authors contributed equally to this work.Abstract: We have isolated the rat ortholog of EFP1 (EF-hand binding protein 1 as a novel interaction partner of the pro-apoptotic protein Par-4 (prostate apoptosis response-4. Rat EFP1 contains two thioredoxin domains, the COOH-terminal one harboring a CGFC motif, and has a similar protein domain structure as members of the protein disulfide isomerase (PDI family. In REF52.2 and CHO cells, EFP1 colocalized with the endoplasmic reticulum (ER marker PDI. Furthermore, EFP1 possesses catalytic activity as demonstrated by an insulin disulfide reduction assay. Western blot analysis revealed two EFP1 protein bands of approximately 136 and 155 kDa, representing different glycosylation states of the protein. Complex formation between EFP1 and Par-4 was confirmed in vitro and in vivo by co-immunoprecipitation, dot blot overlay and pull-down experiments. In CHO cells, coexpression of EFP1 and Par-4 resulted in enhanced Par-4-mediated apoptosis, which required the catalytic activity of EFP1. Interestingly, EFP1 was specifically upregulated in NIH3T3 cells after induction of ER stress by thapsigargin, tunicamycin, and brefeldin A, but not by agents that induce oxidative stress or ER-independent apoptosis. Furthermore, we could show that the induction of apoptosis by Ca2+ stress-inducing agents was significantly decreased after si

  17. RACK1 downregulates levels of the pro-apoptotic protein Fem1b in apoptosis-resistant colon cancer cells.

    Subauste, M Cecilia; Ventura-Holman, Tereza; Du, Liqin; Subauste, Jose S; Chan, Shing-Leng; Yu, Victor C; Maher, Joseph F

    2009-12-01

    Evasion of apoptosis plays an important role in colon cancer progression. Following loss of the Apc tumor suppressor gene in mice, the gene encoding Fem1b is upregulated early in neoplastic intestinal epithelium. Fem1b is a pro-apoptotic protein that interacts with Fas, TNFR1 and Apaf-1, and increased expression of Fem1b induces apoptosis of cancer cells. Fem1b is a homolog of FEM-1, a protein in Caenorhabditis elegans that is negatively regulated by ubiquitination and proteasomal degradation. To study Fem1b regulation in colon cancer progression, we used apoptotis-sensitive SW480 cells, derived from a primary colon cancer, and their isogenic, apoptosis-resistant counterparts SW620 cells, derived from a subsequent metastatic lesion in the same patient. Treatment with proteasome inhibitor increased Fem1b protein levels in SW620 cells, but not in SW480 cells. In SW620 cells we found that endogenous Fem1b co-immunoprecipitates in complexes with RACK1, a protein known to mediate ubiquitination and proteasomal degradation of other pro-apoptotic proteins and to be upregulated in colon cancer. Full-length Fem1b, or the N-terminal region of Fem1b, associated with RACK1 when co-expressed in HEK293T cells, and RACK1 stimulated ubiquitination of Fem1b. RACK1 overexpression in SW620 cells led to downregulation of Fem1b protein levels. Conversely, downregulation of RACK1 led to upregulation of Fem1b protein levels, associated with induction of apoptosis, and this apoptosis was inhibited by blocking Fem1b protein upregulation. In conclusion, RACK1 downregulates levels of the pro-apoptotic protein Fem1b in metastatic, apoptosis-resistant colon cancer cells, which may promote apoptosis-resistance during progression of colon cancer.

  18. Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes.

    Kristy Zera

    Full Text Available Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

  19. BmICE-2 is a novel pro-apoptotic caspase involved in apoptosis in the silkworm, Bombyx mori.

    Yi, Hua-Shan; Pan, Cai-Xia; Pan, Chun; Song, Juan; Hu, Yan-Fen; Wang, La; Pan, Min-Hui; Lu, Cheng

    2014-02-28

    In this study we identified a potential pro-apoptotic caspase gene, Bombyx mori(B. mori)ICE-2 (BmICE-2) which encoded a polypeptide of 284 amino acid residues, including a (169)QACRG(173) sequence which surrounded the catalytic site and contained a p20 and a p10 domain. BmICE-2 expressed in Escherichia coli (E. coli) exhibited high proteolytic activity for the synthetic human initiator caspase-9 substrates Ac-LEHD-pNA, but little activity towards the effector caspase-3 substrates Ac-DEVD-pNA. When BmICE-2 was transiently expressed in BmN-SWU1 silkworm B. mori cells, we found that the high proteolytic activity for Ac-LEHD-pNA triggered caspase-3-like protease activity resulting in spontaneous cleavage and apoptosis in these cells. This effect was not replicated in Spodoptera frugiperda 9 cells. In addition, spontaneous cleavage of endogenous BmICE-2 in BmN-SWU1 cells could be induced by actinomycin D. These results suggest that BmICE-2 may be a novel pro-apoptotic gene with caspase-9 activity which is involved apoptotic processes in BmN-SWU1 silkworm B. mori cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Pro-apoptotic effect of a Mycoplasma hyopneumoniae putative type I signal peptidase on PK(15) swine cells.

    Paes, Jéssica A; Virginio, Veridiana G; Cancela, Martín; Leal, Fernanda M A; Borges, Thiago J; Jaeger, Natália; Bonorino, Cristina; Schrank, Irene S; Ferreira, Henrique B

    2017-03-01

    Mycoplasma hyopneumoniae is an economically significant swine pathogen that causes porcine enzootic pneumonia (PEP). Important processes for swine infection by M. hyopneumoniae depend on cell surface proteins, many of which are secreted by secretion pathways not completely elucidated so far. A putative type I signal peptidase (SPase I), a possible component of a putative Sec-dependent pathway, was annotated as a product of the sipS gene in the pathogenic M. hyopneumoniae 7448 genome. This M. hyopneumoniae putative SPase I (MhSPase I) displays only 14% and 23% of sequence identity/similarity to Escherichia coli bona fide SPase I, and, in complementation assays performed with a conditional E. coli SPase I mutant, only a partial restoration of growth was achieved with the heterologous expression of a recombinant MhSPase I (rMhSPase I). Considering the putative surface location of MhSPase I and its previously demonstrated capacity to induce a strong humoral response, we then assessed its potential to elicit a cellular and possible immunomodulatory response. In assays for immunogenicity assessment, rMhSPase I unexpectedly showed a cytotoxic effect on murine splenocytes. This cytotoxic effect was further confirmed using the swine epithelial PK(15) cell line in MTT and annexin V-flow cytometry assays, which showed that rMhSPase I induces apoptosis in a dose dependent-way. It was also demonstrated that this pro-apoptotic effect of rMhSPase I involves activation of a caspase-3 cascade. The potential relevance of the rMhSPase I pro-apoptotic effect for M. hyopneumoniae-host interactions in the context of PEP is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer′s Disease Mice

    Hui Shen

    2016-01-01

    Conclusions: These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

  2. Vicrostatin - an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities.

    Radu O Minea

    2010-06-01

    Full Text Available Similar to other integrin-targeting strategies, disintegrins have previously shown good efficacy in animal cancer models with favorable pharmacological attributes and translational potential. Nonetheless, these polypeptides are notoriously difficult to produce recombinantly due to their particular structure requiring the correct pairing of multiple disulfide bonds for biological activity. Here, we show that a sequence-engineered disintegrin (called vicrostatin or VCN can be reliably produced in large scale amounts directly in the oxidative cytoplasm of Origami B E. coli. Through multiple integrin ligation (i.e., alphavbeta3, alphavbeta5, and alpha5beta1, VCN targets both endothelial and cancer cells significantly inhibiting their motility through a reconstituted basement membrane. Interestingly, in a manner distinct from other integrin ligands but reminiscent of some ECM-derived endogenous anti-angiogenic fragments previously described in the literature, VCN profoundly disrupts the actin cytoskeleton of endothelial cells (EC inducing a rapid disassembly of stress fibers and actin reorganization, ultimately interfering with EC's ability to invade and form tubes (tubulogenesis. Moreover, here we show for the first time that the addition of a disintegrin to tubulogenic EC sandwiched in vitro between two Matrigel layers negatively impacts their survival despite the presence of abundant haptotactic cues. A liposomal formulation of VCN (LVCN was further evaluated in vivo in two animal cancer models with different growth characteristics. Our data demonstrate that LVCN is well tolerated while exerting a significant delay in tumor growth and an increase in the survival of treated animals. These results can be partially explained by potent tumor anti-angiogenic and pro-apoptotic effects induced by LVCN.

  3. Pro-apoptotic protein Noxa regulates memory T cell population size and protects against lethal immunopathology

    Wensveen, Felix M.; Klarenbeek, Paul L.; van Gisbergen, Klaas P. J. M.; Pascutti, Maria F.; Derks, Ingrid A. M.; van Schaik, Barbera D. C.; ten Brinke, Anja; de Vries, Niek; Cekinovic, Durdica; Jonjic, Stipan; van Lier, René A. W.; Eldering, Eric

    2013-01-01

    Memory T cells form a highly specific defense layer against reinfection with previously encountered pathogens. In addition, memory T cells provide protection against pathogens that are similar, but not identical to the original infectious agent. This is because each T cell response harbors multiple

  4. Bioactives in cactus (Opuntia ficus-indica) stems possess potent antioxidant and pro-apoptotic activities through COX-2 involvement.

    Kim, Jinhee; Soh, Soon Yil; Shin, Juha; Cho, Chi-Woung; Choi, Young Hee; Nam, Sang-Yong

    2015-10-01

    Bioactives extracted from cactus (Opuntia ficus-indica) stems were investigated for their chemopreventive activities using human cancer cells in vitro. The bioactives present in crude extracts were detected and quantified using high-performance liquid chromatography. Among all the extracts, such as hexane, ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20), the MeOH extract had the highest amount of polyphenolic compounds and the acetone extract exhibited the most potent effect at scavenging the 2,2,-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(•+) ) radical. In addition, most of the extracts, with the exception of hexane, exhibited significant cytotoxicity in human SW480 colon and MCF7 breast cancer cells. Overall, the SW480 cells were more sensitive than the MCF7 cells to the cytotoxic effect of the O. ficus-indica extracts (OFEs). Cell death by OFE treatment caused significant inhibition of cyclooxygenase-2 and increased the Bax/Bcl2 ratio in both SW480 and MCF7 cell lines. However, degradation of poly (ADP-ribose) polymerase was significantly increased by OFE only in the MCF7 cells, thereby inducing apoptosis. These findings demonstrate the health-benefit roles, including anti-oxidative and anti-proliferative activities as well as pro-apoptotic effects, of bioactive compounds in OFEs, suggesting a chemopreventive role in human cancer cells. © 2014 Society of Chemical Industry.

  5. Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted Hydroxynaphthanilides on Human Cancer Cell Lines

    Tereza Kauerova

    2016-07-01

    Full Text Available Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of salicylanilides, compounds possessing a wide range of pharmacological activities, including promising anticancer properties. The aim of this study was to evaluate the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides with a special focus on structure-activity relationships. The antiproliferative effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1 assay, and cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay. Protein expression was estimated by Western blotting. Our data indicate that the potential to cause the antiproliferative effect increases with the shift of the nitro substituent from the ortho- to the para-position. The most potent compounds, 3-hydroxy-N-(3-nitrophenylnaphthalene-2-carboxamide (2, and 2-hydroxy-N-(4-nitrophenyl-naphthalene-1-carboxamide (6 showed antiproliferative activity against THP-1 and MCF-7 cancer cells without affecting the proliferation of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1 and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1 protein levels, while the levels of cyclin B1 were not affected. Moreover, compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These results suggest that hydroxynaphthanilides might represent a potential model structure for the development of novel anticancer agents.

  6. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    Young-Mi Lim

    Full Text Available Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1 is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1 and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration.

  7. Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging.

    Beztsinna, N; de Matos, M B C; Walther, J; Heyder, C; Hildebrandt, E; Leneweit, G; Mastrobattista, E; Kok, R J

    2018-02-09

    Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells. The co-staining with specific antibodies and uptake blocking experiments revealed involvement of both clathrin-dependent and -independent pathways in ML1 endocytosis. Co-localization studies demonstrated the toxin transport from early endocytic vesicles to Golgi network; a retrograde road to the endoplasmic reticulum. The pro-apoptotic and antiproliferative activity of ML1 were shown in time lapse movies and subsequently quantified. ML1 cytotoxicity was less affected in multidrug resistant tumor cell line 4T1 in contrast to commonly used chemotherapeutic drug (ML1 resistance index 6.9 vs 13.4 for doxorubicin; IC 50 : ML1 1.4 ng/ml vs doxorubicin 24000 ng/ml). This opens new opportunities for the use of ML1 as an alternative treatment in multidrug resistant cancers.

  8. A novel assay for discovery and characterization of pro-apoptotic drugs and for monitoring apoptosis in patient sera.

    Bivén, K; Erdal, H; Hägg, M; Ueno, T; Zhou, R; Lynch, M; Rowley, B; Wood, J; Zhang, C; Toi, M; Shoshan, M C; Linder, S

    2003-06-01

    We have developed an apoptosis assay based on measurement of a neoepitope of cytokeratin-18 (CK18-Asp396) exposed after caspase-cleavage and detected by the monoclonal antibody M30. The total amount of caspase-cleaved CK18 which has accumulated in cells and tissue culture media during apoptosis is measured by ELISA. The sensitivity is sufficient for use in the 96-well format to allow high-through-put screening of drug libraries. We here describe strategies allowing classification of pro-apoptotic compounds according to their profiles of induction of apoptosis in the presence of pharmacological inhibitors. The time course of induction of CK18 cleavage can furthermore be used to distinguish structurally similar compounds. We propose that compounds that induce rapid CK18 cleavage have mechanisms of actions distinct from conventional genotoxic and microtubuli-targeting agents, and we present one example of an agent that induces almost immediate mitochondrial depolarization and cytochrome c release. Finally, CK18-Asp396 cleavage products are released from cells in tissue culture, and presumably from tumor cells in vivo. These products can be measured in sera from cancer patients. We present evidence suggesting that it will be possible to use the M30-ELISA assay for measuring chemotherapy-induced apoptosis in patient sera, opening possibilities for monitoring therapy.

  9. Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3′,4′,5′-Pentamethoxyflavone Isolated from Lantana ukambensis

    Wamtinga Richard Sawadogo

    2015-12-01

    Full Text Available Lantana ukambensis (Vatke Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population. This plant was extensively used in African folk medicinal traditions to treat chronic wounds but also as anti-leishmanial or cytotoxic remedies, especially in Burkina Faso, Tanzania, Kenya, or Ethiopia. This study investigates the in vitro bioactivity of polymethoxyflavones extracted from a L. ukambensis as anti-proliferative and pro-apoptotic agents. We isolated two known polymethoxyflavones, 5,6,7,3′,4′,5′-hexamethoxyflavone (1 and 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 from the whole plant of L. ukambensis. Their chemical structures were determined by spectroscopic analysis and comparison with published data. These molecules were tested for the anti-proliferative, cytotoxic and pro-apoptotic effects on human cancer cells. Among them, 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 was selectively cytotoxic against monocytic lymphoma (U937, acute T cell leukemia (Jurkat, and chronic myelogenous leukemia (K562 cell lines, but not against peripheral blood mononuclear cells (PBMCs from healthy donors, at all tested concentrations. Moreover, this compound exhibited significant anti-proliferative and pro-apoptotic effects against U937 acute myelogenous leukemia cells. This study highlights the anti-proliferative and pro-apoptotic effects of 5-hydroxy-6,7,3′,4′,5′-pentamethoxyflavone (2 and provides a scientific basis of traditional use of L. ukambensis.

  10. Cytotoxic and Pro-Apoptotic Effects of Honey Bee Venom and Chrysin on Human Ovarian Cancer Cells

    Elaheh Amini

    2015-06-01

    Full Text Available Background: The anti-cancer effects of honey bee venom (BV and chrysin might open a new window for treatment of chemo-resistant cancers. This study was designed to evaluate cytotoxic and pro-apoptotic effects of BV and chrysin on A2780cp cistplatin- resistant human ovarian cancer cells. Methods: As per the study objectives, A2780cp cells were categorized to 4 groups: 3 experiment groups (treated either with BV or chrysin or BV + chrysin and 1 control group (untreated cells.  Experiment group cells were cultured and treated by different concentrations of BV and chrysin for 24 hours. Then, experiment and control cells were studied with MTT assay, Annexin V-FITC, DAPI and Acridine Orange / Propidium Iodide statining, flow cytometry, caspase-3 and -9 assay, measurement of intracellular level of reactive oxygen species (ROS and RT-PCR. Results: MTT assay showed that 8 μg/mL BV, 40 µg/ml chrysin and 6 + 15 μg/mL BV + chrysin co-treatment induced 50% cell death on A2780cp cells compared with controls (P < 0.001. Morphological observations by inverted and fluorescent microscopy revealed ROS generation and apoptotic cell death under exposure to BV or chrysin or BV + chrysin co-treatment. Caspase-3 and -9 assay demonstrated that BV and chrysin triggered apoptosis through intrinsic pathway and RT-PCR demonstrated down-regulation of Bcl-2. Conclusion: Honey bee venom and chrysin are effective for destroying chemoresistant ovarian cancer cells through activation of intrinsic apoptosis, which propose them as potential candidates to be used in development of improved chemotherapeutic agents in the future.

  11. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.

    De Petrocellis, Luciano; Ligresti, Alessia; Schiano Moriello, Aniello; Iappelli, Mariagrazia; Verde, Roberta; Stott, Colin G; Cristino, Luigia; Orlando, Pierangelo; Di Marzo, Vincenzo

    2013-01-01

    Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ(9) -tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells. Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1-10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca(2+)). In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. These data support the clinical testing of CBD against prostate carcinoma. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  12. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Thomale, Jürgen [Institute of Cell Biology, University Duisburg-Essen, 45122 Essen (Germany); Schupp, Nicole [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany)

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  13. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-01-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  14. β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD

    Nair, Madhumathy G.; Desai, Krisha; Prabhu, Jyothi S.; Hari, P.S.; Remacle, Jose; Sridhar, T.S., E-mail: tssridhar@sjri.res.in

    2016-08-01

    Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells. Drug efflux based mechanisms do not contribute to this effect. We show that integrin β3 employs the PI3K-Akt and the MAPK pathway for enabling cell survival and proliferation. Further, our results indicate that integrin β3 helps inhibit epirubicin induced cytotoxicity by repression of the pro-apoptotic protein BAD, thus promoting an anti-apoptotic response. Myristoylated RGT peptide and a monoclonal antibody against integrin β3 brought about a reversal of this effect and chemosensitized the cells. These results identify β3 integrin signaling via repression of BAD as an important survival pathway used by breast cancer cells to evade chemotherapy induced stress. - Highlights: • Integrin β3 signaling promotes chemoresistance to epirubicin in breast cancer cells. • Integrin β3 promotes cell survival and proliferation in drug treated cells through the PI3K and MAPK pathways. • Integrin signaling helps evade drug induced cytotoxicity by repression of pro-apoptotic molecule; BAD.

  15. Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX-Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model.

    Zareba, Ilona; Surazynski, Arkadiusz; Chrusciel, Marcin; Miltyk, Wojciech; Doroszko, Milena; Rahman, Nafis; Palka, Jerzy

    2017-01-01

    The effect of impaired intracellular proline availability for proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis was studied. We generated a constitutively knocked-down PRODH/POX MCF-7 breast cancer cell line (MCF-7shPRODH/POX) as a model to analyze the functional consequences of impaired intracellular proline levels. We have used inhibitor of proline utilization in collagen biosynthesis, 2-metoxyestradiol (MOE), inhibitor of prolidase that generate proline, rapamycin (Rap) and glycyl-proline (GlyPro), substrate for prolidase. Collagen and DNA biosynthesis were evaluated by radiometric assays. Cell viability was determined using Nucleo-Counter NC-3000. The activity of prolidase was determined by colorimetric assay. Expression of proteins was assessed by Western blot and immunofluorescence bioimaging. Concentration of proline was analyzed by liquid chromatography with mass spectrometry. PRODH/POX knockdown decreased DNA and collagen biosynthesis, whereas increased prolidase activity and intracellular proline level in MCF-7shPRODH/POX cells. All studied compounds decreased cell viability in MCF-7 and MCF-7shPRODH/POX cells. DNA biosynthesis was similarly inhibited by Rap and MOE in both cell lines, but GlyPro inhibited the process only in MCF-7shPRODH/POX and MOE+GlyPro only in MCF-7 cells. All the compounds inhibited collagen biosynthesis, increased prolidase activity and cytoplasmic proline level in MCF-7shPRODH/POX cells and contributed to the induction of pro-survival mode only in MCF-7shPRODH/POX cells. In contrast, all studied compounds upregulated expression of pro-apoptotic protein only in MCF-7 cells. PRODH/POX was confirmed as a driver of apoptosis and proved the eligibility of MCF-7shPRODH/POX cell line as a highly effective model to elucidate the different mechanisms underlying proline utilization or generation in PRODH/POX-dependent pro-apoptotic pathways. © 2017 The Author(s). Published by S. Karger AG, Basel.

  16. Exon-skipping strategy by ratio modulation between cytoprotective versus pro-apoptotic clusterin forms increased sensitivity of LNCaP to cell death.

    Abdellatif Essabbani

    Full Text Available BACKGROUND: In prostate cancer the secreted form of clusterin (sCLU has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties. METHODOLOGY: In order to provide new therapeutic approaches targeting CLU, we developed a strategy based on exon skipping by using a lentiviral construct to preferentially induce the nuclear spliced form of the protein. The molecular construct was transduced in LNCaP cells for testing the modulation of sensitivity of the transduced cells to pro-apoptotic stress. RESULTS AND CONCLUSIONS: We showed an increase of nCLU/sCLU expression ratio in the prostate cancer cell line "LNCaP" after lentiviral vector-U7 nCLU transduction. Moreover, we showed a significant inhibition of cell proliferation in nCLU-U7 LNCaP cells after treatment with cisplatin and after exposure to ionizing radiation compared to control cells. Finally, we showed that nCLU-U7 LNCaP cells exposure to UV-C significantly reduced an increase of cell death compared to control. Finally, we showed that modulating nCLU expression had profound impact on Ku70/Bax interaction as well as Rad17 expression which could be a key mechanism in sensitizing cells to cell death. In conclusion, this is the first report showing that increasing of nCLU/sCLU expression ratio by using an "on demand alternative splicing" strategy successfully increased sensitivity to radiotherapy and chemotherapy of prostate cancer cells.

  17. Effect of hrHPV infection on anti-apoptotic gene and pro-apoptotic gene expression in cervical cancer tissue

    Min-Er Tang

    2016-09-01

    Full Text Available Objective: To study the effect of hrHPV infection on anti-apoptotic gene and pro-apoptotic gene expression in cervical cancer tissue. Methods: A total of 56 patients with cervical cancer, 94 cases of patients with cervical intraepithelial neoplasia and 48 cases of patients with chronic cervicitis who were treated in our hospital from May 2013 to December 2015 were selected for study and included in malignant group, precancerous lesion group and benign group respectively. hrHPV infection as well as the expression of anti-apoptotic genes and proapoptotic genes in cervical tissue were detected. Results: hrHPV infection rate and viral load in cervical tissue of malignant group were significantly higher than those of precancerous lesion group and benign group; P27 and p16 levels in cervical tissue of malignant group were significantly lower than those of precancerous lesion group and benign group, and K-ras, c-myc, Prdx4 and TNFAIP8 levels were significantly higher than those of precancerous lesion group and benign group; the greater the HPV virus load, the lower the p27 and p16 levels and the higher the K-ras, c-myc, Prdx4 and TNFAIP8 levels in cervical tissue. Conclusions: hrHPV infection can result in tumor suppressor genes p27 and p16 expression deletion and increase the expression of proto-oncogene and apoptosis-inhibiting genes, and it is associated with the occurrence and development of cervical cancer.

  18. Human colon cancer targeted pro-apoptotic, anti-metastatic and cytostatic effects of binuclear Silver(I)-N-Heterocyclic carbene (NHC) complexes.

    Asif, Muhammad; Iqbal, Muhammad Adnan; Hussein, Mouayed A; Oon, Chern Ein; Haque, Rosenani A; Khadeer Ahamed, Mohamed B; Abdul Majid, Aman Shah; Abdul Majid, Amin Malik Shah

    2016-01-27

    The current mechanistic study was conducted to explore the effects of increased lipophilicity of binuclear silver(I)-NHC complexes on cytotoxicity. Two new silver(I)-N-Heterocyclic Carbene (NHC) complexes (3 and 4), having lypophilic terminal alkyl chains (Octyl and Decyl), were derived from meta-xylyl linked bis-benzimidazolium salts (1 and 2). Each of the synthesized compounds was characterized by microanalysis and spectroscopic techniques. The complexes were tested for their cytotoxicity against a panel of human cancer c as well normal cell lines using MTT assay. Based on MTT assay results, complex 4 was found to be selectively toxic towards human colorectal carcinoma cell line (HCT 116). Complex 4 was further studied in detail to explore the mechanism of cell death and findings of the study revealed that complex 4 has promising pro-apoptotic and anti-metastatic activities against HCT 116 cells. Furthermore, it showed pronounced cytostatic effects in HCT 116 multicellular spheroid model. Hence, binuclear silver(I)-NHC complexes with longer terminal aliphatic chains have worth to be further studied against human colon cancer for the purpose of drug development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Polysaccharide peptide isolated from grass-cultured Ganoderma lucidum induces anti-proliferative and pro-apoptotic effects in the human U251 glioma cell line.

    Wang, Chunhua; Lin, Dongmei; Chen, Quan; Lin, Shuqian; Shi, Songsheng; Chen, Chunmei

    2018-04-01

    The Ganoderma lucidum ( G. lucidum ) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum . GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88.70:11.30. The polysaccharides were composed of l-arabinose, d-mannose and d-glucose at a molar ratio of 1.329:0.372:2.953 and a total of 17 amino acids were detected. The results of the current study demonstrated that GL-PP significantly inhibited U251 cellular proliferation. The proportion of G 0 /G 1 phase cells and sub-G 1 phase cells significantly increased as the concentration of GL-PP increased, as did the activity of caspase-3. These results indicate that GL-PP directly inhibited human glioma U251 proliferation by inducing cell cycle arrest and promoting apoptosis.

  20. Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.

    Shen, Kaikai; Lu, Fangfang; Xie, Jianling; Wu, Minfeng; Cai, Bo; Liu, Yurong; Zhang, Hong; Tan, Hongsheng; Pan, Yingyi; Xu, Hongxi

    2016-08-02

    Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

  1. Design and synthesis of thienopyrimidine urea derivatives with potential cytotoxic and pro-apoptotic activity against breast cancer cell line MCF-7.

    Abdelhaleem, Eman F; Abdelhameid, Mohammed K; Kassab, Asmaa E; Kandeel, Manal M

    2018-01-01

    A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC 50  = 9.29 μM). Moreover, compound 9c showed excellent VEGFR-2 inhibitory activity, at the sub-micromolar level with IC 50 value 0.2 μM, which is 2.1 folds more potent than sorafenib. Moreover, activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Compound 9c showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the expression of the tumor suppressor gene p53, elevation in Bax/BCL-2 ratio and a significant increase in the level of active caspase-3. Quantitative structure-activity relationship (QSAR) studies delivered equations of five 3D descriptors with R 2  = 0.814. This QSAR model provides an effective technique for understanding the observed antitumor properties and thus could be adopted for developing effective lead structures. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Human Thyroid Cancer-1 (TC-1 is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast

    Natalie K. Jones

    2015-07-01

    Full Text Available The human Thyroid Cancer-1 (hTC-1 protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. Here we show that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. Analysis of the 106 residues of hTC-1 in available protein databases revealed direct orthologues in jawed-vertebrates, including mammals, frogs, fish and sharks. No TC-1 orthologue was detected in lower organisms, including yeast. Here we show that TC-1 is a general pro-survival peptide since it prevents the growth- and cell death-inducing effects of copper in yeast. Human TC-1 also prevented the deleterious effects that occur due to the over-expression of a number of key pro-apoptotic peptides, including YCA1, YBH3, NUC1, and AIF1. Even though the protective effects were more pronounced with the over-expression of YBH3 and YCA1, hTC-1 could still protect yeast mutants lacking YBH3 and YCA1 from the effects of copper sulfate. This suggests that the protective effects of TC-1 are not limited to specific pathways or processes. Taken together, our results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.

  3. Reconstitution of the anti-apoptotic Bcl-2 protein into lipid membranes and biophysical evidence for its detergent-driven association with the pro-apoptotic Bax protein.

    Marcus Wallgren

    Full Text Available The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2 protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax, are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23-lauryl-ether (Brij-35 detergent at a level below its critical micelle concentration (CMC. Additional surface plasmon resonance (SPR measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A2 (a known inhibitory ligand of Bcl-2 to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC. Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.

  4. The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM).

    Frank, Daniel O; Dengjel, Jörn; Wilfling, Florian; Kozjak-Pavlovic, Vera; Häcker, Georg; Weber, Arnim

    2015-01-01

    The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.

  5. The pro-apoptotic BH3-only protein Bim interacts with components of the translocase of the outer mitochondrial membrane (TOM.

    Daniel O Frank

    Full Text Available The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM. In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20 by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.

  6. Pro-Apoptotic Role of the Human YPEL5 Gene Identified by Functional Complementation of a Yeast moh1Δ Mutation.

    Lee, Ji Young; Jun, Do Youn; Park, Ju Eun; Kwon, Gi Hyun; Kim, Jong-Sik; Kim, Young Ho

    2017-03-28

    To examine the pro-apoptotic role of the human ortholog (YPEL5) of the Drosophila Yippee protein, the cell viability of Saccharomyces cerevisiae mutant strain with deleted MOH1 , the yeast ortholog, was compared with that of the wild-type (WT)- MOH1 strain after exposure to different apoptogenic stimulants, including UV irradiation, methyl methanesulfonate (MMS), camptothecin (CPT), heat shock, and hyperosmotic shock. The moh1 Δ mutant exhibited enhanced cell viability compared with the WT- MOH1 strain when treated with lethal UV irradiation, 1.8 mM MMS, 100 µ CPT, heat shock at 50°C, or 1.2 M KCl. At the same time, the level of Moh1 protein was commonly up-regulated in the WT- MOH1 strain as was that of Ynk1 protein, which is known as a marker for DNA damage. Although the enhanced UV resistance of the moh1 Δ mutant largely disappeared following transformation with the yeast MOH1 gene or one of the human YPEL1-YPEL5 genes, the transformant bearing pYES2- YPEL5 was more sensitive to lethal UV irradiation and its UV sensitivity was similar to that of the WT- MOH1 strain. Under these conditions, the UV irradiation-induced apoptotic events, such as FITC-Annexin V stainability, mitochondrial membrane potential (ΔΨm) loss, and metacaspase activation, occurred to a much lesser extent in the moh1 Δ mutant compared with the WT- MOH1 strain and the mutant strain bearing pYES2- MOH1 or pYES2- YPEL5 . These results demonstrate the functional conservation between yeast Moh1 and human YPEL5, and their involvement in mitochondria-dependent apoptosis induced by DNA damage.

  7. Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and up-regulation of pro-apoptotic Bax/Bcl-2 ratio.

    Li, W Y; Chiu, Lawrence C M; Lam, W S; Wong, W Y; Chan, Y T; Ho, Y P; Wong, Elaine Y L; Wong, Y S; Ooi, Vincent E C

    2007-02-01

    Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non-specific immunoenhancing properties. Although the plant has been clinically used for treating a variety of diseases, its bioactive ingredients are largely unknown and its mode of action has never been investigated. In this study, the anti-tumor property of ethyl acetate (EA) extract of S. glabra was investigated by determining its in vitro growth-inhibitory effects on a panel of human cancer cell lines of different histotypes. Growth inhibition of the EA extract on the cancer cells seemed to be selective, and the leukemic HL-60 was found to be the most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric studies further illustrated that the extract might interfere with DNA replication and thus arrested the cell cycle at S phase in the leukemic cells, followed by DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after 72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up-regulated by more than 178% of the control level. All these findings suggested that the extract had initiated apoptosis to kill the leukemic cells. Results from this pioneer study help to establish a scientific foundation for future research and development of the bioactive ingredients in EA extract of S. glabra as efficacious anti-cancer agents.

  8. Mode of cell death induced by the HSP90 inhibitor 17-AAG (tanespimycin) is dependent on the expression of pro-apoptotic BAX.

    Powers, Marissa V; Valenti, Melanie; Miranda, Susana; Maloney, Alison; Eccles, Suzanne A; Thomas, George; Clarke, Paul A; Workman, Paul

    2013-11-01

    Inhibitors of the molecular chaperone heat shock protein 90 (HSP90) are of considerable current interest as targeted cancer therapeutic agents because of the ability to destabilize multiple oncogenic client proteins. Despite their resulting pleiotropic effects on multiple oncogenic pathways and hallmark traits of cancer, resistance to HSP90 inhibitors is possible and their ability to induce apoptosis is less than might be expected. Using an isogenic model for BAX knockout in HCT116 human colon carcinoma cells, we demonstrate the induction of BAX-dependent apoptosis at pharmacologically relevant concentrations of the HSP90 inhibitor 17-AAG both in vitro and in tumor xenografts in vivo. Removal of BAX expression by homologous recombination reduces apoptosis in vitro and in vivo but allows a lower level of cell death via a predominantly necrotic mechanism. Despite reducing apoptosis, the loss of BAX does not alter the overall sensitivity to 17-AAG in vitro or in vivo. The results indicate that 17-AAG acts predominantly to cause a cytostatic antiproliferative effect rather than cell death and further suggest that BAX status may not alter the overall clinical response to HSP90 inhibitors. Other agents may be required in combination to enhance tumor-selective killing by these promising drugs. In addition, there are implications for the use of apoptotic endpoints in the assessment of the activity of molecularly targeted agents.

  9. The innate immunity adaptor SARM translocates to the nucleus to stabilize lamins and prevent DNA fragmentation in response to pro-apoptotic signaling.

    Chad R Sethman

    Full Text Available Sterile alpha and armadillo-motif containing protein (SARM, a highly conserved and structurally unique member of the MyD88 family of Toll-like receptor adaptors, plays an important role in innate immunity signaling and apoptosis. Its exact mechanism of intracellular action remains unclear. Apoptosis is an ancient and ubiquitous process of programmed cell death that results in disruption of the nuclear lamina and, ultimately, dismantling of the nucleus. In addition to supporting the nuclear membrane, lamins serve important roles in chromatin organization, epigenetic regulation, transcription, nuclear transport, and mitosis. Mutations and other damage that destabilize nuclear lamins (laminopathies underlie a number of intractable human diseases. Here, we report that SARM translocates to the nucleus of human embryonic kidney cells by using its amino-terminal Armadillo repeat region. Within the nucleus, SARM forms a previously unreported lattice akin to the nuclear lamina scaffold. Moreover, we show that SARM protects lamins from apoptotic degradation and reduces internucleosomal DNA fragmentation in response to signaling induced by the proinflammatory cytokine Tumor Necrosis Factor alpha. These findings indicate an important link between the innate immunity adaptor SARM and stabilization of nuclear lamins during inflammation-driven apoptosis in human cells.

