WorldWideScience

Sample records for financieret af aage

  1. To villaer af Aage Rafn

    DEFF Research Database (Denmark)

    Weylandt, Birgit

    2006-01-01

    Gennem sine værker og skrifter var Rafn med til at forme et nyt arkitekturbegreb gennem en rationel klassicisme, der blev overgangen til en mere international poetisk modernisme. Artiklen fokuserer på forskelle og ligheder, der karakteriserer to udvalgte værker: Villaen Gl. Vartov Vej 22 opført 1...

  2. A Japanese case of autoimmune autonomic ganglionopathy (AAG) and a review of AAG cases in Japan.

    Science.gov (United States)

    Hayashi, Michiyuki; Ishii, Yuko

    2009-03-12

    A 29-year-old woman presented with acute, pure autonomic (both sympathetic and parasympathetic) failure and positive antibody to ganglionic nicotinic acetylcholine receptor; the diagnosis was autoimmune autonomic ganglionopathy (AAG). She had typical symptoms of AAG, although the patient also had coughing episodes and psychiatric symptoms, which are not typical of AAG in Western countries but are common in AAG cases in Japan. In a review of the Japanese literature, 29 cases of AAG had been reported. AAG patients in Japan were younger and more male predominant than in Western countries. Of the patients in these 29 cases, 10 (34.5%) had coughing episodes and 12 (41.4%) had psychiatric symptoms.

  3. Comparison of inhibitory effects of 17-AAG nanoparticles and free 17-AAG on HSP90 gene expression in breast cancer.

    Science.gov (United States)

    Ghalhar, Masoud Gandomkar; Akbarzadeh, Abolfazl; Rahmati, Mohammad; Mellatyar, Hassan; Dariushnejad, Hassan; Zarghami, Nosratallah; Barkhordari, Amin

    2014-01-01

    HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a β-cyclodextrin- 17AAG complex. To assess cytotoxic effects of β-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of β-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. MTT assay confirmed that β-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with β-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). The results demonstrated that β-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced β-cyclodextrin-17AAG uptake by cells. Therefore, β-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

  4. 17-AAG, an Hsp90 inhibitor, causes kinetochore defects: a novel mechanism by which 17-AAG inhibits cell proliferation.

    Science.gov (United States)

    Niikura, Y; Ohta, S; Vandenbeldt, K J; Abdulle, R; McEwen, B F; Kitagawa, K

    2006-07-13

    The Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG), which is currently in clinical trials, is thought to exert antitumor activity by simultaneously targeting several oncogenic signaling pathways. Here we report a novel mechanism by which 17-AAG inhibits cell proliferation, and we provide the first evidence that HSP90 is required for the assembly of kinetochore protein complexes in humans. 17-AAG caused delocalization of several kinetochore proteins including CENP-I and CENP-H but excluding CENP-B and CENP-C. Consistently, 17-AAG induced a mitotic arrest that depends on the spindle checkpoint and induced misalignment of chromosomes and aneuploidy. We found that HSP90 associates with SGT1 (suppressor of G2 allele of skp1; SUGT1) in human cells and that depletion of SGT1 sensitizes HeLa cells to 17-AAG. Overexpression of SGT1 restored the localization of specific kinetochore proteins and chromosome alignment in cells treated with 17-AAG. Biochemical and genetic results suggest that HSP90, through its interaction with SGT1 (SUGT1), is required for kinetochore assembly. Furthermore, time-course experiments revealed that transient treatment with 17-AAG between late S and G2/M phases causes substantial delocalization of CENP-H and CENP-I, a finding that strongly suggests that HSP90 participates in kinetochore assembly in a cell cycle-dependent manner.

  5. Heisenberg Groups as Platform for the AAG key-exchange protocol

    OpenAIRE

    Kahrobaei, Delaram; Lam, Ha T.

    2014-01-01

    Garber, Kahrobaei, and Lam studied polycyclic groups generated by number field as platform for the AAG key-exchange protocol. In this paper, we discuss the use of a different kind of polycyclic groups, Heisenberg groups, as a platform group for AAG by submitting Heisenberg groups to one of AAG's major attacks, the length-based attack.

  6. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

    Science.gov (United States)

    Meira, Lisiane B; Moroski-Erkul, Catherine A; Green, Stephanie L; Calvo, Jennifer A; Bronson, Roderick T; Shah, Dharini; Samson, Leona D

    2009-01-20

    Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

  7. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells.

    Science.gov (United States)

    Newman, Bryan; Liu, Yan; Lee, Hsiu-Fang; Sun, Duxin; Wang, Yin

    2012-09-01

    Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer. ©2012 AACR.

  8. A.A.G. Annual Conference Participation: The Spatial Dimension.

    Science.gov (United States)

    Fairweather, Malcolm

    This paper analyzes the spatial patterning of participants attending four annual conferences of the Association of American Geographers (AAG). The four most recent conventions were selected for the study: Los Angeles in 1981, Louisville in 1980, Philadelphia in 1979, and New Orleans in 1980. A conference participant is defined as a person whose…

  9. Fremtidssikring af kloaknet

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2008-01-01

    Beskrivelse af hvordan man ved udbygning af eksisterende kloaknet og ved nytænkning af planlægning af nye bydele kan sikre sig langsigtet mod konsekvenserne af klimaændinger og kraftigere nedbør...

  10. 17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis.

    Science.gov (United States)

    Siegelin, Markus David; Habel, Antje; Gaiser, Timo

    2009-02-01

    17-AAG is a selective HSP90-inhibitor that exhibited therapeutic activity in cancer. In this study three glioblastoma cell lines (U87, LN229 and U251) were treated with 17-AAG, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Treatment with subtoxic doses of 17-AAG in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, suggesting that this combined treatment may offer an attractive strategy for treating gliomas. 17-AAG treatment down-regulated survivin through proteasomal degradation. In addition, over-expression of survivin attenuated cytotoxicity induced by the combination of 17-AAG and TRAIL. In summary, survivin is a key regulator of TRAIL-17-AAG mediated cell death in malignant glioma.

  11. Effect of 17-AAG on radio-sensitivity of HeLa and V79 cells

    International Nuclear Information System (INIS)

    Pan Yanling; Hong Chengjiao; Zhang Baoguo

    2010-01-01

    In order to investigate the radio-sensitizing effect of 17-AAG, an inhibitor of Heat Shock Protein 90, on human Uterine Cervix Cancer HeLa and V79 cells, Clonogenic assay was used to observe the cell survival rate. The results show that 17-AAG can decrease obviously (p 0.05). This indicates that 17-AAG may enhance the radio-sensitivity of the HeLa cell line and has no effect on the V79 cell line. (authors)

  12. AF Sites

    Science.gov (United States)

    AF Bands Air Force Band Recordings Air National Guard Band of the Midwest Air National Guard Band of U.S. Air Force Bands U.S. Air Force Heartland of America Band U.S. Air Force Heritage of America Band U.S. Air Forces in Europe Band US Air Forces Central Command Band Medical 42d Medical Group 59th

  13. Repercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cells

    KAUST Repository

    Vishal, Chaturvedi; Kumar, Jonnala Ujwal; Veera Brahmendra Swamy, Cherukuvada; Nandini, Rangaraj; Srinivas, Gunda; Kumaresan, Rathinam; Shashi, Singh; Sreedhar, Amere Subbarao

    2011-01-01

    Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects

  14. Energirenovering af parcelhuse

    DEFF Research Database (Denmark)

    Aggerholm, Søren

    af de tre huse består i efterisolering af lofter op til 300 mm, udskiftning af almindelige termoruder til energiruder, og installation af solvarmeanlæg til produktion af varmt brugsvand. I de tre huse er der ved energirenoveringen opnået en reduktion af energiforbruget på 16-22 procent. Rapporten...

  15. Anvendelse af alternative isoleringsmaterialer

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2003-01-01

    Resume af By og Byg Anvisning 207 om anvendelse af alternative isoleringsmaterialer, udarbejdet af Statens Byggeforskningsinstitut under udviklingsprogrammet "Miljø- og arbejdsmiljøvenlig isolering"......Resume af By og Byg Anvisning 207 om anvendelse af alternative isoleringsmaterialer, udarbejdet af Statens Byggeforskningsinstitut under udviklingsprogrammet "Miljø- og arbejdsmiljøvenlig isolering"...

  16. MEK inhibition potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells.

    Science.gov (United States)

    Zhang, Tao; Li, Yanyan; Zhu, Zhenkun; Gu, Mancang; Newman, Bryan; Sun, Duxin

    2010-10-04

    The Ras/Raf/MEK/ERK signaling has been implicated in uncontrolled cell proliferation and tumor progression in pancreatic cancer. The purpose of this study is to evaluate the antitumor activity of MEK inhibitor U0126 in combination with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in pancreatic cancer cells. Western blotting showed that 17-AAG caused a 2- to 3-fold transient activation of MEK/ERK signaling in pancreatic cancer cells. The activation sustained for 6 h before phospho-ERK (p-ERK) destabilization. The selective MEK inhibitor U0126 completely abolished 17-AAG induced ERK1/2 activation and resulted in more than 80% of phospho-ERK degradation after only 15 min treatment. Moreover, U0126 had complementary effect on 17-AAG regulated oncogenic and cell cycle related proteins. Although 17-AAG downregulated cyclin D1, cyclin E, CDK4 and CDK6, it led to cyclin A and CDK2 accumulation, which was reversed by the addition of U0126. Antiproliferation assay showed that combination of U0126 and 17-AAG resulted in synergistic cytotoxic effect. More importantly, 17-AAG alone only exhibited moderate inhibition of cell migration in vitro, while addition of U0126 dramatically enhanced the inhibitory effect by 2- to 5-fold. Taken together, these data demonstrate that MEK inhibitor U0126 potentiates the activity of Hsp90 inhibitor 17-AAG against pancreatic cancer cells. The combination of Hsp90 and MEK inhibition could provide a promising avenue for the treatment of pancreatic cancer.

  17. Design and Evaluation of Micellar Nanocarriers for 17-allyamino-17-demethoxygeldanamycin (17-AAG)

    Science.gov (United States)

    17-Allyamino-17-demethoxygeldanamycin (17-AAG) is a potent anticancer agent currently undergoing phases I and II clinical trials. However, the clinical development of 17-AAG has been hindered by its poor aqueous solubility and hepatotoxicity. This study aimed to devise novel mice...

  18. Structural Forecasts for the Danish Economy Using The Dynamic-AAGE Model

    DEFF Research Database (Denmark)

    Adams, Philip D; Andersen, Lill Thanning; Jacobsen, Lars Bo

    2002-01-01

    developed for MONASH has now been applied to Dynamic-AAGE to generate structural forecasts for the Danish economy. The starting point for the Dynamic-AAGE forecasts is a set of scenarios for the macro economy supplied by a specialist-forecasting agency, currently the Danish Economic Council. Expert...

  19. Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation.

    Science.gov (United States)

    Krishnamoorthy, Gnana Prakasam; Guida, Teresa; Alfano, Luigi; Avilla, Elvira; Santoro, Massimo; Carlomagno, Francesca; Melillo, Rosa Marina

    2013-06-14

    The receptor tyrosine kinase AXL is overexpressed in many cancer types including thyroid carcinomas and has well established roles in tumor formation and progression. Proper folding, maturation, and activity of several oncogenic receptor tyrosine kinases require HSP90 chaperoning. HSP90 inhibition by the antibiotic geldanamycin or its derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) causes destabilization of its client proteins. Here we show that AXL is a novel client protein of HSP90. 17-AAG induced a time- and dose-dependent down-regulation of endogenous or ectopically expressed AXL protein, thereby inhibiting AXL-mediated signaling and biological activity. 17-AAG-induced AXL down-regulation specifically affected fully glycosylated mature receptor present on cell membrane. By using biotin and [(35)S]methionine labeling, we showed that 17-AAG caused depletion of membrane-localized AXL by mediating its degradation in the intracellular compartment, thus restricting its exposure on the cell surface. 17-AAG induced AXL polyubiquitination and subsequent proteasomal degradation; under basal conditions, AXL co-immunoprecipitated with HSP90. Upon 17-AAG treatment, AXL associated with the co-chaperone HSP70 and the ubiquitin E3 ligase carboxyl terminus of HSC70-interacting protein (CHIP). Overexpression of CHIP, but not of the inactive mutant CHIP K30A, induced accumulation of AXL polyubiquitinated species upon 17-AAG treatment. The sensitivity of AXL to 17-AAG required its intracellular domain because an AXL intracellular domain-deleted mutant was insensitive to the compound. Active AXL and kinase-dead AXL were similarly sensitive to 17-AAG, implying that 17-AAG sensitivity does not require receptor phosphorylation. Overall our data elucidate the molecular basis of AXL down-regulation by HSP90 inhibitors and suggest that HSP90 inhibition in anticancer therapy can exert its effect through inhibition of multiple kinases including AXL.

  20. Molecular Mechanism of 17-Allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL Receptor Tyrosine Kinase Degradation*

    Science.gov (United States)

    Krishnamoorthy, Gnana Prakasam; Guida, Teresa; Alfano, Luigi; Avilla, Elvira; Santoro, Massimo; Carlomagno, Francesca; Melillo, Rosa Marina

    2013-01-01

    The receptor tyrosine kinase AXL is overexpressed in many cancer types including thyroid carcinomas and has well established roles in tumor formation and progression. Proper folding, maturation, and activity of several oncogenic receptor tyrosine kinases require HSP90 chaperoning. HSP90 inhibition by the antibiotic geldanamycin or its derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) causes destabilization of its client proteins. Here we show that AXL is a novel client protein of HSP90. 17-AAG induced a time- and dose-dependent down-regulation of endogenous or ectopically expressed AXL protein, thereby inhibiting AXL-mediated signaling and biological activity. 17-AAG-induced AXL down-regulation specifically affected fully glycosylated mature receptor present on cell membrane. By using biotin and [35S]methionine labeling, we showed that 17-AAG caused depletion of membrane-localized AXL by mediating its degradation in the intracellular compartment, thus restricting its exposure on the cell surface. 17-AAG induced AXL polyubiquitination and subsequent proteasomal degradation; under basal conditions, AXL co-immunoprecipitated with HSP90. Upon 17-AAG treatment, AXL associated with the co-chaperone HSP70 and the ubiquitin E3 ligase carboxyl terminus of HSC70-interacting protein (CHIP). Overexpression of CHIP, but not of the inactive mutant CHIP K30A, induced accumulation of AXL polyubiquitinated species upon 17-AAG treatment. The sensitivity of AXL to 17-AAG required its intracellular domain because an AXL intracellular domain-deleted mutant was insensitive to the compound. Active AXL and kinase-dead AXL were similarly sensitive to 17-AAG, implying that 17-AAG sensitivity does not require receptor phosphorylation. Overall our data elucidate the molecular basis of AXL down-regulation by HSP90 inhibitors and suggest that HSP90 inhibition in anticancer therapy can exert its effect through inhibition of multiple kinases including AXL. PMID:23629654

  1. An experimental study on the antitumor effect of 131I-17-AAG in vitro and in vivo.

    Science.gov (United States)

    Wenyong, Tu; Lu, Liu; Daozhen, Chen; Weidong, Yin; Ying, Huang

    2009-02-01

    To observe the antitumor effect of (131)I-17-allylamino-17-demethoxygeldanamycin ((131)I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application. (131)I-17-AAG was prepared by the reaction of 17-AAG with Na [(131)I] in the presence of hydrogen peroxide. The effects of (131)17-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis. Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7 +/- 5.3%, 57.3 +/- 4.3%, and 63.7 +/- 3.1%, in Na(131)I group, 17-AAG group, and (131)I-17-AAG group, respectively. The inhibition rate in the (131)I-17-AAG group differed significantly between N(a131)I group and 17-AAG group (F = 229.49, P AAG group, and (131)I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the (131)I-17-AAG group were significantly smaller than those in the DMSO group (F = 24.18, P AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in (131)I-17-AAG was significantly lower than that in the DMSO group or (131)I group. (131)I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. (131)I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor.

  2. [Gene Expression Profile of Apoptosis in Leukemia Cells Induced by Hsp90 Selective inhibitor 17-AAG].

    Science.gov (United States)

    Wang, Na-Na; Li, Zhi-Heng; Tao, Yan-Fang; Xu, Li-Xiao; Pan, Jian; Hu, Shao-Yan

    2016-06-01

    To investigate the apoptotic effects of Hsp90 selective inhibitor 17-AAG on human leukemia HL-60 and NB4 cells and analyse its possible mechanism. CCK-8 assay was used to quantify the growth inhibition of cells after exposure to 17-AAG for 24 hours. Flow cytometrve with annexin V/propidium iodide staining was used to detect apoptosis of leukemia cells. Then Western blot was used to detect the activation of apoptosis related protein caspase-3 and PARP level. Gene expression profile of NB4 cells treated with 17-AAG was analyzed with real-time PCR arrays. The inhibition of leukemia cell proliferation displayed a dose-dependent manner. Annexin V assay, cell cycle analysis and activation of PARP demonstrate that 17-AAG induced apoptosis leukemia cells. Real-time PCR array analysis showed that expression of 56 genes significantly up-regulated and expression of 23 genes were significantly down-regulated after 17-AAG treatment. The 17-AAG can inhibit the proliferation and induce the apoptosis of leukemia cells. After leukemia cells are treated with 17-AAG, the significant changes of apoptosis-related genes occured, and the cell apoptosis occurs via activating apoptosis related signaling pathway.

  3. Chemotherapeutic potential of 17-AAG against cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.

    Science.gov (United States)

    Santos, Diego M; Petersen, Antonio L O A; Celes, Fabiana S; Borges, Valeria M; Veras, Patricia S T; de Oliveira, Camila I

    2014-10-01

    Leishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and reports of resistance, reinforce the need for the development of new treatment options. Previously, we showed that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis. Exposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dose-dependent parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was dissociated from the production of nitric oxide (NO), superoxide (O(-2)) or inflammatory mediators such as TNF-α, IL-6 and MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG showed a similar effect to amphotericin B regarding the ability to reduce parasite viability. 17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as a new chemotherapeutic alternative for cutaneous Leishmaniasis.

  4. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Science.gov (United States)

    Calvo, Jennifer A; Moroski-Erkul, Catherine A; Lake, Annabelle; Eichinger, Lindsey W; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T; Christiani, David C; Meira, Lisiane B; Samson, Leona D

    2013-04-01

    Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  5. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Directory of Open Access Journals (Sweden)

    Jennifer A Calvo

    2013-04-01

    Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  6. [HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway].

    Science.gov (United States)

    Chen, Kan-Kan; He, Zheng-Mei; Ding, Bang-He; Chen, Yue; Zhang, Li-Juan; Yu, Liang; Gao, Jian

    2016-02-01

    To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism. The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively. The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P AAG concentration, the more high of cell ratio in G1 phase (P AAG, the more long time of culture, the more high of cell ratio in G1 phase (P AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.

  7. The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model.

    Science.gov (United States)

    Xu, Yunze; Zhu, Qi; Chen, Dongning; Shen, Zhoujun; Wang, Weiqing; Ning, Guang; Zhu, Yu

    2015-07-01

    This study aims to investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the malignant pheochromocytoma using a xenograft mouse model. Treatment with 17-AAG induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Furthermore, 17-AAG also significantly inhibited the expression of HSP90 and its client proteins. Our results validated HSP90 as an important target in pheochromocytoma and provided rationale for the testing of HSP90 inhibitors as a promising therapeutic agent in the antitumor therapy of pheochromocytoma.

  8. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

    Science.gov (United States)

    Xiao, Y; Guan, J

    2015-01-01

    Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

  9. Restaurering af Skjern Å

    DEFF Research Database (Denmark)

    Jessen, K.; Boysen Larsen, B.; Bundgaard, P.

    Denne rapport indeholder resultaterne af den natur- og miljøovervågning, der blev iværksat som en del af naturgenopretningen af Skjern Å 1999-2002. Ved projektet ophørte den kunstige afvanding af den vestlige del af Skjern Å dalen. Størstedelen af de dyrkede arealer ændredes til ekstensive græsni...

  10. Alkyladenine DNA glycosylase (Aag) in somatic hypermutation and class switch recombination.

    Science.gov (United States)

    Longerich, Simonne; Meira, Lisiane; Shah, Dharini; Samson, Leona D; Storb, Ursula

    2007-12-01

    Somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes require the cytosine deaminase AID, which deaminates cytosine to uracil in Ig gene DNA. Paradoxically, proteins involved normally in error-free base excision repair and mismatch repair, seem to be co-opted to facilitate SHM and CSR, by recruiting error-prone translesion polymerases to DNA sequences containing deoxy-uracils created by AID. Major evidence supports at least one mechanism whereby the uracil glycosylase Ung removes AID-generated uracils creating abasic sites which may be used either as uninformative templates for DNA synthesis, or processed to nicks and gaps that prime error-prone DNA synthesis. We investigated the possibility that deamination at adenines also initiates SHM. Adenosine deamination would generate hypoxanthine (Hx), a substrate for the alkyladenine DNA glycosylase (Aag). Aag would generate abasic sites which then are subject to error-prone repair as above for AID-deaminated cytosine processed by Ung. If the action of an adenosine deaminase followed by Aag were responsible for significant numbers of mutations at A, we would find a preponderance of A:T>G:C transition mutations during SHM in an Aag deleted background. However, this was not observed and we found that the frequencies of SHM and CSR were not significantly altered in Aag-/- mice. Paradoxically, we found that Aag is expressed in B lymphocytes undergoing SHM and CSR and that its activity is upregulated in activated B cells. Moreover, we did find a statistically significant, albeit low increase of T:A>C:G transition mutations in Aag-/- animals, suggesting that Aag may be involved in creating the SHM A>T bias seen in wild type mice.

  11. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.

    Science.gov (United States)

    Gaspar, Nathalie; Sharp, Swee Y; Pacey, Simon; Jones, Chris; Walton, Michael; Vassal, Gilles; Eccles, Suzanne; Pearson, Andrew; Workman, Paul

    2009-03-01

    Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant GB cell lines were generated. High-resistance levels with resistance indices (RI = resistant line IC(50)/parental line IC(50)) of 20 to 137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilized. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021, and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NAD(P)H/quinone oxidoreductase 1 (NQO1) expression/activity and 17-AAG IC(50) was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors.

  12. The heat shock protein 90 inhibitor, 17-AAG, attenuates thioacetamide induced liver fibrosis in mice.

    Science.gov (United States)

    Abu-Elsaad, Nashwa M; Serrya, Marwa S; El-Karef, Amr M; Ibrahim, Tarek M

    2016-04-01

    Heat shock protein 90 (Hsp90) is proposed to be involved in liver disorders. This study was conducted to test effect of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90, on attenuating thioacetamide induced liver fibrosis in vivo. Four groups of Swiss albino male mice (CD-1 strain) were used as follows: control group; thioacetamide group (received 100mg/kg thioacetamide, ip injection, 3 times/week for 8 weeks); thioacetamide plus 17-AAG groups (received 100mg/kg thioacetamide, ip injection, 3 times/week for 8 weeks plus 25 or 50mg/kg 17-AAG, ip injection, 5 days/week along the last 4 weeks). Fibrosis was quantified by measuring hydroxyproline level and by morphometry and oxidative stress biomarkers were assigned. Relative hepatic mRNA expressions of α-smooth muscle actin (α-SMA), collagen-1-alpha-1 (Col1A1) and tissue inhibitor metalloproteinase-1 (TIMP-1) mRNAs were measured by RT-PCR. Levels of the apoptotic markers caspase-3, factor related apoptosis (Fas) and Hsp-90 were assigned in tissue homogenate. 17-AAG (50mg/kg) significantly decreased fibrosis percentage significantly (pAAG (50mg/kg) compared to other groups. The Hsp90 inhibitor, 17-AAG, can attenuate thioacetamide hepatotoxicity through oxidative stress counterbalance, reducing stellate cells activity and inducing apoptosis. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. 6 belysninger af vejledning

    DEFF Research Database (Denmark)

    Toft, Helle Mary; Jessing, Carla Tønder; Nymann, Anette

    Artiklerne belyser vejledning af unge og vejledning af voksne. I relation til unge drejer det sig om: 1. vejledning af unge med vanskeligheder i forhold til uddannelse - her unge med særlige vejledningsbehov, og mentorordninger for unge, og 2. vejledning af unge i ungdomsuddannelser og i erhvervs...

  14. Undervisning af tosprogede elever

    DEFF Research Database (Denmark)

    Horst, Christian

    2003-01-01

    Artiklen fremdrager hovedresultaterne fra Virginia P. Collier's og Wayne P. Thomas's længdeundersøgelser af tosprogede elever i USA, som formentlig er de mest omfattende undersøgelser af undervisningen af tosprogede elever overhovedet. Resultaterne diskuteres i relation til udviklingen af en...

  15. Lyden-af-Leg

    DEFF Research Database (Denmark)

    Toft, Herdis

    Præsentation af seniorforsker-projekt Lyden-af-Leg i et traderingsperspektiv og med indledende fokus på YouTube som traderings-platform.......Præsentation af seniorforsker-projekt Lyden-af-Leg i et traderingsperspektiv og med indledende fokus på YouTube som traderings-platform....

  16. Energirenovering af Sems Have

    DEFF Research Database (Denmark)

    Jensen, Søren Østergaard; Rose, Jørgen; Mørck, Ove

    Nærværende rapport udgør en del af afrapporteringen af PSO ELFORSK projektet Vejledning for energirenovering af boligblokke til lavenergiklasse 2015 og 2020. Arbejdet har været finansieret af PSO midler via ELFORSK, projekt: 347-023. Formålet med projektet er at udvikle en vejledning for dybtgående...

  17. Energirenovering af Traneparken

    DEFF Research Database (Denmark)

    Rose, Jørgen; Thomsen, Kirsten Engelund; Mørck, Ove

    Nærværende rapport udgør en del af afrapporteringen af PSO ELFORSK projektet Vejledning for energirenovering af boligblokke til lavenergiklasse 2015 og 2020. Arbejdet har været finansieret af PSO midler via ELFORSK, projekt: 347-023. Formålet med projektet er at udvikle en vejledning for dybtgående...

  18. Beregning af nitratudvaskning

    DEFF Research Database (Denmark)

    Petersen, Jens; Petersen, Bjørn Molt; Blicher-Mathiesen, Gitte

    2006-01-01

    I forbindelse med kommunalreformen ønskes en ensartet forvaltning af reglerne for vurdering af virkninger på miljøet (VVM) ved ansøgninger om udvidelse af husdyrbrug, herunder beregning af nitratudvaskningen. Rapporten foreslår et beregningskoncept, der bygger på den ansøgende bedrifts samlede kv...

  19. Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG).

    Science.gov (United States)

    Lee, Chun-Yue I; Delaney, James C; Kartalou, Maria; Lingaraju, Gondichatnahalli M; Maor-Shoshani, Ayelet; Essigmann, John M; Samson, Leona D

    2009-03-10

    The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N(6)-ethenoadenine (epsilonA). The crystal structures of AAG bound to epsilonA have provided insights into the structural basis for substrate recognition, base excision, and exclusion of normal purines and pyrimidines from its substrate recognition pocket. In this study, we explore the substrate specificity of full-length and truncated Delta80AAG on a library of oligonucleotides containing structurally diverse base modifications. Substrate binding and base excision kinetics of AAG with 13 damaged oligonucleotides were examined. We found that AAG bound to a wide variety of purine and pyrimidine lesions but excised only a few of them. Single-turnover excision kinetics showed that in addition to the well-known epsilonA and Hx substrates, 1-methylguanine (m1G) was also excised efficiently by AAG. Thus, along with epsilonA and ethanoadenine (EA), m1G is another substrate that is shared between AAG and the direct repair protein AlkB. In addition, we found that both the full-length and truncated AAG excised 1,N(2)-ethenoguanine (1,N(2)-epsilonG), albeit weakly, from duplex DNA. Uracil was excised from both single- and double-stranded DNA, but only by full-length AAG, indicating that the N-terminus of AAG may influence glycosylase activity for some substrates. Although AAG has been primarily shown to act on double-stranded DNA, AAG excised both epsilonA and Hx from single-stranded DNA, suggesting the possible significance of repair of these frequent lesions in single-stranded DNA transiently generated during replication and transcription.

  20. 17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages.

    Science.gov (United States)

    Petersen, Antonio Luis de Oliveira Almeida; Guedes, Carlos Eduardo Sampaio; Versoza, Carolina Leite; Lima, José Geraldo Bomfim; de Freitas, Luiz Antônio Rodrigues; Borges, Valéria Matos; Veras, Patrícia Sampaio Tavares

    2012-01-01

    Leishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. Pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. Second-line drugs are less efficacious, cause a range of side effects and can be costly. The formulation of new generations of drugs, especially in developing countries, has become mandatory. We investigated the anti-leishmanial effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, in vitro. This inhibitor is currently in clinical trials for cancer treatment; however, its effects against intracellular Leishmania remain untested. Macrophages infected with L. amazonensis were treated with 17-AAG (25-500 nM) and parasite load was quantified using optical microscopy. Parasite load declined in 17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular parasite death became irreversible after 4 h of treatment with 17-AAG, and occurred independent of nitric oxide (NO) and superoxide (O(2) (-)) production. Additionally, intracellular parasite viability was severely reduced after 48 h of treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator production, including TNF-α, IL-6 and MCP-1, yet IL-12 remained unaffected. Electron microscopy revealed morphological alterations, such as double-membrane vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment. The HSP90 inhibitor, 17-AAG, possesses high potency under low dosage and reduces both pro-inflammatory and oxidative molecule production. Therefore, further studies are warranted to investigate this inhibitor's potential in the development of new generations of anti-leishmanials.

  1. PARP inhibitors protect against sex- and AAG-dependent alkylation-induced neural degeneration.

    Science.gov (United States)

    Allocca, Mariacarmela; Corrigan, Joshua J; Fake, Kimberly R; Calvo, Jennifer A; Samson, Leona D

    2017-09-15

    Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag -transgenic ( AagTg ) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1). Here, we tested whether PARP inhibitors can also prevent alkylation-induced retinal and cerebellar degeneration in male and female WT and AagTg mice. Importantly, we found that WT mice display sex-dependent alkylation-induced retinal damage (but not cerebellar damage), with WT males being more sensitive than females. Accordingly, estradiol treatment protects males against alkylation-induced retinal degeneration. In AagTg male and female mice, the alkylation-induced tissue damage in both the retina and cerebellum is exacerbated and the sex difference in the retina is abolished. PARP inhibitors, much like Parp1 gene deletion, protect against alkylation-induced AAG-dependent neuronal degeneration in WT and AagTg mice, regardless of the gender, but their efficacy in preventing alkylation-induced neuronal degeneration depends on PARP inhibitor characteristics and doses. The recent surge in the use of PARP inhibitors in combination with cancer chemotherapeutic alkylating agents might represent a powerful tool for obtaining increased therapeutic efficacy while avoiding the collateral effects of alkylating agents in healthy tissues.

  2. Lyden af musik - er lyden af idealisme

    DEFF Research Database (Denmark)

    Eigtved, Michael

    2015-01-01

    Programartiklen til Det Ny Teaters opsætning af Rodgers & Hammersteins The Sound of Music, undersøger musicalgenrens - og især de konkrete ophavsmænds- affinitet til fremstillingen af såvel idealistiske som ideologiske universer.......Programartiklen til Det Ny Teaters opsætning af Rodgers & Hammersteins The Sound of Music, undersøger musicalgenrens - og især de konkrete ophavsmænds- affinitet til fremstillingen af såvel idealistiske som ideologiske universer....

  3. Styring af kommunal digitalisering

    DEFF Research Database (Denmark)

    Jæger, Birgit

    2017-01-01

    Digitalisering af både interne arbejdsprocesser og kommunikation med borgere og virksomheder har længe været en vigtig faktor i moderniseringen af den offentlige sektor. Derfor er der stort fokus på styring af digitaliseringen. Denne artikel undersøger, dels hvordan digitaliseringen i den kommunale...... sektor styres, og dels hvilke styringsparadigmer der kan identificeres. Med udgangspunkt i en konkret kommune analyseres styringen af digitalisering gennem et hierarki af offentlige digitaliseringsstrategier. Gennem udvikling af en helt ny form for organisering, en såkaldt Digitaliseringsforening...

  4. Validation of Aedes aegypti Aag-2 cells as a model for insect immune studies.

    Science.gov (United States)

    Barletta, Ana Beatriz Ferreira; Silva, Maria Clara L Nascimento; Sorgine, Marcos H Ferreira

    2012-07-24

    The understanding of mosquito immune responses can provide valuable tools for development of novel mosquito control strategies. Aiming the study at insect innate immunity, continuous insect cell lines have been established and used as research tools due to the fact that they constitute more homogeneous, sensitive, and reproducible systems than the insects from which they originated. More recently, Aag-2, an Aedes aegypti cell lineage, began to be frequently used as a model for studies of mosquito immunity. Nevertheless, to our knowledge, no study has systematically characterized the responses of Aag-2 cell line against different kinds of pathogens and compared its response to those exhibited by whole mosquitoes. For this reason, in this study we characterized gene expression profiles of the Aag-2 cell line in response to different kinds of immune challenges, such as Gram negative and positive bacteria, fungi and viruses, comparing the obtained results with the ones already described in the literature for whole mosquitoes. Aedes aegypti Aag-2 cells were exposed to different immune stimuli (gram-positive and gram negative heat inactivated bacteria, zymosan or Sindbis virus) for 24 hours and the expression of selected marker genes from toll, IMD and Jak/STAT pathways was analyzed by qPCR. Also, cells were incubated with fluorescent latex beads for evaluation of its phagocytosis capacity. Aag-2 cells were stimulated with two concentrations of heat-killed Gram negative (Enterobacter cloacae) or Gram positive (Micrococcus luteus) bacteria, Zymosan or infected with Sindbis virus and the expression of key genes from the main immune related pathways, Toll, IMD and Jak/STAT, were investigated. Our results suggest that Toll and IMD pathways are activated in response to both Gram positive and negative bacteria and Zymosan in Aag-2 cells, displaying an immune profile similar to those described in the literature for whole mosquitoes. The same stimuli were also capable of

  5. Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment.

    Science.gov (United States)

    Chen, Yaomin; Wang, Bin; Liu, Dan; Li, Jing Jing; Xue, Yueqiang; Sakata, Kazuko; Zhu, Ling-qiang; Heldt, Scott A; Xu, Huaxi; Liao, Francesca-Fang

    2014-02-12

    The excessive accumulation of soluble amyloid peptides (Aβ) plays a crucial role in the pathogenesis of Alzheimer's disease (AD), particularly in synaptic dysfunction. The role of the two major chaperone proteins, Hsp70 and Hsp90, in clearing misfolded protein aggregates has been established. Despite their abundant presence in synapses, the role of these chaperones in synapses remains elusive. Here, we report that Hsp90 inhibition by 17-AAG elicited not only a heat shock-like response but also upregulated presynaptic and postsynaptic proteins, such as synapsin I, synaptophysin, and PSD95 in neurons. 17-AAG treatment enhanced high-frequency stimulation-evoked LTP and protected neurons from synaptic damage induced by soluble Aβ. In AD transgenic mice, the daily administration of 17-AAG over 7 d resulted in a marked increase in PSD95 expression in hippocampi. 17-AAG treatments in wild-type C57BL/6 mice challenged by soluble Aβ significantly improved contextual fear memory. Further, we demonstrate that 17-AAG activated synaptic protein expression via transcriptional mechanisms through the heat shock transcription factor HSF1. Together, our findings identify a novel function of Hsp90 inhibition in regulating synaptic plasticity, in addition to the known neuroprotective effects of the chaperones against Aβ and tau toxicity, thus further supporting the potential of Hsp90 inhibitors in treating neurodegenerative diseases.

  6. 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Rusmini, Paola; Simonini, Francesca; Crippa, Valeria; Bolzoni, Elena; Onesto, Elisa; Cagnin, Monica; Sau, Daniela; Ferri, Nicola; Poletti, Angelo

    2011-01-01

    Several types of motorneuron diseases are linked to neurotoxic mutant proteins. These acquire aberrant conformations (misfolding) that trigger deleterious downstream events responsible for neuronal dysfunction and degeneration. The pharmacological removal of misfolded proteins might thus be useful in these diseases. We utilized a peculiar motorneuronal disease model, spinobulbar muscular atrophy (SBMA), in which the neurotoxicity of the protein involved, the mutant androgen receptor (ARpolyQ), can be modulated by its ligand testosterone (T). 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) has already been proven to exert beneficial action in SBMA. Here we demonstrated that 17-AAG exerts its pro-degradative activity on mutant ARpolyQ without impacting on proteasome functions. 17-AAG removes ARpolyQ misfolded species and aggregates by activating the autophagic system. We next analyzed the 17-AAG effects on two proteins (SOD1 and TDP-43) involved in related motorneuronal diseases, such as amyotrophic lateral sclerosis (ALS). In these models 17-AAG was unable to counteract protein aggregation. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. 17AAG-induced internalisation of HER2-specific Affibody molecules.

    Science.gov (United States)

    Göstring, Lovisa; Lindegren, Sture; Gedda, Lars

    2016-10-01

    The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled 211 At-ABY-025 and radiometal-labelled 111 In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111 In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter 211 At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells.

  8. An experimental study on the antitumor effect of 131I-17-AAG in vitro and in vivo

    International Nuclear Information System (INIS)

    Tu Wenyong; Liu Lu; Chen Daozhen; Huang Ying; Yin Weidong

    2009-01-01

    The objective of this study was to observe the antitumor effect of 131 I-17-allylamino-17-demethoxygeldanamycin ( 131 I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application. 131 I-17-AAG was prepared by the reaction of 17-AAG with Na [ 131 I] in the presence of hydrogen peroxide. The effects of 131 17-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis. Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7±5.3%, 57.3±4.3%, and 63.7±3.1%, in Na 131 I group, 17-AAG group, and 131 I-17-AAG group, respectively. The inhibition rate in the 131 I-17-AAG group differed significantly between Na 131 I group and 17-AAG group (F=229.49, P 131 I group, 17-AAG group, and 131 I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the 131 I-17-AAG group were significantly smaller than those in the DMSO group (F=24.18, P 131 I group (F=20.68, P 131 I-17-AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in 131 I-17-AAG was significantly lower than that in the DMSO group or 131 I group. 131 I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. 131 I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor. (author)

  9. Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB).

    Science.gov (United States)

    van Loon, Barbara; Samson, Leona D

    2013-03-01

    Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known to repair DNA lesions that are specific substrates of AAG. Here we use immunofluorescence to show that AAG localizes to mitochondria, and we find that native AAG is present in purified human mitochondrial extracts, as well as that exposure to alkylating agent promotes AAG accumulation in the mitochondria. We identify mitochondrial single-stranded binding protein (mtSSB) as a novel interacting partner of AAG; interaction between mtSSB and AAG is direct and increases upon methyl methanesulfonate (MMS) treatment. The consequence of this interaction is specific inhibition of AAG glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrate. By inhibiting AAG-initiated processing of damaged bases, mtSSB potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. In summary, our findings suggest the existence of AAG-initiated BER in mitochondria and further support a role for mtSSB in DNA repair. Copyright © 2012. Published by Elsevier B.V.

  10. Skoling af lyst

    DEFF Research Database (Denmark)

    Bjerg, Helle

    2011-01-01

    På baggrund af interview med tre elevgenerationer fremanalyseres skolens virkningsfuldhed i skoling af lyst i et historisk perspektiv. I afhandlingen udvikles to teoretisk-analytiske optikker: Skolen som ideologisk rum - med inspiration fra Slavoj Zizeks ideologikritik, samt Skolen som affektivt...

  11. Om distributionen af hvidhed

    DEFF Research Database (Denmark)

    Frello, Birgitta

    2007-01-01

    Med udgangspunkt i John Fords Western, Forfølgeren fra 1956, præsenteres en analyse af repræsentationer af race og overskridelse af raceskel, særligt i relation til konstitueringen af subjektpositioner, hvorfra spørgsmål om hvidhed og ikke-hvidhed kan afgøres.......Med udgangspunkt i John Fords Western, Forfølgeren fra 1956, præsenteres en analyse af repræsentationer af race og overskridelse af raceskel, særligt i relation til konstitueringen af subjektpositioner, hvorfra spørgsmål om hvidhed og ikke-hvidhed kan afgøres....

  12. Udforskning af journalistiske moralnormer

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    2010-01-01

    Kirsten Mogensen beskriver professionelle journalistiske normer. Med udgangspunkt i amerikansk tv's dækning af begivenhederne 11. september kombinerer Kirsten Mogensen kvalitative interviews og tekstanalyse for på den måde at beskrive professionelle journalistiske normer. Metoden er en kombinatio...... af halvstrukturerede, udforskende interviews med både kvantitative og kvalitative analyser af den faktiske dækning, og er primært udledt af Alf Ross' essay om normer og direktiver....

  13. En verden af medier

    DEFF Research Database (Denmark)

    Tække, Jesper

    2009-01-01

    Bogen: 'En verden af medier – Medialiseringen af politik, sprog, religion og leg' anmeldes. Anmeldelsen kan læses på: http://ojs.statsbiblioteket.dk/index.php/mediekultur/article/view/1370/1499 Udgivelsesdato: 2009......Bogen: 'En verden af medier – Medialiseringen af politik, sprog, religion og leg' anmeldes. Anmeldelsen kan læses på: http://ojs.statsbiblioteket.dk/index.php/mediekultur/article/view/1370/1499 Udgivelsesdato: 2009...

  14. Ensretning af historieundervisningen

    DEFF Research Database (Denmark)

    Rønhede, Søren

    2008-01-01

    "Det er ikke kun i Putins Rusland, at statsmagten vil dirigere historieundervisningen." (Politiken havde fokuseret på "ensretning af historieundervisningen" i Rusland) "Kanonen fra 2006 er undfanget af Udvalget til Styrkelse af Historie i Folkeskolen. Dette udvalg havde regeringen nedsat; men bid...... bidrager kanonen til faglig styrkelse?" spørges der. Det vises, at flere kanonpunkter ikke er fagligt funderede, men af mytologisk art....

  15. The HSP90 inhibitor 17-AAG potentiates the antileishmanial activity of the ether lipid edelfosine.

    Science.gov (United States)

    Varela-M, Rubén E; Mollinedo-Gajate, Cristina; Muro, Antonio; Mollinedo, Faustino

    2014-03-01

    HSP90 is an abundant protein in Leishmania parasites that plays a major role in the parasite survival under stress conditions. Here we found that the HSP90 inhibitor 17-AAG (≥100nM 17-AAG) induced cell cycle arrest at G0/G1 in Leishmania infantum and Leishmania panamensis promastigotes, and highly potentiated the induction of cell death by an apoptotic-like process mediated by the ether phospholipid edelfosine (5-20μM). These data suggest that the combined treatment of 17-AAG and edelfosine might be a novel and effective approach of combination therapy in the treatment of leishmaniasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Effect of quercetin and 17-AAG on radiosensitivity of rat peripheral blood lymphocyte

    International Nuclear Information System (INIS)

    Chu Xuegang; Hong Chengjiao; Zhang Baoguo

    2012-01-01

    To investigate the effect of quercetin and 17-AAG on proliferation and on radiosensitivity of blood lymphocyte cells. CCK-8 assay is performed to evaluate the cytotoxicity of Quercetin on proliferation of blood lymphocyte cells. CCK-8 assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). CCK-8 results showed that the inhibition of Quercetin on the cells was the dose-dependent and time-dependent, and the results of assay showed the inhibition of 17-AAG on blood lymphocyte cells was the dose-dependent and time-dependent. The study showed that Quercetin and 17-AAG have no effect on the radiosensitivity of the blood lymphocyte cells. (authors)

  17. Behandling af elmesyge

    DEFF Research Database (Denmark)

    Thomsen, Iben Margrete; Kristoffersen, Palle

    2004-01-01

    Ingen midler er p.t. godkendt og dermed lovlige til bekæmpelse af elmesyge i Danmark. Lovprisning af nye behandlinger ses f.eks. på internettet, men dokumentation mangler. Økonomien og nytten ved en kemisk bekæmpelse frem for sanering af syge træer skal afvejes nøje....

  18. Globalisering af uddannelse

    DEFF Research Database (Denmark)

    Jensen, Henning Høgh

    2005-01-01

    Det globale marked for uddannelse er i voldsom vækst og er ved at blive et af Danmarks vigtigste vareområder. Hvorledes kan KVL agere i globaliseringen af uddannelse for at sikre en høj kvalitet af egne kandidater med gode jobmuligheder?...

  19. Livscyklusvurdering af basiskemikalier

    DEFF Research Database (Denmark)

    Olsen, Stig Irving

    1998-01-01

    Dette resumé af metoder og væsentlige erfaringer fra erhvervsforskerprojektet Livscyklusvurdering af basiskemikalier er skrevet i erkendelse af, at hovedrapporten er for omfattende til en hurtig introduktion i problemstillingerne. Formålet med denne rapport er derfor at give et kort overblik over...

  20. Digital formidling af kulturarv

    DEFF Research Database (Denmark)

    En af tidens store kulturelle dagsordner drejer sig om digital tilgængeliggørelse af kulturarv. Fortidens spor dukker op i nye former på nettet - næsten alle kulturinstitutioner arbejder med, og befolkningen har fået helt nye muligheder for at se med og deltage. Digital formidling af kulturarv...

  1. Af Upraktiske Grunde

    DEFF Research Database (Denmark)

    Vaaben, Nana Katrine

    2001-01-01

    som både Claude Levi-Strauss lægger op til i sine klassiske studier af "den vilde tanke", og som Jean Baudrillard siden har lagt op til i sine analyser af samlere som en slags ekstreme forbrugere, der er i færd med at komplettere deres identitet gennem besiddelser af genstande. Imidlertid tillægger...

  2. [Effects of HSP90 inhibitor 17-AAG on cell cycle and apoptosis of human gastric cancer cell lines SGC-7901].

    Science.gov (United States)

    Chen, Meini; Xu, Jinghong; Zhao, Jumei

    2013-02-01

    To study the effect of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on cell proliferation and apoptosis of human cancer SGC-7901 cells and explore the mechanisms. The inhibitory effect of 17-AAG on the proliferation and morphology of SGC-7901 cells was assessed with MTT assay and DNA-PI staining, respectively. Flow cytometry was employed to analyze the changes in cell cycle and apoptosis of the cells following 17-AAG exposure. The cellular expression of Fas protein was detected by immunohistochemistry. 17-AAG significantly suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. After treatment with 17-AAG for 48 h, SGC-7901 cells showed cell cycle arrested at G(2)/M stage, and the cell apoptosis rate increased with the 17-AAG concentration. The expression of Fas protein in the cytoplasm of SGC-7901 cells increased gradually with the increase of 17-AAG concentration. 17-AAG can induce apoptosis, alters the cell cycle distribution and up-regulates the expression of Fas protein in SGC-7901 cells to suppress the cell proliferation.