  10. A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities.

    Carone, Sante E I; Costa, Tássia R; Burin, Sandra M; Cintra, Adélia C O; Zoccal, Karina F; Bianchini, Francine J; Tucci, Luiz F F; Franco, João J; Torqueti, Maria R; Faccioli, Lúcia H; Albuquerque, Sérgio de; Castro, Fabíola A de; Sampaio, Suely V

    2017-10-01

    A new l-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II) was isolated by using a three-step chromatographic procedure based on molecular exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with pI=3.9 and molecular mass=60.36kDa that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53U/mg/mim). We determined part of the primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34 compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK). Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in the NCBI database revealed high similarity (95-97%) with other LAAOs isolated from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect against Leishmania amazonensis (IC 50 =4.56μg/mL) and Trypanosoma cruzi (IC 50 =4.85μg/mL). This toxin also induced cytotoxicity (IC 50 =1.80μg/mL) and apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results reported herein add important knowledge to the field of Toxinology, especially for the development of new therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP

    Barber, Claire; Netherton, Chris; Goatley, Lynnette [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom); Moon, Alice; Goodbourn, Steve [Institute for Infection and Immunity, St. George' s, University of London, London SW17 0RE (United Kingdom); Dixon, Linda, E-mail: linda.dixon@pirbright.ac.uk [The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF (United Kingdom)

    2017-04-15

    The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 or the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α. - Highlights: •The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate translation initiation factor eIF2α (eIF2α). •The residues V{sup 16}, F{sup 18} of DP71L are required for binding to the α, β and γ isoforms of PP1 and for DP71L function. •The sequence LSAVL downstream from the PP1 binding site (residues 57–61) are also important for DP71L function. •DP71L mutants of the LSAVL sequence retain ability to co-precipitate with PP1 showing these sequences have a different role to PP1 binding.

  12. An Involvement of PI3-K/Akt Activation and Inhibition of AIF Translocation in Neuroprotective Effects of Undecylenic Acid (UDA) Against Pro-Apoptotic Factors-Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells.

    Jantas, Danuta; Piotrowski, Marek; Lason, Wladyslaw

    2015-12-01

    Undecylenic acid (UDA), a naturally occurring 11-carbon unsaturated fatty acid, has been used for several years as an economical antifungal agent and a nutritional supplement. Recently, the potential usefulness of UDA as a neuroprotective drug has been suggested based on the ability of this agent to inhibit μ-calpain activity. In order to verify neuroprotective potential of UDA, we tested protective efficacy of this compound against cell damage evoked by pro-apoptotic factors (staurosporine and doxorubicin) and oxidative stress (hydrogen peroxide) in human neuroblastoma SH-SY5Y cells. We showed that UDA partially protected SH-SY5Y cells against the staurosporine- and doxorubicin-evoked cell death; however, this effect was not connected with its influence on caspase-3 activity. UDA decreased the St-induced changes in mitochondrial and cytosolic AIF level, whereas in Dox-model it affected only the cytosolic AIF content. Moreover, UDA (1-40 μM) decreased the hydrogen peroxide-induced cell damage which was connected with attenuation of hydrogen peroxide-mediated necrotic (PI staining, ADP/ATP ratio) and apoptotic (mitochondrial membrane potential, caspase-3 activation, AIF translocation) changes. Finally, we demonstrated that an inhibitor of PI3-K/Akt (LY294002) but not MAPK/ERK1/2 (U0126) pathway blocked the protection mediated by UDA in all tested models of SH-SY5Y cell injury. These in vitro data point to UDA as potentially effective neuroprotectant the utility of which should be further validated in animal studies. © 2015 Wiley Periodicals, Inc.

  13. Pro-Apoptotic Breast Cancer Nanotherapeutics

    2013-07-01

    R.; Hagooly, A.; Chen, Z.; Welch, M. J.; Wooley, K. L. Folate -Mediated Cell Uptake of Shell-Cross- linked Spheres and Cylinders. J. Polym. Sci. Part...Cancer Res. 1995, 55, 3825–3834. 44. Masson, C.; Scherman, D.; Bessodes, M. 2,2,6,6-Tetra- methyl -1-Piperidinyl-Oxyl/[Bis(Acetoxy)-Iodo]Benzene

  14. Surveying multiple health professional team members within institutional settings: an example from the nursing home industry.

    Clark, Melissa A; Roman, Anthony; Rogers, Michelle L; Tyler, Denise A; Mor, Vincent

    2014-09-01

    Quality improvement and cost containment initiatives in health care increasingly involve interdisciplinary teams of providers. To understand organizational functioning, information is often needed from multiple members of a leadership team since no one person may have sufficient knowledge of all aspects of the organization. To minimize survey burden, it is ideal to ask unique questions of each member of the leadership team in areas of their expertise. However, this risks substantial missing data if all eligible members of the organization do not respond to the survey. Nursing home administrators (NHA) and directors of nursing (DoN) play important roles in the leadership of long-term care facilities. Surveys were administered to NHAs and DoNs from a random, nationally representative sample of U.S. nursing homes about the impact of state policies, market forces, and organizational factors that impact provider performance and residents' outcomes. Responses were obtained from a total of 2,686 facilities (response rate [RR] = 66.6%) in which at least one individual completed the questionnaire and 1,693 facilities (RR = 42.0%) in which both providers participated. No evidence of nonresponse bias was detected. A high-quality representative sample of two providers in a long-term care facility can be obtained. It is possible to optimize data collection by obtaining unique information about the organization from each provider while minimizing the number of items asked of each individual. However, sufficient resources must be available for follow-up to nonresponders with particular attention paid to lower resourced, lower quality facilities caring for higher acuity residents in highly competitive nursing home markets. © The Author(s) 2014.

  15. Analysis of Multiple Choice Tests Designed by Faculty Members of Kermanshah University of Medical Sciences

    Reza Pourmirza Kalhori

    2013-12-01

    Full Text Available Dear Editor Multiple choice tests are the most common objective tests in medical education which are used to assess the ind-ividual knowledge, recall, recognition and problem solving abilities. One of the testing components is the post-test analysis. This component includes; first, qualitative analysis of the taxonomy of questions based on the Bloom’s educational objectives and percentage of the questions with no structural problems; and second, the quantitative analysis of the reliability (KR-20 and indices of difficulty and differentiation (1. This descriptive-analytical study was aimed to qualitatively and quan-titatively investigate the multiple-choice tests of the faculty members at Kermanshah University of Medical Sciences in 2009-2010. The sample size comprised of 156 tests. Data were analyzed by SPSS-16 software using t-test, chi-squared test, ANOVA and Tukey multiple comparison tests. The mean of reliability (KR-20, difficulty index, and discrimination index were 0.68 (± 0.31, 0.56 (± 0.15 and 0.21 (± 0.15, respectively, which were acceptable. The analysis of the tests at Mashad University of Medical Sciences indicated that the mean for the reliability of the tests was 0.72, and 52.2% of the tests had inappropriate difficulty index and 49.2% of the tests did not have acceptable differentiation index (2. Comparison of the tests at Kermanshah University of Medical Sciences for the fields of anatomy, physiology, biochemistry, genetics, statistics and behavioral sciences courses at Malaysia Faculty of Medicine (3 and tests at Argentina Faculty of Medicine (4 showed that while difficulty index was acceptable in all three universities, but differentiation indices in Malaysia and Argentina Medical Faculties were higher than that in Kermanshah University of Medical Sciences. The mean for the questions with no structural flaws in all tests, taxonomy I, taxonomy II, and taxonomy III were 73.88% (± 14.88, 34.65% (± 15.78, 41.34% (± 13

  16. Perceived Intrafamilial Connectedness and Autonomy in Families with and without an Anxious Family Member: A Multiple Informant Approach

    de Albuquerque, Jiske E. G.; Schneider, Silvia

    2012-01-01

    Perceived intrafamilial "emotional connectedness" and "autonomy" were investigated within families with and without an anxious family member using a multiple informant approach. The sample consisted of 32 mothers with a current anxiety disorder and 56 controls, their partners, and their anxious and nonanxious teenage children. No differences were…

  17. The β Pictoris association low-mass members: Membership assessment, rotation period distribution, and dependence on multiplicity

    Messina, S.; Lanzafame, A. C.; Malo, L.; Desidera, S.; Buccino, A.; Zhang, L.; Artemenko, S.; Millward, M.; Hambsch, F.-J.

    2017-10-01

    Context. Low-mass members of young loose stellar associations and open clusters exhibit a wide spread of rotation periods. Such a spread originates from the distributions of masses and initial rotation periods. However, multiplicity can also play a significant role. Aims: We aim to investigate the role played by physical companions in multiple systems in shortening the primordial disk lifetime, anticipating the rotation spin up with respect to single stars. Methods: We have compiled the most extensive list to date of low-mass bona fide and candidate members of the young 25-Myr β Pictoris association. We have measured from our own photometric time series or from archival time series the rotation periods of almost all members. In a few cases the rotation periods were retrieved from the literature. We used updated UVWXYZ components to assess the membership of the whole stellar sample. Thanks to the known basic properties of most members we built the rotation period distribution distinguishing between bona fide members and candidate members and according to their multiplicity status. Results: We find that single stars and components of multiple systems in wide orbits (>80 AU) have rotation periods that exhibit a well defined sequence arising from mass distribution with some level of spread likely arising from initial rotation period distribution. All components of multiple systems in close orbits (Pleiades shows that whereas the evolution of F-G stars is well reproduced by angular momentum evolution models, this is not the case for the slow K and early-M stars. Finally, we find that the amplitude of their light curves is correlated neither with rotation nor with mass. Conclusions: Once single stars and wide components of multiple systems are separated from close components of multiple systems, the rotation period distributions exhibit a well defined dependence on mass that allows us to make a meaningful comparison with similar distributions of either younger or older

  18. Effective Multi-Model Motion Tracking Under Multiple Team Member Actuators

    Gu, Yang; Veloso, Manuela

    2009-01-01

    Motivated by the interactions between a team and the tracked target, we contribute a method to achieve efficient tracking through using a play-based motion model and combined vision and infrared sensory information. This method gives the robot a more exact task-specific motion model when executing different tactics over the tracked target (e.g. the ball) or collaborating with the tracked target (e.g. the team member). Then we represent the system in a compact dynamic Bayesian network and use ...

  19. A germline RET proto-oncogene mutation in multiple members of an ...

    Background: Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer associated-syndrome, inherited in an autosomal dominant fashion and caused by germline mutation in RET proto-oncogene. Clinical diagnosis depends on the manifestation of two or more certain endocrine tumors in an individual, such as ...

  20. Age and helium content of the open cluster NGC 6791 from multiple eclipsing binary members. II

    Brogaard, K.; VandenBerg, D. A.; Bruntt, H.

    2012-01-01

    Models of stellar structure and evolution can be constrained by measuring accurate parameters of detached eclipsing binaries in open clusters. Multiple binary stars provide the means to determine helium abundances in these old stellar systems, and in turn, to improve estimates of their age. In th...

  1. Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion.

    Farré, Domènec; Martínez-Vicente, Pablo; Engel, Pablo; Angulo, Ana

    2017-05-01

    Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

    Eudes, Aymerick [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mouille, Maxence [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Robinson, David S. [Joint BioEnergy Institute, Emeryville, CA (United States); Benites, Veronica T. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); San Francisco State Univ., San Francisco, CA (United States); Wang, George [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Roux, Lucien [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Tsai, Yi-Lin [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Baidoo, Edward E. K. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chiu, Tsan-Yu [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Heazlewood, Joshua L. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); The Univ. of Melbourne, Melbourne, VIC (Australia); Scheller, Henrik V. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mukhopadhyay, Aindrila [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Keasling, Jay D. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Technical Univ. of Denmark, Horsholm (Denmark); Deutsch, Samuel [Joint BioEnergy Institute, Emeryville, CA (United States); Loqué, Dominique [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. Claude Bernard Lyon 1, Villeurbanne (France)

    2016-11-21

    . Similarly, we achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. In conclusion, we demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates.

  3. ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways

    Ni, Xiao; Zhang, Xiang; Hu, Cheng-Hui; Langridge, Timothy; Tarapore, Rohinton S.; Allen, Joshua E.; Oster, Wolfgang; Duvic, Madeleine

    2017-01-01

    Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4+ malignant T cells isolated from CTCL patients (n=5). ONC20...

  4. The pro-apoptotic effects of TIPE2 on AA rat fibroblast-like synoviocytes via regulation of the DR5–caspase–NF-κB pathway in vitro

    Shi C

    2016-02-01

    Full Text Available Chunyan Shi,1,2,* Shifeng Zhang,1,3,* Shifu Hong,1 Jinglong Pang,1 Yeletai Yesibulati,1 Ping Yin,4 Guohong Zhuang1 1Organ Transplantation Institute, Anti-Cancer Research Center, Medical College, Xiamen University, Xiamen, Fujian, 2The Department of Oncology, Jiujiang No.1 People’s Hospital, Jiujiang, Jiangxi City, 3Division of Gastroenterology Surgery, Zhongshan Hospital, Gastroenterology Institute of Xiamen University, Gastroenterology Center of Xiamen, 4The Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, People’s Republic of China *These authors contributed equally to this work Abstract: TIPE2, also known as TNFAIP8L2, a member of the tumor necrosis factor- alpha-induced protein-8 (TNFAIP8 family, is known as an inhibitor in inflammation and cancer, and its overexpression induces cell death. We examined the role of TIPE2 with respect to adjuvant arthritis (AA-associated pathogenesis by analyzing the TIPE2 regulation of death receptor (DR5-mediated apoptosis in vitro. The results showed that TIPE2 was detected in normal fibroblast-like synoviocytes (FLSs, but scarcely observed in AA-FLSs. Therefore, recombinant MIGR1/TIPE2+/+ and control MIGR1 lentivirus vectors were transfected to AA-FLSs, which were denoted as TIPE2+/+-FLSs and MIGR1-FLSs, respectively. Our results showed that TIPE2+/+-FLSs were highly susceptible to ZF1-mediated apoptosis, and ZF1 was our own purification of an anti-DR5 single chain variable fragment antibody. Under the presence of TIPE2, the expression of DR5 was significantly increased compared with that of the MIGR1-FLS group. In contrast, the level of phosphorylated nuclear factor-kappa B (pNF-κB was lower in the TIPE2+/+-FLS group treated with ZF1, whereas the activity of caspase was higher. Moreover, the rate of apoptosis in the TIPE2+/+-FLS group, which was pretreated with caspase inhibitor Z-VAD-FMK, was significantly decreased. In contrast, the apoptosis occurrence in the MIGR1

  5. ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways.

    Ni, Xiao; Zhang, Xiang; Hu, Cheng-Hui; Langridge, Timothy; Tarapore, Rohinton S; Allen, Joshua E; Oster, Wolfgang; Duvic, Madeleine

    2017-09-22

    Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4 + malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1.25-10.0 μM. ONC201 also induced apoptosis in tested cells with a narrow concentration range of 2.5-10.0 μM, evidenced by increased Annexin V + cells, accompanied by accumulated sub-G1 portions. ONC201 only induced apoptosis in CD4 + malignant T cells, not in normal CD4 + T cells. The activating transcription factor 4 (ATF4), a hallmark of integrated stress response, was upregulated in response to ONC201 whereas Akt was downregulated. In addition, molecules in JAK/STAT and NF-κB pathways, as well as IL-32β, were downregulated following ONC201 treatment. Thus, ONC201 exerts a potent and selective anti-tumor effect on CTCL cells. Its efficacy may involve activating integrated stress response through ATF4 and inactivating JAK/STAT and NF-κB pathways.

  6. Trophodynamics of the Hanna Shoal Ecosystem (Chukchi Sea, Alaska): Connecting multiple end-members to a rich food web

    McTigue, N. D.; Dunton, K. H.

    2017-10-01

    Predicting how alterations in sea ice-mediated primary production will impact Arctic food webs remains a challenge in forecasting ecological responses to climate change. One top-down approach to this challenge is to elucidate trophic roles of consumers as either specialists (i.e., consumers of predominantly one food resource) or generalists (i.e., consumers of multiple food resources) to categorize the dependence of consumers on each primary producer. At Hanna Shoal in the Chukchi Sea, Alaska, we used stable carbon and nitrogen isotope data to quantify trophic redundancy with standard ellipse areas at both the species and trophic guild levels. We also investigated species-level trophic plasticity by analyzing the varying extents that three end-members were assimilated by the food web using the mixing model simmr (Stable Isotope Mixing Model in R). Our results showed that ice algae, a combined phytoplankton and sediment organic matter composite (PSOM), and a hypothesized microphytobenthos (MPB) component were incorporated by consumers in the benthic food web, but their importance varied by species. Some primary consumers relied heavily on PSOM (e.g, the amphipods Ampelisca sp. and Byblis sp.; the copepod Calanus sp.), while others exhibited generalist feeding and obtained nutrition from multiple sources (e.g., the holothuroidean Ocnus glacialis, the gastropod Tachyrhynchus sp., the sipunculid Golfingia margaritacea, and the bivalves Ennucula tenuis, Nuculana pernula, Macoma sp., and Yoldia hyperborea). Most higher trophic level benthic predators, including the gastropods Buccinum sp., Cryptonatica affinis, and Neptunea sp, the seastar Leptasterias groenlandica, and the amphipod Anonyx sp. also exhibited trophic plasticity by coupling energy pathways from multiple primary producers including PSOM, ice algae, and MPB. Our stable isotope data indicate that consumers in the Hanna Shoal food web exhibit considerable trophic redundancy, while few species were specialists

  7. faloabi@uniben.edu Antiproliferative and Pro-apoptotic activities

    MICHAEL HORSFALL

    Keyword: Persea americana, antiproliferative activity, apoptotic effect, flow ... of the stem bark of Persea americana in MCF-7 cell line by flow cytometer. .... of an electric milling machine. ... Flow Cytometric Measurement Of Cell Proliferation:.

  8. Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL

    Hastie C James

    2006-01-01

    Full Text Available Abstract Background Pim-1, 2 and 3 are a group of enzymes related to the calcium calmodulin family of protein kinases. Over-expression of Pim-1 and Pim-2 in mice promotes the development of lymphomas, and up-regulation of Pim expression has been observed in several human cancers. Results Here we show that the pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells. In vitro mapping showed that Pim-2 predominantly phosphorylated Ser112, while Pim-1 phosphorylated Ser112, but also Ser136 and Ser155 at a reduced rate compared to Ser112. Pim-3 was found to be the least specific for Ser112, and the most effective at phosphorylating Ser136 and Ser155. Pim-3 was also able to phosphorylate other sites in Bad in vitro, including Ser170, another potential in vivo site. Mutation of Ser136 to alanine prevented the phosphorylation of Ser112 and Ser155 by Pim kinases in HEK-293 cells, suggesting that this site must be phosphorylated first in order to make the other sites accessible. Pim phosphorylation of Bad was also found to promote the 14-3-3 binding of Bad and block its association with Bcl-XL. Conclusion All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death.

  9. Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237 on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway

    Niu NK

    2015-03-01

    mesenchymal transition (EMT and the underlying mechanisms in two human OS cell lines U-2 OS and MG-63. The results showed that ALS had potent growth inhibitory, pro-apoptotic, pro-autophagic, and EMT inhibitory effects on U-2 OS and MG-63 cells. ALS remarkably induced G2/M arrest and down-regulated the expression levels of cyclin-dependent kinases 1 and 2 and cyclin B1 in both U-2 OS and MG-63 cells. ALS markedly induced mitochondria-mediated apoptosis with a significant increase in the expression of key pro-apoptotic proteins and a decrease in main anti-apoptotic proteins. Furthermore, ALS promoted autophagic cell death via the inhibition of phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt/mammalian target of rapamycin (mTOR and p38 mitogen-activated protein kinase (p38 MAPK signaling pathways, and activation of 5'-AMP-dependent kinase (AMPK signaling pathway. Inducers or inhibitors of apoptosis or autophagy simultaneously altered ALS-induced apoptotic and autophagic death in both U-2 OS and MG-63 cells, suggesting a crosstalk between these two primary modes of programmed cell death. Moreover, ALS suppressed EMT-like phenotypes with a marked increase in the expression of E-cadherin but a decrease in N-cadherin in U-2 OS and MG-63 cells. ALS treatment also induced reactive oxygen species (ROS generation but inhibited the expression levels of sirtuin 1 and nuclear factor-erythroid-2-related factor 2 (Nrf2 in both cell lines. Taken together, these findings show that ALS promotes apoptosis and autophagy but inhibits EMT via PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways with involvement of ROS- and sirtuin 1-associated pathways in U-2 OS and MG-63 cells. ALS is a promising anticancer agent in OS treatment and further studies are needed to confirm its efficacy and safety in OS chemotherapy. Keywords: ALS, autophagy, apoptosis, osteosarcoma, PI3K/Akt/mTOR pathway, EMT

  10. Family members' caregiving situations in palliative home care when sitting service is received: The understanding of multiple realities.

    Wallerstedt, Birgitta; Andershed, Birgitta; Benzein, Eva

    2014-12-01

    To deepen the understanding of the variation of complexity in family members' caregiving situations, when the private home is the place for care, dying, and sitting service. Seven relatives to a deceased family member from four different families were interviewed twice. Data were analyzed by direct interpretation and categorical aggregation. Various patterns of becoming a caregiver were showed, but family members' willingness to become family caregivers was strongly related to fulfilling the dying persons' wishes to be cared for in their own homes. Important factors for coping with the caregiving situation were their needs of support, the possibility to prepare for death related to a need of communication and planning, the length and predictability of the illness trajectory, and experiences of losses and grief. Sitting service was experienced as supportive for family caregivers when they had possibility to hand over care responsibilities, but as non-supportive when expected help not was received. Family members' experiences of caregiving and their degree of vulnerability must be different, depending on whether it is a self-selected position or an imposed task. In general, family members in this study were willing to participate in caregiving for end-of life care, but subject to their own conditions. One way to decrease vulnerability is to assess the resources and competence in relation to the responsibility the person is expected to assume. The support and other efforts to help family caregivers must be related to their specific needs and reality, not only to what the care organization can offer as a standard solution.

  11. Bacteroides intestinalis DSM 17393, a member of the human colonic microbiome, upregulates multiple endoxylanases during growth on xylan.

    Wang, Kui; Pereira, Gabriel V; Cavalcante, Janaina J V; Zhang, Meiling; Mackie, Roderick; Cann, Isaac

    2016-09-29

    Many human diets contain arabinoxylan, and the ease of genome sequencing coupled with reduced cost have led to unraveling the arsenal of genes utilized by the colonic Bacteroidetes to depolymerize this polysaccharide. The colonic Bacteroidetes with potential to ferment arabinoxylans include Bacteroides intestinalis. In this study, we analyzed the hydrolytic activities of members of a xylan degradation cluster encoded on the genome of Bacteroides intestinalis DSM 17393. Here, it is demonstrated that a cocktail of the xylanolytic enzymes completely hydrolyze arabinoxylans found in human diets. We show that this bacterium and relatives have evolved and secrete a unique bifunctional endoxylanase/arabinofuranosidase in the same polypeptide. The bifunctional enzyme and other secreted enzymes attack the polysaccharides extracellularly to remove the side-chains, exposing the xylan backbone for cleavage to xylo-oligosaccharides and xylose. These end products are transported into the cell where a β-xylosidase cleaves the oligosaccharides to fermentable sugars. While our experiments focused on B. intestinalis, it is likely that the extracellular enzymes also release nutrients to members of the colonic microbial community that practice cross-feeding. The presence of the genes characterized in this study in other colonic Bacteroidetes suggests a conserved strategy for energy acquisition from arabinoxylan, a component of human diets.

  12. Fixed capacity and variable member grouping assignment of orthogonal variable spreading factor code tree for code division multiple access networks

    Vipin Balyan

    2014-08-01

    Full Text Available Orthogonal variable spreading factor codes are used in the downlink to maintain the orthogonality between different channels and are used to handle new calls arriving in the system. A period of operation leads to fragmentation of vacant codes. This leads to code blocking problem. The assignment scheme proposed in this paper is not affected by fragmentation, as the fragmentation is generated by the scheme itself. In this scheme, the code tree is divided into groups whose capacity is fixed and numbers of members (codes are variable. A group with maximum number of busy members is used for assignment, this leads to fragmentation of busy groups around code tree and compactness within group. The proposed scheme is well evaluated and compared with other schemes using parameters like code blocking probability and call establishment delay. Through simulations it has been demonstrated that the proposed scheme not only adequately reduces code blocking probability, but also requires significantly less time before assignment to locate a vacant code for assignment, which makes it suitable for the real-time calls.

  13. Caregiver's Burden, Coping, and Psycho-Education in Indian Households with Single- and Multiple-Affected Members with Schizophrenia.

    Chakraborty, Satabdi; Bhatia, Triptish; Anderson, Carol; Nimgaonkar, Vishwajit L; Deshpande, Smita N

    2013-01-01

    There is considerable evidence that family psycho-education combined with pharmacological intervention for patients with schizophrenia increases family understanding of the illness, reduces the familial burden of care, and improves patient outcomes. However, no studies have determined whether the burden of care is greater for those families with more than one ill member (multiplex) than for families with a single-affected individual (simplex), and whether psycho-educational programs should be adapted to meet the specific needs of multiplex families. This study was conducted at a tertiary care postgraduate teaching hospital in New Delhi, India. Caregivers in simplex [n = 50] and multiplex families [n = 30] were compared with regard to levels of burden, coping, and the impact of psycho-education on family functioning. All the caregiver participants attended eight bimonthly, psycho-educational intervention sessions. They were assessed on the Burden Assessment Schedule (BAS) and the Coping Check List (CCL) before and after psycho-education. Caregivers from the multiplex families reported significantly more burden on two domains of the BAS, but there were no significant differences between the groups with regard to coping on the CCL. Following psycho-education, significant improvement occurred in the majority of domains of the BAS and the CCL; the effect sizes varied by domain and family type. Multiplex families face a greater burden of care compared with simplex families. Currently, available psycho-education programs are moderately effective for such families.

  14. Neuropsychological Performance and Subjective Symptom Reporting in Military Service Members With a History of Multiple Concussions: Comparison With a Single Concussion, Posttraumatic Stress Disorder, and Orthopedic Trauma.

    Cooper, Douglas B; Curtiss, Glenn; Armistead-Jehle, Patrick; Belanger, Heather G; Tate, David F; Reid, Matthew; Bowles, Amy O; Velez, Carmen S; Kennedy, Jan E; Vanderploeg, Rodney D

    To examine differences in objective neurocognitive performance and subjective cognitive symptoms in individuals with a history of a single concussion, multiple concussions, orthopedic injuries, and posttraumatic stress disorder (PTSD). Participants included 116 military service members who sustained a mild traumatic brain injury (mTBI) during combat deployment. Subjects were subdivided into groups based on concussion frequency: a single concussion (n = 42), 2 concussions (n = 21), and 3 or more concussions (n = 53). Eighty-one subjects sustained an orthopedic injury (n = 60) during deployment or were diagnosed with PTSD (n = 21), but had no history of mTBI. Subjects completed a battery of neuropsychological tests and self-report measures of postconcussive symptoms, PTSD symptoms, and psychopathology. No differences were found among the concussion groups on a composite neuropsychological measure. The PTSD group had the highest number of symptom complaints, with the 2-concussion and 3-plus-concussion groups being most similar to the PTSD group. The concussion groups showed a nonsignificant pattern of increasing distress with increasing number of concussions. The current findings are consistent with meta-analytic results showing no differential effect on neuropsychological functioning due to multiple concussions. Results also support the burden of adversity hypothesis suggesting increasing symptom levels with increasing psychological or physically traumatic exposures.

  15. Micro-Economics of Apoptosis in Cancer: ncRNAs Modulation of BCL-2 Family Members.

    Villanova, Lidia; Careccia, Silvia; De Maria, Ruggero; Fiori, Micol E

    2018-03-23

    In the last few years, non-coding RNAs (ncRNAs) have been a hot topic in cancer research. Many ncRNAs were found to regulate the apoptotic process and to play a role in tumor cell resistance to treatment. The apoptotic program is on the frontline as self-defense from cancer onset, and evasion of apoptosis has been classified as one of the hallmarks of cancer responsible for therapy failure. The B-cell lymphoma 2 (BCL-2) family members are key players in the regulation of apoptosis and mediate the activation of the mitochondrial death machinery in response to radiation, chemotherapeutic agents and many targeted therapeutics. The balance between the pro-survival and the pro-apoptotic BCL-2 proteins is strictly controlled by ncRNAs. Here, we highlight the most common mechanisms exerted by microRNAs, long non-coding RNAs and circular RNAs on the main mediators of the intrinsic apoptotic cascade with particular focus on their significance in cancer biology.

  16. Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

    Dimberg Lina Y

    2012-07-01

    Full Text Available Abstract Background Multiple myeloma (MM is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS. Results To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA, geldanamycin (17-AAG, doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion We conclude that Stat1 alters IL-6

  17. Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

    Dimberg, Lina Y; Nilsson, Kenneth; Öberg, Fredrik; Wiklund, Helena Jernberg; Dimberg, Anna; Ivarsson, Karolina; Fryknäs, Mårten; Rickardson, Linda; Tobin, Gerard; Ekman, Simon; Larsson, Rolf; Gullberg, Urban

    2012-01-01

    Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic

  18. Antagonizing Bcl-2 family members sensitizes neuroblastoma and Ewing's sarcoma to an inhibitor of glutamine metabolism.

    Rachelle R Olsen

    Full Text Available Neuroblastomas (NBL and Ewing's sarcomas (EWS together cause 18% of all pediatric cancer deaths. Though there is growing interest in targeting the dysregulated metabolism of cancer as a therapeutic strategy, this approach has not been fully examined in NBL and EWS. In this study, we first tested a panel of metabolic inhibitors and identified the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON as the most potent chemotherapeutic across all NBL and EWS cell lines tested. Myc, a master regulator of metabolism, is commonly overexpressed in both of these pediatric malignancies and recent studies have established that Myc causes cancer cells to become "addicted" to glutamine. We found DON strongly inhibited tumor growth of multiple tumor lines in mouse xenograft models. In vitro, inhibition of caspases partially reversed the effects of DON in high Myc expressing cell lines, but not in low Myc expressing lines. We further showed that induction of apoptosis by DON in Myc-overexpressing cancers is via the pro-apoptotic factor Bax. To relieve inhibition of Bax, we tested DON in combination with the Bcl-2 family antagonist navitoclax (ABT-263. In vitro, this combination caused an increase in DON activity across the entire panel of cell lines tested, with synergistic effects in two of the N-Myc amplified neuroblastoma cell lines. Our study supports targeting glutamine metabolism to treat Myc overexpressing cancers, such as NBL and EWS, particularly in combination with Bcl-2 family antagonists.

  19. Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

    Solti, Izabella; Kvell, Krisztian; Talaber, Gergely

    2015-01-01

    Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first...... mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3......- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus...

  20. Anti-mutagenic and Pro-apoptotic Effects of Apigenin on Human Chronic Lymphocytic Leukemia Cells

    Mehrdad Hashemi

    2010-09-01

    Full Text Available "nDiet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line were cultured in RPMI 1640 (Sigma, supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 ºC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100. Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when expose to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P<0.01 Apoptosis was induced suitably after 48 hours by flow cytometry assay. In Ames test apigenin prevented the reverted mutations and the hindrance percent of apigenin was 98.17%.These results have revealed apigenin induced apoptosis in human lymphoma B cells in vitro.

  1. Anti-mutagenic and Pro-apoptotic Effects of Apigenin on Human Chronic Lymphocytic Leukemia Cells

    Mehrdad Hashemi

    2010-10-01

    Full Text Available Diet can play a vital role in cancer prevention. Nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. The purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. In present study human chronic lymphocytic leukemia (Eheb cell line were cultured in RPMI 1640 (Sigma, supplemented with 10% fetal calf serum, penicillin-streptomycin, L-glutamine and incubated at 37 ºC for 2 days. In addition cancer cell line was treated by and apigenin and cellular vital capacity was determined by MTT assay. Then effect of apigenin in human lymphoma B cells was examined by flow cytometry techniques. The apigenin was subsequently evaluated in terms of anti-mutagenic properties by a standard reverse mutation assay (Ames test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100. Thus, it requires histidine from a foreign supply to ensure its growth. The aforementioned strain gives rise to reverted colonies when expose to sodium azide as a carcinogen substance. During MTT assay, human chronic lymphocytic leukemia revealed to have a meaningful cell death when compared with controls (P

  2. Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

    Sugihara, K; Kobayashi, Y; Suzuki, A; Tamura, N; Motamedchaboki, K; Huang, C-T; Akama, T O; Pecotte, J; Frost, P; Bauer, C; Jimenez, J B; Nakayama, J; Aoki, D; Fukuda, M N

    2014-07-22

    Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.

  3. Association of Pro-apoptotic Bad Gene Expression Changes with Benign Thyroid Nodules.

    Gül, Nurdan; Temel, Berna; Ustek, Duran; Sirma-Ekmekçi, Sema; Kapran, Yersu; Tunca, Fatih; Giles-Şenyürek, Yasemin; Özbek, Uğur; Alagöl, Faruk

    2018-01-01

    This study aimed to investigate the role of the mitochondrial apoptotic pathway in benign thyroid nodules. Paired samples of nodular and normal tissues were collected from 26 patients with nodular goiters undergoing thyroidectomy. Variable expression of Bcl-2, Bax and Bad genes were evaluated by quantitative PCR. Expression level of Bad gene in nodules was found to be significantly decreased compared to normal tissues (p=0.049). A positive correlation was observed between nodule size and Bad expression levels (correlation coefficient=0.563, p=0.004); and this correlation was stronger in hot nodules (n=18, correlation coefficient=0.689, p=0.003). No significant difference was observed between nodular and normal tissue expressions of Bax and Bcl-2. These results suggest that Bad expression correlates with the size of benign thyroid nodules and also its relatively lower expression in nodules, warrant further investigation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Antiproliferative and Pro-apoptotic activities of the stem bark of ...

    Persea americana (Lauraceae) have been used in traditional medicine for a wide range of illness and some of these uses have been proven scientifically. The aim of this present study is to screen for the phytochemical content, determine the proximate parameter and determine the antiproliferative and apoptotic effects of ...

  5. Activation of Pro-apoptotic Caspases in Non-apoptotic Cells During Odontogenesis and Related Osteogenesis

    Švandová, Eva; Veselá, Barbora; Tucker, A. S.; Matalová, Eva

    2018-01-01

    Roč. 9, č. 1 (2018), č. článku 174. ISSN 1664-042X Institutional support: RVO:67985904 Keywords : caspase * differentiation * apoptosis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 4.134, year: 2016

  6. Pro-apoptotic Effect of Pifithrin-α on Preimplantation Porcine Fertilized Embryo Development

    Brendan Mulligan

    2012-12-01

    Full Text Available The aim of this study was to investigate the impact of a reported p53 inhibitor, pifithrin-α (PFT-α, on preimplantation porcine in vitro fertilized (IVF embryo development in culture. Treatment of PFT-α was administered at both early (0 to 48 hpi, and later stages (48 to 168 hpi of preimplantation development, and its impact upon the expression of five genes related to apoptosis (p53, bak, bcl-xL, p66Shc and caspase3, was assessed in resulting d 7 blastocysts, using real-time quantitative PCR. Total cell numbers, along with the number of apoptotic nuclei, as detected by the in situ cell death detection assay, were also calculated on d 7 in treated and non-treated control embryos. The results indicate that PFT-α, when administered at both early and later stages of porcine IVF embryo development, increases the incidence of apoptosis in resulting blastocysts. When administered at early cleavage stages, PFT-α treatment was shown to reduce the developmental competence of porcine IVF embryos, as well as reducing the quality of resulting blastocysts in terms of overall cell numbers. In contrast, at later stages, PFT-α administration resulted in marginally increased blastocyst development rates amongst treated embryos, but did not affect cell numbers. However, PFT-α treatment induced apoptosis and apoptotic related gene expression, in all treated embryos, irrespective of the timing of treatment. Our results indicate that PFT-α may severely compromise the developmental potential of porcine IVF embryos, and is a potent apoptotic agent when placed into porcine embryo culture media. Thus, caution should be exercised when using PFT-α as a specific inhibitor of p53 mediated apoptosis, in the context of porcine IVF embryo culture systems.