  3. HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells.

    Science.gov (United States)

    Rao, Rekha; Fiskus, Warren; Yang, Yonghua; Lee, Pearl; Joshi, Rajeshree; Fernandez, Pravina; Mandawat, Aditya; Atadja, Peter; Bradner, James E; Bhalla, Kapil

    2008-09-01

    Histone deacetylase 6 (HDAC6) is a heat shock protein 90 (hsp90) deacetylase. Treatment with pan-HDAC inhibitors or depletion of HDAC6 by siRNA induces hyperacetylation and inhibits ATP binding and chaperone function of hsp90. Treatment with 17-allylamino-demothoxy geldanamycin (17-AAG) also inhibits ATP binding and chaperone function of hsp90, resulting in polyubiquitylation and proteasomal degradation of hsp90 client proteins. In this study, we determined the effect of hsp90 hyperacetylation on the anti-hsp90 and antileukemia activity of 17-AAG. Hyperacetylation of hsp90 increased its binding to 17-AAG, as well as enhanced 17-AAG-mediated attenuation of ATP and the cochaperone p23 binding to hsp90. Notably, treatment with 17-AAG alone also reduced HDAC6 binding to hsp90 and induced hyperacetylation of hsp90. This promoted the proteasomal degradation of HDAC6. Cotreatment with 17-AAG and siRNA to HDAC6 induced more inhibition of hsp90 chaperone function and depletion of BCR-ABL and c-Raf than treatment with either agent alone. In addition, cotreatment with 17-AAG and tubacin augmented the loss of survival of K562 cells and viability of primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) samples. These findings demonstrate that HDAC6 is an hsp90 client protein and hyperacetylation of hsp90 augments the anti-hsp90 and antileukemia effects of 17-AAG.

  4. Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney.

    Science.gov (United States)

    Ebrahimkhani, Mohammad R; Daneshmand, Ali; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A; Abolhassani, Nona; Jhun, Iny; Muthupalani, Sureshkumar; Ayata, Cenk; Samson, Leona D

    2014-11-11

    Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.

  5. 17-AAG induces cytoplasmic alpha-synuclein aggregate clearance by induction of autophagy.

    Science.gov (United States)

    Riedel, Michael; Goldbaum, Olaf; Schwarz, Lisa; Schmitt, Sebastian; Richter-Landsberg, Christiane

    2010-01-18

    The accumulation and aggregation of alpha-synuclein in nerve cells and glia are characteristic features of a number of neurodegenerative diseases termed synucleinopathies. alpha-Synuclein is a highly soluble protein which in a nucleation dependent process is capable of self-aggregation. The causes underlying aggregate formation are not yet understood, impairment of the proteolytic degradation systems might be involved. In the present study the possible aggregate clearing effects of the geldanamycin analogue 17-AAG (17-(Allylamino)-17-demethoxygeldanamycin) was investigated. Towards this, an oligodendroglial cell line (OLN-93 cells), stably expressing human alpha-synuclein (A53T mutation) was used. In these cells small punctate aggregates, not staining with thioflavine S, representing prefibrillary aggregates, occur characteristically. Our data demonstrate that 17-AAG attenuated the formation of alpha-synuclein aggregates by stimulating macroautophagy. By blocking the lysosomal compartment with NH(4)Cl the aggregate clearing effects of 17-AAG were abolished and alpha-synuclein deposits were enlarged. Analysis of LC3-II immunoreactivity, which is an indicator of autophagosome formation, further revealed that 17-AAG led to the recruitment of LC3-II and to the formation of LC3 positive puncta. This effect was also observed in cultured oligodendrocytes derived from the brains of newborn rats. Inhibition of macroautophagy by 3-methyladenine prevented 17-AAG induced occurrence of LC3 positive puncta as well as the removal of alpha-synuclein aggregates in OLN-A53T cells. Our data demonstrate for the first time that 17-AAG not only causes the upregulation of heat shock proteins, but also is an effective inducer of the autophagic pathway by which alpha-synuclein can be removed. Hence geldanamycin derivatives may provide a means to modulate autophagy in neural cells, thereby ameliorating pathogenic aggregate formation and protecting the cells during disease and aging.

  6. In vivo repair of methylation damage in Aag 3-methyladenine DNA glycosylase null mouse cells

    OpenAIRE

    Smith, Stephen A.; Engelward, Bevin P.

    2000-01-01

    3-Methyladenine (3MeA) DNA glycosylases initiate base excision repair by removing 3MeA. These glycosylases also remove a broad spectrum of spontaneous and environmentally induced base lesions in vitro. Mouse cells lacking the Aag 3MeA DNA glycosylase (also known as the Mpg, APNG or ANPG DNA glycosylase) are susceptible to 3MeA-induced S phase arrest, chromosome aberrations and apoptosis, but it is not known if Aag is solely responsible for repair of 3MeA in vivo. Here we show that in Aag–/– c...

  7. Seronegative and seropositive autoimmune autonomic ganglionopathy (AAG): Same clinical picture, same response to immunotherapy.

    Science.gov (United States)

    Tijero, Beatriz; Del Pino, Rocio; Pérez-Concha, Tomás; Acera, Maria Angeles; Gabilondo, Iñigo; Berganzo, Koldo; Graus, Frances; Martinez-Alday, Jesus Daniel; Barcena, Joseba; Gómez-Esteban, Juan Carlos

    2018-06-15

    Two patients with a syndrome of pandisautonomia with clinical criteria of AAG are provided. Both patients present a similar clinical picture and response to immunosuppressive treatment. One of them has positive antibodies against the ganglionic nicotinic acetylcholine (gAChr) and the other does not. This brief article serves to reflect the spectrum of AAG, at a clinical level, in laboratory tests and in the response to immunotherapy, independently of the presence of positive gAChr antibodies. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Multiple kinase pathways involved in the different de novo sensitivity of pancreatic cancer cell lines to 17-AAG.

    Science.gov (United States)

    Liu, Heping; Zhang, Ti; Chen, Rong; McConkey, David J; Ward, John F; Curley, Steven A

    2012-07-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG) specifically targets heat shock protein (HSP)90 and inhibits its chaperoning functions for multiple kinases involved in cancer cell growth and survival. To select responsive patients, the molecular mechanisms underlying the sensitivity of cancer cells to 17-AAG must be elucidated. We used cytotoxicity assays and Western blotting to explore the effects of 17-AAG and sorafenib on cell survival and expression of multiple kinases in the pancreatic cancer cell lines AsPC-1 and Panc-1. Gene cloning and transfection, siRNA silencing, and immunohistochemistry were used to evaluate the effects of mutant p53 protein on 17-AAG sensitivity. AsPC-1 and Panc-1 responded differently to 17-AAG, with half maximal inhibitory concentration (IC(50)) values of 0.12 and 3.18 μM, respectively. Comparable expression of HSP90, HSP70, and HSP27 was induced by 17-AAG in AsPC-1 and Panc-1 cells. P-glycoprotein and mutant p53 did not affect 17-AAG sensitivity in these cell lines. Multiple kinases are more sensitive to HSP90 inhibition in AsPC-1 than in Panc-1 cells. After 17-AAG treatment, p-Bad (S112) decreased in AsPC-1 cells and increased in Panc-1 cells. Sorafenib markedly increased p-Akt, p-ERK1/2, p-GSK-3β, and p-S6 in both cell lines. Accordingly, 17-AAG and sorafenib acted antagonistically in AsPC-1 and Panc-1 cells, except at high concentrations in AsPC-1 cells. Differential inhibition of multiple kinases is responsible for the different de novo sensitivity of AsPC-1 and Panc-1 cells to HSP90 inhibition. P-glycoprotein and mutant p53 protein did not play a role in the sensitivity of pancreatic cancer cells to 17-AAG. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Optimering af model for spredning af luftforurening

    DEFF Research Database (Denmark)

    Pedersen, Jens Christian

    2008-01-01

    De nuværende luftforureningsmodeller har problemer med at bevare massen af diverse kemiske stoffer og med at der ind i mellem optræder negative værdier. Derfor arbejder specialestuderende Ayoe Buus Hansen på om at forbedre den model DMU bruger til at beskrive transport og spredning af luftforuren...... luftforurening på alle skalaer på den nordlige halvkugle ved at sammenligne tre alternative beregningsmodeller. ...

  10. The AAG Resource Paper Series Should Narrow Its Focus and Broaden Its Audience.

    Science.gov (United States)

    Bell, Thomas L.

    1986-01-01

    Reviews the goals and content of the Association of American Geographers' (AAG) Resource Paper Series which began publication in 1968. Catalogs the titles and content of issues which have sold well and recommends that the series be targeted toward a pedagogical focus on a variety of topics. (JDH)

  11. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.

    NARCIS (Netherlands)

    B.P. Engelward (Bevin); G. Weeda (Geert); M.D. Wyatt; J.L.M. Broekhof (Jose'); J. de Wit (Jan); I. Donker (Ingrid); J.M. Allan (James); B. Gold (Bert); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

    1997-01-01

    textabstract3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA

  12. DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis.

    Science.gov (United States)

    Fahrer, Jörg; Frisch, Janina; Nagel, Georg; Kraus, Alexander; Dörsam, Bastian; Thomas, Adam D; Reißig, Sonja; Waisman, Ari; Kaina, Bernd

    2015-10-01

    Epidemiological studies indicate that N-nitroso compounds (NOC) are causally linked to colorectal cancer (CRC). NOC induce DNA alkylations, including O (6)-methylguanine (O (6)-MeG) and N-methylated purines, which are repaired by O (6)-MeG-DNA methyltransferase (MGMT) and N-alkyladenine-DNA glycosylase (AAG)-initiated base excision repair, respectively. In view of recent evidence of nonlinear mutagenicity for NOC-like compounds, the question arises as to the existence of threshold doses in CRC formation. Here, we set out to determine the impact of DNA repair on the dose-response of alkylation-induced CRC. DNA repair proficient (WT) and deficient (Mgmt (-/-), Aag (-/-) and Mgmt (-/-)/Aag (-/-)) mice were treated with azoxymethane (AOM) and dextran sodium sulfate to trigger CRC. Tumors were quantified by non-invasive mini-endoscopy. A non-linear increase in CRC formation was observed in WT and Aag (-/-) mice. In contrast, a linear dose-dependent increase in tumor frequency was found in Mgmt (-/-) and Mgmt (-/-)/Aag (-/-) mice. The data were corroborated by hockey stick modeling, yielding similar carcinogenic thresholds for WT and Aag (-/-) and no threshold for MGMT lacking mice. O (6)-MeG levels and depletion of MGMT correlated well with the observed dose-response in CRC formation. AOM induced dose-dependently DNA double-strand breaks in colon crypts including Lgr5-positive colon stem cells, which coincided with ATR-Chk1-p53 signaling. Intriguingly, Mgmt (-/-) mice displayed significantly enhanced levels of γ-H2AX, suggesting the usefulness of γ-H2AX as an early genotoxicity marker in the colorectum. This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. ARCgame - gamification af undervisning

    DEFF Research Database (Denmark)

    Jensen, Camilla Gyldendahl

    2014-01-01

    Gamification er et begreb, der anvendes til at beskrive brugen af spilelementer i andre miljøer for at forbedre brugernes oplevelse. Følgende tekst har til formål at behandle emnet i forhold til af opnå en forståelse for de elementer der indvirker på en ”gamification af et undervisningsforløb”, her...

  14. Hvad griner du af?

    DEFF Research Database (Denmark)

    Lorenzen, Tobias Hiort

    2012-01-01

    latterliggørelse indenfor en sådan teori. Sociologiens begreb om ”un-laughter” angives som en mulig udvej af dette problem. I forlængelse af dette kritiseres den moderne humor-psykologis lære om populationers humor-patologi og til slut argumenteres der for at en moderne dannelse af humor må have en moralsk...

  15. Ledelse af projektmyldret

    DEFF Research Database (Denmark)

    større arbejdsgrupper, og det kan være selvorganiserede store udviklingsprogrammer. Et projekt kører sjældent alene, og derfor er der ikke kun tale om projektledelse, men i lige så høj grad om ledelse af projekter. Ledelse af virksomhedens mylder af projekter er ikke let, og forfatterne gennemgår derfor...

  16. Strategisk ledelse af evalueringskulturen

    Directory of Open Access Journals (Sweden)

    Gitte Orlowitz

    2016-02-01

    Full Text Available Hvis evaluering skal anvendes til at udvikle uddannelser, er en af ledelsen vigtigste opgaver at udvikle en strategi for udvikling af evalueringskulturen – herunder strategier for udvikling af kommunikation og evalueringskapacitet. Den strategiske ledelse kan i den sammenhæng anvendes til at håndtere de ofte modsatte krav, som eksterne og interne interessenter stiller til evaluering.

  17. [Effects of 17-AAG on the proliferation and apoptosis of human lung cancer A549 and H446 cells].

    Science.gov (United States)

    Niu, Ben; Lin, Jingshuang; Feng, Tao

    2015-04-01

    To observe the effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) on the apoptosis of human lung cancer cell lines A549 and H446, and to investigate the potential mechanisms. Proliferation inhibition and apoptosis assays, and the cell cycles were detected by MTT and flow cytometry respectively. Western blot was used to determine the expression level of proteins such as Hsp90, Hsp70, AKt, Her-2, Bcl-2 and Bax. After treated with 17-AAG, the proliferation of both A549 and H446 cells was inhibited significantly in a dose-dependent manner; as the concentration of 17-AAG was from 50 to 500 nmol/L, the IC₅₀ values to A549 and H446 cell lines were (222 ± 13) nmol/L and (189 ± 7) nmol/L respectively at 48 h. Cell cycle assays showed that 17-AAG was able to arrest cell cycles of A549 and H446 cell lines at the G₂/M phase. Apoptosis assay showed that 17-AAG was capable of inducing apoptosis in A549 and H446 cell lines. After treated with 17-AAG for 48 h, there were significant differences between the 400 nmol/L groups(46.3% for A549 cell line and 56.9% for H446 cell line) and the control group (11.9% for A549 cell line and 6.9% for H446 cell line, P AAG treatment: Akt and Her-2 decreased significantly while the expression of Hsp70 increased. Meanwhile, the expression of Bcl-2 decreased but that of Bax increased, indicating that 17-AAG was able to promote apoptosis mode in A549 and H446 cells. 17-AAG can regulate the expression level of apoptosis-related proteins such as Bax and Bcl-2 by Hsp90 signaling pathway in A549 and H446 cells, and ultimately inhibit cell proliferation and induce apoptosis.

  18. Parp1 protects against Aag-dependent alkylation-induced nephrotoxicity in a sex-dependent manner.

    Science.gov (United States)

    Calvo, Jennifer A; Allocca, Mariacarmela; Fake, Kimberly R; Muthupalani, Sureshkumar; Corrigan, Joshua J; Bronson, Roderick T; Samson, Leona D

    2016-07-19

    Nephrotoxicity is a common toxic side-effect of chemotherapeutic alkylating agents. Although the base excision repair (BER) pathway is essential in repairing DNA alkylation damage, under certain conditions the initiation of BER produces toxic repair intermediates that damage healthy tissues. We have shown that the alkyladenine DNA glycosylase, Aag (a.k.a. Mpg), an enzyme that initiates BER, mediates alkylation-induced whole-animal lethality and cytotoxicity in the pancreas, spleen, retina, and cerebellum, but not in the kidney. Cytotoxicity in both wild-type and Aag-transgenic mice (AagTg) was abrogated in the absence of Poly(ADP-ribose) polymerase-1 (Parp1). Here we report that Parp1-deficient mice expressing increased Aag (AagTg/Parp1-/-) develop sex-dependent kidney failure upon exposure to the alkylating agent, methyl methanesulfonate (MMS), and suffer increased whole-animal lethality compared to AagTg and wild-type mice. Macroscopic, histological, electron microscopic and immunohistochemical analyses revealed morphological kidney damage including dilated tubules, proteinaceous casts, vacuolation, collapse of the glomerular tuft, and deterioration of podocyte structure. Moreover, mice exhibited clinical signs of kidney disease indicating functional damage, including elevated blood nitrogen urea and creatinine, hypoproteinemia and proteinuria. Pharmacological Parp inhibition in AagTg mice also resulted in sensitivity to MMS-induced nephrotoxicity. These findings provide in vivo evidence that Parp1 modulates Aag-dependent MMS-induced nephrotoxicity in a sex-dependent manner and highlight the critical roles that Aag-initiated BER and Parp1 may play in determining the side-effects of chemotherapeutic alkylating agents.

  19. A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma.

    Science.gov (United States)

    Pacey, Simon; Gore, Martin; Chao, David; Banerji, Udai; Larkin, James; Sarker, Sarah; Owen, Karen; Asad, Yasmin; Raynaud, Florence; Walton, Mike; Judson, Ian; Workman, Paul; Eisen, Tim

    2012-02-01

    A Phase II study to screen for anti-melanoma activity of the heat shock protein 90 (HSP90) inhibitor, 17-AAG (17-allylamino-17-demethoxygeldanamycin) was performed. The primary endpoint was the rate of disease stabilisation in patients with progressive, metastatic melanoma treated with 17-AAG. Secondary endpoints were to determine: the toxicity of 17-AAG, the duration of response(s), median survival and further study the pharmacokinetics and pharmacodynamics of 17-AAG. Patients with metastatic melanoma (progressive disease documented ≤6 months of entering study) were treated with weekly, intravenous 17-AAG. A Simon one sample two stage minimax design was used. A stable disease rate of ≥25% at 6 months was considered compatible with 17-AAG having activity. Fourteen patients (8 male: 6 female) were entered, eleven received 17-AAG (performance status 0 or 1). Median age was 60 (range 29-81) years. The majority (93%) received prior chemotherapy and had stage M1c disease (71%). Toxicity was rarely ≥ Grade 2 in severity and commonly included fatigue, headache and gastrointestinal disturbances. One of eleven patients treated with 17-AAG had stable disease for 6 months and median survival for all patients was 173 days. The study was closed prematurely prior to completion of the first stage of recruitment and limited planned pharmacokinetic and pharmacodynamic analyses. Some evidence of 17-AAG activity was observed although early study termination meant study endpoints were not reached. Stable disease rates can be incorporated into trials screening for anti-melanoma activity and further study of HSP90 inhibitors in melanoma should be considered.

  20. Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG

    International Nuclear Information System (INIS)

    Hadley, Katie E; Hendricks, Denver T

    2014-01-01

    Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status. We used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP. Expression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels. Since NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages

  1. Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG.

    Science.gov (United States)

    Hadley, Katie E; Hendricks, Denver T

    2014-05-15

    Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status. We used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP. Expression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels. Since NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages.

  2. Ledelse af Organisationens Kreativitet

    DEFF Research Database (Denmark)

    Hedemann, Lars

    2008-01-01

    forskel, så er man som leder nødt til at arbejde mere målrettet med de medarbejdere som forventes at præstere et kreativt udbytte. Inspireret af analyseværktøjet "KEYS, Assessing the Work Environment for Creativity" udviklet af den amerikanske psykolog og ledelsesforsker ved Harvard University, Teresa...... Amabile, blev en undersøgelse derfor gennemført i udviklingsafdelingerne, Idéland og Idélab hos Bang og Olufsen, for at få et indblik i anvendeligheden af KEYS som inspirationskilde for succesfuld ledelse af organisationens kreativitet....

  3. Coaching af dit studieliv

    DEFF Research Database (Denmark)

    Hansen, Rasmus Thorning

    2008-01-01

    En generel beskrivelse af de problemer specialestuderende sidder med og hvorledes coaching kan hjælpe med at (gen)skabe motivation og fokus......En generel beskrivelse af de problemer specialestuderende sidder med og hvorledes coaching kan hjælpe med at (gen)skabe motivation og fokus...

  4. Dialektisk billede af Benjamin

    DEFF Research Database (Denmark)

    Bøggild, Jacob

    2004-01-01

    Anmeldelse af Lars Brückner: "Løse blade. Læseren, kritikeren og fortælleren Walter Benjamin"......Anmeldelse af Lars Brückner: "Løse blade. Læseren, kritikeren og fortælleren Walter Benjamin"...

  5. Administration af informationsmodeller

    DEFF Research Database (Denmark)

    Hundebøl, Jesper

    2013-01-01

    En informationsmodel er i denne sammenhæng en digital repræsentation af et givent byggeri. Både offentlige og private bygherrer anvender informationsmodeller, når der 'bygges digitalt'. I denne artikel undersøges det, hvilke konkrete udfordringer der følger af digitaliseringen, hvor gennemgribend...

  6. Raman af hvide pigmenter

    DEFF Research Database (Denmark)

    Reeler, Nini Elisabeth Abildgaard; Nielsen, Ole Faurskov; Sauer, Stephan P. A.

    2013-01-01

    Et samspil mellem kunst og kemi. I et samarbejde mellem Statens Museum for Kunst og Kemisk Institut på KU er Ramanspek-troskopi brugt til at definere sammensætningen af blandinger af blyhvidt og calcit i maleriers hvide pigmenter....

  7. Midtvejsevaluering af EGA handlingsplanen

    DEFF Research Database (Denmark)

    Møller, Niels; Hasle, Peter; Christiansen, Jørgen Møller

    Center for Alternativ Samfundsanalyse (CASA) og Institut for Teknologi og Samfund ved Danmarks Tekniske Universitet har gennemført denne midtvejsevaluering af arbejdsmarkedets parters handlingsplan mod reduktion af ensidigt gentaget arbejde. Undersøgelsen viser, at der er sket en betydelig...

  8. Anvendelse af genmodificerede planter

    DEFF Research Database (Denmark)

    Møller, F.

    I rapporten vurderes mulighederne for at gennemføre velfærdsøkonomiske analyser af anvendelsen af genmodificerede planter. Der gøres rede for kravene til konse-kvensbeskrivelsen og for mulighederne for at prissætte såvel de markedsrelaterede som de ikke-markedsrelaterede konsekvenser. Mulighederne...

  9. Kvalitetsvurdering af sundhedsoplysende materiale

    DEFF Research Database (Denmark)

    Osler, Merete; Bech, Lars; Sybille, Bojlén

    1990-01-01

    Lægeforeningens Hygiejnekomités arbejdsgruppe vedrørende sundhedsoplysning har udarbejdet en "huskeliste" til brug for en kvalitetsvurdering af skriftligt sundhedsoplysende materiale......Lægeforeningens Hygiejnekomités arbejdsgruppe vedrørende sundhedsoplysning har udarbejdet en "huskeliste" til brug for en kvalitetsvurdering af skriftligt sundhedsoplysende materiale...

  10. Implementering af evidensbaseret praksis

    DEFF Research Database (Denmark)

    Scheel, Linda Schumann; Tewes, Marianne; Petersen, Preben Ulrich

    2015-01-01

    Projektet omhandler implementering af den kliniske retningslinje om identifikation, forebyggelse og behandling af delirium – i denne sammenhæng relateret til hjertepatienter. Projektet foregår på to hospitaler i Hjertecentret på Rigshospitalet, et intensivt afsnit og et sengeafsnit, i tæt...

  11. Implementering af evidensbaseret praksis

    DEFF Research Database (Denmark)

    Scheel, Linda Schumann; Hansen, Ida Rode

    2014-01-01

    Projektet omhandler implementering af den kliniske retningslinje om identifikation, forebyggelse og behandling af delirium – i denne sammenhæng relateret til hjertepatienter. Projektet foregår på to hospitaler i Hjertecentret på Rigshospitalet, et intensivt afsnit og et sengeafsnit, i tæt...

  12. Fundering af mindre bygninger

    DEFF Research Database (Denmark)

    Larsen, J.; Ballisager, C.C.

    Denne SBI-anvisning indeholder en gennemgang af de jordbunds- og grundvandsforhold, som er bestemmende for funderingen af en bygning. Specielt gennemgås de betingelser, der skal være opfyldt, for at man på forsvarlig måde kan fundere en mindre bygning i traditionel udformning. Publikationen...