  7. P53-dependent antiproliferative and pro-apoptotic effects of trichostatin A (TSA) in glioblastoma cells.

    Bajbouj, K; Mawrin, C; Hartig, R; Schulze-Luehrmann, J; Wilisch-Neumann, A; Roessner, A; Schneider-Stock, R

    2012-05-01

    Glioblastomas are known to be highly chemoresistant, but HDAC inhibitors (HDACi) have been shown to be of therapeutic relevance for this aggressive tumor type. We treated U87 glioblastoma cells with trichostatin A (TSA) to define potential epigenetic targets for HDACi-mediated antitumor effects. Using a cDNA array analysis covering 96 cell cycle genes, cyclin-dependent kinase inhibitor p21(WAF1) was identified as the major player in TSA-induced cell cycle arrest. TSA slightly inhibited proliferation and viability of U87 cells, cumulating in a G1/S cell cycle arrest. This effect was accompanied by a significant up-regulation of p53 and its transcriptional target p21(WAF1) and by down-regulation of key G1/S regulators, such as cdk4, cdk6, and cyclin D1. Nevertheless, TSA did not induce apoptosis in U87 cells. As expected, TSA promoted the accumulation of total acetylated histones H3 and H4 and a decrease in endogenous HDAC activity. Characterizing the chromatin modulation around the p21(WAF1) promoter after TSA treatment using chromatin immunoprecipitation, we found (1) a release of HDAC1, (2) an increase of acetylated H4 binding, and (3) enhanced recruitment of p53. p53-depleted U87 cells showed an abrogation of the G1/S arrest and re-entered the cell cycle. Immunofluorescence staining revealed that TSA induced the nuclear translocation of p21(WAF1) verifying a cell cycle arrest. On the other hand, a significant portion of p21(WAF1) was present in the cytoplasmic compartment causing apoptosis resistance. Furthermore, TSA-treated p53-mutant cell line U138 failed to show an induction in p21(WAF1), showed a deficient G2/M checkpoint, and underwent mitotic catastrophe. We suggest that HDAC inhibition in combination with other clinically used drugs may be considered an effective strategy to overcome chemoresistance in glioblastoma cells.

  8. Pro-apoptotic effects of the flavonoid luteolin in rat H4IIE cells

    Michels, G.; Waetjen, W.; Niering, P.; Steffan, B.; Thi, Q.-H. Tran; Chovolou, Y.; Kampkoetter, A.; Bast, A.; Proksch, P.; Kahl, R.

    2005-01-01

    Polyphenols are ubiquitous substances in the diet. Their anti-oxidative, anti-inflammatory and anti-viral effects are of interest for human health, and polyphenols such as luteolin are used at high concentrations in food supplements. The aim of this project was to determine the intrinsic effects of luteolin in H4IIE rat hepatoma cells. Luteolin is relatively toxic, cell death was caused via induction of apoptosis as detected by DNA-ladder formation, by nuclear fragmentation and activation of apoptotic enzymes (caspase-2, -3/7, -9 and -8/10). Luteolin (250 μM, 24 h) increased the caspase-3/7 activity four-fold and the caspase-9 activity six-fold. In a time course experiment caspase-9 is activated after 6 h, while caspase-2 and -3/7 are activated after 12 h. After 24 h, caspase-8/10 also displays activation. We found a concentration-dependent increase in malondialdehyde release suggesting a prooxidative effect of luteolin. Furthermore, we analysed DNA strand break formation by luteolin and found a distinct increase of DNA strand breaks after incubation for 3 h with 100 μM luteolin, a concentration which induces oligonucleosomal DNA cleavage at 24 h. In conclusion, the sequence of events is compatible with the assumption that luteolin triggers the mitochondrial pathway of apoptosis, probably by inducing DNA damage

  9. Biological Evaluation of Dipyrromethanes in Cancer Cell Lines: Antiproliferative and Pro-apoptotic Properties

    Jorda, Radek; Lopes, S. M.M.; Řezníčková, Eva; Kryštof, Vladimír; Pinho e Melo, T. M.V.D.

    2017-01-01

    Roč. 12, č. 9 (2017), s. 701-711 ISSN 1860-7179 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : anticancer agents * apoptosis * cell cycle * cytotoxicity * dipyrromethanes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Oncology Impact factor: 3.225, year: 2016

  10. Disruption of mitochondrial electron transport chain function potentiates the pro-apoptotic effects of MAPK inhibition.

    Trotta, Andrew P; Gelles, Jesse D; Serasinghe, Madhavika N; Loi, Patrick; Arbiser, Jack L; Chipuk, Jerry E

    2017-07-14

    The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma arising from the V600E mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAF V600E ), oncogenic signaling enhances glucose-dependent metabolism while reducing mitochondrial ATP production. Likewise, when BRAF V600E is pharmacologically inhibited by targeted therapies ( e.g. PLX-4032/vemurafenib), glucose metabolism is reduced, and cells increase mitochondrial ATP production to sustain survival. Therefore, collateral inhibition of oncogenic signaling and mitochondrial respiration may help enhance the therapeutic benefit of targeted therapies. Honokiol (HKL) is a well tolerated small molecule that disrupts mitochondrial function; however, its underlying mechanisms and potential utility with targeted anticancer therapies remain unknown. Using wild-type BRAF and BRAF V600E melanoma model systems, we demonstrate here that HKL administration rapidly reduces mitochondrial respiration by broadly inhibiting ETC complexes I, II, and V, resulting in decreased ATP levels. The subsequent energetic crisis induced two cellular responses involving cyclin-dependent kinases (CDKs). First, loss of CDK1-mediated phosphorylation of the mitochondrial division GTPase dynamin-related protein 1 promoted mitochondrial fusion, thus coupling mitochondrial energetic status and morphology. Second, HKL decreased CDK2 activity, leading to G 1 cell cycle arrest. Importantly, although pharmacological inhibition of oncogenic MAPK signaling increased ETC activity, co-treatment with HKL ablated this response and vastly enhanced the rate of apoptosis. Collectively, these findings integrate HKL action with mitochondrial respiration and shape and substantiate a pro-survival role of mitochondrial function in melanoma cells after oncogenic MAPK inhibition.

  11. Pro-apoptotic effect of Persea americana var. Hass (avocado) on Jurkat lymphoblastic leukemia cells.

    Bonilla-Porras, Angelica R; Salazar-Ospina, Andrea; Jimenez-Del-Rio, Marlene; Pereañez-Jimenez, Andres; Velez-Pardo, Carlos

    2013-11-05

    Abstract Context: Therapy for leukemia has a limited efficacy. There is a need to search for alternative anti-leukemia therapies. Persea americana Mill var. Hass (Lauraceae) is a tropical fruit (avocado) that might be used against cancer. Objective: To investigate whether P. americana induces death in Jurkat lymphoblastic leukemia cells. Materials and methods: Four ethanol extracts (0.1, 0.5, 1, 2 and 5 mg/mL) from avocado fruit (endocarp, whole seed, seed and leaves) were analyzed against Jurkat cells. Hydrogen peroxide generation by oxidation of 2',7'-dichlorodihydrofluorescein diacetate to the fluorescent compound 2',7'-dichlorfluorescein assay, acridine orange/ethidium bromide staining, flow cytometry analysis of annexin-V/7-amino-actinomycin, mitochondrial membrane potential and immunocytochemistry detection of transcription factor p53, caspase-3 and apoptosis-inducing factor (AIF) were evaluated. Results: Endocarp, seed, whole seed, and leaf (0.1 mg/mL) extracts induced significant apoptosis in Jurkat cells (p avocado and its therapeutic action on leukemia.

  12. Caregiver’s Burden, Coping, and Psycho-Education in Indian Households with Single- and Multiple-Affected Members with Schizophrenia

    Chakraborty, Satabdi; Bhatia, Triptish; Anderson, Carol; Nimgaonkar, Vishwajit L.; Deshpande, Smita N.

    2017-01-01

    There is considerable evidence that family psycho-education combined with pharmacological intervention for patients with schizophrenia increases family understanding of the illness, reduces the familial burden of care, and improves patient outcomes. However, no studies have determined whether the burden of care is greater for those families with more than one ill member (multiplex) than for families with a single-affected individual (simplex), and whether psycho-educational programs should be adapted to meet the specific needs of multiplex families. This study was conducted at a tertiary care postgraduate teaching hospital in New Delhi, India. Caregivers in simplex [n = 50] and multiplex families [n = 30] were compared with regard to levels of burden, coping, and the impact of psycho-education on family functioning. All the caregiver participants attended eight bimonthly, psycho-educational intervention sessions. They were assessed on the Burden Assessment Schedule (BAS) and the Coping Check List (CCL) before and after psycho-education. Caregivers from the multiplex families reported significantly more burden on two domains of the BAS, but there were no significant differences between the groups with regard to coping on the CCL. Following psycho-education, significant improvement occurred in the majority of domains of the BAS and the CCL; the effect sizes varied by domain and family type. Multiplex families face a greater burden of care compared with simplex families. Currently, available psycho-education programs are moderately effective for such families. PMID:29449743

  13. The "11K" gene family members sf68, sf95 and sf138 modulate transmissibility and insecticidal properties of Spodoptera frugiperda multiple nucleopolyhedrovirus.

    Beperet, Inés; Simón, Oihane; Williams, Trevor; López-Ferber, Miguel; Caballero, Primitivo

    2015-05-01

    The "11K" gene family is notable for having homologs in both baculoviruses and entomopoxviruses and is classified as either type 145 or type 150, according to their similarity with the ac145 or ac150 genes of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). One homolog of ac145 (sf138) and two homologs of ac150 (sf68 and sf95) are present in Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV). Recombinant bacmids lacking sf68, sf95 or sf138 (Sf68null, Sf95null and Sf138null, respectively) and the respective repair bacmids were generated from a bacmid comprising the complete virus genome. Occlusion bodies (OBs) of the Sf138null virus were ∼15-fold less orally infective to insects, which was attributed to a 100-fold reduction in ODV infectious titer. Inoculation of insects with Sf138null OBs in mixtures with an optical brightener failed to restore the pathogenicity of Sf138null OBs to that of the parental virus, indicating that the effects of sf138 deletion on OB pathogenicity were unlikely to involve an interaction with the gut peritrophic matrix. In contrast, deletion of sf68 and sf95 resulted in a slower speed-of-kill by 9h, and a concurrent increase in the yield of OBs. Phylogenetic analysis indicated that sf68 and sf95 were not generated after a duplication event of an ancestral gene homologous to the ac150 gene. We conclude that type 145 genes modulate the primary infection process of the virus, whereas type 150 genes appear to have a role in spreading systemic infection within the insect. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Identification and Molecular Characterization of Nuclear Citrus leprosis virus, a Member of the Proposed Dichorhavirus Genus Infecting Multiple Citrus Species in Mexico.

    Roy, Avijit; Stone, Andrew L; Shao, Jonathan; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Levy, Laurene; Nakhla, Mark K; Hartung, John S; Schneider, William L; Brlansky, Ronald H

    2015-04-01

    Citrus leprosis is one of the most destructive diseases of Citrus spp. and is associated with two unrelated virus groups that produce particles primarily in either the cytoplasm or nucleus of infected plant cells. Symptoms of leprosis, including chlorotic spots surrounded by yellow haloes on leaves and necrotic spots on twigs and fruit, were observed on leprosis-affected mandarin and navel sweet orange trees in the state of Querétaro, Mexico. Serological and molecular assays showed that the cytoplasmic types of Citrus leprosis virus (CiLV-C) often associated with leprosis symptomatic tissues were absent. However, using transmission electron microscopy, bullet-shaped rhabdovirus-like virions were observed in the nuclei and cytoplasm of the citrus leprosis-infected leaf tissues. An analysis of small RNA populations from symptomatic tissue was carried out to determine the genome sequence of the rhabdovirus-like particles observed in the citrus leprosis samples. The complete genome sequence showed that the nuclear type of CiLV (CiLV-N) present in the samples consisted of two negative-sense RNAs: 6,268-nucleotide (nt)-long RNA1 and 5,847-nt-long RNA2, excluding the poly(A) tails. CiLV-N had a genome organization identical to that of Orchid fleck virus (OFV), with the exception of shorter 5' untranslated regions in RNA1 (53 versus 205 nt) and RNA2 (34 versus 182 nt). Phylogenetic trees constructed with the amino acid sequences of the nucleocapsid (N) and glycoproteins (G) and the RNA polymerase (L protein) showed that CiLV-N clusters with OFV. Furthermore, phylogenetic analyses of N protein established CiLV-N as a member of the proposed genus Dichorhavirus. Reverse-transcription polymerase chain reaction primers for the detection of CiLV-N were designed based on the sequence of the N gene and the assay was optimized and tested to detect the presence of CiLV-N in both diseased and symptom-free plants.

  15. Cannabidiol inhibits angiogenesis by multiple mechanisms.

    Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

    2012-11-01

    Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  16. Members of the Agency

    2007-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.63) is Palau which deposited its Instrument of Acceptance of the Statute on 2 March 2007. The Attachment hereto shows the dates on which the present 144 Member States became Members [fr

  17. Members of the Agency

    2007-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.63) is Palau which deposited its Instrument of Acceptance of the Statute on 2 March 2007. The Attachment hereto shows the dates on which the present 144 Member States became Members [es

  18. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Liagre, Bertrand

    2013-01-01

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression

  19. Mechanistic Studies of Oligonucleotide Aptamers With Potent Antiproliferative and Pro-Apoptotic Activity Against Prostate Cancer Cells

    2007-05-01

    Quadruplex structures in nucleic acids. Biopolymers , 2000. 56(3): p. 123-46. 16. Mills, M., et al., Unusual DNA conformations: implications for telomeres...scanning autoradiographic films and using UN-SCAN-IT gel software ( Silk Scientific Corporation, UT, USA). Band intensities were normalized as indicated in

  20. Pro-apoptotic and anti-proliferative effects of corn silk extract on human colon cancer cell lines

    Guo, Hao; Guan, Hong; Yang, Wenqin; Liu, Han; Hou, Huiling; Chen, Xue; Liu, Zhenyan; Zang, Chuangang; Liu, Yuchao; Liu, Jicheng

    2016-01-01

    Corn silk is an economically and nutritionally significant natural product as it represents a staple food for a large proportion of the world population. This study investigated the anticancer activity of corn silk extract in human colon cancer cells and human gastric cancer cells. Following treatment with corn silk extract, certain apoptosis-related events were observed, including inhibition of cell proliferation, loss of mitochondrial membrane potential (??m), release of Ca2+ and release of...

  1. Pro-apoptotic and anti-proliferative effects of corn silk extract on human colon cancer cell lines.

    Guo, Hao; Guan, Hong; Yang, Wenqin; Liu, Han; Hou, Huiling; Chen, Xue; Liu, Zhenyan; Zang, Chuangang; Liu, Yuchao; Liu, Jicheng

    2017-02-01

    Corn silk is an economically and nutritionally significant natural product as it represents a staple food for a large proportion of the world population. This study investigated the anticancer activity of corn silk extract in human colon cancer cells and human gastric cancer cells. Following treatment with corn silk extract, certain apoptosis-related events were observed, including inhibition of cell proliferation, loss of mitochondrial membrane potential (ΔΨm), release of Ca2+ and release of cytochrome c from the mitochondria into the cytosol. Our results revealed that corn silk extract inhibited the proliferation of cancer cells and increased the level of apoptosis in a concentration-dependent manner. Western blot analysis revealed that corn silk extract upregulated the levels of Bax, cytochrome c , caspase-3 and caspase-9, but downregulated the levels of B-cell lymphoma 2. These results suggest that corn silk extract may induce apoptosis through the mitochondria-mediated pathway.

  2. Three RNA recognition motifs participate in RNA recognition and structural organization by the pro-apoptotic factor TIA-1

    Bauer, William J.; Heath, Jason; Jenkins, Jermaine L.; Kielkopf, Clara L.

    2012-01-01

    T-cell intracellular antigen-1 (TIA-1) regulates developmental and stress-responsive pathways through distinct activities at the levels of alternative pre-mRNA splicing and mRNA translation. The TIA-1 polypeptide contains three RNA recognition motifs (RRMs). The central RRM2 and C-terminal RRM3 associate with cellular mRNAs. The N-terminal RRM1 enhances interactions of a C-terminal Q-rich domain of TIA-1 with the U1-C splicing factor, despite linear separation of the domains in the TIA-1 sequence. Given the expanded functional repertoire of the RRM family, it was unknown whether TIA-1 RRM1 contributes to RNA binding as well as documented protein interactions. To address this question, we used isothermal titration calorimetry and small-angle X-ray scattering (SAXS) to dissect the roles of the TIA-1 RRMs in RNA recognition. Notably, the fas RNA exhibited two binding sites with indistinguishable affinities for TIA-1. Analyses of TIA-1 variants established that RRM1 was dispensable for binding AU-rich fas sites, yet all three RRMs were required to bind a polyU RNA with high affinity. SAXS analyses demonstrated a `V' shape for a TIA-1 construct comprising the three RRMs, and revealed that its dimensions became more compact in the RNA-bound state. The sequence-selective involvement of TIA-1 RRM1 in RNA recognition suggests a possible role for RNA sequences in regulating the distinct functions of TIA-1. Further implications for U1-C recruitment by the adjacent TIA-1 binding sites of the fas pre-mRNA and the bent TIA-1 shape, which organizes the N- and C-termini on the same side of the protein, are discussed. PMID:22154808

  3. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect

    Ghezali, Lamia; Leger, David Yannick; Limami, Youness [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Cook-Moreau, Jeanne [Université de Limoges, FR 3503 GEIST, UMR CNRS 7276 “Contrôle de la réponse immune B et lymphoproliférations”, Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Beneytout, Jean-Louis [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France); Liagre, Bertrand, E-mail: bertrand.liagre@unilim.fr [Université de Limoges, FR 3503 GEIST, EA 1069 “Laboratoire de Chimie des Substances Naturelles”, GDR CNRS 3049, Faculté de Pharmacie, Laboratoire de Biochimie et Biologie Moléculaire, 2 rue du Docteur Marcland, 87025 Limoges Cedex (France)

    2013-04-15

    Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines. - Highlights: ► Cyclopamine alone but not jervine induces apoptosis in human erythroleukemia cells. ► Cyclopamine and jervine induce COX-2 overexpression. ► COX-2 overexpression is implicated in resistance to cyclopamine-induced apoptosis. ► Apoptotic potential of jervine is restrained by NF-κB pathway activation. ► PKC is involved in cyclopamine-induced apoptosis and COX-2 overexpression.

  4. Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy

    Dong, L.-F.; Jameson, V.J.A.; Tilly, D.; Procházka, L.; Rohlena, Jakub; Vališ, Karel; Truksa, Jaroslav; Zobalová, Renata; Mandavian, E.; Klučková, Katarína; Stantic, M.; Štursa, Jan; Freeman, R.; Witting, P.K.; Norberg, E.; Goodwin, J.; Salvatore, B.A.; Novotná, Jana; Turánek, J.; Ledvina, Miroslav; Hozák, Pavel; Zhivotovsky, B.; Coster, M.; Ralph, S.J.; Smith, R.A.J.; Neužil, Jiří

    2011-01-01

    Roč. 50, č. 11 (2011), s. 1546-1555 ISSN 0891-5849 R&D Projects: GA ČR GA204/08/0811; GA ČR GAP301/10/1937; GA AV ČR IAA500520702; GA AV ČR KAN200520703; GA AV ČR KJB500970904; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50520514; CEZ:AV0Z4055905 Keywords : Triphenyl phosphonium * reactive oxygen species * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.423, year: 2011

  5. Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

    Leno-Durán, E; Ruiz-Magaña, M J; Muñoz-Fernández, R; Requena, F; Olivares, E G; Ruiz-Ruiz, C

    2014-10-10

    Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place. This work was supported by the Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (Grant CTS-6183, Proyectos de Investigación de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educación y Ciencia, Spain and the University of Granada. The authors have no conflict of interest. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex

    Dong, L.F.; Jameson, V.J.A.; Tilly, D.; Černý, Jiří; Mahdavian, E.; Marin-Hernandez, A.; Hernandez-Esquivel, L.; Rodriguez-Enriquez, S.; Štursa, Jan; Witting, P.K.; Stantic, B.; Rohlena, Jakub; Truksa, Jaroslav; Klučková, Katarína; Dyason, J.C.; Ledvina, Miroslav; Salvatore, B.A.; Moreno-Sanchez, R.; Coster, M.; Ralph, S.J.; Smith, A.J.; Neužil, Jiří

    2011-01-01

    Roč. 286, č. 5 (2011), s. 3717-3728 ISSN 0021-9258 R&D Projects: GA ČR(CZ) GA204/08/0811; GA ČR(CZ) GAP301/10/1937; GA AV ČR(CZ) IAA500520702; GA AV ČR(CZ) KAN200520703; GA AV ČR(CZ) KJB500970904 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z4055905 Keywords : Apoptosis induction * proximal ubiquinone-binding site of mitochondrial complex II * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.773, year: 2011

  7. A Novel Membrane-Permeable Breast-Targeting Pro-Apoptotic Peptide for Treatment of Breast Cancer

    Guo, Bin

    2005-01-01

    .... The BH3 peptide of Bid (EDIIRNIARHLAQVGDSMDR) was synthesized with eight d-arginine residues at the N-terminus with a glycine linker residue, followed by a breast-homing sequence (CPGPEGAGC) at the C-terminal...

  8. Metallic gold reduces TNFalpha expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury

    Pedersen, Mie Ostergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    Brain injury represents a major health problem and may result in chronic inflammation and neurodegeneration. Due to antiinflammatory effects of gold, we have investigated the cerebral effects of metallic gold particles following a focal brain injury (freeze-lesion) in mice. Gold particles 20......-45 microm in size or the vehicle (placebo) were implanted in the cortical tissue followed by a cortical freeze-lesioning. At 1-2 weeks post-injury, brains were analyzed by using immunohistochemistry and markers of inflammation, oxidative stress and apoptosis. This study shows that gold treatment...

  9. PKCη confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells

    Rotem-Dai, Noa; Oberkovitz, Galia; Abu-Ghanem, Sara; Livneh, Etta

    2009-01-01

    Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKCη, confers protection against apoptosis induced by the DNA damaging agents, UVC irradiation and the anti-cancer drug - Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKCη in MCF-7 cells, under the control of the tetracycline-responsive promoter, resulted in increased cell survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKCη. Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKCη expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKCη is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKCη could represent a target for intervention aimed to reduce resistance to anti-cancer treatments.

  10. Novel Acylguanidine Derivatives Targeting Smoothened Induce Antiproliferative and Pro-Apoptotic Effects in Chronic Myeloid Leukemia Cells.

    Alessandra Chiarenza

    Full Text Available The most relevant therapeutic approaches to treat CML rely on the administration of tyrosine kinase inhibitors (TKIs like Imatinib, which are able to counteract the activity of Bcr-Abl protein increasing patient's life expectancy and survival. Unfortunately, there are some issues TKIs are not able to address; first of all TKIs are not so effective in increasing survival of patients in blast crisis, second they are not able to eradicate leukemic stem cells (LSC which represent the major cause of disease relapse, and third patients often develop resistance to TKIs due to mutations in the drug binding site. For all these reasons it's of primary interest to find alternative strategies to treat CML. Literature shows that Hedgehog signaling pathway is involved in LSC maintenance, and pharmacological inhibition of Smoothened (SMO, one of the key molecules of the pathway, has been demonstrated to reduce Bcr-Abl positive bone marrow cells and LSC. Consequently, targeting SMO could be a promising way to develop a new treatment strategy for CML overcoming the limitations of current therapies. In our work we have tested some compounds able to inhibit SMO, and among them MRT92 appears to be a very potent SMO antagonist. We found that almost all our compounds were able to reduce Gli1 protein levels in K-562 and in KU-812 CML cell lines. Furthermore, they were also able to increase Gli1 and SMO RNA levels, and to reduce cell proliferation and induce apoptosis/autophagy in both the tested cell lines. Finally, we demonstrated that our compounds were able to modulate the expression of some miRNAs related to Hedgehog pathway such as miR-324-5p and miR-326. Being Hedgehog pathway deeply implicated in the mechanisms of CML we may conclude that it could be a good therapeutic target for CML and our compounds seem to be promising antagonists of such pathway.

  11. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

    Harada, H; Andersen, Jens S.; Mann, M

    2001-01-01

    Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phospho...

  12. Clearance of a persistent Picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses

    Immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in distinct microanatomic compartments of the bovine nasopharynx were investigated using quantitative RT-PCR and whole transcriptome microarray. Analysis of tissue samples obtained during ...

  13. Pro-apoptotic activity of new analog of anthracyclines--WP 631 in advanced ovarian cancer cell line.

    Gajek, Arkadiusz; Denel, Marta; Bukowska, Barbara; Rogalska, Aneta; Marczak, Agnieszka

    2014-03-01

    In this work we investigated the mode of cell death induced by WP 631, a novel anthracycline antibiotic, in the ovarian cancer cell line (OV-90) derived from the malignant ascites of a patient diagnosed with advanced disease. The effects were compared with those of doxorubicin (DOX), a first generation anthracycline. The ability of WP 631 to induce apoptosis and necrosis was examined by double staining with Annexin V and propidium iodide, measurements of the level of intracellular calcium ions and cytochrome c, PARP cleavage. We also investigated the possible involvement of the caspases activation, DNA degradation (comet assay) and intracellular reactive oxygen species (ROS) production in the development of the apoptotic events and their significance for drug efficiency. The results obtained clearly demonstrate that antiproliferative capacity of WP 631 in tested cell line was a few times greater than that of DOX. Furthermore, ovarian cancer cells treated with WP 631 showed a higher mean level of basal DNA damage in comparison to DOX. In conclusion, WP 631 is able to induce caspase - dependent apoptosis in human ovarian cancer cells. Obtained results suggested that WP 631 may be a candidate for further evaluation as chemotherapeutic agents for human cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Targeting pro-apoptotic trail receptors sensitizes HeLa cervical cancer cells to irradiation-induced apoptosis

    Maduro, John H.; de Vries, Elisabeth G. E.; Meersma, Gert-Jan; Hougardy, Brigitte M. T.; van der Zee, Ate G. J.; De Jong, Steven

    2008-01-01

    Purpose: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. Methods and Materials: Recombinant human TRAIL

  15. Pro-oxidative and pro-apoptotic action of defatted seeds of Oenothera paradoxa on human skin melanoma cells.

    Jaszewska, Edyta; Kośmider, Anita; Kiss, Anna K; Naruszewicz, Marek

    2009-09-23

    Three extracts of defatted seeds of Oenothera paradoxa Hudziok, aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract, differing by their total content of phenolic compounds and by their contents of individual polyphenols, were investigated in this study. The extracts exerted cytotoxic action on HTB-140 human skin melanoma cells. After 24 h of incubation, IC(50) values of 169.7 +/- 5.9 micog/mL, 72.4 +/- 3.8 microg/mL, and 155.3 +/- 6.3 microg/mL were obtained for HTB-140 cells with the aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract at the tested concentrations (5-200 microg/mL), respectively, while IC(50) for normal fibroblast cells NHDFs was not attained. Moreover, for HTB-140 cells, LD(50) (concentration at which 50% of cells were dead) of 89.2 +/- 4.3 microg/mL and 181.4 +/- 6.5 microg/mL were obtained with 60% ethanolic extract and 30% isopropanolic extract, respectively. In melanoma cells, all three extracts caused a concentration-dependent increase of ROS production, GSH, and ATP lowering, and appearance of phosphatidylserine on the external surface of cellular membranes where it was bound to annexin V-FITC; furthermore, apoptosis without activation of caspase-3 took place. The most effective was 60% ethanolic extract, which had the greatest total content of phenolic compounds and the greatest content of pentagalloyloglucose (PGG).

  16. Acetylation of the pro-apoptotic factor, p53 in the hippocampus following cerebral ischemia and modulation by estrogen.

    Limor Raz

    Full Text Available Recent studies demonstrate that acetylation of the transcription factor, p53 on lysine(373 leads to its enhanced stabilization/activity and increased susceptibility of cells to stress. However, it is not known whether acetylation of p53 is altered in the hippocampus following global cerebral ischemia (GCI or is regulated by the hormone, 17β-estradiol (17β-E(2, and thus, this study examined these issues.The study revealed that Acetyl p53-Lysine(373 levels were markedly increased in the hippocampal CA1 region after GCI at 3 h, 6 h and 24 h after reperfusion, an effect strongly attenuated by 17β-E(2. 17β-E(2 also enhanced interaction of p53 with the ubiquitin ligase, Mdm2, increased ubiquitination of p53, and induced its down-regulation, as well as attenuated elevation of the p53 transcriptional target, Puma. We also observed enhanced acetylation of p53 at a different lysine (Lys(382 at 3 h after reperfusion, and 17β-E(2 also markedly attenuated this effect. Furthermore, administration of an inhibitor of CBP/p300 acetyltransferase, which acetylates p53, was strongly neuroprotective of the CA1 region following GCI. In long-term estrogen deprived (LTED animals, the ability of 17β-E(2 to attenuate p53 acetylation was lost, and intriguingly, Acetyl p53-Lysine(373 levels were markedly elevated in sham (non-ischemic LTED animals. Finally, intracerebroventricular injections of Gp91ds-Tat, a specific NADPH oxidase (NOX2 inhibitor, but not the scrambled tat peptide control (Sc-Tat, attenuated acetylation of p53 and reduced levels of Puma following GCI.The studies demonstrate that p53 undergoes enhanced acetylation in the hippocampal CA1 region following global cerebral ischemia, and that the neuroprotective agent, 17β-E(2, markedly attenuates the ischemia-induced p53 acetylation. Furthermore, following LTED, the suppressive effect of 17β-E(2 on p53 acetylation is lost, and p53 acetylation increases in the hippocampus, which may explain previous reports of increased sensitivity of the hippocampus to ischemic stress following LTED.

  17. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma.

    Tu, Yong-Sheng; He, Jin; Liu, Huan; Lee, Hans C; Wang, Hua; Ishizawa, Jo; Allen, Joshua E; Andreeff, Michael; Orlowski, Robert Z; Davis, Richard E; Yang, Jing

    2017-10-01

    In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

    Yong-sheng Tu

    2017-10-01

    Full Text Available In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.

  19. Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53

    Banu, Sakhila K.; Stanley, Jone A.; Lee, JeHoon; Stephen, Sam D.; Arosh, Joe A.; Hoyer, Patricia B.; Burghardt, Robert C.

    2011-01-01

    Hexavalent chromium (CrVI) has been widely used in industries throughout the world. Increased usage of CrVI and atmospheric emission of CrVI from catalytic converters of automobiles, and its improper disposal causes various health hazards including female infertility. Recently we have reported that lactational exposure to CrVI induced a delay/arrest in follicular development at the secondary follicular stage. In order to investigate the underlying mechanism, primary cultures of rat granulosa cells were treated with 10 μM potassium dichromate (CrVI) for 12 and 24 h, with or without vitamin C pre-treatment for 24 h. The effects of CrVI on intrinsic apoptotic pathway(s) were investigated. Our data indicated that CrVI: (i) induced DNA fragmentation and increased apoptosis, (ii) increased cytochrome c release from the mitochondria to cytosol, (iii) downregulated anti-apoptotic Bcl-2, Bcl-XL, HSP70 and HSP90; upregulated pro-apoptotic BAX and BAD, (iv) altered translocation of Bcl-2, Bcl-XL, BAX, BAD, HSP70 and HSP90 to the mitochondria, (v) upregulated p-ERK and p-JNK, and selectively translocated p-ERK to the mitochondria and nucleus, (vi) activated caspase-3 and PARP, and (vii) increased phosphorylation of p53 at ser-6, ser-9, ser-15, ser-20, ser-37, ser-46 and ser-392, increased p53 transcriptional activation, and downregulated MDM-2. Vitamin C pre-treatment mitigated CrVI effects on apoptosis and related pathways. Our study, for the first time provides a clear insight into the effect of CrVI on multiple pathways that lead to apoptosis of granulosa cells which could be mitigated by vitamin C.

  20. Glued structural members

    Russell C. Moody; Jen Y. Liu

    1999-01-01

    Glued structural members are manufactured in a variety of configurations. Structural composite lumber (SCL) products consist of small pieces of wood glued together into sizes common for solid-sawn lumber. Glued-laminated timber (glulam) is an engineered stress-rated product that consists of two or more layers of lumber in which the grain of all layers is oriented...

  1. CERN welcomes new members

    2017-08-01

    Lithuania is on course to become an associate member of CERN, pending final approval by the Lithuanian parliament. Associate membership will allow representatives of the Baltic nation to take part in meetings of the CERN Council, which oversees the Geneva-based physics lab.

  2. DUBNA: Member States

    Anon.

    1992-01-01

    The political upheaval in what was the Soviet Union was reflected in an Extraordinary Plenipotentiaries Committee of Joint Institute for Nuclear Research (JINR) Member States, held in Dubna, near Moscow, on 10-13 December, with representatives of eleven sovereign republics of the former Soviet State taking part

  3. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).

    Tibullo, Daniele; Caporarello, Nunzia; Giallongo, Cesarina; Anfuso, Carmelina Daniela; Genovese, Claudia; Arlotta, Carmen; Puglisi, Fabrizio; Parrinello, Nunziatina L; Bramanti, Vincenzo; Romano, Alessandra; Lupo, Gabriella; Toscano, Valeria; Avola, Roberto; Brundo, Maria Violetta; Di Raimondo, Francesco; Raccuia, Salvatore Antonio

    2016-10-01

    Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

  4. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ in Multiple Myeloma (MM

    Daniele Tibullo

    2016-10-01

    Full Text Available Multiple myeloma (MM is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC in the bone marrow (BM leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.

  5. MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

    Noelia Sanchez

    Full Text Available MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

  6. Supporting Members and Friends

    2005-10-01

    Thank you! Over the past year, AGU has received 12,104 gifts, both large and small, from members and friends. The Union has also received corporate contributions, National Science Foundation grants, and support from the National Oceanographic Partnership Program and National Association of Geoscience Teachers. Together their generosity has benefited AGU non revenue producing programs that are critical to our science and the future health of the Union. The following list gratefully acknowledges annual gifts of $100 or more and cumulative giving of $5,000 or more. The 1919 Society ($100,000 or more) and Benefactors ($5,000-$99,999) recognize single major gifts and cumulative contributions. Three circles acknowledge annual giving: President's Circle ($1,000 or more), Leadership Circle ($200-$999), and Supporters Circle ($100-$199). Supporting Life Members, who contribute a one-time gift of $1,200 in addition to lifetime dues, are among our most loyal Supporters.