  13. Evaluering af afdeling H

    DEFF Research Database (Denmark)

    Kjær Minke, Linda; Birkmose, Sofie Meldal

    2016-01-01

    Som led i Kriminalforsorgens flerårsaftale 2013-2016 blev det åbne statsfængsel Søbysøgård i januar 2015 udvidet med 42 lukkede pladser i den nybyggede afdeling H. Nærværende evaluering kortlægger de erfaringer personalet og indsatte har gjort sig i løbet af det første år. Etableringen af den...... lukkede fængselsafdeling H giver en unik mulighed for at følge henholdsvis hvilke faktorer, der bidrager til udvikling af fængselskultur, og hvordan de respektive faktorer influerer på udvikling af fængselskulturen. Evalueringens metoder består af kvalitative og kvantitative metoder såsom dokumentanalyse...

  14. The effect of 17-AAG on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer

    International Nuclear Information System (INIS)

    Wang Renfei; Tan Jian; Li Wei; Meng Zhaowei; Zheng Wei

    2012-01-01

    Objective: To investigate the effect of 17-allylamino-17-demethoxy geldanamycin (17-AAG) on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer (ATC) cells. Methods: Lipofection was used to transfect the recombinant plasmid, namely pcDNA3.1-NIS, into FRO cells (ATC cell line). A stable cell line NIS-FRO was obtained by G418 resistance selection. 125 I was added into the medium, and influx and efflux experiments were performed. Different time-radioactivity curves were drawn, and further analysis was performed between the non-transfected cells (the control group) and NIS-FRO cells treated with 1 μmol/L 17-AAG for 24 h. Student's t-test was used to analyze the data. Results: The iodine uptake ability of the NIS-FRO cells was significantly higher than that of the FRO cells (about 10.68 times, t=45.329, P<0.001). However, 125 I out-flowed rapidly when removed from the medium, and the retention rate of 125 I in the NIS-FRO cells was only 10.5% of the initial amount after 30 rin. After treatment with 1 μmol/L 17-AAG for 24 h, the 125 I uptake ability of NIS-FRO cells further increased. During the 20-60 min incubation with 125 I, the iodine uptake ability of 17-AAG treated NIS-FRO cells increased significantly with radioactive counts of 31771.8- 54815.5 per minute,which was much higher than that of the control group (24020.3-41293.8 per minute; t=3.096, 4.275, 3.055, 4.292 and 5.496, respectively, all P<0.05). The iodine uptake ability increased about 24.8%-35.5%. Furthermore, 5-30 min after removing the medium, the retention rates of 125 I in the 17-AAG treated NIS-FRO cells were significantly increased compared with those of the control group (32.7%-85.2% vs 10.5%-56.8%; t=22.801, 13.096, 19.631, 38.205, 43.519, 29.322, respectively, all P<0.01), and 125 I efflux was reduced. After 30 min, 125 I retention rate of the treatment group was 32.7%, which was 3.1 times higher than that of the control group. Conclusion: The iodine uptake ability can be

  15. Targeting Hsp90 by 17-AAG in leukemia cells: mechanisms for synergistic and antagonistic drug combinations with arsenic trioxide and Ara-C.

    Science.gov (United States)

    Pelicano, H; Carew, J S; McQueen, T J; Andreeff, M; Plunkett, W; Keating, M J; Huang, P

    2006-04-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a new anticancer agent currently in clinical trials. The ability of 17-AAG to abrogate the function of heat-shock protein Hsp90 and modulate cellular sensitivity to anticancer agents has prompted recent research to use this compound in drug combination therapy. Here we report that 17-AAG has striking opposite effects on the activity of arsenic trioxide (ATO) and ara-C. Combination of 17-AAG with ATO exhibited a synergistic effect in leukemia cells, whereas coincubation of 17-AAG and ara-C showed antagonistic activity. Mechanistic studies revealed that ATO exerted cytotoxic action by reactive oxygen species generation, and activated Akt survival pathway. 17-AAG abrogated Akt activation and enhanced the activity of ATO. In contrast, treatment of leukemia cells with 17-AAG caused a G1 arrest, a decrease in DNA synthesis and reduced ara-C incorporation into DNA, leading to antagonism. The ability of 17-AAG to enhance the antileukemia activity of ATO was further demonstrated in primary leukemia cells isolated from patients with acute myeloid leukemia and chronic lymphocytic leukemia, including cells from refractory patients. Our data suggest that combination of 17-AAG and ATO may be an effective therapeutic regimen. Caution should be exercised in using 17-AAG together with ara-C, as their combination effects are schedule dependent.

  16. Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB)

    OpenAIRE

    van Loon, Barbara; Samson, Leona D.

    2013-01-01

    Due to a harsh environment mitochondrial genomes accumulate high levels of DNA damage, in particular oxidation, hydrolytic deamination, and alkylation adducts. While repair of alkylated bases in nuclear DNA has been explored in detail, much less is known about the repair of DNA alkylation damage in mitochondria. Alkyladenine DNA glycosylase (AAG) recognizes and removes numerous alkylated bases, but to date AAG has only been detected in the nucleus, even though mammalian mitochondria are known...

  17. Sundhedseffekter af luftforurening-beregningspriser

    DEFF Research Database (Denmark)

    Andersen, M. S.; Frohn, L. M.; Jensen, S. S.

    Denne rapport afrapporterer det fortsatte arbejde med udvikling af miljøøkonomiske beregningspriser. På grundlag af EcoSense 4.0 fra ExternE-projektet, er der foretaget nye beregninger af eksternaliteter ved luftforurening med sundhedseffekter. Samtidig giver rapporten en vurdering af luftspredni......Denne rapport afrapporterer det fortsatte arbejde med udvikling af miljøøkonomiske beregningspriser. På grundlag af EcoSense 4.0 fra ExternE-projektet, er der foretaget nye beregninger af eksternaliteter ved luftforurening med sundhedseffekter. Samtidig giver rapporten en vurdering af...

  18. NAD(P)H:Quinone Oxidoreductase-1 Expression Sensitizes Malignant Melanoma Cells to the HSP90 Inhibitor 17-AAG.

    Science.gov (United States)

    Kasai, Shuya; Arakawa, Nobuyuki; Okubo, Ayaka; Shigeeda, Wataru; Yasuhira, Shinji; Masuda, Tomoyuki; Akasaka, Toshihide; Shibazaki, Masahiko; Maesawa, Chihaya

    2016-01-01

    The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional induction of genes associated with antioxidant synthesis and detoxification in response to oxidative stress. Previously, we reported that KEAP1 mutation elicits constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine (DTIC) in human melanomas. The present study was conducted to clarify whether an HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma and non-small cell lung carcinoma cell lines with or without KEAP1 mutations, NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines despite the presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2 activation. Because either CDDP or DTIC produces reactive oxygen species that activate NRF2, we determined whether these agents would sensitize NQO1-low melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP combination was detected in four out of five NQO1-low cell lines, but not in the cell line with KEAP1 mutation. These data indicate that 17-AAG could be a potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1 expression.

  19. [Inhibitory effect of 17-AAG combined with paclitaxel on proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro].

    Science.gov (United States)

    Chen, Size; Chen, Xuemei; Li, Yuqi; Yang, Shu; Mo, Xianyi; Zhang, Fan; Mo, Kailan; Ding, Ying

    2015-06-01

    To investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro. Eca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry. Compared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5 µmol/L PTX and 0.625 µmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (PAAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone. 17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.

  20. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer's disease.

    Science.gov (United States)

    Ho, Shuk Wai; Tsui, Yuk Tung Chanel; Wong, Ting Ting; Cheung, Stanley Kwok-Kuen; Goggins, William B; Yi, Lau Ming; Cheng, Kwok Kin; Baum, Larry

    2013-12-17

    Alzheimer's disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

  1. Synergistic effects of rmhTRAIL and 17-AAG on the proliferation and apoptosis of multiple myeloma cells.

    Science.gov (United States)

    Wang, Jing; Li, Yun; Sun, Wei; Liu, Jing; Chen, Wenming

    2018-03-22

    This study aimed to investigate synergistic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 -allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and apoptosis of multiple myeloma (MM) cells. MTT assays evaluated inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and treatment durations on the proliferation of RPMI8226 and U266 cells. The half maximal inhibitory concentration was calculated using OriginPro7.5. Synergistic effects of rmhTRAIL and 17-AAG on apoptosis of MM cells were detected using flow cytometry at 24 and 48 h post-treatment. To evaluate synergistic effects of rmhTRAIL and 17-AAG, the Q-value was calculated using King's formula. rmhTRAIL exhibited significant inhibitory effects on the proliferation of RPMI8226 cells in a dose- and time-dependent manner (>50%), whereas U266 cells were not sensitive to rmhTRAIL (80%). Significant synergistic effects of rmhTRAIL and 17-AAG on the proliferation of RPMI8226 cells were revealed (Q-value > 1.15), whereas synergistic effects were not evident on the proliferation of U266 cells (Q-value effects on apoptosis of RPMI8226 and U266 cells (Q-value > 1.15). The combined application of rmhTRAIL and 17-AAG revealed favorable synergistic effects in the treatment of MM.

  2. Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric nanoparticles for breast cancer.

    Science.gov (United States)

    Saxena, Vipin; Naguib, Youssef; Hussain, M Delwar

    2012-06-01

    Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino-17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90 (HSP90). Folate targeted polylactide-co-glycolide-polyethylene glycol-folic acid (PLGA-PEG-FA) nanoparticles containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded folate targeted nanoparticles was 238.67±3.52 nm, drug loading was 8.25±2.49% and about 80% of drug was released from the nanoparticles over 10 days. Cellular uptake studies showed much higher intracellular uptake of folate targeted nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed 2 fold increase (PAAG loaded PLGA-PEG-FA nanoparticles might be developed as a targeted delivery system for breast and other cancer treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Effects of salinomycin and 17-AAG on proliferation of human gastric cancer cells in vitro

    Science.gov (United States)

    Zhang, Zuwen; Zhao, Jumei; Mi, Zhikuan; Pang, Qiuxia; Wang, Aihong; Chen, Meini; Liu, Xiaobin; Wei, Xiaoli; Liu, Tao

    2017-01-01

    The aim of the present study was to investigate the effects and mechanisms of 17-AAG combined with salinomycin treatment on proliferation and apoptosis of the SGC-7901 gastric cancer cell line. An MTT assay was used to detect the proliferation of SGC-7901 cells. Morphological alterations of cells were observed under inverted phase-contrast and fluorescence microscopes. Cell cycle and apoptosis were assessed by flow cytometry analysis. The protein expression of nuclear factor (NF)-κB p65 and Fas-ligand (L) were evaluated by immunocytochemistry. Salinomycin with a concentration range of 1–32 µmol/l was demonstrated to inhibit growth of SGC-7901 cells effectively, affect the morphology and apoptosis rate of cells, and arrest SGC-7901 cells in S phase. Furthermore, salinomycin significantly increased the protein expression of Fas-L and decreased the protein expression of NF-κB p65. The alterations in SGC-7901 cells co-treated with salinomycin and 17-AAG were more significant compared with cells treated with one drug only. In conclusion, the individual use of salinomycin and combined use with 17-AAG may significantly inhibit SGC-7901 gastric cancer cell proliferation and induce cell apoptosis. The potential mechanisms may be associated with upregulation of Fas-L and downregulation of NF-κB. These results provide a basis for the potential use of salinomycin in gastric cancer treatment. PMID:28627587

  4. 17-AAG and Apoptosis, Autophagy, and Mitophagy in Canine Osteosarcoma Cell Lines.

    Science.gov (United States)

    Massimini, M; Palmieri, C; De Maria, R; Romanucci, M; Malatesta, D; De Martinis, M; Maniscalco, L; Ciccarelli, A; Ginaldi, L; Buracco, P; Bongiovanni, L; Della Salda, L

    2017-05-01

    Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 μM, 1 μM) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy, and mitophagy were assessed by transmission electron microscopy, flow cytometry, and immunofluorescence. A simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

  5. På sporet af innovation

    DEFF Research Database (Denmark)

    Strandgaard, Lone Bak

    organisationen blandt ledere og medarbejdere samt eksternt, uden for organisationen, hos dens kunder. Ph.d.-afhandlingen På sporet af innovation har som formål at bidrage til forståelse af, hvordan organisationers arbejde med digital selvbetjening kan fremmes, set i et innovationsteoretisk perspektiv. Foruden en...... indføring i innovationsteorien og dens udvikling belyser afhandlingens resultater hvordan at innovationspotentialet kan styrkes gennem organisatorisk åbenhed og samarbejde i alle dele af den innovative proces. Dette gælder ved både idéudvikling, realisering og spredning af nye digitale løsninger.......Flere og flere private og offentlige servicer digitaliseres, så kunder, borgere og virksomheder, i øget grad betjener sig selv. Digital selvbetjening kan potentielt effektivisere driften og skabe bedre kundeservice. Men processen har udfordringer, da den kan kræve omfattende omstilling internt i...

  6. Test af Software

    DEFF Research Database (Denmark)

    Dette dokument udgør slutrapporten for netværkssamarbejdet ”Testnet”, som er udført i perioden 1.4.2006 til 31.12.2008. Netværket beskæftiger sig navnlig med emner inden for test af indlejret og teknisk software, men et antal eksempler på problemstillinger og løsninger forbundet med test af...... administrativ software indgår også. Rapporten er opdelt i følgende 3 dele: Overblik. Her giver vi et resumé af netværkets formål, aktiviteter og resultater. State of the art af software test ridses op. Vi omtaler, at CISS og netværket tager nye tiltag. Netværket. Formål, deltagere og behandlede emner på ti...

  7. Supervision af psykoterapi

    DEFF Research Database (Denmark)

    SUPERVISION AF PSYKOTERAPI indtager en central position i uddannelsen og udviklingen af psykoterapeuter. Trods flere lighedspunkter med psykoterapi, undervisning og konsultation er psykoterapisupervision et selvstændigt virksomhedsområde. Supervisor må foruden at være en trænet psykoterapeut kende...... supervisionens rammer og indplacering i forhold til organisation og samfund. En række kapitler drejer sig om supervisors opgaver, roller og kontrolfunktion, supervision set fra supervisandens perspektiv samt betragtninger over relationer og processer i supervision. Der drøftes fordele og ulemper ved de...... forskellige måder, hvorpå en sag kan fremlægges. Bogens første del afsluttes med refleksioner over de etiske aspekter ved psykoterapisupervision. Bogens anden del handler om de særlige forhold, der gør sig gældende ved supervision af en række specialiserede behandlingsformer eller af psykoterapi med bestemte...

  8. Sammenligning af kvaliteten af kommunernes sagsbehandling

    DEFF Research Database (Denmark)

    Rasmussen, Martin

    flere forskellige spørgsmål fra praksis¬undersøgelser i samme sammenligning. Vi foreslår også, at metoder til såkaldte ’multi¬ple sammenligninger’ bruges til dele af undersøgelserne. Det er en ældre og ikke særlig kendt metode, men den er særdeles relevant både i den konkrete anvendelse og i andre...

  9. Effekten af absolut kumulation

    DEFF Research Database (Denmark)

    Kyvsgaard, Britta; Klement, Christian

    2012-01-01

    Som led i finansloven for 2011 blev regeringen og forligspartierne enige om at undersøge reglerne om strafudmåling ved samtidig pådømmelse af flere kriminelle forhold og i forbindelse hermed vurdere konsekvenserne af at ændre de gældende regler i forhold til kapacitetsbehovet i Kriminalforsorgens...... samlet bødesum ved en absolut kumulation i forhold til en modereret kumulation, som nu er gældende....

  10. Genlyden af et nej

    DEFF Research Database (Denmark)

    Östman, Lars

    2011-01-01

    Europa og den vestlige verden er ramt af en økonomisk krise. Det er en krise, der er anderledes, end den vi har været vant til fx fra 1980'erne.......Europa og den vestlige verden er ramt af en økonomisk krise. Det er en krise, der er anderledes, end den vi har været vant til fx fra 1980'erne....

  11. Evaluering af kollegial supervision

    DEFF Research Database (Denmark)

    Petersen, Anne Line Bjerre Folsgaard; Bager, Lene Tortzen; Jørgensen, Mette Eg

    2015-01-01

    Videoen er en evaluering af arbejdet med en metodisk tilgang til kollegial supervision på VIA Ergoterapeutuddannelsen gennem et par år. Evalueringen sætter fokus på selve metoden, der er anvendt til kollegial supervision. Derudover er der fokus på erfaringer og udbytte af at arbejde systematisk med...... kollegial supervision blandt undervisere på VIA Ergoterapeutuddannelsen....

  12. Structural basis for the inhibition of human alkyladenine DNA glycosylase (AAG) by 3,N4-ethenocytosine-containing DNA.

    Science.gov (United States)

    Lingaraju, Gondichatnahalli M; Davis, C Ainsley; Setser, Jeremy W; Samson, Leona D; Drennan, Catherine L

    2011-04-15

    Reactive oxygen and nitrogen species, generated by neutrophils and macrophages in chronically inflamed tissues, readily damage DNA, producing a variety of potentially genotoxic etheno base lesions; such inflammation-related DNA damage is now known to contribute to carcinogenesis. Although the human alkyladenine DNA glycosylase (AAG) can specifically bind DNA containing either 1,N(6)-ethenoadenine (εA) lesions or 3,N(4)-ethenocytosine (εC) lesions, it can only excise εA lesions. AAG binds very tightly to DNA containing εC lesions, forming an abortive protein-DNA complex; such binding not only shields εC from repair by other enzymes but also inhibits AAG from acting on other DNA lesions. To understand the structural basis for inhibition, we have characterized the binding of AAG to DNA containing εC lesions and have solved a crystal structure of AAG bound to a DNA duplex containing the εC lesion. This study provides the first structure of a DNA glycosylase in complex with an inhibitory base lesion that is induced endogenously and that is also induced upon exposure to environmental agents such as vinyl chloride. We identify the primary cause of inhibition as a failure to activate the nucleotide base as an efficient leaving group and demonstrate that the higher binding affinity of AAG for εC versus εA is achieved through formation of an additional hydrogen bond between Asn-169 in the active site pocket and the O(2) of εC. This structure provides the basis for the design of AAG inhibitors currently being sought as an adjuvant for cancer chemotherapy.

  13. A cremophor-free formulation for tanespimycin (17-AAG) using PEO-b-PDLLA micelles: characterization and pharmacokinetics in rats.

    Science.gov (United States)

    Xiong, May P; Yáñez, Jaime A; Kwon, Glen S; Davies, Neal M; Forrest, M Laird

    2009-04-01

    Tanespimycin (17-allylamino-17-demethoxygeldanamycin or 17-AAG) is a promising heat shock protein 90 inhibitor currently undergoing clinical trials for the treatment of cancer. Despite its selective mechanism of action on cancer cells, 17-AAG faces challenging issues due to its poor aqueous solubility, requiring formulation with Cremophor EL (CrEL) or ethanol (EtOH). Therefore, a CrEL-free formulation of 17-AAG was prepared using amphiphilic diblock micelles of poly(ethylene oxide)-b-poly(D,L-lactide) (PEO-b-PDLLA). Dynamic light scattering revealed PEO-b-PDLLA (12:6 kDa) micelles with average sizes of 257 nm and critical micelle concentrations of 350 nM, solubilizing up to 1.5 mg/mL of 17-AAG. The area under the curve (AUC) of PEO-b-PDLLA micelles was 1.3-fold that of the standard formulation. The renal clearance (CL(renal)) increased and the hepatic clearance (CL(hepatic)) decreased with the micelle formulation, as compared to the standard vehicle. The micellar formulation showed a 1.3-fold increase in the half-life (t(1/2)) of the drug in serum and 1.2-fold increase in t(1/2) of urine. As expected, because it circulated longer in the blood, we also observed a 1.7-fold increase in the volume of distribution (V(d)) with this micelle formulation compared to the standard formulation. Overall, the new formulation of 17-AAG in PEO-b-PDLLA (12:6 kDa) micelles resulted in a favorable 150-fold increase in solubility over 17-AAG alone, while retaining similar properties to the standard formulation. Our data indicates that the nanocarrier system can retain the pharmacokinetic disposition of 17-AAG without the need for toxic agents such as CrEL and EtOH.

  14. Formulation and in vitro evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric mixed micelles for glioblastoma multiforme.

    Science.gov (United States)

    Saxena, Vipin; Hussain, Muhammad Delwar

    2013-12-01

    Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in human. 17-Allylamino-17-demethoxy geldanamycin (17-AAG) is an inhibitor of heat shock protein 90 (HSP90). The highly lipophilic nature and selective targeting of tumor cells makes 17-AAG a promising candidate for therapy of GBMs but poor water solubility, short biological half-life and hepatotoxicity limited its clinical use. Polymeric mixed micelles composed of Pluronic® P-123 and F-127 (2:1 (w/w)) containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared micelles were determined in U87MG human glioblastoma cells. The particle size of 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles was 22.2 ± 0.1 nm; drug loading was about 4.0 ± 0.5% (w/w) with 88.2 ± 3.1% (w/w) encapsulation efficiency. About 90% of drug was released from the nanoparticles over 8 days. Cellular uptake studies showed intracellular uptake of mixed micelles. Cytotoxicity study showed 5-fold increase (P AAG-loaded mixed micelles to free 17-AAG. Due to their targeting ability, size, high drug loading and controlled release behavior, 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles might be developed as a delivery system for GBM treatment. © 2013 Elsevier B.V. All rights reserved.

  15. Repercussion of mitochondria deformity induced by anti-Hsp90 drug 17AAG in human tumor cells

    KAUST Repository

    Vishal, Chaturvedi

    2011-06-07

    Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/ MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity. the author(s), publisher and licensee Libertas Academica Ltd.

  16. SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently than 17-AAG.

    Science.gov (United States)

    Wang, Shaoxiang; Wang, Xiao; Du, Zhan; Liu, Yuting; Huang, Dane; Zheng, Kai; Liu, Kaisheng; Zhang, Yi; Zhong, Xueyun; Wang, Yifei

    2014-07-18

    17-Allylamino-17-demethoxygeldanamycin (17-AAG), a typical Hsp90 inhibitor derived from geldanamycin (GA), has entered Phase III clinical trials for cancer therapy. However, it has several significant limitations such as poor solubility, limited bioavailability and unacceptable hepatotoxicity. In this study, the anticancer activity and mechanism of SNX-25a, a novel Hsp90 inhibitor, was investigated comparing with that of 17-AAG. We showed that SNX-25a triggered growth inhibition more sensitively than 17-AAG against many human cancer cells, including K562, SW-620, A375, Hep-2, MCF-7, HepG2, HeLa, and A549 cell lines, especially at low concentrations (AAG, SNX-25a was more potent in arresting the cell cycle at G2 phase, and displayed more potent effects on human cancer cell apoptosis and Hsp90 client proteins. It also exhibited a stronger binding affinity to Hsp90 than 17-AAG using molecular docking. Considering the superiority effects on Hsp90 affinity, cell growth, cell cycle, apoptosis, and Hsp90 client proteins, SNX-25a is supposed as a potential anticancer agent that needs to be explored in detail. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway.

    Science.gov (United States)

    Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

    2015-03-01

    The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.

    Science.gov (United States)

    Tomoda, Keishiro; Tam, Yu Tong; Cho, Hyunah; Buehler, Darya; Kozak, Kevin R; Kwon, Glen S

    2017-01-01

    Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 × 10 -9 m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 × 10 -9 m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) >17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg kg -1 ) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg kg -1 ) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Combination therapy for hepatitis C virus with heat-shock protein 90 inhibitor 17-AAG and proteasome inhibitor MG132.