  7. Offers for our members

    Staff Association

    2018-01-01

    Summer is coming, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 25 € instead of 31 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your Staff Association member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.  

  8. Offers for our members

    Staff Association

    2017-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  9. Offers for our members

    Staff Association

    2017-01-01

    Summer is coming, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  10. [Comment on] BOSP members

    Richman, Barbara T.

    The new Board on Ocean Science and Policy (BOSP) (Eos, June 7, 1983, p. 402) met for the first time on May 4. John B. Slaughter, former director of the National Science Foundation and now chancellor of the University of Maryland in College Park, is the board's chairman. Other board members are D. James Baker, Jr. (University of Washington, Seattle); Kirk Bryan (Geophysical Fluid Dynamics Laboratory, Princeton University); John P. Craven (University of Hawaii); Charles L. Drake (Dartmouth College); Paul M. Fye (Woods Hole Oceanographic Institution); Edward D. Goldberg (Scripps Institution of Oceanography); G. Ross Heath (Oregon State University); Judith T. Kildow (Massachusetts Institute of Technology); John A. Knauss (University of Rhode Island); James J. McCarthy (Museum of Comparative Zoology, Harvard University); H. William Menard (Scripps Institution of Oceanography); C. Barry Raleigh (Lamont-Doherty Geological Observatory); Roger Revelle (University of California, San Diego); David A. Ross (Woods Hole Oceanographic Institution); Brian J. Rothschild (University of Maryland); William M. Sackett (University of South Florida); John H. Steele (Woods Hole Oceanographic Institution); and Carl Wunsch (MIT). Wallace Broecker (Lamont-Doherty Geological Observatory), an original board member, resigned after the first meeting. Broecker told Eos that combining the science and policy boards resulted in a new board whose mission is too broad. A new board member will be appointed in Broecker's place

  11. The Members of the Agency

    2007-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.63) is Palau which deposited its Instrument of Acceptance of the Statute on 2 March 2007. The Attachment hereto shows the dates on which the present 144 Member States became Members

  12. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.67) is Cambodia which deposited its Instrument of Acceptance of the Statute on 23 November 2009. The Attachment hereto shows the dates on which the present 151 Member States became Members

  13. The Members of the Agency

    2008-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.64) is Nepal which deposited its Instrument of Acceptance of the Statute on 8 July 2008. The Attachment hereto shows the dates on which the present 145 Member States became Members

  14. The Members of the Agency

    2006-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.61) are Belize, Mozambique and Malawi, which deposited their Instruments of Acceptance of the Statute on 31 March 2006, 18 September 2006 and 2 October 2006 respectively. The Attachment hereto shows the dates on which the present 142 Member States became Members

  15. The Members of the Agency

    2009-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.66) are Bahrain, Burundi, Congo and Lesotho which deposited their Instruments of Acceptance of the Statute on 23 June 2009, 24 June 2009, 15 July 2009 and 13 July 2009, respectively. The Attachment hereto shows the dates on which the present 150 Member States became Members

  16. The Members of the Agency

    2006-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.62) is Montenegro which deposited its Instrument of Acceptance of the Statute on 30 October 2006. The Attachment hereto shows the dates on which the present 143 Member States became Members

  17. The Members of the Agency

    2009-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.66) are Bahrain, Burundi, Congo and Lesotho which deposited their Instruments of Acceptance of the Statute on 23 June 2009, 24 June 2009, 15 July 2009 and 13 July 2009, respectively. The Attachment hereto shows the dates on which the present 150 Member States became Members [ru

  18. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.67) is Cambodia which deposited its Instrument of Acceptance of the Statute on 23 November 2009. The Attachment hereto shows the dates on which the present 151 Member States became Members [fr

  19. The Members of the Agency

    2006-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.61) are Belize, Mozambique and Malawi, which deposited their Instruments of Acceptance of the Statute on 31 March 2006, 18 September 2006 and 2 October 2006 respectively. The Attachment hereto shows the dates on which the present 142 Member States became Members [fr

  20. The Members of the Agency

    2009-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.66) are Bahrain, Burundi, Congo and Lesotho which deposited their Instruments of Acceptance of the Statute on 23 June 2009, 24 June 2009, 15 July 2009 and 13 July 2009, respectively. The Attachment hereto shows the dates on which the present 150 Member States became Members [fr

  1. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.65) is the Sultanate of Oman which deposited its Instrument of Acceptance of the Statute on 5 February 2009. The Attachment hereto shows the dates on which the present 146 Member States became Members [fr

  2. The Members of the Agency

    2005-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.59) is the Islamic Republic of Mauritania, which deposited the instrument of acceptance of the Statute on 23 November 2004. The Attachment hereto shows the dates on which the present 138 Member States became Members

  3. The Members of the Agency

    2009-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.66) are Bahrain, Burundi, Congo and Lesotho which deposited their Instruments of Acceptance of the Statute on 23 June 2009, 24 June 2009, 15 July 2009 and 13 July 2009, respectively. The Attachment hereto shows the dates on which the present 150 Member States became Members [es

  4. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.67) is Cambodia which deposited its Instrument of Acceptance of the Statute on 23 November 2009. The Attachment hereto shows the dates on which the present 151 Member States became Members [es

  5. The Members of the Agency

    2006-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.60) is Chad, which deposited the instrument of acceptance of the Statute on 2 November 2005. The Attachment hereto shows the dates on which the present 139 Member States became Members

  6. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.65) is the Sultanate of Oman which deposited its Instrument of Acceptance of the Statute on 5 February 2009. The Attachment hereto shows the dates on which the present 146 Member States became Members [es

  7. The Members of the Agency

    2003-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.58) is Kyrgyzstan, which deposited the instrument of acceptance of the Statute on 10 September 2003. The list shows the dates on which the present 137 Member States became Members

  8. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.65) is the Sultanate of Oman which deposited its Instrument of Acceptance of the Statute on 5 February 2009. The Attachment hereto shows the dates on which the present 146 Member States became Members

  9. The Members of the Agency

    2009-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.67) is Cambodia which deposited its Instrument of Acceptance of the Statute on 23 November 2009. The Attachment hereto shows the dates on which the present 151 Member States became Members [ru

  10. Offers for our members

    Staff Association

    2013-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  11. Offers for our members

    Staff Association

    2015-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21,50 € instead of 27 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  12. Offers for our members

    Staff Association

    2016-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 23 € instead of 29 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  13. Cryogenic support member

    Niemann, R.C.; Gonczy, J.D.; Nicol, T.H.

    1987-01-01

    A cryogenic support member is described for restraining a cryogenic system comprising; a rod having a depression at a first end. The rod is made of non-metallic material. The non-metallic material has an effectively low thermal conductivity; a metallic plug; and a metallic sleeve. The plug and the sleeve are shrink-fitted to the depression in the rod and assembled thereto such that the plug is disposed inside the depression of the rod. The sleeve is disposed over the depression in the rod and the rod is clamped therebetween. The shrink-fit clamping the rod is generated between the metallic plug and the metallic sleeve

  14. Thermal effects in concrete members

    Kar, A.K.

    1977-01-01

    When subjected to temperature changes and restrained from free movement, a member develops stresses. Restrained members are sometimes assumed to act independently of other members. A method of analysis and design for thermal stresses in such members is provided. The method of analysis, based on the ultimate strength concept, greatly reduces the computational efforts for determining thermal effects in concrete members. Available charts and tables and the recommendations given herein simplify the design. (Auth.)

  15. SiteBinder: an improved approach for comparing multiple protein structural motifs.

    Sehnal, David; Vařeková, Radka Svobodová; Huber, Heinrich J; Geidl, Stanislav; Ionescu, Crina-Maria; Wimmerová, Michaela; Koča, Jaroslav

    2012-02-27

    There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers.

  16. Offers for our members

    Staff Association

    2013-01-01

    The Courir shops propose the following offer: 15% discount on all articles (not on sales) in the Courir shops (Val Thoiry, Annemasse and Neydens) and 5% discount on sales upon presentation of your Staff Association membership card and an identity card before payment. Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  17. Offers for our members

    Association du personnel

    2013-01-01

    La banque LCL propose aux membres de l’Association du personnel les avantages suivants : – Un barème Privilège sur le Prêt immobilier – Des avantages tarifaires sur l’épargne, notamment l’assurance-vie. – Un taux préférentiel de prêt à la consommation. En outre, jusqu’au 30 septembre 2013, elle offre 50€ à tous les nouveaux clients, membres de l'Association du personnel. Summer is here, enjoy our offers for the aquatic parcs! Tickets "Zone terrestre" : 21 € instead of de 26 €. Access to Aqualibi : 5 euros instead of 8 euros on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Free car park. * * * * * * * Full day ticket: – Children : 30 CHF instead of 39 CHF &...

  18. Offers for our members

    Staff Association

    2013-01-01

    The warm weather arrives, it's time to take advantage of our offers Walibi and Aquapark! Walibi : Tickets "Zone terrestre": 21 € instead of 26 € Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Half-day ticket (5 hours): – Children: 26 CHF instead of 35 CHF – Adults : 32 CHF instead of 43 CHF Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Free for children under 5.

  19. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma.

    Shannon M Matulis

    Full Text Available Arsenic trioxide (ATO has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2-3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

  20. The Members of the Agency

    2003-01-01

    The document lists the 135 Member States of the Agency as of 19 March 2003. The new Member since the last issue of the list (INFCIRC/2/56) is the Republic of Honduras. The dates on which the present 135 Member States became Members are given in an Attachment. It also shows the States whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute

  1. The Members of the Agency

    1999-01-01

    The document lists the 130 Member States of the Agency as of 1 December 1999. The new Member since the last issue of the list (INFCIRC/2/52) is Angola. The dates on which the present 130 Member States became Members, and the state Honduras) whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute are given in an Attachment

  2. The Members of the Agency

    2002-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.55) is the Republic of Botswana, which deposited the instrument of acceptance of the Statute on 20 March 2002. The Attachment hereto shows the dates on which the present 134 Member States became Members. It also shows the State whose application for membership of the Agency has been approved by the General Conference, but which has not yet deposited an instrument of acceptance of the Statute

  3. The Members of the Agency

    2001-01-01

    The document lists the 132 Member States of the Agency as of 1 June 2001. The new Members since the last issue of the list (INFCIRC/2/53) are Central African Republic and Azerbaijan. The dates on which the present 132 Member States became Members are given in an Attachment. It also shows the States whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute

  4. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.69) is the Commonwealth of Dominica, which deposited its instrument of acceptance of the Statute on 17 February 2012. The Attachment hereto shows the dates on which the present 153 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  5. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.70) is Papua New Guinea, which deposited its instrument of acceptance of the Statute on 4 April 2012. The Attachment hereto shows the dates on which the present 154 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  6. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.69) is the Commonwealth of Dominica, which deposited its instrument of acceptance of the Statute on 17 February 2012. The Attachment hereto shows the dates on which the present 153 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  7. The Members of the Agency

    2013-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.74) is Swaziland, which deposited its instrument of acceptance of the Statute on 15 February 2013. The Attachment hereto shows the dates on which the present 159 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  8. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.71) is Rwanda, which deposited its instrument of acceptance of the Statute on 4 September 2012. The Attachment hereto shows the dates on which the present 155 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  9. The Members of the Agency

    2011-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.68) is the Lao People's Democratic Republic which deposited its instrument of acceptance of the Statute on 4 November 2011. The Attachment hereto shows the dates on which the present 152 Member States deposited instruments of ratification or acceptance of the Statue with the depositary Government [fr

  10. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.73) is Trinidad and Tobago, which deposited its instrument of acceptance of the Statute on 9 November 2012. The Attachment hereto shows the dates on which the present 158 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  11. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.70) is Papua New Guinea, which deposited its instrument of acceptance of the Statute on 4 April 2012. The Attachment hereto shows the dates on which the present 154 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [ru

  12. Family members' experiences of autopsy

    Oppewal, F; Meyboom-de Jong, B

    Background. The experiences of family members will teach us how to handle an autopsy, the ultimate quality assessment tool. Objective. The aim of this study was to determine surviving family members' experience of autopsy. Method. Seven GPs were asked to approach surviving family members of

  13. The Members of the Agency

    2014-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.76) is Brunei Darussalam, which deposited its instrument of acceptance of the Statute on 18 February 2014. The Attachment hereto shows the dates on which the present 162 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  14. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.70) is Papua New Guinea, which deposited its instrument of acceptance of the Statute on 4 April 2012. The Attachment hereto shows the dates on which the present 154 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  15. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.71) is Rwanda, which deposited its instrument of acceptance of the Statute on 4 September 2012. The Attachment hereto shows the dates on which the present 155 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  16. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.69) is the Commonwealth of Dominica, which deposited its instrument of acceptance of the Statute on 17 February 2012. The Attachment hereto shows the dates on which the present 153 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  17. The members of the Agency

    1993-01-01

    The 42nd revision of INFCIRC/2 lists the 113 Member States of the International Atomic Energy Agency as of 1 January 1993. It includes Slovenia as a new Member State as of 21 September 1992, Cambodia replaces the former name ''Democratic Kampuchea'' and Czechoslovakia was deleted as it ceased to be a member of the Agency as of 1 January 1993 (INFCIRC/417)

  18. The Members of the Agency

    2011-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.68) is the Lao People's Democratic Republic which deposited its instrument of acceptance of the Statute on 4 November 2011. The Attachment hereto shows the dates on which the present 152 Member States deposited instruments of ratification or acceptance of the Statue with the depositary Government [es

  19. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.73) is Trinidad and Tobago, which deposited its instrument of acceptance of the Statute on 9 November 2012. The Attachment hereto shows the dates on which the present 158 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  20. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.70) is Papua New Guinea, which deposited its instrument of acceptance of the Statute on 4 April 2012. The Attachment hereto shows the dates on which the present 154 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  1. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.71) is Rwanda, which deposited its instrument of acceptance of the Statute on 4 September 2012. The Attachment hereto shows the dates on which the present 155 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  2. The Members of the Agency

    2014-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.76) is Brunei Darussalam, which deposited its instrument of acceptance of the Statute on 18 February 2014. The Attachment hereto shows the dates on which the present 162 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  3. The Members of the Agency

    2012-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.72) are Fiji and Togo, which deposited their instruments of acceptance of the Statute on 2 November 2012 and 1 November 2012, respectively. The Attachment hereto shows the dates on which the present 157 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  4. The Members of the Agency

    2014-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.76) is Brunei Darussalam, which deposited its instrument of acceptance of the Statute on 18 February 2014. The Attachment hereto shows the dates on which the present 162 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  5. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.73) is Trinidad and Tobago, which deposited its instrument of acceptance of the Statute on 9 November 2012. The Attachment hereto shows the dates on which the present 158 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  6. The Members of the Agency

    2011-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.68) is the Lao People's Democratic Republic which deposited its instrument of acceptance of the Statute on 4 November 2011. The Attachment hereto shows the dates on which the present 152 Member States deposited instruments of ratification or acceptance of the Statue with the depositary Government

  7. The Members of the Agency

    2012-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.71) is Rwanda, which deposited its instrument of acceptance of the Statute on 4 September 2012. The Attachment hereto shows the dates on which the present 155 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [ru

  8. The Members of the Agency

    2012-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.72) are Fiji and Togo, which deposited their instruments of acceptance of the Statute on 2 November 2012 and 1 November 2012, respectively. The Attachment hereto shows the dates on which the present 157 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [ru

  9. The Members of the Agency

    2012-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.72) are Fiji and Togo, which deposited their instruments of acceptance of the Statute on 2 November 2012 and 1 November 2012, respectively. The Attachment hereto shows the dates on which the present 157 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  10. The Members of the Agency

    1999-01-01

    The document lists the 129 Member States of the Agency as of 1 June 1999. The new Member since the last issue of the list (INFCIRC/2/51) is Benin. The dates on which the present 129 states became Members, and the state (Honduras) whose application for membership of the Agency has been recommended by the Board of Governors to be considered at the 43rd session of the General Conference are given in an Attachment

  11. The Members of the Agency

    2012-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.72) are Fiji and Togo, which deposited their instruments of acceptance of the Statute on 2 November 2012 and 1 November 2012, respectively. The Attachment hereto shows the dates on which the present 157 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  12. The Members of the Agency

    1995-01-01

    The new member since the last list of Member States of the Agency was issued (INFCIRC/2/Rev.44) is Yemen. The Attachment hereto shows the dates on which the 122 States became members of the Agency, as well as the State whose application for membership of the Agency was approved by the General Conference, but which has not yet deposited an instrument of acceptance of the Statute

  13. The Members of the Agency

    2014-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.75) are San Marino and the Bahamas, which deposited their instruments of acceptance of the Statute on 25 November 2013 and 7 January 2014, respectively. The Attachment hereto shows the dates on which the present 161 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [es

  14. The members of the Agency

    1994-01-01

    The new members since the last list of Member States of the Agency was issued (INFCIRC/2/Rev.42) are: Armenia, Coratia, the Czech Republic, Lithuania, the Marshall Islands, the Slovak Republic and Uzbekistan. The Attachment to the circular shows the dates on which the 120 States became members of the Agency, as well as those States whose application for membership of the Agency was approved by the General Conference, but who have not yet deposited an instrument of acceptance of the Statute

  15. The Members of the Agency

    1998-01-01

    The document lists the 128 Member States of the Agency as of 18 September 1998. The new Member since the last issue of the list (INFCIRC/2/50) is Burkina Faso. In an attachment the dates on which the present 128 states became Members, and the state (Benin) whose application for membership of the Agency has been recommended by the Board of Governors to be considered at the 42nd session of the General Conference are given

  16. The Members of the Agency

    2014-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.75) are San Marino and the Bahamas, which deposited their instruments of acceptance of the Statute on 25 November 2013 and 7 January 2014, respectively. The Attachment hereto shows the dates on which the present 161 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  17. The Members of the Agency

    NONE

    1995-02-13

    The new member since the last list of Member States of the Agency was issued (INFCIRC/2/Rev.44) is Yemen. The Attachment hereto shows the dates on which the 122 States became members of the Agency, as well as the State whose application for membership of the Agency was approved by the General Conference, but which has not yet deposited an instrument of acceptance of the Statute.

  18. The members of the Agency

    1998-01-01

    The document lists the 127 Member States of the Agency as of 1 January 1998. The new Members since the last issue of of the list (INFCIRC/2/49) are Malta and the Republic of Moldova. In an attachment are given the dates on which the present 127 states become Members, the state (Burkina Faso) whose application for membership of the Agency has been approved by the General Conference but which has not deposited an instrument of acceptance of the Statute

  19. The members of the Agency

    NONE

    1998-01-15

    The document lists the 127 Member States of the Agency as of 1 January 1998. The new Members since the last issue of of the list (INFCIRC/2/49) are Malta and the Republic of Moldova. In an attachment are given the dates on which the present 127 states become Members, the state (Burkina Faso) whose application for membership of the Agency has been approved by the General Conference but which has not deposited an instrument of acceptance of the Statute.

  20. The Members of the Agency

    NONE

    1998-09-18

    The document lists the 128 Member States of the Agency as of 18 September 1998. The new Member since the last issue of the list (INFCIRC/2/50) is Burkina Faso. In an attachment the dates on which the present 128 states became Members, and the state (Benin) whose application for membership of the Agency has been recommended by the Board of Governors to be considered at the 42nd session of the General Conference are given

  1. The Members of the Agency

    NONE

    1999-06-16

    The document lists the 129 Member States of the Agency as of 1 June 1999. The new Member since the last issue of the list (INFCIRC/2/51) is Benin. The dates on which the present 129 states became Members, and the state (Honduras) whose application for membership of the Agency has been recommended by the Board of Governors to be considered at the 43rd session of the General Conference are given in an Attachment.

  2. The Members of the Agency

    2014-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.75) are San Marino and the Bahamas, which deposited their instruments of acceptance of the Statute on 25 November 2013 and 7 January 2014, respectively. The Attachment hereto shows the dates on which the present 161 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government [fr

  3. The Members of the Agency

    2001-01-01

    The new Members since the last list of Member States was issued (INFCIRC/2/Rev.54) are the Republic of Tajikistan, which deposited the instrument of acceptance of the Statute on 10 September 2001 and the Federal Republic of Yugoslavia, which deposited the instrument of acceptance of the Statute on 31 October 2001. The Attachment hereto shows the dates on which the present 133 Member States became Members. It also shows the States whose applications for membership of the Agency have been approved by the General Conference, but which have not yet deposited an instrument of acceptance of the Statute

  4. The members of the Agency

    1996-01-01

    The document lists the 124 Member States of the Agency as of 1 September 1996. The new Member since the last issue of the list (INFCIRC/2/Rev.47) is Georgia. In an attachment are given the dates on which the 124 Member States became Members, the State (Latvia) whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the State (Republic of Moldova) whose application for membership has been recommended by the Board of Governors for approval by the General Conference

  5. The members of the Agency

    1996-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.46) is Bosnia and Herzegovina. The Attachment hereto shows the dates on which the present 123 Member States became Members. It also shows the States whose applications for membership of the Agency have been approved by the General Conference but which have not yet deposited an instrument of acceptance of the Statute and the State whose application for membership has been recommended by the Board of Governors for approval by the General Conference

  6. The Members of the Agency

    1995-01-01

    No new Member has joined the Agency since the last list of Member States was issued (INFCIRC/2/Rev.45). The Attachment hereto shows the dates on which the present 122 Member States became Members. It also shows the State whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the States whose applications for membership have been recommended by the Board of Governors for approval by the General Conference

  7. The Members of the Agency

    2003-01-01

    The document lists the 136 Member States of the Agency as of 6 May 2003. The new Members since the last issue of the list (INFCIRC/2/57) are Eritrea and the Republic of Seychelles. Cambodia withdrew from the Agency with effect from 26 March 2003. The dates on which the present 136 Member States became Members are given in an Attachment. It also shows the States whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute

  8. The members of the Agency

    NONE

    1996-09-10

    The document lists the 124 Member States of the Agency as of 1 September 1996. The new Member since the last issue of the list (INFCIRC/2/Rev.47) is Georgia. In an attachment are given the dates on which the 124 Member States became Members, the State (Latvia) whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the State (Republic of Moldova) whose application for membership has been recommended by the Board of Governors for approval by the General Conference.

  9. The Members of the Agency

    NONE

    1995-09-11

    No new Member has joined the Agency since the last list of Member States was issued (INFCIRC/2/Rev.45). The Attachment hereto shows the dates on which the present 122 Member States became Members. It also shows the State whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the States whose applications for membership have been recommended by the Board of Governors for approval by the General Conference.

  10. The members of the Agency

    NONE

    1996-02-26

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.46) is Bosnia and Herzegovina. The Attachment hereto shows the dates on which the present 123 Member States became Members. It also shows the States whose applications for membership of the Agency have been approved by the General Conference but which have not yet deposited an instrument of acceptance of the Statute and the State whose application for membership has been recommended by the Board of Governors for approval by the General Conference.

  11. Members' needs, intragroup conflict, and group performance.

    Chun, Jinseok S; Choi, Jin Nam

    2014-05-01

    Focusing on "what people want in their group" as a critical antecedent of intragroup conflict, the present study theorizes and empirically investigates the relationships among the psychological needs of group members, intragroup conflict, and group performance. It attends to the within-group average and dispersion of members' psychological needs and examines the effects stemming from group composition of needs on multiple types of conflict. The analyses based on multisource data from 145 organizational teams revealed significant relationships between the groups' composition with respect to the members' need for achievement and task conflict, need for affiliation and relationship conflict, and need for power and status conflict. Some of these relationships were moderated by open communication among members. The analyses also demonstrated that when the 3 types of conflict were considered together, task conflict was a positive predictor of group performance, whereas relationship conflict was a negative predictor. The findings highlight the motivational aspects of intragroup conflict, revealing the multilevel dynamics of the psychological needs in social settings. (c) 2014 APA, all rights reserved.

  12. Materials Delivered by Member States

    1969-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials delivered by Members up to 30 June 1969 in compliance with requests the Agency had made under Article IX. D

  13. Materials Delivered by Member States

    1975-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials which Members had delivered up to 30 June 1975, in compliance with requests the Agency had made under Article IX. D

  14. Materials Delivered by Member States

    1974-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials which Members had delivered up to 31 March 1974, in compliance with requests the Agency had made under Article IX. D

  15. Materials Delivered by Member States

    1971-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials which Members had delivered up to the end of 1970, in compliance with requests the Agency had made under Article IX. D

  16. Materials Delivered by Member States

    1973-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials which Members had delivered up to the end of 1972, in compliance with requests the Agency had made under Article IX. D

  17. Materials Delivered by Member States

    1972-01-01

    In this document the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials which Members had delivered up to the end of 1971, in compliance with requests the Agency had made under Article IX. D

  18. Working with Difficult Group Members.

    Kottler, Jeffrey A.

    1994-01-01

    Describes types of group members who are challenging in group settings including entitled, manipulative, and character-disordered clients. Provides suggestions for working with these group members, either as isolated cases or as homogenous populations, emphasizing the protection of other clients' rights. Includes 31 references. (Author/CRR)

  19. The Members of the Agency

    1997-01-01

    The document lists the 125 Member States of the Agency as of 1 September 1997. The new Member since the last issue of the list (INFCIRC/2/Rev.48) is Latvia. In an Attachment are given the dates on which the present 125 States became Members, the State (Republic of Moldova) whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the States (Malta and Burkina Faso) whose applications for membership have been recommended by the Board of Governors for approval by the General Conference

  20. The Members of the Agency

    1994-01-01

    The new members since the last list of Member States of the Agency was issued (INFCIRC/2/Rev.43) are: Kazakhstan and the former Yugoslav Republic of Macedonia. The Democratic People's Republic of Korea withdrew from membership of the Agency as of 13 June 1994. The Attachment hereto shows the dates on which the 121 States became members of the Agency, as well as those States whose application for membership of the Agency was approved by the General Conference, but who have not yet deposited an instrument of acceptance of the Statute

  1. The Members of the Agency

    NONE

    1997-09-22

    The document lists the 125 Member States of the Agency as of 1 September 1997. The new Member since the last issue of the list (INFCIRC/2/Rev.48) is Latvia. In an Attachment are given the dates on which the present 125 States became Members, the State (Republic of Moldova) whose application for membership of the Agency has been approved by the General Conference but which has not yet deposited an instrument of acceptance of the Statute and the States (Malta and Burkina Faso) whose applications for membership have been recommended by the Board of Governors for approval by the General Conference.

  2. Thermal effects in concrete members

    Kar, A.K.

    1977-01-01

    The proposed method of analysis for concrete members subjected to temperature changes is consistent with the requirements of ultimate strength design. This also facilitates the provision of the same safety margin as for other loads. Due to cracks and creep in concrete, thermal stresses are nonlinear; they are dependent on the effective member stiffness, which in turn vary with the magnitude of loading. Therefore it is inconsistent to have an ultimate strength design in conjunction with an analysis based on the linear elastic theory. It is proposed that when the requirements of serviceability are met, the neutral axis corresponding to the ultimate load capacity conditions be considered for temperature-induced loadings. This conforms with the fact that the thermal load, because of creep and formation of cracks in the member, can be self-relieving as the failure load condition or ultimate capacity is approached. The maximum thermal load that can develop in dependent on the effective cross section of the member. Recommendations are made for determining the average effective member stiffness, which lies between the stiffness corresponding to the cracked (at ultimate condition) and the uncracked sections. In the proposed method, thermal stresses are not considered completely self-relieving. The stresses are considered simultaneously with stresses resulting from other causes. A step-by-step approach is presented for analysis and design of concrete members subjected to temperature changes

  3. Pro-apoptotic effect of the landrace Bangla Mahoba of Piper betle on Leishmania donovani may be due to the high content of eugenol.

    Misra, Pragya; Kumar, Awanish; Khare, Prashant; Gupta, Swati; Kumar, Nikhil; Dube, Anuradha

    2009-08-01

    In the absence of effective and safe treatment for visceral leishmaniasis or Kala-azar - a devastating parasitic disease caused by Leishmania donovani - the search for anti-leishmanial agents from natural resources in common use is imperative. Recently, the comparative in vitro anti-leishmanial activity of methanolic extracts from two landraces of Piper betle - P. betle landrace Bangla Mahoba (PB-BM) and P. betle landrace Kapoori Vellaikodi (PB-KV) - has been reported. Here, the putative pathway responsible for death induced by the effective extract of PB-BM methanolic extract in promastigotes, as well as the intracellular amastigote form of L. donovani, was assessed using various biochemical approaches. It was found that PB-BM was capable of selectively inhibiting both stages of Leishmania parasites by accelerating apoptotic events by generation of reactive oxygen species targeting the mitochondria without any cytotoxicity towards macrophages. The study was extended to determine the presence or absence of activity of the methanolic extract of PB-BM and PB-KV on the basis of differences in essential oil composition present in the extract assessed by GC and MS. The essential oil from PB-BM was found to be rich in eugenol compared with that from PB-KV. The anti-leishmanial efficacy of PB-BM methanolic extract mediated through apoptosis is probably due to the higher content of eugenol in the active landrace. This observation emphasizes the need to extend studies related to traditional medicines from bioactive plants below the species level to the gender/landrace level for better efficacy and reproducibility.

  4. In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3

    Hanafi, Mohd M. M.; Afzan, Adlin; Yaakob, Harisun; Aziz, Ramlan; Sarmidi, Mohamad R.; Wolfender, Jean-Luc; Prieto, Jose M.

    2017-01-01

    This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC–MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 μg/mL, SRB staining of PC3 cells). PMID:29326585

  5. Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts

    Chang, J.-K.; Li, C.-J.; Liao, H.-J.; Wang, C.-K.; Wang, G.-J.; Ho, M.-L.

    2009-01-01

    It has been reported that anti-inflammatory drugs (AIDs) inhibited bone repair in animal studies, and suppressed proliferation and induced cell death in rat osteoblast cultures. In this study, we further investigated the molecular mechanisms of AID effects on proliferation and cell death in human osteoblasts (hOBs). We examined the effects of dexamethasone (10 -7 and 10 -6 M), non-selective non-steroidal anti-inflammatory drugs (NSAIDs): indomethacin, ketorolac, piroxicam and diclofenac (10 -5 and 10 -4 M), and COX-2 inhibitor: celecoxib (10 -6 and 10 -5 M) on proliferation, cytotoxicity, cell death, and mRNA and protein levels of cell cycle and apoptosis-related regulators in hOBs. All the tested AIDs significantly inhibited proliferation and arrested cell cycle at G0/G1 phase in hOBs. Celecoxib and dexamethasone, but not non-selective NSAIDs, were found to have cytotoxic effects on hOB, and further demonstrated to induce apoptosis and necrosis (at higher concentration) in hOBs. We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27 kip1 and decreased those of cyclin D2 and p-cdk2 in hOBs. Bak expression was increased by celecoxib and dexamethasone, while Bcl-XL level was declined only by dexamethasone. Furthermore, the replenishment of PGE1, PGE2 or PGF2α did not reverse the effects of AIDs on proliferation and expressions of p27 kip1 and cyclin D2 in hOBs. We conclude that the changes in expressions of regulators of cell cycle (p27 kip1 and cyclin D2) and/or apoptosis (Bak and Bcl-XL) by AIDs may contribute to AIDs caused proliferation suppression and apoptosis in hOBs. This effect might not relate to the blockage of prostaglandin synthesis by AIDs

  6. cAMP signalling of Bordetella adenylate cyclase toxin through the SHP-1 phosphatase activates the BimEL-Bax pro-apoptotic cascade in phagocytes

    Ahmad, Jawid Nazir; Černý, Ondřej; Linhartová, Irena; Mašín, Jiří; Osička, Radim; Šebo, Peter

    2016-01-01

    Roč. 18, č. 3 (2016), s. 384-398 ISSN 1462-5814 R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : FORKHEAD TRANSCRIPTION FACTOR * HUMAN T- CELL S * DENDRITIC CELL S Subject RIV: EE - Microbiology, Virology Impact factor: 4.554, year: 2016

  7. ARP2, a novel pro-apoptotic protein expressed in epithelial prostate cancer LNCaP cells and epithelial ovary CHO transformed cells.

    Mas-Oliva, Jaime; Navarro-Vidal, Enrique; Tapia-Vieyra, Juana Virginia

    2014-01-01

    Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+)-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2) associated to a lethal influx of Ca(2+) in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line) transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event.

  8. Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.

    Gómez, Natalia; Santos, Diego; Vázquez, Ramiro; Suescun, Leopoldo; Mombrú, Alvaro; Vermeulen, Monica; Finkielsztein, Liliana; Shayo, Carina; Moglioni, Albertina; Gambino, Dinorah; Davio, Carlos

    2011-08-01

    In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress

    Yan M

    2016-02-01

    Full Text Available Ming Yan,1,* Yun Zhang,2,* Haiyan Qin,3 Kezhou Liu,1 Miao Guo,1 Yakun Ge,1 Mingen Xu,1 Yonghong Sun,4 Xiaoxiang Zheng4 1Department of Biomedical Engineering, College of Life Information Science and Instrument Engineering, Hangzhou Dianzi University, Hangzhou, 2Basic Medical Sciences, College of Medicine, Shaoxing University, Shaoxing, 3Department of Chemistry, Zhejiang University, 4Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Department of Biomedical Engineering, Zhejiang University, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Cadmium telluride quantum dots (CdTe QDs have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs. However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (–21.63±0.91 mV, with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature. The endocytosis inhibitors (methyl-β-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2α-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2α and elevated level of activating transcription factor 4. CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase-4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our findings provide important new insights into QDs toxicity and reveal potential cardiovascular risks for the future applications of QDs. Keywords: quantum dots, human umbilical vein endothelial cells, endocytosis, ER stress, apoptosis

  10. Study of morphological changes in breast cancer cells MCF-7 under the action of pro-apoptotic agents with laser modulation interference microscope MIM-340

    Nebogatikov, V.; Nikitiuk, A.; Konysheva, A.; Ignatyev, P.; Grishko, V.; Naimark, O.

    2017-09-01

    Quantitative phase microscopy is a new method to measure and evaluate the microlevel processes characterized by the high resolution and providing ample opportunities to quantitatively analyze various parameters, including specimens from biological matter. In this study, a laser interference microscope was used to evaluate the state of cancer cells (living and apoptotic). Apoptotic cancer cells were obtained by treatment of MCF-7 cells with the use of betulin-based α-bromomethyl ketone (BMK) derivative. When using the microscope, the main differences in the morphometric parameters of living and apoptotic cells such as height, diameter, perimeter, area and volume were appraised. The criteria that can be used as markers of apoptosis activation were identified.

  11. Mitochondria play a central role in apoptosis induced by alpha-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptor-mediated pro-apoptotic signaling

    Weber, T. D.; Dalen, H.; Anděra, Ladislav; Negre-Salvayre, A.; Auge, N.; Sticha, M.; Lloret, A.; Terman, A.; Witting, P. K.; Higuchi, M.; Plasilova, M.; Zivny, J.; Gellert, N.; Weber, C.; Neuzil, J.

    2003-01-01

    Roč. 42, č. 14 (2003), s. 4277-91 ISSN 0006-2960 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : apoptosis, TRAIL, TOS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.922, year: 2003

  12. SLC5A8-Mediated Switching of STAT3 from a Pro-Oncogenic Signal into a Pro-Apoptotic Signal in Breast Cancer

    2011-06-01

    provokes lung metastasis. (5) Both STAT3 and SLC5A8 knockout showed the similar phenotype, like mammary gland involution delay, mastitis and...100 ng/ml cholera toxin, 0.01mg/ml bovine insulin and 500 ng/ml hydrocortisone. HBL100 cells was grown in McCoy 5A with 10% FBS. MCF7 and BT20

  13. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    Sharma, Deep Raj; Sunkaria, Aditya; Bal, Amanjit; Bhutia, Yangchen D.; Vijayaraghavan, R.; Flora, S.J.S.; Gill, Kiran Dip

    2009-01-01

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  14. Evidence of a pro-apoptotic effect of specific antibodies in a bovine macrophage model of infection with Mycobacterium avium subsp. paratuberculosis.

    Jolly, Ana; Lompardía, Silvina; Hajos, Silvia E; Mundo, Silvia L

    2016-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease (JD), a chronic granulomatous enteritis in ruminants. Understanding the protective immune response following infection is crucial to improve the diagnosis and the development of vaccines against this disease. The goal of this work was to assess whether specific antibodies were able to modulate the macrophage response to MAP infection by evaluating apoptosis and TNF-α secretion in an in vitro model. Sera from healthy (n=2), MAP-infected (n=3) and lipoarabinomannan (LAM)-immunized (n=3) bovines were evaluated. LAM was chosen as immunogen due to its relevant role in mycobacterial pathogenesis. We demonstrated by two different techniques (Acridine Orange/Ethidium Bromide microscopy and Annexin V/7-Amino-Actinomycin D flow cytometry) that the immune sera from both, MAP-infected and LAM-immunized bovines, significantly increased macrophage apoptosis in infected cultures. Comparable levels of apoptosis were detected when MAP was pre-incubated with purified specific antibodies instead of whole serum. Furthermore, this effect was accompanied by a significantly higher secretion of TNF-α. These results strongly suggest that specific antibodies could limit the impact of MAP on the apoptosis of bovine cells. This work would contribute to elucidate the role of the specific antibody response in bovine JD and its prevention. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo

    Yihong Cai

    2018-01-01

    Full Text Available Infantile hemangioma (IH is a common and benign vascular neoplasms, which has a high incidence in children. Although IH is benign, some patients experience complications such as pain, functional impairment, and permanent disfigurement. Treatment options for IH include corticosteroids, surgery, vincristine, interferon or cyclophosphamide. However, none of these modalities are ideal due to restrictions or potential serious side effects. There is thus a great need to explore novel treatments for IH with less side effects. Angiogenesis, vasculogenesis and tumorigenesis are the main features of IH. Tanshen is mostly used in Chinese traditional medicine to treat hematological abnormalities. Therefore, the aim of our study was to evaluate anti-proliferation and anti-angiogenesis effects on hemangiomas cells by extracted Tanshen compounds compared with propranolol, the first-line treatment for IH currently, both in vitro and in vivo. Cell viability, apoptosis, protein expression and anti-angiogenesis were analyzed by CCK8, Annexin V staining, Western blot and tube formation, respectively. The anti-tumor activity in vivo was evaluated using a mouse xenograft model. Fourteen major compounds extracting from Tanshen were screened for their ability to inhibit hemangiomas cells. Of the 14 compounds investigated, 15,16-Dihydrotanshinone I (DHTS was the most potent modulator of EOMA cell biology. DHTS could significantly decrease EOMA cells proliferation by inducing cell apoptosis, which is much more efficient than propranolol in vitro. DHTS increased the expression of several apoptosis-related proteins, including caspase9, caspase3, PARP, AIF, BAX, cytochrome c, caspase8 and FADD and significantly inhibited angiogenesis, as indicated by reduced tube formation and diminished expression of vascular endothelial cell growth factor receptor 2 and matrix metalloproteinase 9. In nude mice xenograft experiment, DHTS (10 mg/kg could significantly inhibit the tumor growth of EOMA cells as well as propranolol (40 mg/kg. Our study showed that DHTS was much more effective than propranolol in inhibiting hemangiomas proliferation and angiogenesis in vitro and in vivo, which could have potential therapeutic applications for treatment of IH.

  16. Anti-adhesive and pro-apoptotic effects of 2-hydroxyethyl methacrylate on human gingival fibroblasts co-cultured with Streptococcus mitis strains

    Zara, S; Di Giulio, M; D’Ercole, S; Cellini, L; Cataldi, A

    2011-01-01

    Aim To evaluate and observe the cellular reactions that occur during the interaction/integration between 2-hydroxyethyl methacrylate/host tissue/microbial environment, in a co-culture of human gingival fibroblasts (HGF) and Streptococcus mitis strains. Methodology Streptococcus mitis were cultured with strains in the presence of 3 mmol L−1 HEMA for 48 h and 72 h. Cytotoxicity was evaluated by the trypan blue dye exclusion test. Apoptosis was evaluated by TUNEL analysis. Adhesion was evaluated by immunofluorescence and western blot analyses. Quantitative analyses of the results were acquired by Qwin Plus 3.5 and QuantityOne I-D analysis software, respectively. The statistical significance of the results was evaluated using t-tests and linear regression tests. Results The trypan blue dye test revealed 47.3% and 46.5% of dead fibroblasts after 48 and 72 h HEMA treatment, respectively, while bacterial viability was not influenced by the presence of HEMA and fibroblasts. The expression of pro-collagen I, involved in fibroblast adhesion, in untreated samples ranged from 12.49% to 6.91% of the positive area after 48 and 72 h, respectively, dropping to below 2% of the positive area in the other experimental conditions. Unlike the trypan blue test, co-cultured samples treated with HEMA showed 20% and 25% versus 17% and 21% (after 48 and 72 h, respectively) of apoptotic cells. Conclusions The evidence for HEMA toxicity and anti-adhesive effects against eukaryotic cells was reduced in the presence of bacteria, suggesting that dental resins should be well polymerized to avoid the spread of toxic monomers within the mouth. PMID:21902700

  17. Burnout in Female Faculty Members.

    Cassidy-Vu, Lisa; Beck, Keli; Moore, Justin B

    2017-04-01

    Despite approximately equal numbers of male and female medical school graduates, women are entering academic medicine at a lower rate than their male colleagues. Of those who do assume a faculty position, female faculty members report higher levels of burnout, often attributable to gender-specific difficulties in clinical expectations and maintenance of work-life balance. Many of these struggles are attributable to issues that are amenable to supportive policies, but these policies are inconsistent in their availability and practice. This commentary presents evidence for inconsistencies in the day-to-day experience of female faculty members, and proposes solutions for the mitigation of the challenges experienced more often by female faculty members with the goal of diversifying and strengthening academic medicine.

  18. Materials Delivered by Member States

    1966-01-01

    The information given in this document is divided into two parts. In part I the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials delivered by Members up to 31 December 1965 in compliance with requests the Agency had made under Article IX. D. Part III contains information about materials which had not been delivered by 31 December but which had been allocated, in accordance with Article XI. F. 1 of the Statute, to approved Agency projects for which project arrangements were in force on that date

  19. Materials Delivered by Member States

    1965-01-01

    The information given in this document is divided into two parts. In part I the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials delivered by Members up to 31 December 1964 in compliance with requests the Agency had made under Article IX. D. Part II contains information about materials which had not been delivered by 31 December but which had been allocated, in accordance with Article XI. F. 1 of the Statute, to approved Agency projects for which project arrangements were in force on that date

  20. Materials Delivered by Member States

    1968-01-01

    The information given in this document is divided into two parts. In part I the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials delivered by Members up to 30 June 1968 in compliance with requests the Agency had made under Article IX,D. Part II contains information about materials which had not been delivered by 30 June 1968 but which had been allocated, in accordance with Article XI.F.I of the Statute, to approved Agency projects for which project arrangements were in force on that date

  1. ALA Salary Survey: Personal Members

    American Libraries, 1971

    1971-01-01

    A survey of the members of the American Library Association revealed that the principal salary determinants are academic degree, type of employer and sex. The obvious differences in the earnings of men and women is not only found in the early experience years but any narrowing which does take place in the wage gap seems to take place at the…

  2. Slovenia joins IPPOG as member

    'marcelloni, claudia

    2018-01-01

    Slovenia became an official member of IPPOG on 19 April 2018. The MOU was signed by the head of Particle Physics Department at Jozef Stefan Institute representing Slovenia participation at IPPOG. Andrej Gorišek, country representative for Slovenia in IPPOG, brought the document to the meeting in Italy where IPPOG chairs signed it, confirming Slovenia membership to the collaboration.

  3. Gender Difference and Church Member Satisfaction: An Appraisal ...

    A number of practitioner books, web-sites, and lay-leader seminars have appeared in recent years with the intent of addressing this issue while offering multiple theories to explain this trend. However, empirical evidence and systematic development of male member profiles that would aid in the development of marketing ...

  4. Improving Acceptance, Integration, and Health Among LGBT Service Members

    2017-10-01

    through multiple rounds of internal testing and quality assurance procedures. Recruitment for the Phase II survey was initiated on August 25, 2017...Award Numbers: W81XWH-15-1-0701 Title: Improving Acceptance, Integration, and Health Among LGBT Service Members Principal Investigators...burden to Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis

  5. Multiple Perspectives / Multiple Readings

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  6. Understanding Heterogeneous Preferences of Cooperative Members

    Kalogeras, N.; Pennings, J.M.E.; Lans, van der I.A.; Garcia, P.; Dijk, van G.

    2009-01-01

    We study the heterogeneity in the preference structure of cooperative members. Using conjoint analysis the utility that members attach to intra-organizational and strategic attributes of their cooperative is elicited. Recognizing that members are not homogenous, a concomitant finitemixture

  7. Community Members Draw the Line

    Gregory Freeland

    2014-06-01

    Full Text Available This study investigates whether a community-based task force’s redistricting plan in Ventura County, California, positively affected fair representation, social equity issues, community interests, and the electoral process. Examination and evaluation of the organizational strategies and collaborations involved in the task force’s redistricting process find that the Board of Supervisors districts that members of the community drew were successful in improving and maintaining fair representation. This finding is based on comparing supervisorial votes and policies with community members’ votes on state propositions and local measures, in addition to conducting interviews with task force members, politicians, and community activists. This study finds that citizen participation in governmental processes improves overall community health and political participation.

  8. Power reactors in member states

    1975-01-01

    This is the first issue of a periodical computer-based listing of civilian nuclear power reactors in the Member States of the IAEA, presenting the situation as of 1 April 1975. It is intended as a replacement for the Agency's previous annual publication of ''Power and Research Reactors in Member States''. In the new format, the listing contains more information about power reactors in operation, under construction, planned and shut down. As far as possible all the basic design data relating to reactors in operation have been included. In future these data will be included also for other power reactors, so that the publication will serve to give a clear picture of the technical progress achieved. Test and research reactors and critical facilities are no longer listed. Of interest to nuclear power planners, nuclear system designers, nuclear plant operators and interested professional engineers and scientists

  9. New offer for our members

    Staff Association

    2018-01-01

    Evolution 2, your specialist for Outdoor Adventures Be it for a ski lesson, a parachute jump or for a mountain bike descent, come live an unforgettable experience with our outdoor specialists. Benefit from a 10 % discount on all activities: Offer is open to SA members and their family members living in the same household, upon presentation of the membership card. Offer available for all bookings made between 1 June 2018 and 30 May 2019. Offer available on all the Evoltion2 sites. A wide range of summer and winter activities. More information on http://evolution2.com/ Contact and reservation : +33 (0)4.50.02.63.35 management@evolution2.com

  10. Materials Delivered by Member States

    1962-01-01

    The information given in this document is divided into two parts. In part I the Director General is reporting to the Members of the Agency, under Article IX. G of the Statute, the quantities of materials delivered up to 30 September 1962 by Member States in compliance with requests the Agency has made under Article IX. D. Part II contains information about materials which have not yet been delivered but which have been allocated, in accordance with Article XI. F. 1 of the Statute, to approved Agency projects for which project agreements were in force on 30 September 1962. Reports on subsequent deliveries of materials and revised information about allocated but undelivered materials will be issued from time to time

  11. Communication Among Melanoma Family Members

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  12. New support line for members

    AGU has recently established a new customer "support line"—solutions@agu.org—as the point of contact on AGU's staff for members and other individual constituents who have not been able to resolve issues or get questions answered promptly or to their satisfaction through customary channels.Over the past year, there have been many changes at AGU. Unfortunately—and perhaps as a result of these changes—communication with members and individual constituents has suffered. Some individuals report, for example, that e-mail messages are not answered to their satisfaction, or in a timely manner. Instructions on AGU's Web site are unclear in some areas. Problems related specifically to the transition to electronic publishing are cropping up.

  13. Towards mobile staff members management

    Encheva, Sylvia

    2017-07-01

    Todays project management requires a number of abilities which involve finding quick solutions to shortage of staff members with possession of specific qualities. When persons with team responsibilities are under pressure or due to various circumstances are unable to perform exhaustive search in databases, an interactive visualization tool can come in quite handy in finding good solutions unforeseen occurrences. In particular we propose application of selected graphs for facilitating mobile human resource management.

  14. Shielding member for thermonuclear device

    Onozuka, Masanori

    1997-06-30

    In a thermonuclear device for shielding fast neutrons by shielding members disposed in a shielding vessel (vacuum vessel and structures such as a blanket disposed in the vacuum vessel), the shielding member comprises a large number of shielding wires formed fine and short so as to have elasticity. The shielding wires are sealed in a shielding vessel together with water, and when the width of the shielding vessel is changed, the shielding wires follow after the change of the width while elastically deforming in the shielding vessel, so that great stress and deformation are not formed thereby enabling to improve reliability. In addition, the length, the diameter and the shape of each of the shielding wires can be selected in accordance with the shielding space of the shielding vessel. Even if the shape of the shielding vessel is complicated, the shielding wires can be inserted easily. Accordingly, the filling rate of the shielding members can be changed easily. It can be produced more easily compared with a conventional spherical pebbles. It can be produced more easily than existent spherical shielding pebbles thereby enabling to reduce the production cost. (N.H.)

  15. Multiple sclerosis

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  16. 7 CFR 1425.19 - Member cooperatives.

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Member cooperatives. 1425.19 Section 1425.19... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COOPERATIVE MARKETING ASSOCIATIONS § 1425.19 Member cooperatives. A CMA may obtain loans or LDP's on behalf of a member cooperative when the member...

  17. MULTIPLE OBJECTS

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  18. Effect of Fiber Reinforcement on the Response of Structural Members

    Fischer, Gregor; Li, Victor

    2007-01-01

    This paper describes a series of investigations on the effect of fiber reinforcement on the response of structural members in direct tension and flexure under reversed cyclic loading conditions. The design approach of the fiber reinforced cementitious composite is based on fracture mechanics...... principles, which will be described in the first part of the paper along with an introduction of the relevant material properties of the resulting engineered cementitious composite (ECC). This class of composites is characterized by strain hardening and multiple cracking properties in uniaxial tension...... and an ultimate tensile strain capacity on the order of several percent. Subsequently, the synergistic effects of composite deformation mechanisms in the ECC and structural members subjected to large shear reversals are identified. Beneficial effects observed in the reinforced ECC structural members as compared...

  19. FISCAL SOVEREIGNTY IN ROMANIA – EUROPEAN UNION MEMBER STATE

    Lidia Daniela I. Roman

    2008-01-01

    The Romania`s adhesion to the European Union involves multiple transformations with a direct impact upon many fields, such as law`s field, especially economic, fiscal laws. Taxation system should be both efficient and equitableone of the important problem is sovereignty of state became member of one regional organization, his fiscal sovereignty, state’s atributes in this field. Who can decide fiscal policy, direct taxes or taxes upon consumption? Is it attended by this adhesion to the soverei...

  20. Modeling and characterization of strengthened concrete tension members

    Hansen, Christian Skodborg; Stang, Henrik

    2011-01-01

    The structural potential for cracking of externally strengthened concrete tension members, can be predicted with three parameters, describing the structural cracking potential based on fracture mechanical properties of the of concrete and interface between concrete and strengthening medium....... With these parameters, it is possible to design reinforcement and obtain a required cracking behavior of a given structure. Design recommendations for single and multiple cracking of the tension specimen are given in terms of fracture mechanical parameters, and a structural stiffness parameter....

  1. Multiple sclerosis

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  2. International Focus: Highlighting APPA Members Worldwide

    Glazner, Steve, Comp.

    2011-01-01

    While most APPA member institutions are located in the United States and Canada, there are also 45 of member institutions located internationally--from Australia and New Zealand to Southeast Asia to the Middle East to Europe. This article focuses on four of its international members: (1) American University of Kuwait (AUK); (2) American University…

  3. The Members of the Agency (French Edition)

    2013-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.74) is Swaziland, which deposited its instrument of acceptance of the Statute on 15 February 2013. The Attachment hereto shows the dates on which the present 159 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  4. The Members of the Agency (Spanish Edition)

    2013-01-01

    The new Member since the last list of Member States was issued (INFCIRC/2/Rev.74) is Swaziland, which deposited its instrument of acceptance of the Statute on 15 February 2013. The Attachment hereto shows the dates on which the present 159 Member States deposited instruments of ratification or acceptance of the Statute with the depositary Government

  5. Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

    Saha, Manujendra N; Jiang, Hua; Yang, Yijun; Zhu, Xiaoyun; Wang, Xiaoming; Schimmer, Aaron D; Qiu, Lugui; Chang, Hong

    2012-01-01

    The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK

  6. Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

    Manujendra N Saha

    Full Text Available The low frequency of p53 alterations e.g., mutations/deletions (∼10% in multiple myeloma (MM makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP analysis showed that activated c-Jun binds to the activator protein-1 (AP-1 binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with

  7. Multiple homicides.

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  8. Members of the LHC Resources Review Boards

    Maximilien Brice

    2002-01-01

    Photo 01: Members of the LHCRRB visiting Point 2, hosting the ALICE experiment From l. to r. : W. Korda, Head of the VIP Office; P. Rimmer, CERN public relations, J. Seed, Member of the LHCRRB, J.-P. Revol, ALICE CERN Team Leader; J. Bartke, Member of the LHCRRB; F. Suransky, Member of the LHCRRB; J. Schukraft, Spokesperson, ALICE experiment and S. Molinari, VIP Office. Photo 02: Members of the LHC Resources Review Boards visiting the ALICE magnet at Point 2. L. to. r.: O. Dines-Hansen, H. Boggild, S. Irgens-Jensens, H.A. Gustafsson Photo 03: Members of the LHCRRB visiting Point 2, hosting the ALICE experiment From l. t to r.: J.Richter, Member of the LHCRRB; H. Gutbrod, Deputy Spokesperson, ALICE experiment; G. Paic, ALICE experiment; D. Muller, Member of the LHCRRB; P. Brau-Munzinger, ALICE experiment; R. Santo, Member of the LHCRRB, A. Van Rijn, Member of the LHCRRB; J. Engelen, Member of the LHCRRB.

  9. Multiple Sclerosis

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  10. Multiple myeloma.

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  11. Multiple mononeuropathy

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  12. Multiple sclerosis and herpesvirus interaction

    Guilherme Sciascia do Olival

    2013-09-01

    Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

  13. [Multiple meningiomas].

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Evolving Four Part Harmony Using a Multiple Worlds Model

    Scirea, Marco; Brown, Joseph Alexander

    2015-01-01

    This application of the Multiple Worlds Model examines a collaborative fitness model for generating four part harmonies. In this model we have multiple populations and the fitness of the individuals is based on the ability of a member from each population to work with the members of other...

  15. Multiple familial trichoepithelioma: a rare cutaneous tumour

    Arfan-ul-Bari; Simeen-ber-Rehman

    2004-01-01

    Multiple familial trichoepithelioma (MFT) is a rare autosomal dominant skin disease that presents as many small tumours predominantly on the face. We report a case of multiple familial trichoepithelioma occurring in three members of a family. They were diagnosed simultaneously. Only one was treated with medium depth chemical peeling with partial response. (author)

  16. Finding Street Gang Members on Twitter

    Balasuriya, Lakshika; Wijeratne, Sanjaya; Doran, Derek; Sheth, Amit

    2016-01-01

    Most street gang members use Twitter to intimidate others, to present outrageous images and statements to the world, and to share recent illegal activities. Their tweets may thus be useful to law enforcement agencies to discover clues about recent crimes or to anticipate ones that may occur. Finding these posts, however, requires a method to discover gang member Twitter profiles. This is a challenging task since gang members represent a very small population of the 320 million Twitter users. ...

  17. Multiple sclerosis

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  18. Multiple myeloma

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  19. Multiple sclerosis

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  20. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  1. Multiple sclerosis

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  2. Multiple sclerosis

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  3. Multiple Sclerosis.

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  4. Parenting Multiples

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  5. 7 CFR 1425.14 - Member business.

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Member business. 1425.14 Section 1425.14 Agriculture... business. (a) At least 50 percent of a crop of an authorized commodity acquired by, or delivered to, a CMA... not be considered in determining the volume of member or nonmember business. ...

  6. Spirituality and job satisfaction among hospice interdisciplinary team members.

    Clark, Leah; Leedy, Stephen; McDonald, Laurie; Muller, Barbara; Lamb, Cheryl; Mendez, Tracy; Kim, Sehwan; Schonwetter, Ronald

    2007-12-01

    As a continuing effort to enhance the quality of palliative care for the dying, this study examined (1) the prevalence of spirituality among hospice interdisciplinary team (IDT) members; (2) whether spirituality is related to job satisfaction; and (3) the structural path relationships among four variables: spiritual belief, integration of spirituality at work, self actualization and job satisfaction. The study surveyed 215 hospice IDT members who completed the Jarel Spiritual Well-Being Scale, the Chamiec-Case Spirituality Integration and Job Satisfaction Scales. Multiple regression and structural path modeling methods were applied to explain the path relationships involving all four variables. The IDT members surveyed were: nurses, 46.4%; home health aids, 24.9%; social workers, 17.4%; chaplains, 4.2%; physicians, 2.3%; and other, 4.8%. Ninety-eight percent of the respondents viewed themselves as having spiritual well-being. On a 0-100 scale, IDT staff reported high spiritual belief (mean = 89.4) and they were self-actualizing (mean = 82.6). Most reported high job satisfaction (mean = 79.3) and spiritual integration (mean = 67.9). In multiple regression, spirituality, integration and self-actualization explained 22% of the variation in job satisfaction (R = 0.48; adjusted R(2) = 0.218; df = 3,175; F = 17.2; p = 0.001). Structural path models revealed that job satisfaction is more likely to be realized by a model that transforms one's spirituality into processes of integrating spirituality at work and self actualization (chi(2) = 0.614; df = 1; p = 0.433) than a model that establishes a direct path from spirituality to job satisfaction (chi(2) = 1.65; df = 1; p = 0.199). Hospice IDT member's integration of their spirituality at work and greater self actualization significantly improve job satisfaction.

  7. Multiple sclerosis

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  8. Humanizing Outgroups Through Multiple Categorization

    Prati, Francesca; Crisp, Richard J.; Meleady, Rose; Rubini, Monica

    2016-01-01

    In three studies, we examined the impact of multiple categorization on intergroup dehumanization. Study 1 showed that perceiving members of a rival university along multiple versus simple categorical dimensions enhanced the tendency to attribute human traits to this group. Study 2 showed that multiple versus simple categorization of immigrants increased the attribution of uniquely human emotions to them. This effect was explained by the sequential mediation of increased individuation of the outgroup and reduced outgroup threat. Study 3 replicated this sequential mediation model and introduced a novel way of measuring humanization in which participants generated attributes corresponding to the outgroup in a free response format. Participants generated more uniquely human traits in the multiple versus simple categorization conditions. We discuss the theoretical implications of these findings and consider their role in informing and improving efforts to ameliorate contemporary forms of intergroup discrimination. PMID:26984016

  9. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-11-14

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  10. Defense Health Care: DOD Lacks Assurance That Selected Reserve Members Are Informed about TRICARE Reserve Select

    2011-06-01

    percentages include members of the Selected Reserve and their dependents. Selected Reserve members living overseas, in unknown locations, and in Puerto Rico ...8 Diabetes mellitush 1.7 Asthmai 1.8 9 Adjustment reaction 1.7 Acute upper respiratory infections of multiple or unspecified sites 1.6 10 Special...heterogeneous disorders that have an increase in blood glucose concentrations. The current classifications for diabetes mellitus Types 1 through 4

  11. Concerns raised over new EPA members

    Gwynne, Peter

    2017-12-01

    The Trump administration has nominated three new members of the Environmental Protection Agency (EPA) who critics say are undermining laws and “pampering” the industries they are supposed to regulate.

  12. Energy outlooks of young members of parliament

    Tolonen, P.

    1999-01-01

    Pekka Tolonen Energy outlooks of young members of parliament The main theme is 'youth and nuclear energy'. This article presents opinions of young opinion leaders over energy policy and nuclear energy

  13. Member states buoy up beleagured EMBL

    Balter, M

    1999-01-01

    EMBL's governing council, made up of delegates from the lab's 16 member countries, agreed in principle to meet the costs of a multimillion-dollar pay claim, the result of a recent ruling by the ILO in Geneva (1 page).

  14. Israel, CERN’s new Member State

    Brice, Maximilien

    2014-01-01

    On Wednesday, 15 January 2014, the official Israeli Flag-raising Ceremony took place to mark the accession of Israel to Membership of CERN, bringing the Organization’s number of Member States to 21.

  15. Team Members | Center for Cancer Research

    Our Team Members The Foregut Team includes experts in the diagnosis and treatment of the diseases listed below. Our clinical experience and active research offers patients the highest quality care in the setting of groundbreaking clinical trials.

  16. STRUCTURAL PERFORMANCE OF DEGRADED REINFORCED CONCRETE MEMBERS

    Braverman, J.I.; Miller, C.A.; Ellingwood, B.R.; Naus, D.J.; Hofmayer, C.H.; Bezler, P.; Chang, T.Y.

    2001-01-01

    This paper describes the results of a study to evaluate, in probabilistic terms, the effects of age-related degradation on the structural performance of reinforced concrete members at nuclear power plants. The paper focuses on degradation of reinforced concrete flexural members and shear walls due to the loss of steel reinforcing area and loss of concrete area (cracking/spalling). Loss of steel area is typically caused by corrosion while cracking and spalling can be caused by corrosion of reinforcing steel, freeze-thaw, or aggressive chemical attack. Structural performance in the presence of uncertainties is depicted by a fragility (or conditional probability of failure). The effects of degradation on the fragility of reinforced concrete members are calculated to assess the potential significance of various levels of degradation. The fragility modeling procedures applied to degraded concrete members can be used to assess the effects of degradation on plant risk and can lead to the development of probability-based degradation acceptance limits

  17. miR-34a: Multiple Opposing Targets and One Destiny in Hepatocellular Carcinoma.

    Yacoub, Radwa Alaa; Fawzy, Injie Omar; Assal, Reem Amr; Hosny, Karim Adel; Zekri, Abdel-Rahman Nabawy; Esmat, Gamal; El Tayebi, Hend Mohamed; Abdelaziz, Ahmed Ihab

    2016-12-28

    Background and Aims: The role of miR-34a in hepatocellular carcinoma (HCC) is controversial and several unresolved issues remain, including its expression pattern and relevance to tumor etiology, tumor stage and prognosis, and finally, its impact on apoptosis. Methods: miR-34a expression was assessed in hepatitis C virus (HCV)-induced non-metastatic HCC tissues by RT-Q-PCR. Huh-7 cells were transfected with miR-34a mimics and the impact of miR-34a was examined on 84 pro-apoptotic/anti-apoptotic genes using PCR array; its net effect was tested on cell viability via MTT assay. Results: miR-34a expression was up-regulated in HCC tissues. Moreover, miR-34a induced a large set of pro-apoptotic/anti-apoptotic genes, with a net result of triggering apoptosis and repressing cell viability. Conclusions: HCC-related differential expression of miR-34a could be etiology-based or stage-specific, and low expression of miR-34a may predict poor prognosis. This study's findings also emphasize the role of miR-34a in apoptosis.

  18. Multiple inflation

    Murphy, P.J.

    1987-01-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bond on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact

  19. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family

    Ambjørn, Malene; Asmussen, Johanne W; Lindstam, Mats

    2007-01-01

    outgrowth and survival. MT-mediated neurite outgrowth was furthermore inhibited by an anti-megalin serum. EmtinB-mediated inhibition of apoptosis occurred without a reduction of caspase-3 activity, but was associated with reduced expression of the pro-apoptotic B-cell leukemia/lymphoma-2 interacting member...

  20. ADA members weigh in on critical issues.

    Burgess, Karen; Ruesch, Jon D; Mikkelsen, Matthew C; Wagner, Karen Schaid

    2003-01-01

    Science, new technology, patient care, dental reimbursement and government regulations all affect today's dental practitioners. To find out more about how such challenges may affect current private practitioners, the American Dental Association conducted the 2000 Membership Needs and Opinions Survey. A questionnaire was sent to 6,310 ADA members in January 2000 with follow-up mailings in February, March and April 2000. Data collection was completed in July 2000. The survey included questions on critical professional issues, and on perceptions of the ADA and ADA priorities. A total of 3,558 completed surveys were received for an adjusted response rate of 59.5 percent. Members rated the identified issues' level of importance to them. The top three issues included "maintaining my ability to recommend the treatment option I feel is most appropriate for my patients," "receiving fair reimbursement for the dental services I provide," and "protecting myself, my staff and my patients from communicable diseases." New dentists found other items to be more significant to them compared with members overall. Although ADA members as a whole had similar views on critical issues facing dentistry and ADA priorities, there were significant differences regarding some issues. New dentists were far more concerned about securing funds for their practice and paying off debt than were all ADA members. Minority dentists expressed greater levels of concern about certain issues than did all ADA members. When planning and implementing ADA activities, the Association should continue to take into account members' relative rankings of professional issues and note issues of special interest to selected membership subgroups.

  1. Migration processes in SCO member states

    Valentina Sergeevna Antonyuk

    2012-12-01

    Full Text Available The article concerns modern state and development of migration processes in SCO member states. As a main method of research statistical analysis was applied. The article shows that migration streams between SCO member states are rather intensive, and the problem of labor migration becomes more and more urgent. The countries of consuming and supplying of labour force are clearly differentiated in the region. For some countries, labor export is the key sector of economy. At the same time, interstate relations between SCO member states sometimes are rather disputed. The most urgent factors causing the development of migration processes in the region were determined. Among them, thefactor of growing outflows from China isespecially noted. It is noted that migration processes are discussed by SCO member states nowadays in terms of illegal migration and international criminality connected with it. It means that the question of labor migration is a real problem. It is indicated that the creation of a specific joint commission on migration policy affiliated with the Council of Foreign Ministers of SCO member states is the necessary condition of effective interaction in migration questions within the framework of Shanghai Cooperation Organization.

  2. Static Members of Classes in C#

    Adrian LUPASC

    2017-12-01

    Full Text Available The C# language is object-oriented, which is why the declared member data must be part of a class. Thus, there is no possibility to declare certain variables that can be accessed from anywhere within the application, as it happens, for example, with global variables at the C language level. Making this work in C# is possible through static members of the class. Declaring a class implies defining some of its member data that later receive values when creating each object. A static member of the class can be interpreted as belonging only to the class, not to the objects subsequently created, which means that for the non-static data, there are as many children as there were objects created, while for the static ones there is only one copy, regardless of the number of created objects. In this regard, this paper presents the main aspects that characterize these abstract concepts of object oriented programming in general and C# language in particular, detailing how to develop an application that includes both static and non-static members. At the same time, particularities in the mirror for the two types of data, restrictions on use and potential limitations are presented.

  3. Does formal mentoring for faculty members matter? A survey of clinical faculty members.

    Mylona, Elza; Brubaker, Linda; Williams, Valerie N; Novielli, Karen D; Lyness, Jeffrey M; Pollart, Susan M; Dandar, Valerie; Bunton, Sarah A

    2016-06-01

    Mentoring relationships, for all medical school faculty members, are an important component of lifelong development and education, yet an understanding of mentoring among medical school clinical faculty members is incomplete. This study examined associations between formal mentoring relationships and aspects of faculty members' engagement and satisfaction. It then explored the variability of these associations across subgroups of clinical faculty members to understand the status of mentoring and outcomes of mentoring relationships. The authors hypothesised that academic clinical faculty members currently in formal mentoring relationships experience enhanced employee engagement and satisfaction with their department and institution. Medical school faculty members at 26 self-selected USA institutions participated in the 2011-2014 Faculty Forward Engagement Survey. Responses from clinical faculty members were analysed for relationships between mentoring status and perceptions of engagement by faculty members. Of the 11 953 clinical faculty respondents, almost one-third reported having a formal mentoring relationship (30%; 3529). Most mentored faculty indicated the relationship was important (86%; n = 3027), and over three-fourths were satisfied with their mentoring experience (77%; n = 2722). Mentored faculty members across ranks reported significantly higher levels of satisfaction and more positive perceptions of their roles in the organisation. Faculty members who were not receiving mentoring reported significantly less satisfaction with their workplace environment and lower overall satisfaction. Mentored clinical faculty members have significantly greater satisfaction with their department and institution. This multi-institutional study provides evidence that fostering mentoring opportunities may facilitate faculty members' satisfaction and engagement, which, in turn, may help medical schools retain high-quality faculty staff committed to the multidimensional

  4. Cracking in Flexural Reinforced Concrete Members

    Rasmussen, Annette Beedholm; Fisker, Jakob; Hagsten, Lars German

    2017-01-01

    The system of cracks developing in reinforced concrete is in many aspects essential when modelling structures in both serviceability- and ultimate limit state. This paper discusses the behavior concerning crack development in flexural members observed from tests and associates it with two different...... existing models. From the investigations an approach is proposed on how to predict the crack pattern in flexural members involving two different crack systems; primary flexural cracks and local secondary cracks. The results of the approach is in overall good agreement with the observed tests and captures...... the pronounced size effect associated with flexural cracking in which the crack spacing and crack widths are approximately proportional to the depth of the member....

  5. Stress and Depressive Symptoms in Cancer Survivors and Their Family Members: Korea Community Health Survey, 2012.

    Han, Mi Ah

    2017-09-01

    This study examined the prevalence of perceived stress and depressive symptoms in cancer survivors and their family members compared with subjects without cancer and without family members with cancer. The subjects of this cross-sectional study were adults ≥19 years old who participated in the 2012 Korea Community Health Survey. Stress and depressive symptoms in cancer survivors and their family members were assessed and compared to symptoms in control groups by chi-square tests and multiple logistic regression analyses. Of the 6783 cancer survivors, 26.9% and 8.7% reported having stress and depressive symptoms, respectively, and 27.7% and 5.9% of family members of cancer survivors reported having stress and depressive symptoms, respectively. Cancer survivors showed higher adjusted odds ratio (aOR) for stress (aOR = 1.26, 95% confidence interval (CI) = 1.16-1.37) and depressive symptoms (aOR = 1.82, 95% CI = 1.57-2.11) than subjects without cancer history. Family members of cancer survivors showed a higher OR for stress and depressive symptoms than subjects without a family member who survived cancer. Cancer survivors and family members of cancer survivors had more stress and depressive symptoms than controls. Careful management for cancer patients and their family members should include screening for stress and depression to improve mental health associated with cancer survivorship.