    Science.gov (United States)

    Ujino, Saneyuki; Yamaguchi, Saori; Shimotohno, Kunitada; Takaku, Hiroshi

    2010-03-09

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Here, we report a new and effective strategy for inhibiting HCV replication using an inhibitor of heat-shock protein 90, 17-AAG (17-allylamino-17demethoxygeldanamycin), and a proteasome inhibitor, MG132. To explore the virological basis of combination therapy, we analysed the effects of 17-AAG and MG132, singly and in combination on HCV replication in an HCV replicon cell system. In HCV replicon cells, HCV RNA replication was suppressed by 17-AAG in a dose-dependent manner. As shown in the present study, the 50% inhibitory concentration values were 0.82 nM for 17-AAG and 0.21 nM for MG132. Low concentrations of MG132 had strong synergistic inhibitory effects with low toxicity on HCV replicon cells. The results of this study suggest that the different effects and synergistic actions of 17-AAG and MG132 could provide a new therapeutic approach to HCV infection.

  20. 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway

    Science.gov (United States)

    Ye, Xiang-Yun; Luo, Qing-Quan; Xu, Yun-Hua; Tang, Nai-Wang; Niu, Xiao-Min; Li, Zi-Ming; Shen, Sheng-Ping; Lu, Shun; Chen, Zhi-Wei

    2015-01-01

    The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC. PMID:25712415

  1. Anvendeligheden af GIS

    DEFF Research Database (Denmark)

    Winstrup, Mie; Levin, Gregor

    2011-01-01

    Fragmentering af naturen er en trussel mod biodiversiteten, og etablering af økologiske forbindelser/korridorer mellem naturområderne er én måde hvorved nedgangen i biodiversitet kan stoppes. Med Næstved Kommune som case-område har jeg undersøgt, hvordan analyser i GIS kan bruges til at udvælge...... omdannet til reelle korridorer, hvor bredden afhænger af arealdækket som forbindelserne krydser. I implementerings øjemed er det anvendeligt at vide om nogle forbindelser er særlig vigtige for at skabe mere sammenhængende natur. GIS er anvendeligt hertil, idet GIS kan bruges til at bestemme den enkelte...

  2. Videoanalyse af social interaktion

    DEFF Research Database (Denmark)

    Igennem de sidste 40 år er videooptagelser af praksis blevet anvendt som et redskab i forskning af social interaktion inden for f.eks. læring, design, mediering, kommunikationstræning og i sundhedsvæsenet. Videoanalyse af social interaktion giver et stærkt metodisk, teoretisk og praktisk blik ind i...... videoanalyse og viser, hvordan man som forsker og studerende kan bruge videoanalyse til at undersøge social interaktion. Bogens temaer og spørgsmål udgør således en grundsten i arbejdet med videoanalyse på professions-, universitets- og forskeruddannelser såvel som i forskning mere generelt og omfatter: - de...

  3. Realisering af Vision 2020

    DEFF Research Database (Denmark)

    Bertelsen, Niels Haldor; Hansen, Ernst Jan de Place

    Repræsentanter for byggesektoren har på 11 dialogmøder drøftet Erhvervs- og Byggestyrelsens "Vision 2020 - Byggeri med mening". Drøftelserne førte til formulering af en lang række initiativforslag til realisering af visionen. Den mest centrale udfordring bliver at reducere fejl og mangler i...... byggeriet. Branchen lægger også vægt på, at styringen af Vision 2020s reaisering sker i byggesektoren. Initiativforslagene er i rapporten samlet under 3 hovedområder. Det første hovedområde lægger vægt på bygningerne, brugerbehov og det globale samfund. Det andet omhandler processen og leverancesystemet...

  4. Centralisering af FM organisationer

    DEFF Research Database (Denmark)

    Nielsen, Susanne Balslev

    2016-01-01

    Centralisering af FM organisationer kan let føre til mange frustrerende arbejds- dage for medarbejdere og deres ledere. Denne artikel giver et bud på hvad kom- muner og andre kan gøre for at komme bedre igennem en omorganisering.......Centralisering af FM organisationer kan let føre til mange frustrerende arbejds- dage for medarbejdere og deres ledere. Denne artikel giver et bud på hvad kom- muner og andre kan gøre for at komme bedre igennem en omorganisering....

  5. Kuratering af Samtidskunst

    DEFF Research Database (Denmark)

    Kuratering af Samtidskunst er den første bogudgivelse i Danmark, der fokuserer på kuratering som fag og praksis. Kuratering spiller en stadig større rolle i samtidskunsten. Bogen er en introduktion til skiftende forståelser af udstillings- og kuratorpraksisser og deres udfordringer, indkredset ge...... Kofod Olsen, Teresa Gleadowe, Helle Ryberg, Kirse Junge-Stevnsborg, Malene Natascha Ratcliffe, Pelin Uran, Jacob Fabricius, Lotte Juul Petersen, Jacob Lillemose, Solvej Helweg Ovesen, Frederikke Hansen & Tone Olaf Nielsen (kuratorisk aktion) og Temporary Services....

  6. Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway.

    Science.gov (United States)

    Wagatsuma, Akira; Takayama, Yuzo; Hoshino, Takayuki; Shiozuka, Masataka; Yamada, Shigeru; Matsuda, Ryoichi; Mabuchi, Kunihiko

    2017-12-16

    We have shown that pharmacological inhibition of HSP90 ATPase activity induces apoptosis of myoblasts during their differentiation. However, the signaling pathways remain not fully characterized. We report that pharmacological targeting of HSP90 with 17-AAG activates the intrinsic pathway including caspase-dependent and caspase-independent pathways. 17-AAG induces the typical apoptotic phenotypes including PARP cleavage, chromatin condensation, and nuclear fragmentation with mitochondrial release of cytochrome c, Smac/DIABLO, procaspase-9 processing, and caspase-3 activation. AIF and EndoG redistribute from the mitochondria into the cytosol and are partially translocated to the nucleus in 17-AAG-treated cells. These results suggest that caspase-dependent and caspase-independent pathways should be considered in apoptosis of myogenic cells induced by inhibition of HSP90 ATPase activity.

  7. A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) in Patients with Hormone-Refractory Metastatic Prostate Cancer

    Science.gov (United States)

    Heath, Elisabeth I.; Hillman, David W.; Vaishampayan, Ulka; Sheng, Shijie; Sarkar, Fazlul; Harper, Felicity; Gaskins, Melvin; Pitot, Henry C.; Tan, Winston; Ivy, S. Percy; Pili, Roberto; Carducci, Michael A.; Liu, Glenn

    2011-01-01

    Purpose 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with anti-proliferative activity in several mouse xenograft models including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design Patients with at least one prior systemic therapy and a rising PSA were eligible. Patients received 17-AAG at a dose of 300 mg/m2 IV weekly for three out of four weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, to measure IL-6, IL-8 and maspin levels and quality of life. Results Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of 2 cycles. Severe adverse events included: grade 3 fatigue (4 pts), grade 3 lymphopenia (2 pts) and grade 3 back pain (2 pts). The median PSA progression free survival was 1.8 months (95% CI: 1.3–3.4 months). The six-month overall survival was 71% (95% CI: 52%–100%). Conclusion 17-AAG did not show any activity with regards to PSA response. Due to insufficient PSA response, enrollment was stopped at end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m2 IV weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted. PMID:19047126

  8. Evaluering af naturfaglige kompetencer

    DEFF Research Database (Denmark)

    Dolin, Jens; Nielsen, Jan Alexis; Tidemand, Sofie

    2017-01-01

    Artiklen skitserer kort de sidste 40-50 års udvikling i naturfagene op til det nuværende fokus på undersøgelsesbaseret undervisning og udvikling af kompetencer. Den påpeger hvorledes mange traditionelle evalueringsformer, især brugt ved eksamen, ikke er i stand til at indfange de ønskede kompeten...

  9. Opfindelsen af naturen

    DEFF Research Database (Denmark)

    Thomsen, Torsten Bøgh

    2016-01-01

    Kritisk omtale og kontekstualisering af Andrea Wulfs, "The Invention of Nature: Alexander von Humboldt’s New World". Der er en direkte forbindelse imellem oplysningstidens naturforståelse og den nuværende klimakrisevirkelighed. Alexander von Humboldt opfandt ikke bare naturen, han påpegede også det...

  10. Digitalisering af undervisning

    DEFF Research Database (Denmark)

    Christiansen, René B.; Hansen, Søren; Rossen, Svend

    2010-01-01

    Rapporten er et bestillingsarbejde fra FU (Forskning og Udvikling) og viser en række eksempler på hvorledes undervisningsforløb kan konstrueres online. Herunder ved brug af både LMS-systemer og web 2.0-værktøjer...

  11. Definition af et landdistrikt

    DEFF Research Database (Denmark)

    Søgaard, Villy

    2008-01-01

    Forskellige lande arbejder med meget forskellige definitioner af begrebet landdistrikt. Arbejdspapiret diskuterer først en række generelle krav til definitioner og anbefaler på den baggrund konkrete justeringer i forhold til den hidtidige danske praksis på området. Arbejdspapiret er blevet til i...

  12. En verden af medier

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    selvstændig institution, der forvalter samfundets fælles kommunikation, sætter de spillereglerne for andre aktører, og de er samtidig en selvfølgelig del af hverdagslivets kommunikation mellem familie, venner og kolleger. I samspillet mellem de gamle massemedier og nye interaktive medier opstår forandringer...

  13. Anmeldelse af: Gruppepsykologi

    DEFF Research Database (Denmark)

    Christensen, Bodil

    2009-01-01

    , kreativitet og nytænkning. Det er her, videnskabens virkelige fremskridt sker.” Sådan lyder et citat af Albert Einstein, som Lars Svedberg bruger for at sætte sin faglige fremstilling om gruppepsykologi i perspektiv. Gruppeorganisationen er nemlig ofte rum for/ eller kan være rum for denne synergieffekt, der...

  14. Benchmarking af kommunernes sagsbehandling

    DEFF Research Database (Denmark)

    Amilon, Anna

    Fra 2007 skal Ankestyrelsen gennemføre benchmarking af kommuernes sagsbehandlingskvalitet. Formålet med benchmarkingen er at udvikle praksisundersøgelsernes design med henblik på en bedre opfølgning og at forbedre kommunernes sagsbehandling. Dette arbejdspapir diskuterer metoder for benchmarking...

  15. En skygge af modernitet

    DEFF Research Database (Denmark)

    Skov, Christian Egander

    2015-01-01

    Artiklen vil kort skitsere forskellige, samtidige konservative reaktioner på teknikken, hvis destruktive potentiale var blevet åbenbart i og med Første Verdenskrig, og derefter gennem en læsning af Drachmanns politiske og skønlitterære forfatterskab identificere nøgleelementer og begreber i Drach...

  16. Konsekvensanalyse af Kulturby 96

    DEFF Research Database (Denmark)

    Fridberg, Torben; Koch-Nielsen, Inger

    1997-01-01

    Rapporten om Kulturby 96 indeholder en beskrivelse af kulturbyårets aktiviteter og responsen herpå fra publikum, turister, presse og samarbejdspartnere i øvrigt. Der redegøres for projektets organisatoriske struktur, herunder Kulturbysekretariatets organisation og rolle. Rapporten indeholder...

  17. På kanten af ungdomslivet

    DEFF Research Database (Denmark)

    Sørensen, Niels Ulrik; Pless, Mette

    2015-01-01

    ). Parallelt hermed fortælles moderne ungdomsliv (i ungdomssociologien) frem gennem ”…theoretical frameworks based on urban experiences which capture neither the lives of rural young people nor the spatial dimensions of the structures and cultures that make up contemporary youth.” (Farrugia 2013......, at yderområder er hårdt ramt af ungdomsarbejdsløshed (Bjørnsted & Andersen 2013), at områderne er præget af høj koncentration af unge med arbejderklassebaggrund (Ottosen et a 2010), mens de uddannelsesorienterede og ressourcestærke unge er tilbøjelige til at flytte væk og ind til byerne (Helve 2003). Og ser man...... stedstilknytning og stedbundne ressourcer. Teoretiske perspektiver, der peger på vigtigheden af en mere ”..spatialised youth sociology that is sensitive to macro-level processes producing different spaces, as well as the local, emplaced ways in which young people are responding to social changest hat shape...

  18. Boligboblen pustes op af bankerne

    DEFF Research Database (Denmark)

    Ravn, Ib

    2017-01-01

    Den aktuelle boligboble blæses i vejret af bankerne, der gennem opkøb af realkreditobligationer skaber nye penge og dermed presser boligpriserne i vejret - en kreditfinansieret bolig- eller finansboble....

  19. 17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.

    Science.gov (United States)

    Joshi, Sandeep S; Jiang, Shunlin; Unni, Emmanual; Goding, Stephen R; Fan, Tao; Antony, Paul A; Hornyak, Thomas J

    2018-01-01

    Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

  20. Effects of 17-AAG on the cell cycle and apoptosis of H446 cells and the associated mechanisms.

    Science.gov (United States)

    Zhao, Xuerong; Wang, Jianping; Xiao, Lijun; Xu, Qian; Zhao, Enhong; Zheng, Xin; Zheng, Huachuan; Zhao, Shuang; Ding, Shi

    2016-08-01

    As a heat shock protein 90 inhibitor, 17-allylamino-17‑demethoxygeldanamycin (17-AAG) has been studied in numerous types of cancer, however the effects of 17-AAG on apoptosis and the cell cycle of H446 cells remain unclear. In the current study, the MTT method was used to evaluate the inhibitory effects of different durations and doses of 17‑AAG treatment on the proliferation of H446 cells. The cells were stained with Annexin-fluorescein isothiocyanate/propidium iodide and measured by flow cytometry, and the gene and protein expression levels of signal transducer and activator of transcription 3 (STAT3), survivin, cyclin D1, cyt‑C, caspase 9 and caspase 3 were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The results indicated that with treatment with 1.25‑20 mg/l 17‑AAG for 24 and 48 h, significant inhibition of H446 cell proliferation was observed in a time‑ and dose‑dependent manner. With treatment of 3.125, 6.25 and 12.5 mg/l 17‑AAG for 48 h, significant apoptosis and cell cycle arrest was observed. The results indicated that the gene and protein expression levels of STAT3, survivin and cyclin D1 were downregulated, and cyt‑C, caspase 9 and caspase 3 were upregulated by 17‑AAG in a dose-dependent manner when the cells were treated with 3.125 and 6.25 mg/l 17-AAG for 48 h. The results indicated that 17‑AAG is able to inhibit the cell proliferation, induce apoptosis and G2/M arrest and downregulate the gene and protein expression levels of STAT3, survivin and cyclin D1, and upregulate gene and protein expression of cyt‑C, caspase 9, caspase 3.

  1. 17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

    Science.gov (United States)

    Unni, Emmanual; Goding, Stephen R.; Fan, Tao; Antony, Paul A.; Hornyak, Thomas J.

    2018-01-01

    Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

  2. Dannelsen af den ansvarlige elev

    DEFF Research Database (Denmark)

    Larsen, Jesper

    2010-01-01

    Denne artikel handler om den del af lærergerningen, der har at gøre med udarbejdelse af elevplaner. Der tages udgangspunkt i en foucaultsk forståelse, hvor beskrivelsen af den enkelte elev udtrykker et særligt normativt ideal om, hvilke former for elevhed der er de ønskværdige i den danske...

  3. Udlejers godkendelse af ny erhvervslejer

    DEFF Research Database (Denmark)

    Munk-Hansen, Carsten

    2009-01-01

    I artiklen er taget udgangspunkt i den »klassiske« afståelsessituation, hvor en lejer vil afhænde den i de lejede lokaler drevne virksomhed, og lejeren har afståelsesret til en af udlejer godkendt lejer, uden at kravene til den ny lejer er specificeret. På baggrund af Vestre Landsrets dom af 9/2 ...

  4. Anmeldelse af Evolution, Literature and Film

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2011-01-01

    Diskussion af basisproblemer i evolutionær fiktionsteori med udgangspunkt i en anmeldelse af Evolution, Literature and Film......Diskussion af basisproblemer i evolutionær fiktionsteori med udgangspunkt i en anmeldelse af Evolution, Literature and Film...

  5. En genlæsning af John Rawls i lyset af hans diskussion af forholdet til fremtidige generationer

    DEFF Research Database (Denmark)

    Lübcke, Poul

    2009-01-01

    På grundlag af en konsekventialistisk rekonstruktion af Rawls' politiske position gøres der rede for Rawls eksplicitte og implicitte vurdering af vores ansvar over for fremtidige generationer......På grundlag af en konsekventialistisk rekonstruktion af Rawls' politiske position gøres der rede for Rawls eksplicitte og implicitte vurdering af vores ansvar over for fremtidige generationer...

  6. På sporet af sprogpsykologi

    DEFF Research Database (Denmark)

    2005-01-01

    Sprogpsykologi beskæftiger sig med, hvordan sprog og mennesker hænger sammen, og hvilke følger sammenhængen får for vore forståelser af verden og os selv. Denne antologi henvender sig til den sproginteresserede, der ønsker at gå et lag dybere end sprogets grammatiske sider. Sprog er ikke kun et l...

  7. Tilbagebetaling af sociale ydelser

    DEFF Research Database (Denmark)

    Hielmcrone, Nina Elisabeth von

    konstateres, at der foreligger fejl og forsømmelser hos både modtager og myndighed. Dermed stilles der også spørgsmålstegn ved de såkaldt "objektive" tilbagebetalingsbestemmelser som f.x. i boligstøttelovens § 47 stk. 1 og 2.       Bogen behandler desuden de mange og vanskelige fortolkningsproblemer, der...... knytter sig til anvendelsen af tilbagebetalingsbestemmelserne i de sociale love....

  8. Hvordan integration af it?

    DEFF Research Database (Denmark)

    Toft, Herdis

    2008-01-01

    Fokus i artiklen er den måde, hvorpå børn positionerer sig på i skolerummet, og på, hvordan børn gennem brug af it opbygger og integrerer digital kompetence forstået som færdigheder, kundskaber og holdninger, der skal sætte dem i stand til at agere i det lærende samfund. Med udgangspunkt i et Bou...

  9. Innovation af innovation

    DEFF Research Database (Denmark)

    Harste, Gorm

    2009-01-01

    , at innovation af innovationen forsøges gennemført på en måde, hvor tiden kræves at forholde sig til sin egen tidslighed i form af fremtid, nutid, fortid og ikke mindst i form af samtidighed. I tiden skal vi iagttage, hvordan vi iagttager tiden. Vi dobbelt-koder tiden på samme måde, som forskning forsker i...... organisationssystemerne. De to typer systemer kan noget helt bestemt med fænomenet tid. De kan synkronisere. Analyseres organisationssystemer ser vi, imidlertid at innovation kræver ro. Stærkt innovative systemer er militærsystemet og kunstsystemet, der også inddrages, og hvor vi ser paradokset mellem innovation og...... involution. Tid er med et medium og ikke et lufttomt rum. Tid er end ikke en gasart, men udgør et solidt fluidum, som samfundet bader i og flyder i, konstant i bevægelse. Reformer forudsætter former, og innovation forudsætter involution. Kun sådan muliggøres evolution....

  10. Alkylation induced cerebellar degeneration dependent on Aag and Parp1 does not occur via previously established cell death mechanisms.

    Directory of Open Access Journals (Sweden)

    Carrie M Margulies

    Full Text Available Alkylating agents are ubiquitous in our internal and external environments, causing DNA damage that contributes to mutations and cell death that can result in aging, tissue degeneration and cancer. Repair of methylated DNA bases occurs primarily through the base excision repair (BER pathway, a multi-enzyme pathway initiated by the alkyladenine DNA glycosylase (Aag, also known as Mpg. Previous work demonstrated that mice treated with the alkylating agent methyl methanesulfonate (MMS undergo cerebellar degeneration in an Aag-dependent manner, whereby increased BER initiation by Aag causes increased tissue damage that is dependent on activation of poly (ADP-ribose polymerase 1 (Parp1. Here, we dissect the molecular mechanism of cerebellar granule neuron (CGN sensitivity to MMS using primary ex vivo neuronal cultures. We first established a high-throughput fluorescent imaging method to assess primary neuron sensitivity to treatment with DNA damaging agents. Next, we verified that the alkylation sensitivity of CGNs is an intrinsic phenotype that accurately recapitulates the in vivo dependency of alkylation-induced CGN cell death on Aag and Parp1 activity. Finally, we show that MMS-induced CGN toxicity is independent of all the cellular events that have previously been associated with Parp-mediated toxicity, including mitochondrial depolarization, AIF translocation, calcium fluxes, and NAD+ consumption. We therefore believe that further investigation is needed to adequately describe all varieties of Parp-mediated cell death.

  11. Lapatinib and 17AAG Reduce Zr-89-Trastuzumab-F(ab')(2) Uptake in SKBR3 Tumor Xenografts

    NARCIS (Netherlands)

    Munnink, Thijs H. Oude; de Vries, Elisabeth G. E.; Vedelaar, Silke R.; Timmer-Bosscha, Hetty; Schroder, Carolina P.; Brouwers, Adrienne H.; Lub-de Hooge, Marjolijn N.

    2012-01-01

    Human epidermal growth factor receptor-2 (HER2) directed therapy potentially can be improved by insight in drug effects on HER2 expression. This study evaluates the effects of the EGFR/HER2 tyrosine kinase inhibitor lapatinib, the heat shock protein-90 inhibitor 17AAG, and their combination, on HER2

  12. Alkylation induced cerebellar degeneration dependent on Aag and Parp1 does not occur via previously established cell death mechanisms.

    Science.gov (United States)

    Margulies, Carrie M; Chaim, Isaac Alexander; Mazumder, Aprotim; Criscione, June; Samson, Leona D

    2017-01-01

    Alkylating agents are ubiquitous in our internal and external environments, causing DNA damage that contributes to mutations and cell death that can result in aging, tissue degeneration and cancer. Repair of methylated DNA bases occurs primarily through the base excision repair (BER) pathway, a multi-enzyme pathway initiated by the alkyladenine DNA glycosylase (Aag, also known as Mpg). Previous work demonstrated that mice treated with the alkylating agent methyl methanesulfonate (MMS) undergo cerebellar degeneration in an Aag-dependent manner, whereby increased BER initiation by Aag causes increased tissue damage that is dependent on activation of poly (ADP-ribose) polymerase 1 (Parp1). Here, we dissect the molecular mechanism of cerebellar granule neuron (CGN) sensitivity to MMS using primary ex vivo neuronal cultures. We first established a high-throughput fluorescent imaging method to assess primary neuron sensitivity to treatment with DNA damaging agents. Next, we verified that the alkylation sensitivity of CGNs is an intrinsic phenotype that accurately recapitulates the in vivo dependency of alkylation-induced CGN cell death on Aag and Parp1 activity. Finally, we show that MMS-induced CGN toxicity is independent of all the cellular events that have previously been associated with Parp-mediated toxicity, including mitochondrial depolarization, AIF translocation, calcium fluxes, and NAD+ consumption. We therefore believe that further investigation is needed to adequately describe all varieties of Parp-mediated cell death.

  13. The heat shock protein 90 inhibitor 17-AAG suppresses growth and induces apoptosis in human cholangiocarcinoma cells.

    Science.gov (United States)

    Zhang, Jianjun; Zheng, Zhichao; Zhao, Yan; Zhang, Tao; Gu, Xiaohu; Yang, Wei

    2013-11-01

    The aim of this study was to investigate the effects of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, on the proliferation, cell cycle, and apoptosis of human cholangiocarcinoma (CCA) cells. Cell proliferation and cell cycle distribution were measured by the MTT assay and flow cytometry analysis, respectively. Induction of apoptosis was determined by flow cytometry and Hoechst staining. The expressions of cleaved poly ADP-ribose polymerase (PARP), Bcl-2, Survivin, and Cyclin B1 were detected by Western blot analysis. The activity of caspase-3 was also examined. We found that 17-AAG inhibited cell growth and induced G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP. Moreover, increased caspase-3 activity was also observed in CCA cells treated with 17-AAG. In conclusion, our data suggest that the inhibition of HSP90 function by 17-AAG may provide a promising therapeutic strategy for the treatment of human CCA.

  14. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells.

    Science.gov (United States)

    Sauvageot, Claire Marie-Elisabeth; Weatherbee, Jessica Leigh; Kesari, Santosh; Winters, Susan Elizabeth; Barnes, Jessica; Dellagatta, Jamie; Ramakrishna, Naren Raj; Stiles, Charles Dean; Kung, Andrew Li-Jen; Kieran, Mark W; Wen, Patrick Yung Chih

    2009-04-01

    Glioblastoma multiforme (GBM) arises from genetic and signaling abnormalities in components of signal transduction pathways involved in proliferation, survival, and the cell cycle axis. Studies to date with single-agent targeted molecular therapy have revealed only modest effects in attenuating the growth of these tumors, suggesting that targeting multiple aberrant pathways may be more beneficial. Heat-shock protein 90 (HSP90) is a molecular chaperone that is involved in the conformational maturation of a defined group of client proteins, many of which are deregulated in GBM. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a well-characterized HSP90 inhibitor that should be able to target many of the aberrant signal transduction pathways in GBM. We assessed the ability of 17-AAG to inhibit the growth of glioma cell lines and glioma stem cells both in vitro and in vivo and assessed its ability to synergize with radiation and/or temozolomide, the standard therapies for GBM. Our results reveal that 17-AAG is able to inhibit the growth of both human glioma cell lines and glioma stem cells in vitro and is able to target the appropriate proteins within these cells. In addition, 17-AAG can inhibit the growth of intracranial tumors and can synergize with radiation both in tissue culture and in intracranial tumors. This compound was not found to synergize with temozolomide in any of our models of gliomas. Our results suggest that HSP90 inhibitors like 17-AAG may have therapeutic potential in GBM, either as a single agent or in combination with radiation.

  15. Functional autonomy, bone mineral density (BMD) and serum osteocalcin levels in older female participants of an aquatic exercise program (AAG).

    Science.gov (United States)

    Pernambuco, Carlos Soares; Borba-Pinheiro, Claudio Joaquim; Vale, Rodrigo Gomes de Souza; Di Masi, Fabrizio; Monteiro, Paola Karynne Pinheiro; Dantas, Estelio H M

    2013-01-01

    The aim of the present study was to evaluate the effects of an AAG on BMD, osteocalcin and functional autonomy in older women. The sample consisted of eighty-two post-menopausal women with low BMD, randomly divided into two groups: the Aquatic Aerobics Group [AAG; n=42; age: 66.8±4.2years], submitted to two weekly sessions over eight months, and the Control Group (GC; n=42; age: 66.9±3.2years), which did not participate in regular exercise. BMD was measured by Dual Energy X-ray Absorptiometry [DXA] of the lumbar and femur, and serum osteocalcin was measured using electrochemiluminescence. A functional autonomy assessment protocol (GDLAM, 2004) was also applied. Statistical analyses used were repeated measures ANOVA and Tukey's post hoc tests. The results showed a significant improvement in tests following the GDLAM protocol: 10 meters walk (10mw) -p=0.003; rising from a ventral decubitus position (RVDP) - Δ%=0.78, pAAG when compared to the CG. The AAG achieved the best results for BMD; however, no inter or intragroup statistical differences were recorded for total femur -p=0.975 and lumbar L(2)-L(4)p=0.597. For serum osteocalcin, intra and intergroup statistical differences of p=0.042 and p=0.027 were observed in the AAG, respectively. This demonstrates that an eight-month aquatic aerobic exercise program can improve functional autonomy and osteocalcin levels, although training did not improve lumbar and total femur BMD in the older women. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Can RNAi-mediated hsp90α knockdown in combination with 17-AAG be a therapy for glioma?

    Science.gov (United States)

    Mehta, Adi; Shervington, Amal; Howl, John; Jones, Sarah; Shervington, Leroy

    2013-01-01

    Heat shock protein 90 promotes tumor progression and survival and has emerged as a vital therapeutic target. Previously we reported that the combinatorial treatment of 17AAG/sihsp90α significantly downregulated Hsp90α mRNA and protein levels in Glioblastoma Multiforme (GBM). Here we investigated the ability of cell penetrating peptide (Tat48-60 CPP)-mediated siRNA-induced hsp90α knockdown as a single agent and in combination with 17-allylamino-17-demethoxygeldanamycin (17-AAG) to induce tumor growth inhibition in GBM and whether it possessed therapeutic implications. GBM and non-tumorigenic cells exposed to siRNA and/or 17-AAG were subsequently assessed by qRT-PCR, immunofluorescence, FACS analysis, quantitative Akt, LDH leakage and cell viability assays. PAGE was performed for serum stability assessment. A combination of siRNA/17-AAG treatment significantly induced Hsp90α gene and protein knockdown by 95% and 98%, respectively, concomitant to 84% Akt kinase activity attenuation, induced cell cycle arrest and tumor-specific cytotoxicity by 88%. Efficient complex formation between CPP and siRNA exhibited improved serum stability of the siRNA with minimal intrinsic toxicity in vitro. The preliminary in vivo results showed that combination therapy induced hsp90α knockdown and attenuated Akt kinase activity in intracranial glioblastoma mouse models. The results imply that RNAi-mediated hsp90α knockdown increases 17-AAG treatment efficacy in GBM. In addition, the cytotoxic response observed was the consequence of downregulation of hsp90α gene expression, reduced Akt kinase activity and S-G2/M cell cycle arrest. These results are novel and highlight the ability of Tat to efficiently deliver siRNA in GBM and suggest that the dual inhibition of Hsp90 has therapeutic potentials.

  17. 17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal autophagic death induced by transient global cerebral ischemia.

    Science.gov (United States)

    Li, Jianxiong; Yang, Fei; Guo, Jia; Zhang, Rongrong; Xing, Xiangfeng; Qin, Xinyue

    2015-06-12

    Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Relevansen af Aristoteles' etik for konceptionen af eksistentiel terapi

    DEFF Research Database (Denmark)

    Dræby, Anders

    Siden sin undfangelse i begyndelsen af det 20. århundrede har den eksistentielle terapi repræsenteret et filosofisk funderet alternativ til de former for terapeutisk praksis, der er funderet i den funktionalistiske medicinske metafysik. Anvendelse af elementer fra Aristoteles' etik muliggør en...... fremhævelse af den eksistentielle terapi som en praktisk eksistensfænomenologisk livskunst, hvis anliggende er en frembringelse af det enkelte menneskes muligheder fra det skjulte og ind i det uskjulte, så mennesket viser sig som det er ved sig selv...

  19. Anvendelse af MIP ved kildekarakterisering og vurdering af nedbrydning af chlorerede opløsningsmidler

    DEFF Research Database (Denmark)

    Broholm, Mette Martina; Janniche, Gry Sander; Damgaard, Ida

    2014-01-01

    Membrane Interface Probing (MIP) er et 'direct push' screeningsværktøj, som kan anvendes ved karakterisering af forurenede grunde. Karakterisering af kildeområder med chlorerede opløsningsmidler (som DNAPL) udgør et vigtigt led i udviklingen af den konceptuelle forståelse, som er essentiel...... for risikovurdering og valg af afværgestrategi. Integreret karakterisering med en række metoder for direkte såvel som indirekte dokumentation af DNAPL i moræneler, herunder MIP, er beskrevet i Kerrn-Jespersen et al. (2013). Det samlede DNAPL-karakteriseringsprojekt er beskrevet i detaljer i Janniche et al. (2013). En...... vurdering af anvendte detektorer for MIP er foretaget af Olsson (2013). Ved karakterisering af forurening med bl.a. chlorerede opløsningsmidler er der behov for en vurdering af forureningssammensætning og nedbrydning. Tilsvarende vurdering er nødvendig, når udviklingen af stimuleret reduktiv dechlorering...

  20. Energiforbrug til opvarmning af bygninger

    DEFF Research Database (Denmark)

    Budde, J.; Pedersen, D.O.

    Rapporten giver oplysninger om enhedsforbrug til varme og varmt brugsvand i forskellige typer af bygninger baseret på en analyse af et omfattende datamateriale. Formålet med undersøgelsen har været at ajourføre denne del af grundlaget for både landsdækkende og lokal varmeplanlægning i Danmark....

  1. Coaching af sygedagpengemodtagere

    DEFF Research Database (Denmark)

    Coop Henriksen, Annemette

    SFI gennemførte i foråret 2008 til foråret 2009 en pilotundersøgelse om coaching. Undersøgelsen var designet som et lodtrækningsforsøg og omfattede 42 kvindelige sygedagpengemodtagere fra Rødovre Jobcenter, der var sygemeldt med psykiske lidelser i form af stress, depression eller udbrændthed eller...... med lidelser i bevægeapparatet. Undersøgelsen er bestilt og finansieret af Rødovre Jobcenter. I rapporten undersøges, om coaching kan bidrage til at bringe sygedagpengemodtagere i arbejde eller tættere på arbejdsmarkedet målt ved, om deltagerne får fx øget motivation, mere selvtillid, øget afklaring...... og færre symptomer på sygdom. Undersøgelsen viser, at gruppen, der har modtaget coaching, oplever en positiv udvikling i forhold til stress, depression og udbrændthed. Gruppen, der modtog coaching, har den tydeligste positive udvikling, men begge grupper har oplevet en helbredsmæssig fremgang i...

  2. Overførsel af viden ved flytning af produktion

    DEFF Research Database (Denmark)

    Madsen, Erik Skov; Riis, Jens Ove; Wæhrens, Brian Vejrum

    2010-01-01

    Empiriske studier i tre industrielle virksomheder har afsløret, at selv virksomheder med mange års erfaring i at overføre produktion til andre lande hovedsagelig fokuserer på planlægning af den fysiske overflytning af produktionsudstyr og fokuserer på den eksplicitte viden, der er tilknyttet prod...

  3. Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1.

    Science.gov (United States)

    Zsebik, Barbara; Citri, Ami; Isola, Jorma; Yarden, Yosef; Szöllosi, János; Vereb, György

    2006-04-15

    ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in approximately 30-40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5-10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30-40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may

  4. Synthesis of (131)I-labeled-[(131)I]iodo-17-allylamino-17-demethoxy geldanamycin ([(131)I]iodo-17-AAG) and its biodistribution in mice.

    Science.gov (United States)

    Daozhen, Chen; Lu, Liu; Min, Yang; Xinyu, Jiang; Ying, Huang

    2007-10-01

    The aim of this study was to examine the radioiodinating condition of 17-allylamino-17-demethoxy geldanamycin (17-AAG) and observe its biodistribution in the hepatoma cell line HepA tumorearing ICR mice for understanding the possibility of its application in nuclear medicine. [(131)I]iodo-17-AAG was prepared by the reaction of 17-AAG with Na[(131)I] in the presence of hydrogen peroxide. [(131)I]iodo-17-AAG was purified by high-performance liquid chromatography (HPLC). The stability of [(131)I]iodo-17-AAG was measured by thin-layer chromatography (TLC). The distributions in HepA tumor-bearing ICR mice at 0.5, 1, 4, 8, 24, and 48 hours after injection of [(131)I]iodo-17-AAG were measured. Tumor uptake studies were performed in HepA tumor-bearing ICR mice. The labeling yield was over 83%. The radiochemical purity of [(131)I]iodo-17-AAG was 99.6% after purification. The specific activity was greater than 4 Ci/micromol. The labeled compound was stable for at least 120 hours in saline at 4 degrees C. It was initially in blood at 5 minutes with 4.79% of injected dose per g of tissue (%ID/g), and then dropped 0.33% ID/g at 24 hours. The uptake in liver, lung, and kidney at 4.44% ID/g, 2.03% ID/g, and 2.17% ID/g decreased with time, and less than 1% ID/g was measured after 24 hours in those organs. There was rapid tumor uptake, which reached 1.26% ID/g at 0.5 hours, the highest uptake at 8 hours. Yet, the [(131)I]iodo-17-AAG in the contralateral muscle was at a low level during the 48 hours. The tumor-contralateral muscle (T/CM) radioactivity ratio for [(131)I]iodo-17-AAG remained constant at all time points. [(131)I]iodo-17-AAG can be efficiently radiolabeled at high specific activity, purified by HPLC and stored with little radiolysis at this specific activities. [(131)I]iodo-17-AAG is a promising radiopharmaceutical in nuclear medicine, especially for tumor-targeted radionuclide brachytherapy.

  5. Aag Hypoxanthine-DNA Glycosylase Is Synthesized in the Forespore Compartment and Involved in Counteracting the Genotoxic and Mutagenic Effects of Hypoxanthine and Alkylated Bases in DNA during Bacillus subtilis Sporulation.

    Science.gov (United States)

    Ayala-García, Víctor M; Valenzuela-García, Luz I; Setlow, Peter; Pedraza-Reyes, Mario

    2016-12-15

    Aag from Bacillus subtilis has been implicated in in vitro removal of hypoxanthine and alkylated bases from DNA. The regulation of expression of aag in B. subtilis and the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptional aag-lacZ fusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably, aag-lacZ expression was higher inside the forespore than in the mother cell compartment, and this expression was abolished in a sigG-deficient background, suggesting a forespore-specific mechanism of aag transcription. Two additional findings supported this suggestion: (i) expression of an aag-yfp fusion was observed in the forespore, and (ii) in vivo mapping of the aag transcription start site revealed the existence of upstream regulatory sequences possessing homology to σ G -dependent promoters. In comparison with the wild-type strain, disruption of aag significantly reduced survival of sporulating B. subtilis cells following nitrous acid or methyl methanesulfonate treatments, and the Rif r mutation frequency was significantly increased in an aag strain. These results suggest that Aag protects the genome of developing B. subtilis sporangia from the cytotoxic and genotoxic effects of base deamination and alkylation. In this study, evidence is presented revealing that aag, encoding a DNA glycosylase implicated in processing of hypoxanthine and alkylated DNA bases, exhibits a forespore-specific pattern of gene expression during B. subtilis sporulation. Consistent with this spatiotemporal mode of expression, Aag was found to protect the sporulating cells of this microorganism from the noxious and mutagenic effects of base deamination and alkylation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity?

    Science.gov (United States)

    Mayor-López, Leticia; Tristante, Elena; Carballo-Santana, Mar; Carrasco-García, Estefanía; Grasso, Silvina; García-Morales, Pilar; Saceda, Miguel; Luján, Juan; García-Solano, José; Carballo, Fernando; de Torre, Carlos; Martínez-Lacaci, Isabel

    2014-10-01

    The use of heat shock protein 90 (Hsp90) inhibitors is an attractive antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) and the novel isoxazole resorcinol-based Hsp90 inhibitor NVP-AUY922 in a panel of pancreatic and colorectal carcinoma cell lines and in colorectal primary cultures derived from tumors excised to patients. PANC-1, CFPAC-1, and Caco-2 cells were intrinsically resistant to 17-AAG but sensitive to NVP-AUY922. Other cellular models were sensitive to both inhibitors. Human epidermal growth factor receptor receptors and their downstream signaling pathways were downregulated in susceptible cellular models, and concurrently, Hsp70 was induced. Intrinsic resistance to 17-AAG did not correlate with expression of ATP-binding cassette transporters involved in multidrug resistance. Some 17-AAG-resistant, NVP-AUY922-sensitive cell lines lacked quinone oxidoreductase 1 (NQO1) enzyme and activity. However, colorectal LoVo cells still responded to both drugs in spite of having undetectable levels and activity of NQO1. Pharmacological and biologic inhibition of NQO1 did not confer resistance to 17-AAG in sensitive cell lines. Therefore, even though 17-AAG sensitivity is related to NQO1 protein levels and enzymatic activity, the absence of NQO1 does not necessarily convey resistance to 17-AAG in these cellular models. Moreover, NVP-AUY922 does not require NQO1 for its action and is a more potent inhibitor than 17-AAG in these cells. More importantly, we show in this report that NVP-AUY922 potentiates the inhibitory effects of chemotherapeutic agents, such as gemcitabine or oxaliplatin, and other drugs that are currently being evaluated in clinical trials as antitumor agents.

  7. Virkelighedsflugt og masser af sex

    DEFF Research Database (Denmark)

    Lorentzen, Rasmus Fink

    2011-01-01

    I artiklen laves en læsning af ungdomsromanen "6" (2010) af Ronni Andersen. Dernæst udfoldes en række litteraturpædagogiske forslag tilen undervisning i romanen i skolens ældste klasser. Arbejdsforslagene er baseret på en kompetencetilgang til danskfaget og rummer fire værksteder hvor eleverne sk...

  8. I Frans af Assisis fodspor

    DEFF Research Database (Denmark)

    Bonde, Lisbeth

    2015-01-01

    En fodrejse fra Assisi til Rom i Frans af Assisis fodspor sætter gang i tankerne og giver anledning til nye ideer......En fodrejse fra Assisi til Rom i Frans af Assisis fodspor sætter gang i tankerne og giver anledning til nye ideer...

  9. Ledelse af forandringer i folkeskolen

    DEFF Research Database (Denmark)

    Kjer, Mikkel; Rosdahl, Anders

    2016-01-01

    Dette notat bygger på kvalitative interview på seks folkeskoler i efteråret 2015. Skolerne ligger i forskellige egne af landet og i landområder, mindre og store byer. Skolerne er af forskellig størrelse, og deres elevgrundlag, dvs. forældrenes sociale baggrund, varierer også. Notatet bygger primæ...

  10. Forhastet regulering af de store

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2013-01-01

    Christiansborg gennemfører sandsynligvis en markant skærpet regulering af de store finansielle virksomheder. Det vil virke kontraktivt og medvirke til erhvervslivets kredittørke.......Christiansborg gennemfører sandsynligvis en markant skærpet regulering af de store finansielle virksomheder. Det vil virke kontraktivt og medvirke til erhvervslivets kredittørke....

  11. Masser af information uden betydning

    DEFF Research Database (Denmark)

    Brier, Søren

    en diskussion af informationsteorien i Tor Nørretranders "Mærk verden" og en skitse til et alternativ baseret på anden ordens kybernetik og semiotik......en diskussion af informationsteorien i Tor Nørretranders "Mærk verden" og en skitse til et alternativ baseret på anden ordens kybernetik og semiotik...

  12. Anbefalinger til organisering af uddannelserne

    DEFF Research Database (Denmark)

    Andersen, Lars; Andersen, Lars Døvling; Hornemann, Birte C.

    2009-01-01

    Notatet sammenfatter de diskussioner, som det af fakulteterne nedsatte udvalg vedrørende nye undervisnings- og eksamensformer har haft, og de anbefalinger til en omlægning af vores uddannelsessystem, som udvalget har valgt at give. Notatet er samtidig en begyndelse på en erfaringsudveksling om ny...

  13. Modeller af komplicerede systemer

    DEFF Research Database (Denmark)

    Mortensen, J.

    emphasizes their use in relation to technical systems. All the presented models, with the exception of the types presented in chapter 2, are non-theoretical non-formal conceptual network models. Two new model types are presented: 1) The System-Environment model, which describes the environments interaction...... with conceptual modeling in relation to process control. It´s purpose is to present classify and exemplify the use of a set of qualitative model types. Such model types are useful in the early phase of modeling, where no structured methods are at hand. Although the models are general in character, this thesis......This thesis, "Modeller af komplicerede systemer", represents part of the requirements for the Danish Ph.D.degree. Assisting professor John Nørgaard-Nielsen, M.Sc.E.E.Ph.D. has been principal supervisor and professor Morten Lind, M.Sc.E.E.Ph.D. has been assisting supervisor. The thesis is concerned...

  14. [HSP90 inhibitor 17-AAG plays an important role in JAK3/STAT5 signaling pathways in HTLV-1 infection cell line HUT-102].

    Science.gov (United States)

    Yang, Q Q; Tan, H; Fu, Z P; Ma, Q; Song, J L

    2017-08-14

    Objective: To analyze whether heat-shock protein 90 (HSP90) be involved in a permanently abnormal activated JAK/STAT signaling in ATL cells in vitro. Methods: The effect of 17-AAG on proliferation of ATL cell lines HUT-102 was assessed using CCK8 at different time points. Cell apoptosis was measured by flow cytometry. The specific proteins HSP90, STAT5, p-STAT5 and JAK3 were detected by Western blotting. Results: Overexpression of HSP90 in HUT-102 cell lines was disclosed ( P AAG led to reduced cell proliferation, but there was no significant change in terms of cell proliferation when the concentration of 17-AAG between 2 000-8 000 nmol/L ( P >0.05) . 17-AAG induced cell apoptosis in different time-points and concentrations. 17-AAG don't affect the expression of JAK3 gene. Conclusion: This study indicated that JAK3 as HSP90 client protein was aberrantly activated in HTLV-1-infected T-cell lines, leading to constitutive activation of p-STAT5 in JAK/STAT signal pathway, which demonstrated that HSP90-inhibitors 17-AAG inhibited the growth of HTLV-1-infected T-cell lines by reducing cell proliferation and inducing cell apoptosis.

  15. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells.

    Science.gov (United States)

    Choi, Young Eun; Battelli, Chiara; Watson, Jacqueline; Liu, Joyce; Curtis, Jennifer; Morse, Alexander N; Matulonis, Ursula A; Chowdhury, Dipanjan; Konstantinopoulos, Panagiotis A

    2014-05-15

    The promise of PARP-inhibitors(PARPis) in the management of epithelial ovarian cancer(EOC) is tempered by the fact that approximately 50% of patients with homologous recombination (HR)-proficient tumors do not respond well to these agents. Combination of PARPis with agents that inhibit HR may represent an effective strategy to enhance their activity in HR-proficient tumors. Using a bioinformatics approach, we identified that heat shock protein 90 inhibitors(HSP90i) may suppress HR and thus revert HR-proficient to HR-deficient tumors. Analysis of publicly available gene expression data showed that exposure of HR-proficient breast cancer cell lines to HSP90i 17-AAG(17-allylamino-17-demethoxygeldanamycin) downregulated HR, ATM and Fanconi Anemia pathways. In HR-proficient EOC cells, 17-AAG suppressed HR as assessed using the RAD51 foci formation assay and this was further confirmed using the Direct Repeat-GFP reporter assay. Furthermore, 17-AAG downregulated BRCA1 and/or RAD51 protein levels, and induced significantly more γH2AX activation in combination with olaparib compared to olaparib alone. Finally, sublethal concentrations of 17-AAG sensitized HR-proficient EOC lines to olaparib and carboplatin but did not affect sensitivity of the HR-deficient OVCAR8 line arguing that the 17-AAG mediated sensitization is dependent on suppression of HR. These results provide a preclinical rationale for using a combination of olaparib/17-AAG in HR-proficient EOC.

  16. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease

    Science.gov (United States)

    2013-01-01

    Alzheimer’s disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation. PMID:24344631

  17. Health Information in Somali (Af-Soomaali )

    Science.gov (United States)

    ... and Wound Healing - Af-Soomaali (Somali) Bilingual PDF Health Information Translations Fasting Blood Sugar Test - Af-Soomaali (Somali) Bilingual PDF Health Information Translations GTT (Glucose Tolerance Test) - Af-Soomaali ( ...