  6. Geneva University honours two CERN staff members

    2001-01-01

    Albert Hofmann Steve Myers On 8 June, two CERN staff members will receive Geneva University's highest distinction. On the proposal of the University's particle physicists, Steve Myers and Albert Hoffmann, who orchestrated LEP commissioning and operation and were instrumental in its success, will awarded the distinction of doctor honoris causa. The ceremony, interspersed with musical interludes, will be followed by a formal reception and is open to all. The Uni Dufour car park will be free to members of the public attending the ceremony. 8 June 2001 at 10.00 a.m. Uni Dufour, Auditoire Piaget 24, rue Général Dufour, Geneva.

  7. Migration from New EU Member Countries

    Pytlikova, Mariola

    2007-01-01

    The main purpose of the paper is to give predictions of the migration potential from the 7 new EU member countries to the EEA/EU-13 countries. Being able to analyze 'real' migration behavior from these particular countries over the period 1990-2000 helps me to avoid problems related to (double) o...

  8. Role Orientations of Members of Parliament

    Thomassen, Jacques J.A.; Esaiasson, Peter

    2006-01-01

    To what extent would a change of the Dutch electoral system, strengthening the bond between individual Members of Parliament (MPs) and specific constituencies, improve the quality of political representation, and increase the legitimacy of the political system in the process? In order to answer this

  9. Boron--epoxy tubular structure members

    Shakespeare, W. B. J.; Nelson, P. T.; Lindkvist, E. C.

    1973-01-01

    Composite materials fabricate thin-walled tubular members which have same load-carrying capabilities as aluminum, titanium, or other metals, but are lighter. Interface between stepped end fitting and tube lends itself to attachments by primary as well as secondary bonding. Interlaminar shear and hoop stress buildup in attachment at end fitting is avoided.

  10. Phylogenetic relationships among members of the Pachydactylus ...

    The Pachydactylus capensis group is a phenetically-defined assemblage of five small-bodied geckos broadly distributed in eastern southern Africa. Several additional small-bodied Pachydactylus have been historically considered subspecies of P. capensis or members of this group. To assess evolutionary relationships ...

  11. WTO Members' Commitments in Education Services

    Xu, Jian

    2009-01-01

    The establishment of World Trade Organization is in line with the conclusion reached at the end of the Uruguay Round in April 1994 by the bulk of the world's trading nations. WTO is in charge of managing multilateral trading system. WTO's "General Agreement on Trade in Services" (GATS) requires member nations to comply with the following…

  12. Issues Causing Stress among Business Faculty Members

    Adrian, C. Mitchell; Cox, Susie S.; Phelps, Lonnie D.; Schuldt, Barbara A.; Totten, Jeff W.

    2014-01-01

    This study examines factors contributing to faculty stress. Factors including demographics, tenure, discipline, and teaching medium are all examined. Whereas once faculty members were inundated with learning new electronic technology (and the stress it created), many appear to have become somewhat comfortable with this change and have adapted to…

  13. Important characteristics of operational force members

    Van Heerden, Adelai

    2017-10-01

    Full Text Available The operational forces military context is generally acknowledged as one of the most stressful contexts as it is demanding of members on a physical, psychological, social level with organisational, intra- and inter-personal demands of an extreme...

  14. Israel, CERN’s new Member State

    Anaïs Schaeffer

    2014-01-01

    On Wednesday, 15 January 2014, the official Israeli Flag-raising Ceremony took place to mark the accession of Israel to Membership of CERN, bringing the Organization’s number of Member States to 21.     For more information, click here.

  15. 7 CFR 983.42 - Initial members and nomination of successor members.

    2010-01-01

    ...) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF... alternate is selected shall serve in place of that member on the committee, and shall have and be able to... members of the committee shall serve for terms of two years: Provided, That four of the initially selected...

  16. New agents that target senescent cells : The flavone, fisetin, and the BCL-X-L inhibitors, A1331852 and A1155463

    Zhu, Yi; Doornebal, Ewald J.; Pirtskhalava, Tamar; Giorgadze, Nino; Wentworth, Mark; Fuhrmann-Stroissnigg, Heike; Niedernhofer, Laura J.; Robbins, Paul D.; Tchkonia, Tamara; Kirkland, James L.

    2017-01-01

    Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory

  17. Why 4-H Members Leave: A Study of Discontinuance through Both Current 4-H Members and Former Members

    Chilek, Kevin Dwayne

    2012-01-01

    4-H members quit. It is part of every 4-H program, and according to the research, it is even part of growing up. If only we knew why they quit, we could possibly do something about it. To date, the reasons youth join 4-H have been more thoroughly researched than the reasons they quit. This study explores why youth choose to discontinue membership…

  18. Design of Multiple Bolted Connections for Laminated Veneer Lumber

    Borjen Yeh; Douglas Rammer; Jeff Linville

    2014-01-01

    The design of multiple bolted connections in accordance with Appendix E of the National Design Specification for Wood Construction (NDS) has incorporated provisions for evaluating localized member failure modes of row and group tear-out when the connections are closely spaced. Originally based on structural glued laminated timber (glulam) members made with all L1...

  19. The experiences of family members in the nursing home to hospital transfer decision

    Kathleen Abrahamson

    2016-11-01

    Full Text Available Abstract Background The objective of this study was to better understand the experiences of family members in the nursing home to hospital transfer decision making process. Semi-structured interviews were conducted with 20 family members who had recently been involved in a nursing home to hospital transfer decision. Results Family members perceived themselves to play an advocacy role in their resident’s care and interview themes clustered within three over-arching categories: Family perception of the nursing home’s capacity to provide medical care: Resident and family choices; and issues at ‘hand-off’ and the hospital. Multiple sub-themes were also identified. Conclusions Findings from this study contribute to knowledge surrounding the nursing home transfer decision by illuminating the experiences of family members in the transfer decision process.

  20. [Music in human terminality: the family members' conceptions].

    Sales, Catarina Aparecida; da Silva, Vladimir Araujo; Pilger, Calíope; Marcon, Sonia Silva

    2011-03-01

    This qualitative study was performed using the multiple case study method and Heidegger's existential phenomenology for data analysis. The objective was to understand how family members perceive the influence of musical experiences on the physical and mental health of a relative living with a terminal illness. Participants were seven individuals belonging to two families. Data collection was performed through interviews and observation from May to June 2009. Results showed that using music while providing care to beings living with cancer can provide well-being to patients as well as their caregivers. Considering the deficit of leisure and the monotony of the home environment, using music contemplates the philosophical and humanitarian precepts of palliative care, thus being characterized as a complementary resource to nursing care, as besides being a communication resource, it improves the interpersonal relationship between patients and their families.

  1. Strategy-Proof Assignment Of Multiple Resources

    Erlanson, Albin; Szwagrzak, Karol

    2015-01-01

    We examine the strategy-proof allocation of multiple resources; an application is the assignment of packages of tasks, workloads, and compensations among the members of an organization. In the domain of multidimensional single-peaked preferences, we find that any allocation mechanism obtained by ...

  2. Substance abusers' personality disorders and staff members' emotional reactions

    Hesse Morten

    2008-04-01

    Full Text Available Abstract Background Previous research has indicated that aggressive behaviour and DSM-IV cluster B personality disorders (PD may be associated with professionals' emotional reactions to clients, and that cluster C PD may be associated with positive emotional reactions. Methods Staff members recruited from workshops completed a self-report inventory of emotional reactions to patients, the Feeling Word Checklist-58, and substance abusers completed a self-report of DSM-IV personality disorder, the DSM-IV and ICD-10 Personality Disorder Questionnaire. Correlational analysis and multiple regression analysis was used to assess the associations between personality disorders and emotional reations. Results Cluster B disorder features were associated with feeling distance to patients, and cluster C disorder features were associated with feeling helpful towards patients. Cluster A disorders had no significant impact on emotional reactions. Conclusion The findings confirm clinical experiences that personality disorder features in patients with substance abuse have an impact on staff members reactions to them. These reactions should be considered in supervision of staff, and in treatment models for patients with co-morbid personality disorders and substance abuse.

  3. Members of the Forum Engelberg visit CERN

    Patrive Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996. Photo 01: CERN Director-General Prof. Luciano Maiani (left) speaks to Forum members and public figures from the Geneva area during the visit. In the background is Jean-Claude Landry from the Department of the Interior, Agriculture and Environment, State of Geneva. Photo 02: CERN Director-General Prof. Luciano Maiani (left) speaks to Forum members and public figures from the Geneva area during the visit. In the background is Bernard Ecoffey, Founder of the Forum Engelberg.

  4. Surface modifying method for metal member

    Amano, Kazuo; Enomoto, Kunio; Hirano, Akihiko; Hirano, Atsuya; Hattori, Shigeo; Hayashi, Eisaku; Ueyama, Toshiharu; Hayashi, Makoto

    1998-01-01

    A surface of a metal member such as carbon steel to be used in a corrosion circumstance such as in a nuclear power plant and a thermoelectric plant are polished. A printing method is conducted for removing obstacles on the surface of the member. Namely, a photographing printing paper immersed in a diluted sulfuric acid solution is appended tightly to the portion with its surface polished smoothly. Sulfur present in the form of an obstacle of MnS or present alone in the material reacts with the sulfuric acid to form a sulfuric acid gas, and reacts with Ag of the printing paper to discolor the printing paper to brown. When a peeled printing paper is discolored to brown, sulfur printing is repeated. After conforming that the peeled printing paper is white, the surface is washed. Subsequently, surface plasticization is conducted by water jet peening or shot peening. (I.N.)

  5. Identifying New Members of Nearby Moving Groups

    Holmbeck, Erika; Vican, Laura

    2014-06-01

    Our group has assembled a sample of 14,000 stars of spectral types B9-M9 with measured UVW Galactic space velocities and lying within 125 pc of Earth. We have identified candidate members of three nearby young (less than 100 Myr) moving groups. For stars of spectral types G5 and later, we have used the Kast spectrometer on the Shane 3m telescope at Lick Observatory to measure lithium abundance in order to determine stellar ages. With the data we have obtained from this run, we will be able to establish whether our candidates are bona fide members of the moving groups in question. I will be presenting the preliminary results from this survey, including spectra of the ~50 stars observed thus far. These nearby young stars will make excellent targets for direct imaging followup surveys, since any giant planets around young stars will still be warm, and will therefore be bright enough to detect with instruments like GPI.

  6. Lithuania to become Associate Member of CERN

    Dačkus, Robertas

    2017-01-01

    On 27 June 2017, in Vilnius, Lithuania, CERN Director General, Fabiola Gianotti, and the Minister of Foreign Affairs of the Republic of Lithuania, Linas Linkevičius, in the presence of the President of the Republic of Lithuania, Dalia Grybauskaitė, signed the Agreement admitting Lithuania as an Associate Member of CERN. The last step for the Agreement to enter into force requires final approval by the Government of Lithuania.

  7. Mapping organizational members' sense of fit

    Billsberry, Jon; Marsh, Philip; Moss-Jones, John

    2004-01-01

    Despite its importance in the organizational behavior literature, person–organization (P–O) fit remains an elusive construct. One reason for this is the lack of research about organizational members’ own sense of their P–O fit. In this paper we report an empirical study that explored organizational members’ own sense of fit using storytelling and causal mapping techniques. The results suggest that organizational members categorize their perceptions of their fit into five discrete domains (job...

  8. Service Member Suicide and Readiness: An Analysis

    2017-05-25

    command, and degrades the morale of those still serving, as well as the American public.8 A shrinking number of qualified volunteers and reductions...to Sri Aurobindo’s Philosophy of Integral Non-Dualism,” in The Integral Philosophy of Sri Aurobindo, ed. Haridas Chaudhuri and Frederic Spiegelberg...potentially unsolvable problem should not prevent attempts to develop solutions. In a moral sense, service member suicide should elicit greater diligence

  9. Member State Event: Telling CERN's story !

    2004-01-01

    As part of the events to mark the Laboratory's fiftieth anniversary, members of the CERN personnel are telling the story of CERN. Robert Cailliau (on the right), currently responsible for CERN's external communications, and Chiara Mariotti (in the center), a physicist working at CMS, were invited to talk about the history of CERN and the Web at a conference in the 'Science Thursdays' series entitled 'From the Quark to the Web' in Turin on 26 February.

  10. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996. He is pictured here (right) alongside CERN Director-General Prof. Luciano Maiani during the visit of Forum members to CERN.

  11. REGISTRATION OF VEHICLES IN SWITZERLAND: MEMBERS OF THE FAMILY OF A MEMBER OF THE PERSONNEL

    Service des Relations avec les Pays Hôtes

    1999-01-01

    The Permanent Mission of Switzerland to the International Organisations in Geneva has informed CERN that members of the family of a member of the personnel who hold a carte delégitimation or a Ci permit may not register a vehicle in Switzerland. Only those members of the family who are of Swiss nationality or hold an ordinary permit (e.g. a 'B' or 'C' permit) may register vehicles in their own names.Relations with the Host States Servicehttp://www.cern.ch/relations/Tel. 72848

  12. Member State Event: Telling CERN's Story

    2004-01-01

    As part of the events to mark the Laboratory's fiftieth anniversary, members of the CERN personnel are telling the story of CERN. Robert Cailliau (on the right of the photograph), co-inventor of the Web and currently responsible for CERN's external communications, and Chiara Mariotti (in the center), a physicist working at CMS, were invited to talk about the history of CERN and the Web at a conference in the 'Science Thursdays' series entitled 'From the Quark to the Web' in Turin on 26 February. This was not their first appearance before a non-specialist audience (almost 1000 people that day!) eager to find out what goes on in a unique research centre like CERN as talking about the Laboratory's activities and its history are part and parcel of their work for the Organization. Anniversary Events in the Member States: This 'Science Thursday' event devoted to CERN was one of Italy's contributions to CERN's fiftieth anniversary celebrations. Coming up soon in the Member States: Italy International Centre...

  13. Multiplicity in Early Stellar Evolution

    Reipurth, B.; Clarke, C. J.; Boss, A. P.; Goodwin, S. P.; Rodríguez, L. F.; Stassun, K. G.; Tokovinin, A.; Zinnecker, H.

    Observations from optical to centimeter wavelengths have demonstrated that multiple systems of two or more bodies is the norm at all stellar evolutionary stages. Multiple systems are widely agreed to result from the collapse and fragmentation of cloud cores, despite the inhibiting influence of magnetic fields. Surveys of class 0 protostars with millimeter interferometers have revealed a very high multiplicity frequency of about 2/3, even though there are observational difficulties in resolving close protobinaries, thus supporting the possibility that all stars could be born in multiple systems. Near-infrared adaptive optics observations of class I protostars show a lower binary frequency relative to the class 0 phase, a declining trend that continues through the class II/III stages to the field population. This loss of companions is a natural consequence of dynamical interplay in small multiple systems, leading to ejection of members. We discuss observational consequences of this dynamical evolution, and its influence on circumstellar disks, and we review the evolution of circumbinary disks and their role in defining binary mass ratios. Special attention is paid to eclipsing PMS binaries, which allow for observational tests of evolutionary models of early stellar evolution. Many stars are born in clusters and small groups, and we discuss how interactions in dense stellar environments can significantly alter the distribution of binary separations through dissolution of wider binaries. The binaries and multiples we find in the field are the survivors of these internal and external destructive processes, and we provide a detailed overview of the multiplicity statistics of the field, which form a boundary condition for all models of binary evolution. Finally, we discuss various formation mechanisms for massive binaries, and the properties of massive trapezia.

  14. A Non-Member Spouse's Entitlement To The Member's Pension Interest

    Motseotsile Clement Marumoagae

    2014-12-01

    Full Text Available It is important that married couples seek legal advice with regard to the assets falling within their joint estate, more particularly their retirement benefits. This article reflects on the entitlement (if any of non-member spouses to their spouses' retirement fund benefits. Pension benefits can be due before, during or after divorce, and parties to the marriage should be aware of their rights with regard to the accruing pension benefits of their spouses. While it is settled law that non-member spouses are entitled to receive a portion of their member spouses' pension benefits (known as "pension interest" immediately on divorce, it is not particularly clear whether non-member spouses are also entitled to receive the same before or sometime after divorce. In this article I provide a contextual understanding of the entitlements (if any which spouses or former spouses of members of pension funds have on such member spouses' retirement benefits. Furthermore, it shown in this article that various divisions of South African High Courts have been inconsistent in how they have approached the issue of the pension interest between divorcing spouses or divorced ex-spouses.

  15. A germline RET proto-oncogene mutation in multiple members of an ...

    Makia Marafie

    2016-09-17

    Sep 17, 2016 ... The Egyptian Journal of Medical Human Genetics (2017) 18, 193–197. HOSTED BY ... been reported in 85% of tested individuals, nearly 50% of them are amino acid .... [1] Krampitz GW, Norton JA. RET gene mutations ...

  16. Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

    Eudes, Aymerick; Mouille, Maxence; Robinson, David S.

    2016-01-01

    the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters. Similarly, we achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol...

  17. Multiple Input - Multiple Output (MIMO) SAR

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  18. Post-fire assessment of structural wood members

    Robert J. Ross; Brian K. Brashaw; Xiping Wang; Robert H. White; Roy F. Pellerin

    2005-01-01

    Since the interior of a charred wood member normally retains its structural integrity, large structural wood members often do not need to be replaced after a fire. Engineering judgement is required to determine which members can remain and which members need to be replaced or repaired. Due to the lack of established methods to directly determine the residual capacity...

  19. Suicidal behavior among members of Gamblers Anonymous.

    Frank, M L; Lester, D; Wexler, A

    1991-09-01

    A national sample of 500 members of Gamblers Anonymous was surveyed by mail in order to gather information on suicidal history. One hundred sixty two usable surveys were returned representing 32.4% of the original sample. Compulsive gamblers who had a history of suicidal preoccupation began gambling at an earlier age than nonsuicidal gamblers and were more likely to have stolen to support their gambling. They also tended to have addicted relatives and children more than nonsuicidal gamblers did. The data suggest that those gamblers who had been suicidal tend to be more serious gamblers than nonsuicidal respondents.

  20. Looking Backward, Looking Forward: MLA Members Speak

    Alliston, April; Ammons, Elizabeth; Arnold, Jean; Baym, Nina; Beckett, Sandra L; Beidler, Peter G; Berger, Roger A; Bermann, Sandra; Wilson, J. J; Boone, Troy; Booth, Alison; Booth, Wayne C; Phelan, James; Borroff, Marie; Hassan, Ihab

    2000-01-01

    In 1997 I was asked to organize humanities outreach activities at the University of California, Irvine. The result was the formation of Humanities Out There (HOT). In our workshops, faculty members and graduate students supervise teams of undergraduates in order to take the methods and materials of the university into the larger community. I believe that programs like these will  become increasingly important in the next century, as economic, cultural, and educational divisions deepe...

  1. Members of the State Council of Geneva

    Maximilien Brice

    2002-01-01

    Luncheon hosted by the Director-General for members of the State Council of Geneva: From left to right A. Naudi; J. May; M. Carlo Lamprecht, State Council - Employement, Foreign Office and Economic Departement; M. Robert Hensler, State Chancellor; L. Maiani, CERN Director General; H.F. Hoffmann; M. Robert Cramer, State Council - Environment, Agriculture and Interior Departement; J.Van Der Boon; M. Laurent Moutinot, State Council - Installation, equipment and housing Departement; C. Détraz; C. Wyss; P. Jenni; G. Hentsch; M. Pierre-François Unger, State Council - Health and Social Action Departement; G. Stassinakis; M. Bourquin, CERN Council President.

  2. Cooperation with COMECON members in coke chemistry

    Medricky. Z

    1987-05-01

    Discusses activities of the coking industry division of the standing committee for iron metallurgy of the COMECON. The following cooperation fields are analyzed: raw material basis for coking industry, coal charge preparation and methods for reducing proportion of coking coal in a coal charge (heat treatments, formed coke processes, partial briquetting, pelletizing, increasing coking temperature, packing etc.), coking technology, coke quenching, screening, chemical processing of coal gas, environmental protection in the coking industry, environmental effects of coking, pitch coke production, methods for increasing labor productivity. Research programs coordinated by member countries are reviewed. Programs in which Czechoslovakia participates are discussed.

  3. BVA members wow judges in photo competition.

    2016-09-03

    Earlier this year, BVA ran its inaugural photo competition, giving members the opportunity to showcase the work of the veterinary profession and the animals and wildlife they encounter. Standing out from over 400 high-quality entries, judges picked the images reproduced in this month's BVA News as the winning and highly commended photos. To see all the entries and hear from the winners, visit www.bva.co.uk/vet-photos-2016/. There will be another photo competition in 2017 with more categories to be announced. British Veterinary Association.

  4. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Photo 01: Members of the Forum Engelberg and public figures from Geneva visit SM18, the test hall for LHC magnets: (left to right) N. Siegel, Prof. Dr. Med. Bernard Mach, Mr Alexander Höchli, H. Wenninger, Mrs Mireille Quirina, Mme Konrade Von Bremen, Mrs Thérèse Wolf, Prof. Roger Berthouzoz, Mrs Marie-Anne Heimo, Mr Bernard Ecoffey.

  5. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996. Horst Wenninger (left) in animated discussion with Alexander Höchli, member of the Institutional Committee of Forum Engelberg and former Landammann of the canton of Obwalden.

  6. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996. Photo 01: Thérèse Wolf, Secretary of Forum Engelberg; Alain Hervé; Horst Wenninger; and Alexander Höchli, Forum member and former Landammann of the canton of Obwalden, at the CMS detector's assembly site.

  7. Czech Republic joins IPPOG as member

    'marcelloni, claudia

    2018-01-01

    Czech Republic became an official IPPOG member on April 21 2018. The MOU between Czech Republic and IPPOG was previously signed by the director of the Institute of Physics of the Academy of Sciences of the Czech Republic. IPPOG chairs confirmed the agreement by signing the MOU during the meeting in Pisa in presence of IPPOG representative for Czech Republic dr. Vojtech Pleskot from the Faculty of Mathematics and Physics, Charles University in Prague. Dr. Vojtech Pleskot replaces Dr. Jiri Rames who did an excellent job during his long term work in the EPPOG and IPPOG.

  8. Reactor vessel supported by flexure member

    Crawford, J.D.; Pankow, B.

    1977-01-01

    According to the present invention there is provided an improved arrangement for supporting a reactor vessel within a containment structure against static and dynamic vertical loadings capable of being imposed as a result of a serious accident as well as during periods of normal plant operation. The support arrangement of the invention is, at the same time, capable of accommodating radial displacements that normally occur between the reactor vessel and the containment structure due to operational transients. The arrangement comprises a plurality of vertical columns connected between the reactor vessel and a support base within the containment structure. The columns are designed to accommodate relative displacements between the vessel and the containment structure by flexing. This eliminates the need for relative sliding movements and thus enables the columns to be securely fixed to the vessel. This elimination of a provision for relative sliding movements avoids the spaces or gaps between the retention members and the retained elements as occurred in prior art arrangements and, concomitantly, the danger of establishing impact forces on the retention members in the event of an accident is reduced. (author)

  9. The dying child and surviving family members.

    Shrier, D K

    1980-12-01

    This overview of death and dying focuses on the dying child and surviving family members. Children's concepts of death at different developmental stages are reviewed. These range from an inability to distinguish death from other forms of separation prior to age 3, through partial concepts of death until, by age 10 to 15 years, children are able to conceptualize death as universal, inevitable and final. The importance of adults assisting in the child's growing comprehension of death is stressed. The stages of grief and mourning, as outlined by Kubler-Ross, are reviewed from the perspective of the child and family: denial, anger, bargaining, depression and acceptance. Recognition is given to the variations in coping styles among different family members. The special circumstances related to the death of an infant and the impact of the death of a child on the surviving siblings are discussed. Specific helpful interventions to assist families in coping with mourning are described. The death of a child remains one of the most painful and difficult events for a family and its physician to accept.

  10. To all members of the personnel

    2005-01-01

    Temporary work for children of members of the personnel During the period mid-June to mid-September 2005, a limited number of vacancies for temporary work at CERN (normally unskilled work of a routine nature) will be available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of vacancies available, no children having previously worked at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks and the allowance for the period will be CHF 1621.- net. Candidates should apply via the HR Department's electronic recruitment system (E-rt) : http://humanresources.web.cern.ch/humanresources/internal/personnel/pmd/cr/Staff-kids-05.pdf Completed application forms must be returned to this Service by 8 April 2005 ...

  11. To all members of the personnel

    HR Department

    2011-01-01

    Summer work for children of members of the personnel During the period from 13 June to 16 September 2011 inclusive, there will be a limited number of jobs for summer work at CERN (normally unskilled work of a routine nature), which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of all contracts will be 4 weeks and the allowance will be 1717 CHF for this period. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_intranet/wd_pds?p_web_site_id=1&p_web_page_id=8886&p_no_apply=&p_show=N Completed application forms must be returned by 11 April 2011 at the latest. The results of the selection will be available by the end of May 2011. For further information, please con...

  12. TO ALL MEMBERS OF THE PERSONNEL

    2003-01-01

    Temporary work for children of members of the personnel During the period mid-June to mid-September 2003, there will be a limited number of vacancies for temporary work at CERN (normally unskilled work of routine nature) which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of vacancies available, no children previously appointed at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1582.- for this period. Application form can be obtained from Martine PLAZA, HR Division (by using the slip in the bulletin or by electronic mail to Martine.Plaza@cern.ch) or at http://cern.ch/hr-web/internal/general/HN-personnel/ Completed application forms must be returne...

  13. TO ALL MEMBERS OF THE PERSONNEL

    2003-01-01

    Temporary work for children of members of the personnel During the period mid-June to mid-September 2003, there will be a limited number of vacancies for temporary work at CERN (normally unskilled work of routine nature) which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of vacancies available, no children previously appointed at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1582.- for this period. Application form can be obtained from Martine PLAZA, HR Division (by electronic mail to Martine.Plaza@cern.ch) or at http://cern.ch/hr-web/internal/general/HN-personnel/ Completed application forms must be returned to this service by 2 May 2003 at th...

  14. TO ALL MEMBERS OF THE PERSONNEL

    2003-01-01

    Temporary work for children of members of the personnel During the period mid-June to mid-September 2003, there will be a limited number of vacancies for temporary work at CERN (normally unskilled work of routine nature) which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of vacancies available, no children previously appointed at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1582.- for this period. Application form can be obtained from Martine PLAZA, HR Division (by electronic mail to Martine.Plaza@cern.ch) or at http://cern.ch/hr-web/internal/general/HN-personnel/ Completed application forms must be returned to this service by 2 May 2003 at t...

  15. To all members of the personnel

    HR Department

    2009-01-01

    Temporary work for children of members of the personnel During the period from 15 June to 11 September 2009 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of routine nature), which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of all appointments will be 4 weeks and the allowance will be CHF 1717. - for this period. Candidates should apply via HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6970 Completed application forms must be returned by 10 April 2009 at the latest. The results of the selection will be available on 22 May 2009. For further information, please contact: mailto:Inger.Carriero@cern.c...

  16. To all members of the personnel

    HR Department

    2009-01-01

    Temporary work for children of members of the personnel During the period from 15 June to 11 September 2009 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of a routine nature), which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of all appointments will be 4 weeks and the allowance will be CHF 1717. - for this period. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6970 Completed application forms must be returned by 10 April 2009 at the latest. The results of the selection will be available on 22 May 2009. For further information, please contact: mailto:Inger.Carriero@...

  17. To all members of the personnel

    HR Department

    2008-01-01

    Temporary work for children of members of the personnel During the period from 16 June to 12 September 2008 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of a routine nature), which will be open to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of appointments will be 4 weeks and the allowance for this period will be 1663.- CHF. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6160 Completed application forms must be made on-line by 13 April 2008 at the latest. The results of the selection will be available on 18 May 2008. For further information, please contact: Geraldine.Ballet@cern.ch HR ...

  18. To all members of the personnel

    2006-01-01

    Temporary work for children of members of the personnelDuring the period 12 June to 15 September 2006 included, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of routine nature) which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of jobs available, no children who have previously worked at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1640.- for this period. Candidates should apply via HR department's electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=4691 Completed application forms must be returned to this service by 17 April 2006 at the latest. The results of t...

  19. To all members of the personnel

    HR Department

    2008-01-01

    Temporary work for children of members of the personnel During the period from 16 June to 12 September 2008 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of a routine nature), which will be open to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of appointments will be 4 weeks and the allowance for this period will be 1663 CHF. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6160 Completed application forms must be submitted on-line by 13 April 2008 at the latest. The results of the selection will be available on 18 May 2008. For further information, please contact: mailto:Geraldine.Ballet@cern....

  20. To all members of the personnel

    HR Department

    2010-01-01

    Summer work for children of members of the personnel During the period from 14 June to 17 September 2010 inclusive, a limited number of jobs for summer work at CERN (normally unskilled work of a routine nature) will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of all contracts will be 4 weeks and the allowance will be 1717 CHF for this period. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=7716 Completed application forms must be returned by 9 April 2010 at the latest. The results of the selection will be available on 21 May 2010. For further information, please contact: Inger.Carriero@cern.ch Tel. 71372

  1. To all members of the personnel

    Martine Briant

    2006-01-01

    Temporary work for children of members of the personnelDuring the period 12 June to 15 September 2006 included, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of routine nature) which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of jobs available, no children who have previously worked at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1640.- for this period. Candidates should apply via HR department's electronic recruitment system (E-rt) : https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=4691 Completed application forms must be returned to this service by 17 April 2006 at the latest. The results of ...

  2. To all members of the personnel

    FI Department

    2008-01-01

    Temporary work for children of members of the personnel During the period from 16 June to 12 September 2008 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of routine nature), which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of appointments will be 4 weeks and the allowance for this period will be 1663.- CHF. Candidates should apply via HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6160 Completed application forms must be made on-line by 13 April 2008 at the latest. The results of the selection will be available on 18 May 2008. For further information, please contact: mailto:Geraldine.Ballet@cer...

  3. To all members of the personnel

    HR Department

    2009-01-01

    Temporary work for children of members of the personnel During the period from 15 June to 11 September 2009 inclusive, there will be a limited number of jobs for temporary work at CERN (normally unskilled work of a routine nature), which will be made available to children of members of the personnel (i.e. anyone holding an employment or association contract with the Organization). Candidates must be aged between 18 and 24 inclusive on the first day of the contract, and must have insurance coverage for both illness and accident. The duration of all appointments will be 4 weeks and the allowance will be CHF 1717. - for this period. Candidates should apply via the HR Department’s electronic recruitment system (E-rt): https://ert.cern.ch/browse_www/wd_pds?p_web_page_id=6970 Completed application forms must be returned by 10 April 2009 at the latest. The results of the selection will be available on 22 May 2009. For further information, please contact: mailto:Inger.Carriero...

  4. Transfer pricing rules in EU member states

    Veronika Solilová

    2010-01-01

    Full Text Available One of the important area of international taxes is transfer pricing. Transfer price is a price set by a taxpayer when selling to, buying from, or sharing resources with a related (associated person. The tran­sac­tions between these persons should be assessed at their arm’s length price in according the arm’s length principle – international accepted standard – as the price which would have been agreed between unrelated parties in free market conditions. This paper is focused on the tranfer pricing rules used in particular EU Member States so as if EU Member States apply the arm’s length principle, define the related persons, apply recommendations of the OECD Guidelines, use the transfer pricing methods, require TP Documentation, exercise specific transfer pricing audit or impose specific penalties and apply APAs. Transfer pricing rules should prevent taxpayers from shifting income to related person organized in tax havens or in countries where they enjoy some special tax benefit.

  5. Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63.

    Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

    2016-11-01

    Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations.

  6. Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis.

    Binet, François; Cavalli, Hélène; Moisan, Eliane; Girard, Denis

    2006-02-01

    The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

  7. Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-dependent Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In Vitro

    Řezníčková, Eva; Weitensteiner, S.; Havlíček, Libor; Jorda, Radek; Gucký, Tomáš; Berka, K.; Bazgier, Václav; Zahler, S.; Kryštof, Vladimír; Strnad, Miroslav

    2015-01-01

    Roč. 86, č. 6 (2015), s. 1528-1540 ISSN 1747-0277 R&D Projects: GA ČR GAP305/12/0783; GA ČR GA14-19590S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : angiogenesis * apoptosis * aurora A Subject RIV: CE - Biochemistry Impact factor: 2.802, year: 2015 http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=CCC&DestLinkType=FullRecord&UT=000367376800022

  8. Grief elaboration in families with handicapped member.

    Calandra, C; Finocchiaro, G; Raciti, L; Alberti, A

    1992-01-01

    Families with handicapped member seem to follow the same five stages (rejection and isolation, anger, dealing with the problem, depression, acceptance) of Kubler-Ross grief elaboration theory while dealing with the narcissistic wound of a handicapped child. Some of these families show a block in one of the stages. The effort of psychotherapy is to remove the block and let them reach the last stage. In this paper families under systemic psychotherapeutic treatment are analyzed, who had in common the birth of a child with low or modest invalidating signs and psychotic or autistic features. The families structure did not show the characteristics of a psychotic family. Nevertheless either one or both parents ignored the evidence of their child disease and they built a "disease-incongrous" wait around the child, trying to push away the painful reality. The authors explain the importance of this approach for the improvement of the autistic traits.

  9. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996.Seated here at a presentation by Peter Jenni, spokesperson for the ATLAS collaboration, during the visit of Forum members and Geneva public figures are Bernard Ecoffey, Founder of the Forum Engelberg (left), and Jean-Claude Landry, Department of the Interior, Agriculture and Environment, state of Geneva. Photo 01: (left to right) Bernard Ecoffey, Jean-Claude Landry and Peter Jenni. Photos 02, 03: (left to right) Jean-Claude Landry, Bernard Ecoffey and Peter Jenni.

  10. Migration from the new EU member countries

    Pedersen, Louise Møller; Lund Thomsen, Trine

    2012-01-01

    investigates the potentials, limitations and conflicts of interests that are connected with temporary employment of Eastern European migrant workers within the unskilled labour sectors seen from the perspective of Danish labour market actors; politicians, labour marked unions, Danish employers, Danish......During the past four years more than 52.500 Eastern European EU citizens have worked and lived in Denmark. Migrant workers from the new EU countries are characterized by a high degree of mobility, flexibility and eagerness in terms of working and adapting to working conditions. Poorer socioeconomic...... and working conditions in their home countries as well as being of another cultural background than their Danish colleagues brings with it many challenges. This article examines the consequences of low-skilled labour migration to Denmark from the new EU member countries in Eastern Europe. The article...

  11. Table of members of quasi-bands

    Sakai, Mitsuo.