  18. Anmeldelse af World Drug Report 2005

    DEFF Research Database (Denmark)

    Møller, Kim

    2005-01-01

    Internationale udfordringer i spændingsfeltet mellem organiseret kriminalitet og narkotika. Værdien af det illegale narkotikamarked. Skabelsen af et Illicit Drug Index. Ny organisationsstruktur bag udgivelsen af denne WDR. Udgivelsesdato: December......Internationale udfordringer i spændingsfeltet mellem organiseret kriminalitet og narkotika. Værdien af det illegale narkotikamarked. Skabelsen af et Illicit Drug Index. Ny organisationsstruktur bag udgivelsen af denne WDR. Udgivelsesdato: December...

  19. 17-AAG improves cognitive process and increases heat shock protein response in a model lesion with Aβ25-35.

    Science.gov (United States)

    Ortega, Laura; Calvillo, Minerva; Luna, Félix; Pérez-Severiano, Francisca; Rubio-Osornio, Moisés; Guevara, Jorge; Limón, Ilhuicamina Daniel

    2014-08-01

    Molecular chaperones, or heat shock proteins (HSP), have been implicated in numerous neurodegenerative disorders characterized by the accumulation of protein aggregates, such as Alzheimer disease. The agglomeration of insoluble structures of Aβ is thought to be responsible for neuronal death, which in turn leads to the loss of cognitive functions. Recent findings have shown that the induction of HSP decreases the level of abnormal protein aggregates, as well as demonstrating that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an analogue of geldanamycin (GA), increases Aβ clearance through the induction of molecular chaperones in cell culture. In light of this discovery that HSP overexpression can be neuroprotective, the search for a way to pharmacologically induce the overexpression of HSP and other associated chaperones may lead to a promising approach for the treatment of neurodegenerative diseases. The aim of our study was to evaluate both the effect of 17-AAG on the cognitive process and the HSP response in rats injected with Aβ25-35 into the CA1 of the hippocampus. The results show that the injection of Aβ caused a significant increase in the expression of the HSP involved in the regulation of cellular proteostasis. While the HSP did not reverse excitotoxic damage, given that experimental subjects showed learning and memory deficits, the administration of 17-AAG prior to the injection of Aβ25-35 did show an improvement in the behavioral assessment that correlated with the upregulation of HSP70 in subjects injured with Aβ. Overall, our data shows that the pharmacological induction of HSP using 17-AAG may be an alternative treatment of neurodegenerative diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.

    Science.gov (United States)

    Weber, Helga; Valbuena, José R; Barbhuiya, Mustafa A; Stein, Stefan; Kunkel, Hana; García, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A; Kurtz, Stephen E; Tyner, Jeffrey W; Calderon, Juan Francisco; Corvalán, Alejandro H; Grez, Manuel; Pandey, Akhilesh; Leal-Rojas, Pamela; Roa, Juan C

    2017-04-18

    Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.

  1. Heat Shock Protein 90 Inhibitor (17-AAG) Induces Apoptosis and Decreases Cell Migration/Motility of Keloid Fibroblasts.

    Science.gov (United States)

    Yun, In Sik; Lee, Mi Hee; Rah, Dong Kyun; Lew, Dae Hyun; Park, Jong-Chul; Lee, Won Jai

    2015-07-01

    The regulation of apoptosis, proliferation, and migration of fibroblasts is altered in keloids. The 90-kDa heat shock protein (heat shock protein 90) is known to play a key role in such regulation. Therefore, the authors investigated whether the inhibition of heat shock protein 90 in keloid fibroblasts could induce apoptosis and attenuate keloid fibroblast proliferation and migration. The authors evaluated heat shock protein 90 expression in keloid tissues with immunohistochemistry. The authors used cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays and annexin V/propidium iodide staining for apoptosis, a wound healing model and cell tracking system to assess cell migration, and Akt Western blotting analysis in keloid fibroblasts after inhibition of heat shock protein 90 with 17-allylaminodemethoxygeldanamycin (17-AAG). The expression of heat shock protein 90 in keloid tissues was significantly increased compared with normal tissues. The 17-AAG-treated keloid fibroblasts showed significantly decreased proliferation, promotion of apoptosis, and decreased expression of Akt. Furthermore, a dose-dependent decrease in cell migration was noted after 17-AAG treatment of keloid fibroblasts. The 17-AAG-treated keloid fibroblasts had less directionality to the wound center and migrated a shorter distance. The authors confirmed that the inhibition of heat shock protein 90 in keloid fibroblasts could promote apoptosis and attenuate proliferation and migration of keloid fibroblasts. Therefore, the authors think that the inhibition of heat shock protein 90 is a key factor in the regulation of biological processes in keloids. With further preclinical study, the authors will be able to apply these results clinically for keloid treatment.

  2. Intelligent styring af dynamisk LED belysning

    DEFF Research Database (Denmark)

    Thorseth, Anders; Corell, Dennis Dan; Hansen, Søren Stentoft

    Denne slutrapport giver en kort beskrivelse af arbejdet, der er udført af DTU Fotonik i projektet ”Intelligent styring af dynamisk LED belysning” støttet af EUDP. Arbejdet er udført i perioden 2011‐2012 i samarbejde med Lighten.......Denne slutrapport giver en kort beskrivelse af arbejdet, der er udført af DTU Fotonik i projektet ”Intelligent styring af dynamisk LED belysning” støttet af EUDP. Arbejdet er udført i perioden 2011‐2012 i samarbejde med Lighten....

  3. Nyttigt bidrag til professionalisering af revisionsudvalg

    DEFF Research Database (Denmark)

    Thomsen, Steen

    2009-01-01

    Anmeldelse af: KPMG. 2009, Audit Committee Institute. Revisionsudvalg i Praksis. 2. reviderede udgave.......Anmeldelse af: KPMG. 2009, Audit Committee Institute. Revisionsudvalg i Praksis. 2. reviderede udgave....

  4. Study on the toxic side effect of 131I-17-AAG treatment in ovarian cancer-bearing nude mice

    International Nuclear Information System (INIS)

    Gao Wen

    2007-01-01

    Objective: To investigate the toixc side effect on bone marrow and hepatic function of 131 I-17-allylamino-17-demethoxy geldanamycin ( 131 I-17 AAG) treatment for ovarian-cancer-bearing nude mice models. Methods: Ovarian-cancer- bearing nude mice models (n=40) were prepared with cancer cell inoculation. 131 I labelled 17 AAG originally prepared in this laboratory was used intravenously for treatment at a single dose of 3 mCi in 20 models and the remain 20 models were used as controls. Rontine bllod examination (CBC, Hgb, platalet) and liver function test (ALT, AST, ALP and r-GT) were performed in these models at lwk and 2wk after treatment. Results: CBC and Hgb in the treated models were not much different from those in controls at 2wk with the exception of a higher platalet count (P 0.05). Conclusion: Toxic side-effect of 131 I-17-AAG treatment on hematologyical and hepatic function in the models was rather mild and there was a tendency toward recovery at 2wk after treatment. (authors)

  5. Roles of Aag, Alkbh2, and Alkbh3 in the Repair of Carboxymethylated and Ethylated Thymidine Lesions.

    Science.gov (United States)

    You, Changjun; Wang, Pengcheng; Nay, Stephanie L; Wang, Jianshuang; Dai, Xiaoxia; O'Connor, Timothy R; Wang, Yinsheng

    2016-05-20

    Environmental and endogenous genotoxic agents can result in a variety of alkylated and carboxymethylated DNA lesions, including N3-ethylthymidine (N3-EtdT), O(2)-EtdT, and O(4)-EtdT as well as N3-carboxymethylthymidine (N3-CMdT) and O(4)-CMdT. By using nonreplicative double-stranded vectors harboring a site-specifically incorporated DNA lesion, we assessed the potential roles of alkyladenine DNA glycosylase (Aag); alkylation repair protein B homologue 2 (Alkbh2); or Alkbh3 in modulating the effects of N3-EtdT, O(2)-EtdT, O(4)-EtdT, N3-CMdT, or O(4)-CMdT on DNA transcription in mammalian cells. We found that the depletion of Aag did not significantly change the transcriptional inhibitory or mutagenic properties of all five examined lesions, suggesting a negligible role of Aag in the repair of these DNA adducts in mammalian cells. In addition, our results revealed that N3-EtdT, but not other lesions, could be repaired by Alkbh2 and Alkbh3 in mammalian cells. Furthermore, we demonstrated the direct reversal of N3-EtdT by purified human Alkbh2 protein in vitro. These findings provided important new insights into the repair of the carboxymethylated and alkylated thymidine lesions in mammalian cells.

  6. Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance.

    Science.gov (United States)

    O'Malley, Katherine J; Langmann, Gabrielle; Ai, Junkui; Ramos-Garcia, Raquel; Vessella, Robert L; Wang, Zhou

    2012-07-01

    Advanced prostate cancer is currently treated with androgen deprivation therapy (ADT). ADT initially results in tumor regression; however, all patients eventually relapse with castration-resistant prostate cancer. New approaches to delay the progression of prostate cancer to castration resistance are in desperate need. This study addresses whether targeting Heat shock protein 90 (HSP90) regulation of androgen receptor (AR) can inhibit prostate cancer progression to castration resistance. The HSP90 inhibitor 17-AAG was injected intraperitoneally into nude mice bearing LuCaP35 xenograft tumors to determine the effect of HSP90 inhibition on prostate cancer progression to castration resistance and host survival. Administration of 17-AAG maintained androgen-sensitivity, delayed the progression of LuCaP35 xenograft tumors to castration resistance, and prolonged the survival of host. In addition, 17-AAG prevented nuclear localization of endogenous AR in LuCaP35 xenograft tumors in castrated nude mice. Targeting Hsp90 or the mechanism by which HSP90 regulates androgen-independent AR nuclear localization and activation may lead to new approaches to prevent and/or treat castration-resistant prostate cancer. Copyright © 2011 Wiley Periodicals, Inc.

  7. Modellering af elforbrug til netanalyse

    DEFF Research Database (Denmark)

    Østergaard, Jacob

    I denne rapport undersøges mulighederne for at etablere en model for elforbruget, der kan anvendes ved analyser af det østdanske transmissionsnet. Rapporten henvender sig til ingeniører og beslutningstagere, der ønsker viden om betydningen af en nøjagtig elforbrugsmodel og om mulighederne for i p...... simuleringsresultater med mindre usikkerhed, og der opnås en integration mellem eksisterende systemer, idet data fra en række systemer bl.a. Panda, elforbrugsprognoser, elforbrugspaneler og stationsprognoser kan udnyttes til etableringen af en model....

  8. The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG.

    Science.gov (United States)

    Lv, Chao; Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Chuang; Fang, Ting; Yang, Pei-Ming; Wu, Tong; Zhou, Yu-Dong; Nagle, Dale G; Zhang, Wei-Dong

    2018-02-07

    Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.

  9. The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

    Science.gov (United States)

    Georgakis, Georgios V; Li, Yang; Rassidakis, Georgios Z; Medeiros, L Jeffrey; Younes, Anas

    2006-12-01

    Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

  10. Rating af banker og banksystemer

    DEFF Research Database (Denmark)

    Grosen, Anders

    2010-01-01

    Banksystemer over hele verdenen er med nød og næppe blevet reddet af diverse statslige hjælpepakker. Derfor er der i disse år øget fokus på banker og banksystemers rating. Denne interesse bliver ikke mindre af, at de statslige garantier til bankerne i mange lande udløber i de kommende år. Rating ...

  11. Analyse og design af produktionssystemer

    DEFF Research Database (Denmark)

    Johansen, John; Riis, Jens Ove; Arlbjørn, Jan Stentoft

    lys, men til vores store glæde og overraskelse har vi erfaret, at dele af materialet stadigvæk er anvendt på en del ingeniør- og økonomiuddannelser i Danmark. Nogle af de tanker og metoder som blev udviklet i ViPSprogrammet har overlevet og opfattes fortsat som relevante og anvendelige også til...

  12. Kants Kritik af dømmekraften

    DEFF Research Database (Denmark)

    Introduktion til Kants Kritik af dømmekraften bestående af otte artikler, der følger værkets egen tematiske opbygning......Introduktion til Kants Kritik af dømmekraften bestående af otte artikler, der følger værkets egen tematiske opbygning...

  13. Bilag til forskningsoversigt - Effekterne af Cooperative Learning

    DEFF Research Database (Denmark)

    Larsen, Lea Lund

    Ved en opsamling af de empiriske studier vedrørende effekten af CL inden for voksenundervisningsfeltet ses en overvægt af studier, som rapporterer en positiv effekt af CL i forhold til de voksne lærendes faglige udbytte. En meta-analyse over 168 amerikanske undersøgelser på universitetsniveau vis...

  14. Beregning af luftlydisolation mellem to rum

    DEFF Research Database (Denmark)

    Donovan, A.

    Meddelelsen bringer resultaterne af en forundersøgelse af to beregningsmetoder. Den ene metode belyses nærmere gennem nogle forenklede eksempler, der viser omfanget af regnearbejdet og peger på nogle af de vanskeligheder det vil indebære at opstille en praktisk anvendelig beregningsmetode....

  15. På sporet af de gyldne opskrifter?

    DEFF Research Database (Denmark)

    Poulfelt, Flemming

    2015-01-01

    Børsen Ledelse. Markedet for kogebøger er stort. For der produceres hvert år et hav nye af slagsen. Nogle udgives af kendte kokke, nogle af særlige eksperter inden for kost og motion, og andre af personer, der har en ægte interesse inden for gastronomi og mad. På ledelsesområdet findes en...

  16. Udvikling af systemleverancer, parametri og BIM

    DEFF Research Database (Denmark)

    Kortegaard, Per

    2016-01-01

    Seminaret rummede indlæg fra både nogle af projektets tidligere ph.d.-studerende og forskellige kompetente professionelle personer fra forskellige grene af praksis. Seminaret gav samlet et fint billede af status indenfor udviklingen af systemleverancer og deres anvendelse i relation til BIM...

  17. Test af spørgeskema

    DEFF Research Database (Denmark)

    Hermansen, Jonathan

    2017-01-01

    Denne bog gennemgår alle surveyarbejdets faser og giver en praktisk indføring i •design af undersøgelsen og udvælgelse af stikprøver, •formulering af spørgeskemaer samt indsamling og kodning af data, •metoder til at analysere resultaterne....

  18. Professor: Lær af Canada

    DEFF Research Database (Denmark)

    Greve, Carsten

    2013-01-01

    Transportdebatten: En mulig finansiering af fremtidige infrastrukturprojekter kunne være OPP. Danmark bør tage ved lære af erfaringer fra Canada.......Transportdebatten: En mulig finansiering af fremtidige infrastrukturprojekter kunne være OPP. Danmark bør tage ved lære af erfaringer fra Canada....

  19. Fremtidens biblioteksbetjening af børn

    DEFF Research Database (Denmark)

    Høyrup, Helene

    2008-01-01

    Rapporten er resultatet af et tværministerielt udvalgsarbejde nedsat af Kulturministeriet.  Kommissoriet har været at nytænke biblioteksbetjeningen af børn, så den passer til vidensamfundet.  Udvalgsarbejdet munder ud i ti bud for fremtidens biblioteksbetjening af børn....

  20. Regulering af det psykiske arbejdsmiljø

    DEFF Research Database (Denmark)

    Nielsen, Klaus T.

    nationale informationer om reguleringen af det psykiske arbejdsmiljø. Rapport er bygget op med ◊ et internationalt overblik over regulering af psykisk arbejdsmiljø ◊ en bredere diskussion af reguleringens dilemmaer ◊ en gennemgang af den aktuelle danske udvikling ◊ udfordringerne på området...

  1. Implementering af MultifunC

    DEFF Research Database (Denmark)

    Henze-Pedersen, Sofie; Kohl, Katrine Syppli; Oldrup, Helene

    (MultifunC), som allerede havde vist lovende resultater i Norge og Sverige. I 2011 og 2012 åbnede to danske MultifunC-institutioner derfor i henholdsvis København og Aarhus. Denne rapport undersøger, hvordan implementeringen af MultifunC-programmet er forløbet i Danmark. Undersøgelsen viser, at ingen af de...... to danske institutioner lykkedes med at implementere MultifunC tilfredsstillende i løbet af implementeringsperioden. Det har fx været vanskeligt at implementere det tætte tværfaglige samarbejde mellem medarbejdere med forskellige fagprofessionelle baggrunde, som behandlingsprogrammet indebærer. Det har...... desuden været særdeles vanskeligt for de danske MultifunC-institutioner at få etableret det eksterne samarbejde med de sociale myndigheder i kommunerne, politiet, skoler og praktiksteder samt fritidstilbud i nærområdet, som også er en væsentlig del af behandlingsprogrammet. Undersøgelsen af finansieret af...

  2. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    Pradhan, Roshan; Poudel, Bijay Kumar; Choi, Ju Yeon; Choi, Im Soon; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-01-01

    In the present study, we developed the novel 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate and poloxamer 407 as the anionic and non-ionic surfactant for stabilization. The PLGA NPs were prepared by emulsification/solvent evaporation method. Both the drug/polymer ratio and phase ratio were 1:10 (w/w). The optimized formulation of 17-AAG-loaded PLGA NPs had a particle size and polydispersity index of 151.6 ± 2.0 and 0.152 ± 0.010 nm, respectively, which was further supported by TEM image. The encapsulation efficiency and drug loading capacity were 69.9 and 7.0%, respectively. In vitro release study showed sustained release. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.468, which suggested that the drug was released by anomalous or non-Fickian diffusion. In addition, 17-AAG-loaded PLGA NPs in 72 h, displayed approximately 60% cell viability reduction at 10 µg/ml 17-AAG concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of 17-AAG into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  3. 17-AAG, a Hsp90 inhibitor, attenuates the hypoxia-induced expression of SDF-1alpha and ILK in mouse RPE cells.

    Science.gov (United States)

    Wang, Ye Qing; Zhang, Xiao Mei; Wang, Xiao Dan; Wang, Bin Jie; Wang, Wei

    2010-03-01

    The aim of this study was to investigate the changes of SDF-1alpha and ILK expression in mouse retinal pigment epithelium (RPE) cells in response to hypoxia, and the effect of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (Hsp90) inhibitor, on the hypoxia-induced expression of SDF-1alpha and ILK. RPE cells were cultured with 200 micromol/L cobalt chloride (CoCl(2)) for different times (1, 3, 6, 12, 24, 72 h) to imitate chemical hypoxia. Pretreatment of 17-AAG was 1 h prior to hypoxic insult. Cellular viability after 17-AAG treatment was assessed by MTT assay, and the changes of SDF-1alpha and ILK expression were examined by RT-PCR and Western blot. Up-regulation of SDF-1alpha and ILK expression in response to hypoxia was observed. One hour pretreatment of 17-AAG could remarkably decreased the hypoxia-induced SDF-1alpha and ILK expression in vitro. Our results indicated that SDF-1alpha and ILK involved in the hypoxic response of RPE cells, and 1 h pretreatment of 17-AAG had an inhibitive effect on the hypoxia-induced SDF-1alpha and ILK expression.

  4. Cytotoxic effects of the newly-developed chemotherapeutic agents 17-AAG in combination with oxaliplatin and capecitabine in colorectal cancer cell lines.

    Science.gov (United States)

    Mohammadian, Mahshid; Zeynali, Shima; Azarbaijani, Anahita Fathi; Khadem Ansari, Mohammad Hassan; Kheradmand, Fatemeh

    2017-12-01

    The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) has been recently introduced as an attractive anticancer therapy. It has been shown that 17-AAG may potentiate the inhibitory effects of some classical anticolorectal cancer (CRC) agents. In this study, two panels of colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in combination with capecitabine and oxaliplatin as double and triple combination therapies on the proliferation of CRC cell lines. HT-29 and all HCT-116 cell lines were seeded in culture media in the presence of different doses of the mentioned drugs in single, double, and triple combinations. Water-soluble tetrazolium-1 (WST-1) assay was used to investigate cell proliferation 24 h after treatments. Then, dose-response curves were plotted using WST-1outputs, and IC 50 values were determined. For double and triple combinations respectively 0.5 × IC 50 and 0.25 × IC 50 were used. Data was analyzed with the software CompuSyn. Drug interactions were analyzed using Chou-Talalay method to calculate the combination index (CI).The data revealed that 17-AAG shows a potent synergistic interaction (CI 1) in HT-29 and a synergistic effect (CI AAG with oxaliplatin or capecitabine might be effective against HCT-116 and HT-29 cell lines. However, in triple combinations, positive results were seen only against HCT-116. Further investigation is suggested to confirm the effectiveness of these combinations in clinical trials.

  5. Brug af alternativ isolering i forbindelse med renovering af ældre etageejendomme

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2003-01-01

    Resume af rapport om praktiske erfaringer med brug af alternative isoleringsmaterialer i en renoveringsopgave, udarbejdet af Byfornyelse København m.fl. under Energistyrelsens udviklingsprogram "Miljø- og arbejdsmiljøvenlig isolering"...

  6. Hsp90 inhibitor 17-AAG sensitizes Bcl-2 inhibitor (-)-gossypol by suppressing ERK-mediated protective autophagy and Mcl-1 accumulation in hepatocellular carcinoma cells.

    Science.gov (United States)

    Wang, Bin; Chen, Linfeng; Ni, Zhenhong; Dai, Xufang; Qin, Liyan; Wu, Yaran; Li, Xinzhe; Xu, Liang; Lian, Jiqin; He, Fengtian

    2014-11-01

    Natural BH3-memitic (-)-gossypol shows promising antitumor efficacy in several kinds of cancer. However, our previous studies have demonstrated that protective autophagy decreases the drug sensitivities of Bcl-2 inhibitors in hepatocellular carcinoma (HCC) cells. In the present study, we are the first to report that Hsp90 inhibitor 17-AAG enhanced (-)-gossypol-induced apoptosis via suppressing (-)-gossypol-triggered protective autophagy and Mcl-1 accumulation. The suppression effect of 17-AAG on autophagy was mediated by inhibiting ERK-mediated Bcl-2 phosphorylation while was not related to Beclin1 or LC3 protein instability. Meanwhile, 17-AAG downregulated (-)-gossypol-triggered Mcl-1 accumulation by suppressing Mcl-1(Thr163) phosphorylation and promoting protein degradation. Collectively, our study indicates that Hsp90 plays an important role in tumor maintenance and inhibition of Hsp90 may become a new strategy for sensitizing Bcl-2-targeted chemotherapies in HCC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Børn af veteraner

    DEFF Research Database (Denmark)

    Frederiksen, Signe; Lausten, Mette

    Siden starten af 1990’erne har Danmark sendt over 30.000 soldater og andet personel på internationale missioner – langt de fleste til Eks-Jugoslavien, Afghanistan og Irak. Denne undersøgelse handler om de børn, hvis fædre har været udsendt på militære missioner i udlandet. For hvordan håndterer...... spørgsmål er fokus for undersøgelsen. Undersøgelsen bygger på en spørgeskemaundersøgelse blandt børn af veteraner på henholdsvis 7, 11 og 15 år. Undersøgelsen er gennemført for og i samarbejde med Veterancentrets Videncenter, som er en del af Forsvarsministeriets Personalestyrelse....

  8. Styring af international transfer pricing

    DEFF Research Database (Denmark)

    Reuther, Peter; Rossing, Christian Plesner

    2011-01-01

    Nærværende artikel introducerer international transfer pricing, dels som et skatteretligt fænomen og dels som et værktøj til planlægning og økonomisk styring af koncernforbundne selskaber i en multinational virksomhed (MNV). Med udgangspunkt i en case-analyse af MNV’en gives der et konkret eksempel...... på hvordan transfer pricing håndteres i praksis. Artiklens formål er at give et praktisk eksempel på at transfer pricing handler om at efterleve regler, ikke omgå dem. På baggrund af case-analysen argumenteres der for, at såvel akademikere som praktikere bør tage virksomhedens tilgang til...... international transfer pricing i betragtning, når økonomiske styringssystemer i en MNV skal anvendes til planlægning og opfølgning....