    1984-04-01

    The probable members of the quasi-bands in even-even nuclei for Z between 6 and 100 are listed in this table. The terms quasi-bands have been introduced in the so-called spherical regions as the counter parts of the collective bands in the deformed regions. In the present compilation, the data for deformed nuclei are classified for convenience under the same titles, Quasi-Ground Band, Quasi-Beta Band and Quasi-Gamma Band, as are used for other nuclear regions. The present edition covers the literature through September, 1983. Fifteen newly discovered nuclides are included. The classification of energy level into quasi-bands is made on the basis of the systematic trend in the data over large groups of nuclei. (Kato, T.)

  12. Czech Republic to Become Member of ESO

    2006-12-01

    Today, an agreement was signed in Prague between ESO and the Czech Republic, aiming to make the latter become a full member of ESO as of 1 January 2007. "The future membership of the Czech Republic in ESO opens for the Czech astronomers completely new opportunities and possibilities. It will foster this discipline on the highest quality level and open new opportunities for Czech industry to actively cooperate in research and development of high-tech instruments for astronomical research," said Miroslava Kopicová, Minister of Education, Youth and Sports of the Czech Republic. ESO PR Photo 52/06 ESO PR Photo 52/06 Signing Ceremony "We warmly welcome the Czech Republic as the thirteenth member of ESO," said Catherine Cesarsky, ESO's Director General. "The timing couldn't be better chosen: with the Very Large Telescope, Europe is now at the forefront of ground-based astronomy, and with the construction of ALMA and the final studies for the European Extremely Large Telescope, we will ensure that this will remain so for several decades. We look forward to working together with our Czech colleagues towards these successes." The signing event took place at the Czech Ministry of Education, Youth and Sports in Prague. Following ratification by the Czech Parliament, the Czech Republic with thus join the twelve present member states of ESO, the European Organisation for Astronomical Research in the Southern Hemisphere: Belgium, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. The Czech Republic is the first country from Central and Eastern Europe to join ESO. Astronomy in the Czech Republic has a very long tradition that dates from as far back as 3500 BC. Four centuries ago, Tycho Brahe and Johannes Kepler established themselves in Prague at the invitation of the emperor Rudolph II, laying the ground for the first golden age in astronomy. Later, eminent scientists such as Christian Doppler, Ernst Mach and

  13. Sensory loss amongst old family members

    Rasmussen, Jon Dag; Winther, Ida Wentzel

    2018-01-01

    and their close family. Our tentative findings point towards a prominence of different insecurities and discomforts in social life that directly links to the decreased sensory abilities. Experiences of being ‘lost’, ‘set afloat’ and disconnected in everyday life interactions are broadly described by all...... on the old people suffering a decline in sensory abilities, but also on family members as individual loss becomes collective loss in the context of family and kinship. The paper presentation takes its point of departure in rough pieces of empirical material (e.g. film-clips, sound......-clips/montage and ethnographic description) and through exposition of tentative analysis and research findings we aim to initiate a discussion around central themes of the work....

  14. (ReTranslating as Re-membering

    Julie Tarif

    2016-07-01

    Full Text Available This paper explores how (retranslation – interlingual and intersemiotic – can be perceived as a way of both remembering the literary legacy of other cultures but also as a way of re-membering/re-generating the body of literature(s of the importing culture. It focuses on what is called “a classic” and anchors its reflexion in polysystem theory and in the metaphorical vision of literary works as an organic living body. To do so, it concentrates on the British literary classic Oliver Twist and its translations and adaptations into French. The article addresses the following questions: What is to be remembered of certain works? Why, how and by whom are those works remembered?

  15. OSART Works to Help Member States

    Kaiser, Peter

    2013-01-01

    Full text: Nuclear safety is a never ending pursuit for improvement, and one of the more prominent IAEA efforts that help Member States achieve higher levels of safety is the Operational Safety Review Team (OSART) programme. In OSART missions, the IAEA coordinates internationally-based teams of experts who conduct reviews of operational safety performance at nuclear power plants. The IAEA on 14 June 2013 marked the 30th anniversary of OSART. In 1983, the Agency conducted its first OSART mission to the Kori Nuclear Power Plant in the Republic of Korea, and it conducted a total of 174 OSART missions over the following 30 years. The reviews have been done in 34 nations at 103 nuclear sites. (author)

  16. Members of the Forum Engelberg visit CERN

    Patrice Loïez

    2002-01-01

    The Forum Engelberg is an annual interdisciplinary conference held in Engelberg, Switzerland intended to act as an international platform for debate and exchange of views on key issues affecting scientific research, technology, economics and philosophy. Its President is Hubert Curien - former French Minister of Research and Space Research, and President of the CERN Council from 1994 to 1996. Photo 01: Raymond Battistella - Director-General of SIG, Geneva's utilities provider (left) - and Bernard Ecoffey, Founder of the Forum Engelberg. In the background is the CMS magnet system under construction. The red concentric rings are part of the barrel yoke, which returns the magnetic flux generated by the superconducting coil. Supported from the innermost barrel ring is the outer cylinder of the vacuum tank that will house the superconducting coil. Photo 02: Alexander Höchli, member of the Institutional Committee of Forum Engelberg and former Landammann of the canton of Obwalden (left), with Raymond Battistella, Di...

  17. APPARATUS FOR NON-DESTRUCTIVE INSPECTION OF CANTILEVERED MEMBERS

    Taylor, E.R.; Mahoney, C.H.; Lay, C.R.

    1961-10-24

    An apparatus for non-destructive inspection of cantilevered members, such as compressor blades, is described. The member under inspection is vibrated with a regulated source of air under pressure. The amplitude of vibration of the member is maintained at its natural frequency. The frequency of vibration of the member is measured. An indication of an excessive decay or erratic shifting in the measured frequency above an allowable hysteretic decay is provided as an indication of a fault in the member. The member is vibrated for a selected test period. (AEC)

  18. Perspectives and expectations of union member and non- union member teachers on teacher unions

    Tuncer FİDAN

    2015-12-01

    Full Text Available Unions, which can be regarded as one of the constitutive elements of democracy, are the pressure groups in political and social fields. Unions were born out of industrial confrontations and expanded into the field of public services over time, and thus teachers – who are also public employees-, also obtained the right to establish and affiliate to unions. In this research the views of union member and non-union member teachers on the most important functions and operational effectiveness of unions, teachers’ expectations from unions and teachers’ evaluation of the solidarity, competition and cooperation between unions were determined and the perspectives of teachers on unionization were revealed. qualitative research design was used. The data needed were collected through semi-structured interviews from volunteering union member and non-union member teachers who were working in the primary and secondary schools in Ankara province and who were selected through “maximum variation sampling approach”. The data were then analyzed by using the content analysis technique. In conclusion, it was found that political ideology was the most important reason for membership of teachers’ unions. Protection and development of personal rights was found to be the most important function of teacher unions and unions were thought to be insufficient in performing those functions.

  19. Family Members' Reports of the Technology Use of Family Members with Intellectual and Developmental Disabilities

    Palmer, S. B.; Wehmeyer, M. L.; Davies, D. K.; Stock, S. E.

    2012-01-01

    Background: A nationwide survey of family members of people with intellectual and developmental disabilities ranging in age from birth through adulthood was conducted to replicate a similar effort by Wehmeyer and update the knowledge base concerning technology use by people with intellectual and developmental disabilities. Method: Survey responses…

  20. Inflation persistence: is it similar in the new EU member states and the euro area members?

    Franta, Michal; Saxa, Branislav; Šmídková, K.

    -, 25/2008 (2008), s. 1-35 Grant - others:Česká národní banka(CZ) B4/2003 Institutional research plan: CEZ:AV0Z70850503 Keywords : inflation persistence * new EU member states * new hybrid Phillips curve Subject RIV: AH - Economics http://ies.fsv.cuni.cz/default/file/download/id/9070

  1. Inflation persistence in new EU member states: is it different than in the euro area members?

    Franta, Michal; Saxa, Branislav; Šmídková, Kateřina

    -, č. 10 (2007), s. 1-37 ISSN 1803-2397 Institutional research plan: CEZ:AV0Z70850503 Keywords : inflation persistence * new hybrid Phillips curve * new EU member states Subject RIV: AH - Economics http://www.cnb.cz/m2export/sites/www.cnb.cz/en/research/research_publications/cnb_wp/download/cnbwp_2007_10.pdf

  2. Ten Warning Signs Your Older Family Member May Need Help

    ... Warning Signs Your Older Family Member May Need Help Changes in physical and cognitive abilities that may ... and their family members, friends, and caregivers. To help in determining when an older adult may need ...

  3. 48 CFR 6301.2 - Qualifications of members.

    2010-10-01

    ... contract law. ... CONTRACT APPEALS BOARD OF CONTRACT APPEALS 6301.2 Qualifications of members. Each member of the Board must... administrative law judges appointed pursuant to section 3105 of title 5 of the United States Code, with the...

  4. Training Needs of Cooperative Members and Marketing of ...

    Training Needs of Cooperative Members and Marketing of Agricultural Products in Akwa Ibom State, Nigeria. ... of multi-purpose cooperative society members and the marketing of agricultural products ... EMAIL FULL TEXT EMAIL FULL TEXT

  5. 78 FR 28243 - Senior Executive Service; Performance Review Board; Members

    2013-05-14

    ... NATIONAL CAPITAL PLANNING COMMISSION Senior Executive Service; Performance Review Board; Members AGENCY: National Capital Planning Commission. ACTION: Notice of Members of Senior Executive Service... Senior Executive Service. The PRB established for the National Capital Planning Commission also makes...

  6. 76 FR 29013 - Senior Executive Service; Performance Review Board; Members

    2011-05-19

    ... NATIONAL CAPITAL PLANNING COMMISSION Senior Executive Service; Performance Review Board; Members AGENCY: National Capital Planning Commission. ACTION: Notice of Members of Senior Executive Service... Senior Executive Service. The PRB established for the National Capital Planning Commission also makes...

  7. Members of FOX family could be drug targets of cancers.

    Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua

    2018-01-01

    FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Ombuds' Corner: Users and Staff Members

    Vincent Vuillemin

    2010-01-01

    In this series, the Bulletin aims to explain the role of the Ombuds at CERN by presenting practical examples of misunderstandings that could have been resolved by the Ombuds if he had been contacted earlier. Please note that, in all the situations we present, the names are fictitious and used only to improve clarity. 
     Pam* and Jeff* are both physicists working on the same project for an experiment. Pam is from a collaborating institute and Jeff is a CERN staff member. As the project is being developed at CERN they both share the same technical support available in the Laboratory. At the beginning they organised themselves so they could get the support that both of them needed. When some milestones concerning the delivery of parts became urgent, they started to actually compete for the same resources, which could not possibly satisfy all requests at the same time. With the time pressure increasing, Jeff started to accuse Pam of diverting the resources for her own share of the proj...

  9. TO ALL MEMBERS OF THE PERSONNEL

    2001-01-01

    During the period mid-June to mid-September 2001, there will be a limited number of vacancies for temporary work at CERN (normally unskilled work of a routine nature) which will be made available to children of members of the personnel (that is, anyone holding an employment or association contract with CERN). It should be noted that candidates must be aged between 18 and 24 inclusive on the first day of the contract, and that they must have insurance cover for both illness and accident. In view of the limited number of vacancies available, no children previously appointed at CERN under this scheme can be considered. The duration of all appointments will be 4 weeks, the allowance being CHF 1538.- net for this period. Application forms can be obtained via the Web at the following address: http://cern.web.cern.ch/CERN/Divisions/PE/ under the heading 'Other Useful Links' or from Paula Barriere, Personnel Management Group (by using the slip below or by electronic mail to Paula.Barriere@.cern.ch). Completed applic...

  10. The relationship between mental health workers and family members

    van de Bovenkamp, H.M.; Trappenburg, M.J.

    2010-01-01

    Objective To study the relationship between family members and mental health care workers to learn more about the support available to family members of mental health patients. Methods Eighteen interviews were conducted with family members, seven with professionals and two with patients.

  11. Using artificial team members for team training in virtual environments

    Diggelen, J. van; Muller, T.; Bosch, K. van den

    2010-01-01

    In a good team, members do not only perform their individual task, they also coordinate their actions with other members of the team. Developing such team skills usually involves exercises with all members playing their role. This approach is costly and has organizational and educational drawbacks.

  12. Party member recruitment and the representativeness of party membership

    Kosiara-Pedersen, Karina

    Party membership figures are in decline. However, parties are still recruiting party members. Are there any differences in the social and political characteristics of old and new party members? If there is a difference, are new party members more or less representative for party voters than old...

  13. Mental Wellbeing of Family Members of Autistic Adults

    Herrema, Renske; Garland, Deborah; Osborne, Malcolm; Freeston, Mark; Honey, Emma; Rodgers, Jacqui

    2017-01-01

    Family members are often the primary caregiver for autistic adults and this responsibility may impact on the carer's wellbeing and quality of life. 109 family members of autistic adults completed an online survey assessing their wellbeing relating to their caring role for their autistic relative. Family members who were supporting an autistic…

  14. 21 CFR 13.10 - Members of a Board.

    2010-04-01

    ... BEFORE A PUBLIC BOARD OF INQUIRY General Provisions § 13.10 Members of a Board. (a) All members of a... to be free from bias or prejudice concerning the issues involved. A member of a Board may be a full...

  15. 29 CFR 1400.735-19 - Influencing Members of Congress.

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Influencing Members of Congress. 1400.735-19 Section 1400... Responsibilities § 1400.735-19 Influencing Members of Congress. No money appropriated to the Service shall be used... devices intended to influence any Member of Congress regarding any legislation or appropriation before the...

  16. 38 CFR 1.507 - Disclosures to members of Congress.

    2010-07-01

    ... Congress. 1.507 Section 1.507 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Disclosures to members of Congress. Members of Congress shall be furnished in their official capacity in any... which may not be furnished a claimant, the member of Congress shall be advised that the information is...

  17. 48 CFR 1305.403 - Requests from Members of Congress.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requests from Members of Congress. 1305.403 Section 1305.403 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE... from Members of Congress. Requests from Members of Congress shall be handled in accordance with the...

  18. 45 CFR 703.9 - Reimbursement of members.

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Reimbursement of members. 703.9 Section 703.9... AND FUNCTIONS OF STATE ADVISORY COMMITTEES § 703.9 Reimbursement of members. (a) Advisory Committee members may be reimbursed by the Commission by a per diem subsistence allowance and for travel expenses at...

  19. 49 CFR 805.735-10 - Member and employee indebtedness.

    2010-10-01

    ... TRANSPORTATION SAFETY BOARD EMPLOYEE RESPONSIBILITIES AND CONDUCT § 805.735-10 Member and employee indebtedness. Members and employees shall pay each just financial obligation in a proper and timely manner, especially... 49 Transportation 7 2010-10-01 2010-10-01 false Member and employee indebtedness. 805.735-10...

  20. Magnetic resonance in multiple sclerose twins

    Polman, C.H.; UitdeHaag, B.M.J.; Koetsier, C.J.; Valk, J.; Lucas, C.J.

    1989-01-01

    Magnetic resonance imaging (MR) examinations were performed in a series of 7 twin sets (4 monozygotic and 3 dizygotic) and one triplet set who were clinically discordant for multiple sclerosis (MS). MRI abnormalities were detected in a number of the unaffected members of the nonzygotic twin pairs. The authors discuss the possible implications of their findings for the present view on the aetiology of MS. (author). 3 refs.; 1 fig.; 1 tab

  1. Discrepant perceptions of communication, teamwork and situation awareness among surgical team members.

    Wauben, L S G L; Dekker-van Doorn, C M; van Wijngaarden, J D H; Goossens, R H M; Huijsman, R; Klein, J; Lange, J F

    2011-04-01

    To assess surgical team members' differences in perception of non-technical skills. Questionnaire design. Operating theatres (OTs) at one university hospital, three teaching hospitals and one general hospital in the Netherlands. Sixty-six surgeons, 97 OT nurses, 18 anaesthetists and 40 nurse anaesthetists. All surgical team members, of five hospitals, were asked to complete a questionnaire and state their opinion on the current state of communication, teamwork and situation awareness at the OT. Ratings for 'communication' were significantly different, particularly between surgeons and all other team members (P ≤ 0.001). The ratings for 'teamwork' differed significantly between all team members (P ≤ 0.005). Within 'situation awareness' significant differences were mainly observed for 'gathering information' between surgeons and other team members (P communication, teamwork and situation awareness. Future research needs to ascertain whether these discrepancies are linked to greater risk of adverse events or to process as well as systems failures. Establishing this link would support implementation and use of complex team interventions that intervene at multiple levels of the healthcare system.

  2. Nurses' views of forensic care in emergency departments and their attitudes, and involvement of family members.

    Linnarsson, Josefin Rahmqvist; Benzein, Eva; Årestedt, Kristofer

    2015-01-01

    To describe Nurses' views of forensic care provided for victims of violence and their families in EDs, to identify factors associated with Nurses' attitudes towards families in care and to investigate if these attitudes were associated with the involvement of patients' families in care. Interpersonal violence has serious health consequences for individuals and family members. Emergency departments provide care for victims of violence, and nurses play a key role in forensic care. However, there is limited knowledge of their views and their involvement of family members. A cross-sectional design was used with a sample of all registered nurses (n = 867) in 28 emergency departments in Sweden. A self-report questionnaire, including the instrument Families' Importance in Nursing Care - Nurses' Attitudes, was used to collect data. Descriptive statistics, multiple linear regression and ordinal regression were used to analyse data. Four hundred and fifty-seven nurses completed the questionnaire (53%). Most nurses provided forensic care, but few had specific education for this task. Policy documents and routines existed for specific patient groups. Most nurses involved family members in care although education and policy documents rarely included them. Being a woman, policy documents and own experience of a critically ill family member were associated with a positive attitude towards family. A positive attitude towards family members was associated with involving patients' families in care. Many emergency department nurses provided forensic care without having specific education, and policy documents only concerned women and children. Nurses' positive attitude to family members was not reflected in policies or education. These results can inspire clinical forensic care interventions in emergency departments. Educational efforts for nurses and policies for all groups of victims of violence are needed. Emergency departments may need to rethink how family members are included

  3. Insider Research with Family Members who have a Member Living with Rare Cancer

    Jan Foster PhD

    2009-12-01

    Full Text Available In this article the author explores insider research in relation to family members facing a diagnosis of rare cancer, using her experiences as one such family member undertaking doctoral research into journeys similar to hers. The “insider” issue is explored through three realms: the ethical realm, including issues of “fitness” to undertake the research; the methodological realm, including how data are obtained and used; and the trustworthiness realm, including research rigor. The exploration of her insider experiences includes personal challenges in relation to facing familiar emotionally charged experiences, insights gained as a result of her insider status, and her ability to join with participants in ways that might not be possible for an outsider. In the paper the author challenges taken-for-granted assumptions that trustworthiness can be assured only from the position of “objective” researcher. Rather, this analysis places knowledge gained through the processes and products of research as constituted and contextualized.

  4. Behaviour of Mechanically Laminated CLT Members

    Kuklík, P.; Velebil, L.

    2015-11-01

    Cross laminated timber (CLT) is one of the structural building systems based on the lamination of multiple layers, where each layer is oriented perpendicularly to each other. Recent requirements are placed to develop an alternative process based on the mechanical lamination of the layers, which is of particular interest to our research group at the University Centre for Energy Efficient Buildings. The goal is to develop and verify the behaviour of mechanically laminated CLT wall panels exposed to shear stresses in the plane. The shear resistance of mechanically jointed CLT is ensured by connecting the layers by screws. The paper deals with the experimental analysis focused on the determination of the torsional stiffness and the slip modulus of crossing areas for different numbers of orthogonally connected layers. The results of the experiments were compared with the current analytical model.

  5. Family matters: The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent years, there has been greater recognition of the important position of parents and siblings of people with (profound) intellectual (and multiple) disabilities and the importance of the wellbeing of all ...

  6. VizieR Online Data Catalog: NGC 6802 dwarf cluster members and non-members (Tang+, 2017)

    Tang, B.; Geisler, D.; Friel, E.; Villanova, S.; Smiljanic, R.; Casey, A. R.; Randich, S.; Magrini, L.; San, Roman I.; Munoz, C.; Cohen, R. E.; Mauro, F.; Bragaglia, A.; Donati, P.; Tautvaisiene, G.; Drazdauskas, A.; Zenoviene, R.; Snaith, O.; Sousa, S.; Adibekyan, V.; Costado, M. T.; Blanco-Cuaresma, S.; Jimenez-Esteban, F.; Carraro, G.; Zwitter, T.; Francois, P.; Jofre, P.; Sordo, R.; Gilmore, G.; Flaccomio, E.; Koposov, S.; Korn, A. J.; Lanzafame, A. C.; Pancino, E.; Bayo, A.; Damiani, F.; Franciosini, E.; Hourihane, A.; Lardo, C.; Lewis, J.; Monaco, L.; Morbidelli, L.; Prisinzano, L.; Sacco, G.; Worley, C. C.; Zaggia, S.

    2016-11-01

    The dwarf stars in NGC 6802 observed by GIRAFFE spectrograph are separated into four tables: 1. cluster members in the lower main sequence; 2. cluster members in the upper main sequence; 3. non-member dwarfs in the lower main sequence; 4. non-member dwarfs in the upper main sequence. The star coordinates, V band magnitude, V-I color, and radial velocity are given. (4 data files).

  7. Multiple-Ring Digital Communication Network

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  8. 19 CFR 122.75b - Electronic manifest requirement for crew members and non-crew members onboard commercial aircraft...

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Electronic manifest requirement for crew members... THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial...

  9. Multiple fuel rod gripper

    Shields, E.P.

    1987-01-01

    An apparatus is described for gripping an array of rods comprising: (a) gripping members grippingly engageable with the rods, each of which has a hollow portion terminating in an open end for receiving the end of one of the rods; (b) a closing means for causing the hollow portion of each of the gripping members to apply substantially the same gripping force onto the end of its respective rod, including (i) a locking plate having a plurality of tapered holes registrable with the array of rods, wherein the exterior of each of the gripping members is tapered and nested within one of the tapered holes, (ii) a withdrawing means having a hydraulic plunger operatively connected to each of the gripping members for applying a substantially identical withdrawing force on each of the gripping members, whereby the hollow portion of each of the gripping members applies substantially the same gripping force on its respective rod, and (c) means for detecting whether each of the gripping members has grippingly engaged its respective rod

  10. Prevalence, Knowledge and Attitudes Towards Smoking Among SEPAR Members.

    Solano Reina, Segismundo; Jiménez Ruiz, Carlos A; de Higes Martinez, Eva; Garcia Rueda, Marcos; Callejas González, Francisco J; de Granda Orive, Jose I; Vaquero Lozano, Paz; de Lucas Ramos, Pilar; Alfageme Michavila, Inmaculada

    2016-12-01

    The aims of this study were to estimate the prevalence of smoking among SEPAR members, and their approach to smoking cessation in their patients. An online survey was completed by 640 members (496 pulmonologists, 45 nurses, 34 thoracic surgeons, 37 physiotherapists, and 28 other specialists). Of the members interviewed, 5% confessed that they were smokers: 3.5% pulmonologists; 8.9% nurses; 8.8% thoracic surgeons, and 13.5% physiotherapists. A total of 96% of members assign a lot or quite a lot of importance to setting an example; 98% of members always or often ask their patients about their smoking habit. The most effective anti-smoking intervention, according to 77% of members, is a combination of drugs and psychological support. These results are an indicator of the awareness and commitment of SEPAR members to smoking and its cessation. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Generalized internal multiple imaging

    Zuberi, Mohammad Akbar Hosain

    2014-12-04

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green\\'s function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green\\'s function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green\\'s function and renders the higher order internal multiple image for display on a display device.

  12. MultipleColposcopyJCO

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  13. Salmonella Infections - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Salmonella Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Salmonella Infections - Multiple Languages To use the sharing features ...

  14. Health Literacy - Multiple Languages

    ... Here: Home → Multiple Languages → All Health Topics → Health Literacy URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Health Literacy - Multiple Languages To use the sharing features on ...

  15. Cosmetic Dentistry - Multiple Languages

    ... Here: Home → Multiple Languages → All Health Topics → Cosmetic Dentistry URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Cosmetic Dentistry - Multiple Languages To use the sharing features on ...

  16. Atrial Fibrillation - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  17. Zika Virus - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Zika Virus URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Zika Virus - Multiple Languages To use the sharing features on ...

  18. Elder Abuse - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Elder Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Elder Abuse - Multiple Languages To use the sharing features on ...

  19. Herbal Medicine - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Herbal Medicine URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Herbal Medicine - Multiple Languages To use the sharing features on ...

  20. Generalized internal multiple imaging

    Zuberi, Mohammad Akbar Hosain; Alkhalifah, Tariq

    2014-01-01

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green's function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green's function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green's function and renders the higher order internal multiple image for display on a display device.

  1. Domestic Violence - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Domestic Violence URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Domestic Violence - Multiple Languages To use the sharing features on ...

  2. Multiple Primary Tumors

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  3. Diabetic Foot - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Diabetic Foot URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Diabetic Foot - Multiple Languages To use the sharing features on ...

  4. Child Abuse - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Child Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Child Abuse - Multiple Languages To use the sharing features on ...

  5. Fatigue and Multiple Sclerosis

    ... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  6. Rotavirus Infections - Multiple Languages

    ... Are Here: Home → Multiple Languages → All Health Topics → Rotavirus Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Rotavirus Infections - Multiple Languages To use the sharing features ...

  7. Neutron Multiplicity Analysis

    Frame, Katherine Chiyoko [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-28

    Neutron multiplicity measurements are widely used for nondestructive assay (NDA) of special nuclear material (SNM). When combined with isotopic composition information, neutron multiplicity analysis can be used to estimate the spontaneous fission rate and leakage multiplication of SNM. When combined with isotopic information, the total mass of fissile material can also be determined. This presentation provides an overview of this technique.

  8. Family matters : The experiences and opinions of family members of persons with (severe) or profound intellectual disabilities

    Luijkx, Jorien

    2016-01-01

    “I love my sister, but sometimes I don’t”. This is one of the statements made in the study focused on the experiences of family members of people with (profound) intellectual (and multiple) disabilities (both of individuals living in a residential facility as persons living at home). In recent

  9. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis.

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with

  10. Neutron multiplication measurement instrument

    Nixon, K.V.; Dowdy, E.J.; France, S.W.; Millegan, D.R.; Robba, A.A.

    1983-01-01

    The Advanced Nuclear Technology Group of the Los Alamos National Laboratory is now using intelligent data-acquisition and analysis instrumentation for determining the multiplication of nuclear material. Earlier instrumentation, such as the large NIM-crate systems, depended on house power and required additional computation to determine multiplication or to estimate error. The portable, battery-powered multiplication measurement unit, with advanced computational power, acquires data, calculates multiplication, and completes error analysis automatically. Thus, the multiplication is determined easily and an available error estimate enables the user to judge the significance of results

  11. Job satisfaction and its influential factors in dental academic members in tehran, iran.

    Seraj, B; Ghadimi, S; Mirzaee, M; Ahmadi, R; Bashizadeh, H; Ashofteh-Yazdi, K; Sahebjamee, M; Kharazi, Mj; Jahanmehr, M

    2014-03-01

    Assessment of job satisfaction of the faculty members and its underlying factors may increase career fulfillment and raise the educational and research productivity, leading to higher quality of dental services at the community level, ultimately improving public oral health status. This study assessed job satisfaction and its influential factors in dental academic members in Tehran. The job satisfaction level of 203 faculty members was assessed using a Likert scale questionnaire from 0 to 4, with 4 representing very satisfied and 0 not at all satisfied. The analysis of variance was used to compare the responses among dental faculty members of three different universities. The impact of age, gender, academic rank, employment status and the date of employment on the overall faculty job satisfaction was identified by multiple linear regression analysis. The mean professional satisfaction score among faculty members was 1.5 (0.5) out of four. Among the studied underlying factors, only the date of employment was seen to have a statistically significant impact on the faculties' overall job satisfaction (P= 0.05). There was no difference in job compensation observed between the three dental faculties. Dissatisfying aspects of the academic work included educational and research policies, monetary strategies, quality of leadership and administration, promotion and tenure policies, job security, educational environment, equipments, and facilities. The only satisfying factor was the interaction between faculty colleagues and students. Faculty members of Tehran Dental Schools are dissatisfied with their work environments in Tehran Dental Schools. Issues such as salary and remuneration, facilities, equipments, promotion and tenure policies are strongly believed to account for the dissatisfaction.

  12. Assessing the place of neurobiological explanations in accounts of a family member's addiction.

    Meurk, Carla; Fraser, Doug; Weier, Megan; Lucke, Jayne; Carter, Adrian; Hall, Wayne

    2016-07-01

    The brain disease model of addiction posits that addiction is a persistent form of neural dysfunction produced by chronic drug use, which makes it difficult for addicted persons to become and remain abstinent. As part of an anticipatory policy analysis of addiction neuroscience, we engaged family members of addicted individuals to assess their views on the place and utility of brain-based accounts of addiction. Fifteen in-depth qualitative interviews were conducted and used to develop a quantitative online survey that was completed by 55 family members. This article reports responses on what addiction is and how it is caused and responses to explanations of the brain disease model of addiction. Participants gave multiple reasons for their family members developing an addiction and there was no single dominant belief about the best way to describe addiction. Participants emphasised the importance of both scientific and non-scientific perspectives on addiction by providing multifactorial explanations of their family members' addictions. Most family members acknowledged that repeated drug use can cause changes to the brain, but they varied in their reactions to labelling addiction a 'brain disease'. They believed that understanding addiction, and how it is caused, could help them support their addicted relative. Participants' beliefs about neurobiological information and the brain disease model of addiction appeared to be driven by empathetic, utilitarian considerations rather than rationalist ones. We discuss the importance of providing information about the nature and causes of addiction. [Meurk C, Fraser D, Weier M, Lucke J, Carter A, Hall W. Assessing the place of neurobiological explanations in accounts of a family member's addiction. Drug Alcohol Rev 2016;35:461-469]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  13. Towards easing the configuration and new team member accommodation for open source software based portals

    Fu, L.; West, P.; Zednik, S.; Fox, P. A.

    2013-12-01

    For simple portals such as vocabulary based services, which contain small amounts of data and require only hyper-textual representation, it is often an overkill to adopt the whole software stack of database, middleware and front end, or to use a general Web development framework as the starting point of development. Directly combining open source software is a much more favorable approach. However, our experience with the Coastal and Marine Spatial Planning Vocabulary (CMSPV) service portal shows that there are still issues such as system configuration and accommodating a new team member that need to be handled carefully. In this contribution, we share our experience in the context of the CMSPV portal, and focus on the tools and mechanisms we've developed to ease the configuration job and the incorporation process of new project members. We discuss the configuration issues that arise when we don't have complete control over how the software in use is configured and need to follow existing configuration styles that may not be well documented, especially when multiple pieces of such software need to work together as a combined system. As for the CMSPV portal, it is built on two pieces of open source software that are still under rapid development: a Fuseki data server and Epimorphics Linked Data API (ELDA) front end. Both lack mature documentation and tutorials. We developed comparison and labeling tools to ease the problem of system configuration. Another problem that slowed down the project is that project members came and went during the development process, so new members needed to start with a partially configured system and incomplete documentation left by old members. We developed documentation/tutorial maintenance mechanisms based on our comparison and labeling tools to make it easier for the new members to be incorporated into the project. These tools and mechanisms also provided benefit to other projects that reused the software components from the CMSPV

  14. Nurse IOM members' contributions to the Institute of Medicine.

    Grey, Margaret; Holzemer, William L; Larson, Elaine

    2012-01-01

    Nursing is the largest health care profession, and Institute of Medicine (IOM) nurse members have the potential to contribute to health policy through IOM activities. We studied reported activities of IOM nurse members. To describe activities of IOM nurse members within the IOM. An e-mail survey was conducted that asked nurse IOM members to assess self-reported IOM activities. Of 57 members, 47 had functioning e-mail addresses, and 33 usable responses were received. The survey consisted of 9 questions dealing with roles and responsibilities undertaken in the previous 5 years. Data analyses were descriptive. The data suggest that nurses have made considerable contributions to the IOM and their participation seems to be as high, or higher, than other disciplines. In an era of health care reform, there is additional opportunity for nurse IOM members to enhance their work in the IOM. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Recent advances in the field of 16-membered macrolide antibiotics.

    Cui, W; Ma, S

    2011-10-01

    The continuing emergence of bacterial resistance has provided an incentive for recent intensified research on macrolide antibiotics. Belonging to the macrolide family, 16-membered macrolides also experience a renewed interest in further exploration. The medicinal potential of 16-membered macrolides in search for new antibacterials stems from some advantages over 14-membered macrolides, such as gastrointestinal tolerability, structural flexibility, and lack of inducible resistance. Thus, compared with abundant articles on various 14-membered macrolide derivatives in the literature, this review will highlight some representative 16-membered macrolide antibiotics and their recently discovered analogs. Furthermore, the action and resistance mechanisms of 16-membered macrolide antibiotics will be elucidated as well to assist the drug design.

  16. Measurement and comparison of nursing faculty members' critical thinking skills.

    Blondy, Laurie C

    2011-03-01

    Nursing faculty members strive to teach students to think critically. It has long been assumed that nursing faculty members are good at critical thinking because they are expected to teach these skills to students, but this assumption has not been well supported empirically. Faculty members question their ability to think critically and are unsure of their skills. The purpose of this study was to address this assumption by measuring nursing faculty members' critical thinking skills and compare the faculty mean score to that of a student norming group, and to the mean scores of other nursing faculty studies. Findings can be used to increase nursing faculty members' understanding of their critical thinking skills, prompt discussion about critical thinking skills, and to help faculty members address concerns and uncertainty about the concept of critical thinking. This study also helps establish an empirical basis for future research.

  17. Netball team members, but not hobby group members, distinguish team characteristics from group characteristics.

    Stillman, Jennifer A; Fletcher, Richard B; Carr, Stuart C

    2007-04-01

    Research on groups is often applied to sport teams, and research on teams is often applied to groups. This study investigates the extent to which individuals have distinct schemas for groups and teams. A list of team and group characteristics was generated from 250 individuals, for use in this and related research. Questions about teams versus groups carry an a priori implication that differences exist; therefore, list items were presented to new participants and were analyzed using signal detection theory, which can accommodate a finding of no detectable difference between a nominated category and similar items. Participants were 30 members from each of the following: netball teams, the general public, and hobby groups. Analysis revealed few features that set groups apart from teams; however, teams were perceived as more structured and demanding, requiring commitment and effort toward shared goals. Team and group characteristics were more clearly defined to team members than they were to other participant groups. The research has implications for coaches and practitioners.

  18. IDENTIFYING COMPETENCIES OF VOLUNTEER BOARD MEMBERS OF COMMUNITY SPORTS CLUBS

    A. BALDUCK; A. VAN ROSSEM; M. BUELENS

    2009-01-01

    This study contributes to the emerging empirical studies on roles and responsibilities of boards in nonprofit organizations by identifying competencies of volunteer board members. We identified how two types of constituents—volunteer board members and sports members—perceived competencies of volunteer board members in community sports clubs. We used the repertory grid technique to draw cognitive maps and to reveal the perceived reality of these constituents. Our results suggest that constitue...

  19. Fuel safety criteria in NEA member countries - Compilation of responses received from member countries

    2003-03-01

    In 2001 the Committee on the Safety of Nuclear Installations (CSNI) issued a report on Fuel Safety Criteria Technical Review. The objective was to review the present fuel safety criteria and judge to which extent they are affected by the 'new' design elements, such as different cladding materials, higher burnup, the use of MOX fuels, etc. The report stated that the current framework of fuel safety criteria remains generally applicable, being largely unaffected by the 'new' or modern design elements. The levels (numbers) in the individual safety criteria may, however, change in accordance with the particular fuel and core design features. Some of these levels have already been - or are continuously being - adjusted. The level adjustments of several other criteria (RIA, LOCA) also appears to be needed, on the basis of experimental data and the analysis thereof. As a follow-up, among its first tasks, the CSNI Special Expert Group on Fuel Safety Margins (SEG FSM) initiated the collection of information on the present fuel safety criteria used in NEA member states with the objective to solicit national practices in the use of fuel safety criteria, in particular to get information on their specific national levels/values, including their recent adjustments, and to identify the differences and commonalties between the different countries. Two sources of information were used to produce this report: a compilation of responses to a questionnaire prepared for the June 2000 CNRA meeting, and individual responses from the SEGFSM members to the new revised questionnaire issued by the task Force preparing this report. In accordance with the latter, the fuel safety criteria discussed in this report were divided into three categories: (A) safety criteria - criteria imposed by the regulator; (B) operational criteria - specific to the fuel design and provided by the fuel vendor as part of the licensing basis; (C) design criteria - limits employed by vendors and/or utilities for fuel

  20. Scientific collaboration between 'old' and 'new' member states

    Makkonen, Teemu; Mitze, Timo Friedel

    2016-01-01

    following the two enlargement waves 2004 and 2007 has significantly increased the co-publication intensity of the new member states with other member countries. The empirical results based on data collected from the Web of Science database and Difference-in-Difference estimations point towards a conclusion...... that joining the EU indeed has had an additional positive impact on the co-publication intensity between the new and old member states and, in particular, between the new member states themselves. These results give tentative support for the successfulness of the EU’s science policies in achieving a common...

  1. Flame-Resistant Composite Materials For Structural Members

    Spears, Richard K.

    1995-01-01

    Matrix-fiber composite materials developed for structural members occasionally exposed to hot, corrosive gases. Integral ceramic fabric surface layer essential for resistance to flames and chemicals. Endures high temperature, impedes flame from penetrating to interior, inhibits diffusion of oxygen to interior where it degrades matrix resin, resists attack by chemicals, helps resist erosion, and provides additional strength. In original intended application, composite members replace steel structural members of rocket-launching structures that deteriorate under combined influences of atmosphere, spilled propellants, and rocket exhaust. Composites also attractive for other applications in which corrosion- and fire-resistant structural members needed.

  2. Posttraumatic stress disorder in women with war missing family members.

    Baraković, Devla; Avdibegović, Esmina; Sinanović, Osman

    2014-12-01

    Research in crisis areas indicate that survivors' responses to the forced disappearance of family members are similar to reactions to other traumatic events. The aim of this study was to determine the presence of symptoms of posttraumatic stress disorder (PTSD) in women with war missing family members in Bosnia and Herzegovina 18 years after the war in this region (1992-1995). The study included 160 women aged 47.1±14.0 from three regions of Bosnia and Herzegovina. It was carried out in the period from April 2010 to May 2011. Of the 160 participants, 120 women had a war missing family member and 40 women had no war missing family members. The Harvard Trauma Questionnaire (HTQ), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HAMA) were used for data collection. Basic socio-demographic data and data concerning the missing family members were also collected. Women with war missing family members experienced significantly more traumatic war experiences (18.43±5.27 vs 6.57±4.34, pfamily members. Women with war missing family members showed significantly more severe PTSD symptoms. Based on the results of this study, it was determined that the forced disappearance of a family member is an ambiguous situation that can be characterized as a traumatic experience.

  3. An Analysis of Generational Differences Among Active Duty Members

    Skibo, Stephanie

    2004-01-01

    .... Clearly, these observed differences have implications for managers and leaders. Actions taken by leaders might be misunderstood by junior organizational members, leading to undesirable outcomes...

  4. E-Commerce in OIC members: Facts - Challenges - Prospects

    Al-Abdali, Abid

    2005-01-01

    The study seeks to explore the importance of E-Commerce and ICT and their impact on economies of OIC members. Challenges and obstacles of E-Commerce application in member states are analyzed and discussed. The study has concluded that E-Commerce has become an important application in most member states. It also showed that despite there has been growth in the application of E-Commerce in some countries, but in general OIC members as a whole are still behind in the track compared to other grou...

  5. TEACHING IN ONLINE COURSES: Experiences of Instructional Technology Faculty Members

    Omur AKDEMIR

    2008-04-01

    Full Text Available The Internet and computer technology have altered the education landscape. Online courses are offered throughout the world. Learning about the experiences of faculty members is important to guide practitioners and administrators. Using qualitative research methodology, this study investigated the experiences of faculty members teaching online courses. A convenience sampling was used to select the instructional technology faculty members to investigate their experiences in online courses. Semi-structured interviews with faculty members teaching online courses were used as the primary source to collect data about the experiences of faculty members in online courses. Results of the study showed that faculty members' interest in using technology and the amount of time available to them for online course design affected the quality of online courses. The findings of this study also indicated that design quality of online courses is affected by the interest of faculty members to use the technology and the time that they can devote to planning, designing, and developing online courses. The poor design of existing online courses, high learning expectations of ndividuals from these courses, and the future of online courses are the concerns of faculty members. Higher education institutions should support workshops and trainings to increase the skills and interests of non-instructional design faculty members to design and develop online courses.

  6. Collective Care: Multiple Caregivers and Multiple Care Recipients in Mexican American Families.

    Evans, Bronwynne C; Coon, David W; Belyea, Michael J; Ume, Ebere

    2017-07-01

    Specific stressors associated with caregiving in Mexican American (MA) families are not well documented, yet caregiving issues are paramount because informal care for parents is central to their culture. Although MA families who band together to provide care for one member are not unique, the literature does not describe the phenomenon of collective caregiving, which may be widespread but unrecognized. This article describes these understudied families who are poorly served by contemporary health systems because their characteristics are unknown. Descriptive, multisite, longitudinal mixed-methods study of MA caregiving families. We identified three types of collective caregivers: those providing care for multiple family members simultaneously, those providing care successively to several family members, and/or those needing care themselves during their caregiving of others. Collective caregiving of MA elders warrants further investigation. Exploration of collective caregiving may provide a foundation for tailored family interventions.

  7. Community Reintegration, Participation, and Employment Issues in Veterans and Service Members With Traumatic Brain Injury.

    Dillahunt-Aspillaga, Christina; Powell-Cope, Gail

    2018-02-01

    Traumatic brain injury (TBI) has been called the signature injury of the post-9/11 wars in Iraq, Afghanistan, and neighboring countries. Although similarities exist between veterans and service members with TBI, levels of severity and different constellations of coexisting comorbid conditions affect them differently. These conditions affect physical, cognitive, and emotional function, which in turn can complicate community reintegration (CR), or the ability to return to family, vocational, and community life. This special supplement of the Archives of Physical Medicine and Rehabilitation consists of articles written by accomplished teams from multiple disciplines, including anthropology, neuropsychology, nursing, occupational therapy, psychology, and rehabilitation sciences. Each article brings a different perspective to bear on what CR means for veterans and service members from examination of predictors and perceptions of veterans and service members and others to measurement studies. Collectively, this group of articles represents current thinking about CR and lays the groundwork for testing interventions to improve CR outcomes for veterans and service members (eg, employment, living situation, family life). Published by Elsevier Inc.

  8. Calculus detection calibration among dental hygiene faculty members utilizing dental endoscopy: a pilot study.

    Partido, Brian B; Jones, Archie A; English, Dana L; Nguyen, Carol A; Jacks, Mary E

    2015-02-01

    Dental and dental hygiene faculty members often do not provide consistent instruction in the clinical environment, especially in tasks requiring clinical judgment. From previous efforts to calibrate faculty members in calculus detection using typodonts, researchers have suggested using human subjects and emerging technology to improve consistency in clinical instruction. The purpose of this pilot study was to determine if a dental endoscopy-assisted training program would improve intra- and interrater reliability of dental hygiene faculty members in calculus detection. Training included an ODU 11/12 explorer, typodonts, and dental endoscopy. A convenience sample of six participants was recruited from the dental hygiene faculty at a California community college, and a two-group randomized experimental design was utilized. Intra- and interrater reliability was measured before and after calibration training. Pretest and posttest Kappa averages of all participants were compared using repeated measures (split-plot) ANOVA to determine the effectiveness of the calibration training on intra- and interrater reliability. The results showed that both kinds of reliability significantly improved for all participants and the training group improved significantly in interrater reliability from pretest to posttest. Calibration training was beneficial to these dental hygiene faculty members, especially those beginning with less than full agreement. This study suggests that calculus detection calibration training utilizing dental endoscopy can effectively improve interrater reliability of dental and dental hygiene clinical educators. Future studies should include human subjects, involve more participants at multiple locations, and determine whether improved rater reliability can be sustained over time.

  9. Brazilian Credit Union Member Groups: Borrower-dominated, Saver-dominated or Neutral Behavior?

    Valéria Gama Fully Bressan

    2013-01-01

    Full Text Available Theoretical models concerning Credit Unions (CUs suggest that the type of CU domination determines the way it allocates the monetary value it generates. A borrower- (saver- dominated CU benefits borrower (saver members at the expenses of saver (borrower members, and a neutral CU equally benefits its member groups.This paper applies direct measure of monetary benefits to each member group (Patin & McNiel, 1991a to testfor the existence of dominated behavior in Brazilian CUs, and is the first to apply panel data regressions to identify the determinants of CUs behavior. We use a unique panel data with 40,664 observations taken from 533 CUs affiliated with the largest Brazilian cooperative network. Results indicate Brazilian CUs are dominated by borrowers, but behave close to neutrality. Panel regression estimates show that common or multiple bond type,size and overdue loans of a CU have no effect on its behavior, the greater the total amount of loans over social capital and adjusted equity over total assets are the more likely a CU is borrower dominated, and the greater the age and current operational expenses over total asset of a CU are the more likely a CU is saver dominated.

  10. Bcl-2 family of proteins as drug targets for cancer chemotherapy: the long way of BH3 mimetics from bench to bedside.

    Vela, Laura; Marzo, Isabel

    2015-08-01

    Bcl-2 proteins are key determinants in the life-death balance. In recent years, proteins in this family have been identified as drug targets in the design of new anti-tumor therapies. Advances in the knowledge of the mechanism of action of anti-apoptotic and pro-apoptotic members of the Bcl-2 family have enabled the development of the so-called 'BH3 mimetics'. These compounds act by inhibiting anti-apoptotic proteins of the family, imitating the function of the BH3-only subset of pro-apoptotic members. Combinations of BH3-mimetics with anti-tumor drugs are being evaluated in both preclinical models and clinical trials. Recent advances in these approaches will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Expanding access to naloxone for family members: The Massachusetts experience.

    Bagley, Sarah M; Forman, Leah S; Ruiz, Sarah; Cranston, Kevin; Walley, Alexander Y

    2018-05-01

    The Massachusetts Department of Public Health Overdose Education and Naloxone Distribution Program provides overdose education and naloxone rescue kits to people at risk for overdose and bystanders, including family members. Using Massachusetts Department of Public Health data, the aims are to: (i) describe characteristics of family members who receive naloxone; (ii) identify where family members obtain naloxone; and (iii) describe characteristics of rescues by family members. We conducted a retrospective review using program enrollee information collected on a standardised form between 2008 and 2015. We calculated descriptive statistics, including demographics, current substance use, enrolment location, history of witnessed overdoses and rescue attempt characteristics. We conducted a stratified analysis comparing family members who used drugs with those who did not. Family members were 27% of total program enrollees (n = 10 883/40 801). Family members who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3% non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone most frequently at HIV prevention programs. Family members who did not report substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic white, 35.3% had witnessed an overdose, and they obtained naloxone most frequently at community meetings. Family members were responsible for 20% (n = 860/4373) of the total rescue attempts. The Massachusetts experience demonstrates that family members can be active participants in responding to the overdose epidemic by rescuing family members and others. Targeted intervention strategies for families should be included in efforts to expand overdose education and naloxone in Massachusetts. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  12. Accurate scaling on multiplicity

    Golokhvastov, A.I.

    1989-01-01

    The commonly used formula of KNO scaling P n =Ψ(n/ ) for descrete distributions (multiplicity distributions) is shown to contradict mathematically the condition ΣP n =1. The effect is essential even at ISR energies. A consistent generalization of the concept of similarity for multiplicity distributions is obtained. The multiplicity distributions of negative particles in PP and also e + e - inelastic interactions are similar over the whole studied energy range. Collider data are discussed. 14 refs.; 8 figs

  13. Leader--member exchange, differentiation, and psychological contract fulfillment: a multilevel examination.

    Henderson, David J; Wayne, Sandy J; Shore, Lynn M; Bommer, William H; Tetrick, Lois E

    2008-11-01

    Prior integrations of the leader-member exchange (LMX) and psychological contract literatures have not clarified how within-group LMX differentiation influences employees' attitudes and behaviors in the employment relationship. Therefore, using a sample of 278 members and managers of 31 intact work groups at 4 manufacturing plants, the authors examined how LMX operating at the within-group level (relative LMX, or RLMX) and the group level influenced perceptions of psychological contract fulfillment and employee-level outcomes. Controlling for individual-level perceptions of LMX quality, results indicated a positive relationship between RLMX and fulfillment, which was strengthened as group-level variability in LMX quality increased. Perceptions of fulfillment mediated the relationship between RLMX and performance and sportsmanship behaviors. The importance of conceptualizing LMX as simultaneously operating at multiple levels is highlighted.

  14. Marketing Strategies for Recruiting 4-H Members in West Virginia.

    Wingenbach, Gary J.; Nestor, Cheryl; Lawrence, Layle D.; Gartin, Stacy A.; Woloshuk, Jean; Mulkeen, Patricia

    2000-01-01

    According to a survey of 174 West Virginia 4-H members aged 13-18, the Internet and word of mouth were most effective in recruiting new members. Active messages stressing camps, fun, and friendship had the most influence on retention. A statewide marketing plan was recommended. (SK)

  15. Problems and Counselling Needs of Corps Members in Nigeria (Pp ...

    Nekky Umera

    1973-05-22

    May 22, 1973 ... major problems and counseling needs of Corps Members were psychological in nature. ... and must be resolved sufficiently at a given stage if the individual is to cope successfully with ... (ii) Is there any difference between the problems of male and female ... youth corps member of different age group?

  16. The New Faculty Members' Concerns: The Case of Jordanian Universities

    Qudais, Mahmoud Abu; Al-Omari, Aieman; Smadi, Rana

    2009-01-01

    The present study aimed to identify and interpret concerns of the new faculty members in Jordanian universities. A total of 336 new faculty members who participated in this study were asked to rate their perceptions of issues related to teaching, research, service, balancing work and home life and the academic culture of their workplace. Means and…

  17. Perceived Family Resources Based on Number of Members with ADHD

    Corwin, Melinda; Mulsow, Miriam; Feng, Du

    2012-01-01

    Objective: This study examines how the number of family members with ADHD affects other family members' perceived resources. Method: A total of 40 adolescents diagnosed with ADHD and their mothers, fathers, and adolescent siblings living in the household participated. Hierarchical linear modeling was used to analyze family-level data from a total…

  18. Easy access to 6-membered iminoalditols - important glycosidase inhibitors

    Lundt, Inge

    of 6-membered iminoalditols were observed. The use of triethylamine in methanol thus gave methylesters of 6-membered iminouronic acids. Reduction of the ester group with sodium borohydride gave the target compounds. The mechanisms of the reactions will be discussed as well as specific results obtained...

  19. Union members at the polls in diverse trade union landscapes

    Arndt, Christoph; Rennwald, Line

    2016-01-01

    still enjoy important support from trade union members, but at the same time are under fierce competition from bourgeois and green parties among members of white-collar confederations. This reinforces the challenges for social democracy to build new voters’ coalitions in post-industrial societies....

  20. Understanding the Everyday Practice of Individualized Education Program Team Members

    Hartmann, Elizabeth S.

    2016-01-01

    The Individuals with Disabilities Education Improvement Act of 2004 states that individualized education program (IEP) teams are composed of members with distinct identities, roles, expertise, and histories. Although team members must work together to implement educational and related services for learners with special needs, little is known about…

  1. Support for Teens When a Family Member has Cancer

    When a parent, brother, or sister has been diagnosed with cancer, family members need extra support. Information to help teens learn how to cope, talk with family members, manage stress, and get support from counselors when a loved one has been diagnosed with, or is being treated for, cancer.

  2. Space strategy and governance of ESA small member states

    Sagath, Daniel; Papadimitriou, Angeliki; Adriaensen, Maarten; Giannopapa, Christina

    2018-01-01

    The European Space Agency (ESA) has twenty-two Member States with a variety of governance structures and strategic priorities regarding their space activities. The objective of this paper is to provide an up-to date overview and a holistic assessment of the national space governance structures and strategic priorities of the eleven smaller Member States (based on annual ESA contributions). A link is made between the governance structure and the main strategic objectives. The specific needs and interests of small and new Member States in the frame of European Space Integration are addressed. The first part of the paper focuses on the national space governance structures in the eleven smaller ESA Member States. The governance models of these Member States are identified including the responsible ministries and the entities entrusted with the implementation of space strategy/policy and programmes of the country. The second part of this paper focuses on the content and analysis of the national space strategies and indicates the main priorities and trends in the eleven smaller ESA Member States. The priorities are categorised with regards to technology domains, the role of space in the areas of sustainability and the motivators for space investments. In a third and final part, attention is given to the specific needs and interests of the smaller Member States in the frame of European space integration. ESA instruments are tailored to facilitate the needs and interests of the eleven smaller and/or new Member States.

  3. 1978-79 Directory of Physics & Astronomy Staff Members.

    American Inst. of Physics, New York, NY.

    This directory gives names, addresses, and telephone numbers of staff members of astronomy and physics departments. The listings are made under the following headings: (1) American Institute of Physics and its member societies; (2) geographic listing of academic institutions and faculty - U.S., Canada, Mexico, and Central America; (3) U.S.…

  4. Evolution properties of the community members for dynamic networks

    Yang, Kai; Guo, Qiang; Li, Sheng-Nan; Han, Jing-Ti; Liu, Jian-Guo

    2017-03-01

    The collective behaviors of community members for dynamic social networks are significant for understanding evolution features of communities. In this Letter, we empirically investigate the evolution properties of the new community members for dynamic networks. Firstly, we separate data sets into different slices, and analyze the statistical properties of new members as well as communities they joined in for these data sets. Then we introduce a parameter φ to describe community evolution between different slices and investigate the dynamic community properties of the new community members. The empirical analyses for the Facebook, APS, Enron and Wiki data sets indicate that both the number of new members and joint communities increase, the ratio declines rapidly and then becomes stable over time, and most of the new members will join in the small size communities that is s ≤ 10. Furthermore, the proportion of new members in existed communities decreases firstly and then becomes stable and relatively small for these data sets. Our work may be helpful for deeply understanding the evolution properties of community members for social networks.

  5. 48 CFR 605.403 - Requests from members of Congress.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requests from members of Congress. 605.403 Section 605.403 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION... members of Congress. The Procurement Executive is the agency head for the purposes of FAR 5.403. [59 FR...

  6. 5 CFR 842.209 - Members of Congress.

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Members of Congress. 842.209 Section 842.209 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Eligibility § 842.209 Members of Congress. (a...

  7. 48 CFR 405.403 - Requests from Members of Congress.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Requests from Members of Congress. 405.403 Section 405.403 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE... Members of Congress. The head of the contracting activity (HCA) is the agency head designee pursuant to...

  8. 48 CFR 1405.403 - Requests from Members of Congress.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Requests from Members of Congress. 1405.403 Section 1405.403 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... from Members of Congress. For purposes of this subpart, the agency head is the HCA with the power of...

  9. 48 CFR 2905.403 - Requests from Members of Congress.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Requests from Members of Congress. 2905.403 Section 2905.403 Federal Acquisition Regulations System DEPARTMENT OF LABOR ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Release Of Information 2905.403 Requests from Members of Congress...

  10. Analysis of Member State RED implementation. Final Report (Task 2)

    Peters, D.; Alberici, S.; Toop, G. [Ecofys, Utrecht (Netherlands); Kretschmer, B. [Institute for European Environmental Policy IEEP, London (United Kingdom)

    2012-12-15

    This report describes the way EU Member States have transposed the sustainability and chain of custody requirements for biofuels as laid down in the Renewable Energy Directive (RED) and Fuel Quality Directive (FQD). In the assessment of Member States' implementation, the report mainly focuses on effectiveness and administrative burden. Have Member States transposed the Directives in such a way that compliance with the sustainability criteria can be ensured as effectively as possible? To what extent does the Member States' implementation lead to unnecessary administrative burden for economic operators in the (bio)fuel supply chain? The report focuses specifically on the transposition of the sustainability and chain of custody requirements, not on the target for renewables on transport. This means that for example the double counting provision is not included as part of the scope of this report. This report starts with an introduction covering the implementation of the Renewable Energy (and Fuel Quality) Directive into national legislation, the methodology by which Member States were assessed against effectiveness and administrative burden and the categorisation of Member State's national systems for RED-implementation (Chapter 1). The report continues with a high level description of each Member State system assessed (Chapter 2). Following this, the report includes analysis of the Member States on the effectiveness and administrative burden of a number of key ('major') measures (Chapter 3). The final chapter presents the conclusions and recommendations (Chapter 4)

  11. Faculty Member Perceptions of Academic Leadership Styles at Private Colleges

    Gidman, Lori Kathleen

    2013-01-01

    The leadership style of academic leaders was studied through the eyes of faculty members. This empirical study looked at faculty perceptions of academic leadership with the use of a numerical survey as the basis for observation. Faculty members at six private liberal arts institutions completed the Multifactor Leadership Questionnaire (MLQ) in…

  12. Influence of group member familiarity on online collaborative learning

    Janssen, J.J.H.M.; Erkens, G.; Kirschner, P.A.; Kanselaar, G.

    2009-01-01

    This study investigated the effects of group member familiarity during computer-supported collaborative learning. Familiarity may have an impact on online collaboration, because it may help group members to progress more quickly through the stages of group development, and may lead to higher group

  13. Role Perception among Faculty Members at Teacher Education Colleges

    Grobgeld, Esther; Teichman-Weinberg, Ariela; Wasserman, Egoza; Barchilon Ben-Av, Mercedes

    2016-01-01

    The goal of this study was to examine how faculty members at academic colleges of education perceive their role and to consider elements of their work that need to be included in a professional profile definition. All faculty of one college of education were asked: "What are the tasks/obligations of a faculty member at a college of education?…

  14. Members of the Committee | Women in Science | Initiatives | Indian ...

    Members of the Committee. Rohini M Godbole; Rajinder J Hans-Gill; D. Balasubramanian. Charge of the Committee. The members of the committee were assigned to formulate the terms of reference and to define appropriate action points to be followed for its work. The committee had come up with many initiatives and ...

  15. Leading Teams of Leaders: What Helps Team Member Learning?

    Higgins, Monica; Young, Lissa; Weiner, Jennie; Wlodarczyk, Steven

    2010-01-01

    School districts are moving toward a new form of management in which superintendents need to form and nurture leadership teams. A study of 25 such teams in Connecticut suggests that a team's effectiveness is maximized when the team members are coached by other team members, not the superintendent, and when they are coached on task-related…

  16. 32 CFR 884.17 - Commander's instruction letter to member.

    2010-07-01

    ... instruction letter to member. Subject: Instructions in Case of Release on Bail or Personal Recognizance 1. You... 32 National Defense 6 2010-07-01 2010-07-01 false Commander's instruction letter to member. 884.17... civilian custody on bail or on your own recognizance, report immediately in person or by telephone to the...

  17. 22 CFR 19.10 - Types of annuities to members.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Types of annuities to members. 19.10 Section 19.10 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.10 Types of annuities to members. ...

  18. Education of ethics committee members: experiences from Croatia.

    Borovecki, A.; Have, H.A.M.J. ten; Oreskovic, S.

    2006-01-01

    OBJECTIVES: To study knowledge and attitudes of hospital ethics committee members at the first workshop for ethics committees in Croatia. DESIGN: Before/after cross-sectional study using a self administered questionnaire. SETTING: Educational workshop for members of hospital ethics committees,

  19. Cooperative CEO Identity and Efficient Governance: Member or Outside CEO?

    Q.X. Liang (Qiao Xin); G.W.J. Hendrikse (George)

    2012-01-01

    textabstractA principal-agent model is formulated to capture the efficiency of cooperatives with a member CEO and cooperatives with an employed outsider as CEO. Results of the model show that the incentive strength regarding the member CEO is stronger compared to that of the outside CEO in order to

  20. Teaching Styles and Occupational Stress among Chinese University Faculty Members

    Zhang, Li-fang

    2007-01-01

    The primary aim of this research is to investigate the predictive power of occupational stress for teaching style among university faculty members. A sample of 144 faculty members from a large university in the People's Republic of China rated themselves on three ability scales and responded to the Thinking Styles in Teaching Inventory and to four…

  1. 78 FR 52995 - Senior Executive Service: Performance Review Board Members

    2013-08-27

    ... SMALL BUSINESS ADMINISTRATION Senior Executive Service: Performance Review Board Members AGENCY: U. S. Small Business Administration. ACTION: Notice of Members for the FY 2014 Performance Review Board. SUMMARY: Title 5 U.S.C. 4314(c)(4) requires each agency to publish notification of the appointment of...

  2. 76 FR 64421 - Senior Executive Service: Performance Review Board Members

    2011-10-18

    ... SMALL BUSINESS ADMINISTRATION Senior Executive Service: Performance Review Board Members AGENCY: U.S. Small Business Administration. ACTION: Notice of Members for the FY 2011 Performance Review Board. SUMMARY: Title 5 U.S.C. 4314(c)(4) requires each agency to publish notification of the appointment of...

  3. 77 FR 70204 - Senior Executive Service: Performance Review Board Members

    2012-11-23

    ... SMALL BUSINESS ADMINISTRATION Senior Executive Service: Performance Review Board Members AGENCY: U.S. Small Business Administration. ACTION: Notice of Members for the FY 2012 Performance Review Board. SUMMARY: Title 5 U.S.C. 4314(c)(4) requires each agency to publish notification of the appointment of...

  4. 75 FR 71785 - Senior Executive Service: Performance Review Board Members

    2010-11-24

    ... SMALL BUSINESS ADMINISTRATION Senior Executive Service: Performance Review Board Members AGENCY: U.S. Small Business Administration. ACTION: Notice of Members for the FY 2010 Performance Review Board. SUMMARY: Title 5 U.S.C. 4314(c)(4) requires each agency to publish notification of the appointment of...

  5. Effect of corrosion on the buckling capacity of tubular members

    Øyasæter, F. H.; Aeran, A.; Siriwardane, S. C.; Mikkelsen, O.

    2017-12-01

    Offshore installations are subjected to harsh marine environment and often have damages from corrosion. Several experimental and numerical studies were performed in the past to estimate buckling capacity of corroded tubular members. However, these studies were either based on limited experimental tests or numerical analyses of few cases resulting in semi-empirical relations. Also, there are no guidelines and recommendations in the currently available design standards. To fulfil this research gap, a new formula is proposed to estimate the residual strength of tubular members considering corrosion and initial geometrical imperfections. The proposed formula is verified with results from finite element analyses performed on several members and for varying corrosion patch parameters. The members are selected to represent the most relevant Eurocode buckling curve for tubular members. It is concluded that corrosion reduces the buckling capacity significantly and the proposed formula can be easily applied by practicing engineers without performing detailed numerical analyses.

  6. CE: Military Sexual Trauma in Male Service Members.

    Eckerlin, Denise M; Kovalesky, Andrea; Jakupcak, Matthew

    2016-09-01

    : The experience of military sexual trauma (MST), which can result from assault, battery, or harassment of a sexual nature, may jeopardize the mental health of service members as well as that of their family members, colleagues, and community members. Although a greater proportion of female than male service members are subjected to MST, the Department of Defense estimates that the absolute numbers of affected men and women, across all ranks and branches of military service, are nearly equal because roughly 85% of military members are men. Little research has explored the effects of MST on men. This article discusses the unique ways in which men may experience MST, and examines how social stereotypes of masculinity, myths surrounding sexual assault, and military culture and structure often influence a man's interpretation of an attack and his likelihood of reporting the incident or seeking treatment. It describes current treatments for MST-related mental health conditions and addresses implications for nurses and other health care professionals.

  7. The Foreign Policies of European Union Member States

    Foreign Policies of EU Member States provides a clear and current overview of the motivations and outcomes of EU Member States regarding their foreign policy-making within and beyond the EU. It provides an in-depth analysis of intra-EU policy-making and sheds light, in an innovative and understan......Foreign Policies of EU Member States provides a clear and current overview of the motivations and outcomes of EU Member States regarding their foreign policy-making within and beyond the EU. It provides an in-depth analysis of intra-EU policy-making and sheds light, in an innovative...... prerogative exercised by all EU Member States is to construct their own foreign policies on everything from trade and defence with the rest of the world. This combination of clarity, thematic structure and empirical case studies make this an ideal textbook for all upper-level students of European foreign...

  8. An RNAi-Enhanced Logic Circuit for Cancer Specific Detection and Destruction

    2013-02-01

    monomeric protein secreted by Corynebacterium diphtheriae, and pro-apoptotic members of Bcl-2 family: mBax (Mus musculus), hBax ( Homo sapiens ), and its...Gata3 mStaple. Intron- feature sequences – donor site, branch point, poly- pyrimidine tract, and acceptor site – were selected based on previously...sequences found in literature our intron features were chosen according SplicePort [4], an online analyzer that detects the likelihood of splicing to

  9. FOXO3a Provides a Quickstep from Autophagy Inhibition to Apoptosis in Cancer Therapy.

    Codogno, Patrice; Morel, Etienne

    2018-03-12

    FOXO3a, a member of the Forkhead transcription factor family, has roles in apoptosis and autophagy. In this issue of Developmental Cell, Fitzwalter et al. (2018) describe how the blockade of FOXO3a turnover, which normally occurs through autophagy, sensitizes cancer cells to apoptosis through FOXO3a-mediated stimulation of pro-apoptotic PUMA/BBC3 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. ALICE Photon Multiplicity Detector

    Nayak, T

    2013-01-01

    Photon Multiplicity Detector (PMD) measures the multiplicity and spatial distribution of photons in the forward region of ALICE on a event-by-event basis. PMD is a pre-shower detector having fine granularity and full azimuthal coverage in the pseudo-rapidity region 2.3 < η < 3.9.

  11. Body Weight - Multiple Languages

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Body Weight URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Body Weight - Multiple Languages To use the sharing features on this page, ...

  12. Multiplicity in difference geometry

    Tomasic, Ivan

    2011-01-01

    We prove a first principle of preservation of multiplicity in difference geometry, paving the way for the development of a more general intersection theory. In particular, the fibres of a \\sigma-finite morphism between difference curves are all of the same size, when counted with correct multiplicities.

  13. Applying Multiple Intelligences

    Christodoulou, Joanna A.

    2009-01-01

    The ideas of multiple intelligences introduced by Howard Gardner of Harvard University more than 25 years ago have taken form in many ways, both in schools and in other sometimes-surprising settings. The silver anniversary of Gardner's learning theory provides an opportunity to reflect on the ways multiple intelligences theory has taken form and…

  14. Formation of multiple networks

    Magnani, Matteo; Rossi, Luca

    2013-01-01

    we introduce the first network formation model for multiple networks. Network formation models are among the most popular tools in traditional network studies, because of both their practical and theoretical impact. However, existing models are not sufficient to describe the generation of multiple...

  15. Orchestrating Multiple Intelligences

    Moran, Seana; Kornhaber, Mindy; Gardner, Howard

    2006-01-01

    Education policymakers often go astray when they attempt to integrate multiple intelligences theory into schools, according to the originator of the theory, Howard Gardner, and his colleagues. The greatest potential of a multiple intelligences approach to education grows from the concept of a profile of intelligences. Each learner's intelligence…

  16. Assessing Children's Multiplicative Thinking

    Hurst, Chris; Hurrell, Derek

    2016-01-01

    Multiplicative thinking is a "big idea" of mathematics that underpins much of the mathematics learned beyond the early primary school years. This paper reports on a current study that utilises an interview tool and a written quiz to gather data about children's multiplicative thinking. The development of the tools and some of the…

  17. Ongoing and planned fuel safety research in NEA member states - Compiled from SEGFSM Members' Contributions

    2002-10-01

    This report is in response to an action placed on SEGFSM members to compile ongoing and planned fuel safety research in NEA member states with the aim of providing CSNI an overview on related R and D international programmes and projects, along with the identification of current and future needs and priorities. A questionnaire was distributed to SEGFSM members on 18 October 2000, requesting them to identify fuel safety research programmes and to provide information on achievements and future plans. The questionnaire required respondents to provide information on the ongoing R and D programmes under the following headings: Title; Research Laboratory/Sponsor(s); Objectives/Goals; Status of Work; Brief description/presentation of the main results achieved; Future plans; References. Replies were received from organizations in the following countries: Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, Korea, Norway (Halden Reactor Project), Sweden, Switzerland, United Kingdom, USA. The report is based on the information provided in the replies received, as a consequence it cannot be viewed as comprehensive; programmes may well be in progress in addition to those detailed here. It is also possible that the detailed results of some programmes may remain proprietary and therefore not available in the short term. The report is organized in topic sections relating to: fuel and clad studies, integral fuel rod tests and PIE, LOCA and RIA studies including whole rods and bundles as well as single effects studies of fuel and cladding, code development for both steady state and transient fuel behaviour, thermal hydraulics, reactor physics codes and finally severe accident studies. The main issues for the current generation of reactors are those of high burn-up performance in normal operations, LOCA and RIA conditions and the main goal for the industry is to consolidate the safety issues to bring all countries up to a licensed discharge burn-up of ∼60 MWd/kg in

  18. 19 CFR 122.49b - Electronic manifest requirement for crew members and non-crew members onboard commercial aircraft...

    2010-04-01

    ...” means air carrier employees and their family members and persons traveling onboard a commercial aircraft...), air carrier employees, their family members, and persons onboard for the safety of the flight are...) Date of birth; (iii) Place of birth (city, state—if applicable, country); (iv) Gender (F = female; M...

  19. Recognition of Epstein-Barr Virus in Multiple Sclerosis

    G.P. van Nierop (Gijs)

    2018-01-01

    textabstractMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Symptoms of MS include cognitive, motoric, sensory and visual impairment, pain and fatigue. The genetic background of the host and infection with the herpesvirus family member Epstein-Barr virus

  20. An Exploratory Study on Multiple Intelligences and Social Work Education

    Matto, Holly; Berry-Edwards, Janice; Hutchison, Elizabeth D.; Bryant, Shirley A.; Waldbillig, Amy

    2006-01-01

    This study surveyed social work educators about the importance of multiple intelligences for social work practice and social work education. The sample consisted of 91 faculty members who responded to an online survey that asked them to rate the importance of 7 intelligences (linguistic, logical-mathematical, musical, bodily-kinesthetic, spatial,…