  9. Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery.

    Science.gov (United States)

    Won, Young-Wook; Yoon, Sun-Mi; Sonn, Chung Hee; Lee, Kyung-Mi; Kim, Yong-Hee

    2011-05-24

    A wide variety of drug delivery systems have been developed for the delivery of anticancer agents. One of the most frequently used natural biomaterials in drug delivery systems is polysaccharides; however, they are difficult to digest and to eliminate from the body after systemic administration due to their high molecular weight natures and the absence of degrading enzymes. Therefore, the development of degradable and eliminable natural biomaterials is critical for successful in vivo applications. In the present study, we report the development of self-assembled biodegradable nanoparticles based on recombinant human gelatin (rHG) modified with alpha-tocopheryl succinate (TOS). The rHG-TOS nanoparticles efficiently encapsulated 17-AAG (17-allylamino-17-demethoxygeldanamycin), a small molecular anticancer drug targeting heat shock protein 90. The formation of 17-AAG-loaded nanoparticles was confirmed using TEM and dynamic light scattering analysis and found to be within the size of 90-220 nm. The loading efficiency, sustained release pattern, and stability of 17-AAG from the rHG-TOS nanoparticles were determined using HPLC. Furthermore, the passive targeting of rHG-TOS nanoparticles to the tumor area via enhanced permeability and retention effect was examined by noninvasive live animal imaging in a tumor mouse model. Finally, the 17-AAG-loaded nanoparticles were nonimmunogenic and more efficient than free 17-AAG in manifesting an anticancer effect in the tumor model. Overall, our data demonstrate rHG-TOS as a promising tool for the delivery of 17-AAG featuring therapeutic efficacy and biocompatibility.

  10. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    Science.gov (United States)

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  11. Strategi til udbredelse og udvikling af aquaponik

    OpenAIRE

    Bartholin, Aline; Nielsen, Per

    2014-01-01

    Denne rapport omhandler, hvorledes aquaponik i fremtiden skal udbredes med henblik på at produktionsmetoden bliver en del af den etablerede fødevaresektor. Ud fra et interview med PlanteLaboratoriet som er en del af foreningen Akvaponisk Selskab, samt observationer af en workshop afholdt af PlanteLaboratoriet forsøger vi at kortlægge den førte strategi til udbredelse og udvikling af aquaponik, samt undersøge hvorledes aquaponik som innovation bliver taget imod af mulige adoptere. Empirien sam...

  12. Kortlægning af evalueringer og undersøgelser af vejledning knyttet til vejledning af unge i UU-regi

    DEFF Research Database (Denmark)

    Skovhus, Randi Boelskifte; thomsen, rie

    2013-01-01

    Kortlægning af evalueringer og undersøgelser af vejledning knyttet til vejledning af unge i UU-regi 2004-2013. Et arbejdspapir......Kortlægning af evalueringer og undersøgelser af vejledning knyttet til vejledning af unge i UU-regi 2004-2013. Et arbejdspapir...

  13. Logning af teledata i lyset af Tele2-dommen

    DEFF Research Database (Denmark)

    Lentz, Lene Wacher

    2017-01-01

    De danske teleudbydere har siden 2007 været underlagt en pligt efter logningsbekendtgørelsen til at registrere data om al telekommunikation for at sikre at data er tilgængelige ved en eventuel senere efterforskning. Logningspligten må nu revideres og i vidt omfang afvikles som følge af EU-domstol...

  14. Undersøgelse af kommunernes administration af bygningsreglementets elevatorkrav

    DEFF Research Database (Denmark)

    Grangaard, Sidse

    Denne rapport undersøger kommunernes praksis omkring administrationen af bygningsreglementets krav om elevator ved nybyggeri og ombygning. Blandt de 26 kommuner, der har deltaget i undersøgelsen, var der generelt konsensus om at stille krav om elevator ved nybyggeri. Kommunerne modtager kun meget...

  15. Betydningen af pesticider for forekomsten af vilde bier

    DEFF Research Database (Denmark)

    Bruus, Marianne; Dupont, Yoko Luise; Grant, Ruth

    Både i Danmark og andre steder er der observeret en nedgang i de insekter, der bestøver landmandens afgrøder og de vilde planter. Tilbagegangen falder sammen med, at landbrugsdriften er blevet mere intensiv, og anvendelsen af pesticider er øget. Vi ved imidlertid ikke, hvilken rolle pesticiderne ...

  16. Forekomst af resistente bakterier og forbrug af antibiotika til hunde

    DEFF Research Database (Denmark)

    Pedersen, Karl; Pedersen, Kristina; Jensen, Helene

    2007-01-01

    ), Pasteurella multocida (n=25), Bordetella bronchiseptica (n=14), Proteus spp. (n=29), og E. coli (n=449). I undersøgelsen anvendtes data fra VetStat databasen. Størstedelen af de antibiotika, der bruges til hunde er bredspektrede. Penicilliner med udvidet spektrum, cephalosporiner samt sulphonamider...

  17. Transkateterlukning af venstre atriums aurikel til forebyggelse af apoplexia cerebri

    DEFF Research Database (Denmark)

    Loupis, Anastasia M; De Backer, Ole; Ihlemann, Nikolaj

    2014-01-01

    In patients with atrial fibrillation (AF) and increased risk of stroke, oral anticoagulation (OAC) is the standard treatment for stroke prevention - however, this therapy also carries a high risk of bleeding. Percutaneous closure of the left atrial appendage (LAA) has been suggested to be an alte...

  18. The Hsp90 inhibitor 17-AAG represses calcium-induced cytokeratin 1 and 10 expression in HaCaT keratinocytes.

    Science.gov (United States)

    Miyoshi, Sadanori; Yamazaki, Shota; Uchiumi, Asato; Katagata, Yohtaro

    2012-01-01

    Hsp90 is essential for maintaining the activity of numerous signaling factors, and plays a key role in cellular signal transduction networks. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an ansamycin antibiotic that binds to Hsp90 and inhibits its function. HaCaT human keratinocytes were used to investigate the cellular and molecular functions of Hsp90 in keratinocyte differentiation. Inhibition of Hsp90 by 17-AAG leads to downregulation of the differentiation markers cytokeratin 1 and cytokeratin 10 at the protein and mRNA levels.

  19. Ledelse af ledelse i udviklingssamtaler

    DEFF Research Database (Denmark)

    Ryberg, Birgit

    2012-01-01

    Hvem sætter dagsorden for udvikling? Udviklingssamtaler er præget af forskellige ledende interessser, der ikke blot konkurrerer om at vinde indflydelse, men også skaber tvetydigheder og doublebind, som ledere og medarbejdere må forholde sig til....

  20. Kvalifikation af skattesubjekter og traktatbeskyttelse

    DEFF Research Database (Denmark)

    Bolander, Jane

    2014-01-01

    Artiklen er baseret på generalrapporten og den danske nationalrapport om emnet “Qualification of taxable entities and treaty protection”, der er udarbejdet til IFA-kongressen 2014 i Mumbai. Artiklen opsummerer konklusionerne fra generalrapportens komparative studier, og forhold af særlig dansk...

  1. Afgivelse af formue til trusts

    DEFF Research Database (Denmark)

    Feldthusen, Rasmus Kristian

    2009-01-01

    Kravet om at en stifter skal have foretaget en "uigenkaldelig og effektiv udskillelse" for at dansk skatteret vil anerkende at der foreligger en trust vurderes. Kravet er senest lagt til grund i SKM 2009.249 SR. Forfatteren opfordrer til, at SKAT i stedet foretager en konkret vurdering af selve...

  2. Digitalisering af det eksisterende byggeri

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke; Øien, Turid Borgestrand

    2010-01-01

    Digitalisering af det eksisterende byggeri er en vanskelig og uendelig opgave. Det giver kun mening at digitalisere eksisterende byggeri, når man har et konkret behov, og da kun at indhente og lagre de informationer, som man strategisk eller konkret har behov for. Erhvervs og Byggestyrelsen har i...

  3. Evaluering af Animationsbaseret Sketching Workshop

    DEFF Research Database (Denmark)

    Vistisen, Peter; Hautopp, Heidi

    2017-01-01

    Formålet med workshoppen var at styrke forskere fra Ild-Lab i at anvende animationsbaseret sketching og prototyping i deres undervisning således, at undervisningen understøtter designbaserede tilgange, der er mere produkt- og teknologiorienteret. På denne led kan vi styrke materialiseringen af hu...

  4. Udredning af xerostomi og hyposalivation

    DEFF Research Database (Denmark)

    Pedersen, Anne Marie Lynge; Dynesen, Anja Weirsøe; Jensen, Siri Beier

    2011-01-01

    Mundtørhed kræver grundig undersøgelse Xerostomi er ofte associeret til betydelig nedsat spytsekretion, men kan forekomme, uden at der objektivt kan påvises nedsat spytsekretion. Udredning af patienter, som klager over mundtørhed, bør således altid inkludere en omhyggelig anamnese, en detaljeret ...

  5. Danskernes brug af nyhedsmedier 2018

    DEFF Research Database (Denmark)

    Schrøder, Kim Christian; Ørsten, Mark; Eberholst, Mads Kæmsgaard

    Hvis der er ét begreb, der i 2018 er blevet slået fast med syvtommersøm i den offentlige debat verden over, så er det ’fake news’! Bekymringen over fænomenet er vokset eksplosivt, samtidig med at det er blevet mere og mere uklart, hvad ’fake news’ egentlig dækker over. I dette års analyse af...... brugen af nyhedsmedier sætter Reuters Institute Digital News Report, og også denne specialrapport om Danmark, analytisk fokus på ’fake news’ og kaster lys over borgernes opfattelse af fænomenet på en måde, så vi får nuancerne i det komplekse begreb med. Et andet emne, der er blevet diskuteret...... for fake news og egne oplevelser af fake news, og danskernes viden om, hvordan nyheder bliver lavet (nyheds-literacy)....

  6. Overholdelse af kravene i bygningsreglementet

    DEFF Research Database (Denmark)

    Christensen, Toke Haunstrup; Jensen, Jesper Ole; Gram-Hanssen, Kirsten

    Denne rapport undersøger, hvorvidt bestemmelserne i bygningsreglementet BR10 omkring energieffektivisering ved renoveringen af bygninger bliver overholdt. Der fokuseres især på parcelhuse, da problemet med manglende overholdelse menes at være størst her, ligesom potentialet for energibesparelser...

  7. Ledelsesroller i globalisering af cleantech

    DEFF Research Database (Denmark)

    Knudsen, Poul Frøjk; Tambo, Torben

    2011-01-01

    nyeste teknologier, globalisering af salg, installation og produktion, og at vækstdagsordenen er blevet fastholdt. Den globale satsning på cleantech sætter disse ledelsesmæssige kvaliteter under pres. Dette studie ser på en mellemstor komponentleverandør til vindindustrien, og dennes kamp...

  8. Virksomhedernes opfattelse af arbejdsmarkedets "restgrupper"

    DEFF Research Database (Denmark)

    Larsen, Christian Albrekt

    2010-01-01

    Artiklen beskriver, hvorledes danske arbejdsgivere opfatter ældre ledige, ledige indvandrere og ledige med lang forudgående ledighed. Det teoretiske udgangspunkt er, at arbejdsmarkedets fundamentale informationsproblemer fører til brug af statistisk diskrimination og frygt for «lemons». Analyserne...

  9. På sporet af fremtidens konkurrenceevne

    DEFF Research Database (Denmark)

    Boje Rasmussen, Martin Møller

    2013-01-01

    Michael Porter og Harvard Business School står bag nyt banebrydende initiativ, Social Progress Index, som måler et samfunds evne til at skabe livskvalitet for borgerne. Dette aktualiserer debatten om udviklingen af helt nye konkurrencemodeller. Der er tale om et valg mellem tre forskellige typer...

  10. Sygeplejestuderendes brug af portfolio i klinisk undervisning

    DEFF Research Database (Denmark)

    Hjorth, Anne Charlotte Overgaard; Bruhn, Helle

    2014-01-01

    Brugen af portfolio var mangelfuld, men et udviklingsprojekt i samarbejde med den kommunale sygepleje motiverede både sygeplejestuderende og kliniske vejledere til at anvende læringsdelen af portfolio aktivt.......Brugen af portfolio var mangelfuld, men et udviklingsprojekt i samarbejde med den kommunale sygepleje motiverede både sygeplejestuderende og kliniske vejledere til at anvende læringsdelen af portfolio aktivt....

  11. Udviklingen af rumopfattelsen 1600-2000

    DEFF Research Database (Denmark)

    Brock, Steen

    2010-01-01

    Hovedtræk af rumopfattelsens idehistorie fra Descartes til Wittgenstein med speciel vægt på Kant, værkbegrebet, modelbegrebet og den fænomenologiske opfattelse af rummet som handlingens sted......Hovedtræk af rumopfattelsens idehistorie fra Descartes til Wittgenstein med speciel vægt på Kant, værkbegrebet, modelbegrebet og den fænomenologiske opfattelse af rummet som handlingens sted...

  12. Identifikation af referencevandløb til implementering af vandrammedirektivet i Danmark

    DEFF Research Database (Denmark)

    Kristensen, Esben Astrup; Baattrup-Pedersen, Annette; Skriver, Jens

    Definition og beskrivelse af referencetilstanden er centralt for implementering af vandrammedirektivet, da bedømmelse af den økologiske tilstand sker som afvigelsen fra den upåvirkede referencetilstand. I denne rapport præsenteres analyser af danske, udenlandske og historiske data med det formål...

  13. Aspekter af integrationsindsatsen i 6 kommuner

    DEFF Research Database (Denmark)

    Rosdahl, Anders

    Dette arbejdspapir præsenterer resultaterne af en mindre kvalitativ undersøgelse af kommuners indsats for at bringe nyankomne flygtninge og indvandrere i beskæftigelse. Undersøgelsen er en opfølgning på en kvantitativ benchmarkanalyse, som er gennemført af Amternes og Kommunernes Forskningsinstit...

  14. Registrering af biometriske og biologiske personoplysninger

    DEFF Research Database (Denmark)

    Blume, Peter Erik; Herrmann, Janne Rothmar

    2009-01-01

    Med udgangspunkt i menneskeretsdomstolens Marper dom drøftes i artiklen indretningen af dansk rets regler om registrering af fingeraftryk og dna-profil med tilhørende biologisk materiale, og om dommen nødvendiggør ændringer af disse regler....

  15. Delegation af lovgivningsmagt: risiko for ringere regulering?

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk; Christensen, Geert Laier; Ravn, Jacob

    2016-01-01

    kortsigtetede, politiske incitamenter. Samtidig underlægges delegation ikke samme grad af kvalitetskontrolmekanismer som almindelig lovgivning; dette kunne ellers kompensere for den mere politiserede delegation. En øget brug af bekendtgørelser kan derfor betyde en stigende risiko for regulering af lavere...

  16. Registrering og Benchmarking af Modus 2 Forskning

    DEFF Research Database (Denmark)

    Duus, Henrik Johannsen; Jørgensen, Jens E.

    2004-01-01

    Fremvæksten af modus 2 forskning stiller krav om en revurdering af højere læreanstalters evaluerings- og meriteringspraksis. Den endimensionale prioritering af modus 1 forskning såvel som dennes ligeså endimensionale evaluering via publikationer må afvises som utidssvarende. Som en konsekvens her...

  17. Energioptimering af bæredygtighedscertificeringsprocesserne

    DEFF Research Database (Denmark)

    Christensen, Dorthe Holmberg; Carlsen, Mads; Alon, Shlomo Nevo

    2014-01-01

    Større fokus på bæredygtighedscertificeringer som DGNB har yderligere øget kompleksiteten af designet af bygninger. Introduktionen af teknologier som building information modelling (BIM) og proces metoder som integreret design proces (IDP) kan hjælpe med at reducere kompleksiteten og bedre...

  18. Regulering af jødiske kroppe

    DEFF Research Database (Denmark)

    Schleicher, Marianne

    2014-01-01

    på teori dels af Michel Foucault om, hvordan kultur sikrer sin egen overlevelse ved at indsamle viden om bl.a. kroppe med henblik på at regulere brugen af dem, dels af Judith Butler, der bl.a. forklarer, hvordan kultur trods alt er åben for såkaldt subversion, idet det bidrager til at udvide og...

  19. Magtens repræsentation af danskhed

    DEFF Research Database (Denmark)

    Madsen, Carsten

    2016-01-01

    Med udgangspunkt i Maurice Charlands begreb om konstitutiv retorik og Jacques Derridas dekonstruktion af repræsentationslogik foretager artiklen en kritisk analyse og fortolkning af repræsentationen af dansk nationalidentitet, sådan som den kommer til udtryk i Dronning Margrethes nytårstaler...

  20. Prøvetagning af grundvand

    DEFF Research Database (Denmark)

    Sørensen, Inga

    Bogen fokuserer på prøveatgning af grundvand og drikkevand til forskellige formål såsom undersøgelse af forurenede grunde, grundvandsmonitering samt produktion af drikkevand. Da grundvand i sagens natur findes under jordoverfladen, beskriver bogen også væsentlige forhold om hydrogeologi og...

  1. Modelanalyser af mobilitet og miljø

    DEFF Research Database (Denmark)

    Christensen, Linda; Gudmundsson, Henrik

    Begrebet bæredygtig transport diskuteres og ved hjælp af persontrafikmodellen ALTRANS belyses mulighederne for at fremme bæredygtig udvikling gennem en række scenarier. Desuden præsenteres en mere detaljeret analyse af ændringer i CO2-belastningen ved forbedring af den kollektive trafiks servicen...

  2. Hærdeteknologi og Holdbarhed af Betonkonstruktioner

    DEFF Research Database (Denmark)

    Sørensen, Eigil V.

    Kurset Hærdeteknologi og Holdbarhed af Betonkonstruktioner afholdes i 1. og 2. periode af forårssemesteret 2006. Kurset sigter på at give de studerende en grundlæggende forståelse af, hvorledes man designer og udfører holdbare betonkonstruktioner....

  3. Påvisning af PCV2

    DEFF Research Database (Denmark)

    Neumann, Katrine; Buse, Katja Strøm; Hjulsager, Charlotte Kristiane

    2018-01-01

    Mængden af PCV2-virus i poolede serumprøver kan anvendes til at finde grise med meget PCV2-virus, hvorimod mængden af PCV2-virus i spyt og fæces er velegnede til at vurdere tilstedeværelsen af eller tidspunktet for en begyndende PCV2-infektion...

  4. Påvisning af PCV2

    DEFF Research Database (Denmark)

    Neumann, Katrine; Buse, Katja Strøm; Hjulsager, Charlotte Kristiane

    Mængden af PCV2-virus i poolede serumprøver kan anvendes til at finde grise med meget PCV2-virus, hvorimod mængden af PCV2-virus i spyt og fæces er velegnede til at vurdere tilstedeværelsen af eller tidspunktet for en begyndende PCV2-infektion...

  5. Produktion og afsætning af nicheprodukter

    DEFF Research Database (Denmark)

    Jensen, Jonas Baungaard; Hansen, Henning Otte

    2016-01-01

    . Egnsmærker opnår generelt en merpris på 20-30 pct. Det er dog bemærkelsesværdigt, at landmanden “kun” har omkring 13 pct. af forbrugerkronen på Lammefjords-kartofler. Her er der tale om unikke produkter, hvor det i praksis udelukkende er landmanden og landmandens placering og produktion, som skaber de unikke...

  6. Kuidas peaks õpetaja karistama ülekäte läinud õpilast? / Aage Õunap, Toomas Palu, Aivar Haller, Maia Erm

    Index Scriptorium Estoniae

    2008-01-01

    Haridusministri hinnangul peaks koolil olema õigus korda rikkuvaid õpilasi trahvida. Oma arvamust selle kohta avaldavad Viljandimaa Lasterikaste Perede Ühenduse juht Aage Õunap, UNICEF Eesti rahvuskomitee esindaja Toomas Palu, Eesti Lastevanemate Liidu juhatuse liige Aivar Haller ja Pärnu Koidula Gümnaasiumi õppealajuhataja Maia Erm

  7. Effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on Akt protein expression is more effective in head and neck cancer cell lineages that retain PTEN protein expression.

    Science.gov (United States)

    Pontes, Flávia Sirotheau C; Pontes, Hélder A R; de Souza, Lucas L; de Jesus, Adriana S; Joaquim, Andrea M C; Miyahara, Ligia A N; Fonseca, Felipe P; Pinto Junior, Décio S

    2018-03-01

    The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein. Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF. Treatment with EGF resulted in increased levels of Akt, PTEN and p53 in all cell lineages. The expression of Mdm2 was constant in HN30 and HN6 lineages, while in HN19 showed slightly decreased expression. Under the action 17-AAG, in HN6 and HN19, the expression of PTEN and p53 proteins was suppressed, while Akt and Mdm2 expression was reduced. Finally, in the HN30 cell lineage were absolute absence of expression of Akt, Mdm2 and p53 and decreased expression of PTEN. These data allow us to speculate on the particular utility of 17-AAG for HNSCC treatment through the inhibition of Akt protein expression, especially in the cases that retain the expression of PTEN protein. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Barrierer for ibrugtagning af videooptaget universitetsundervisning

    DEFF Research Database (Denmark)

    Rattleff, Pernille

    2009-01-01

    tilgængelige for studerende og andre interesserede. Der kan således iagttages nogle barrierer i forhold til ibrugtagning af videooptaget undervisning på universitetsniveau, idet underviserne for en umiddelbar betragtning tilsyneladende for det første har nogle forbehold af psykologisk, for det andet af...... begrebsafklaring, præsenterer forfatterne i denne artikel erfaringerne med tilbud af videostreamet og podcastet universitetsundervisning til studerende på Danmarks Pædagogiske Universitetsskole med henblik på en diskussion af de potentialer og især de barrierer, der kan iagttages i forhold til en mere systematisk...

  9. A combination of Trastuzumab and 17-AAG induces enhanced ubiquitinylation and lysosomal pathway-dependent ErbB2 degradation and cytotoxicity in ErbB2-overexpressing breast cancer cells.

    Science.gov (United States)

    Raja, Srikumar M; Clubb, Robert J; Bhattacharyya, Mitra; Dimri, Manjari; Cheng, Hao; Pan, Wei; Ortega-Cava, Cesar; Lakku-Reddi, Alagarsamy; Naramura, Mayumi; Band, Vimla; Band, Hamid

    2008-10-01

    ErbB2 (or Her2/Neu) overexpression in breast cancer signifies poorer prognosis, yet it has provided an avenue for targeted therapy as demonstrated by the success of the humanized monoclonal antibody Trastuzumab (Herceptin). Resistance to Trastuzumab and eventual failure in most cases, however, necessitate alternate ErbB2-targeted therapies. HSP90 inhibitors such as 17-allylaminodemethoxygeldanamycin (17-AAG), potently downregulate the cell surface ErbB2. While the precise mechanisms of Trastuzumab or 17-AAG action remain unclear, ubiquitinylation-dependent proteasomal or lysosomal degradation of ErbB2 appears to play a substantial role. As Trastuzumab and 17-AAG induce the recruitment of distinct E3 ubiquitin ligases, Cbl and CHIP respectively, to ErbB2, we hypothesized that 17-AAG and Trastuzumab combination could induce a higher level of ubiquitinylation and downregulation of ErbB2 as compared to single drug treatments. We present biochemical and cell biological evidence that combined 17-AAG and Trastuzumab treatment of ErbB2-overexpressing breast cancer cell lines leads to enhanced ubiquitinylation, downregulation from the cell surface and lysosomal degradation of ErbB2. Importantly, combined 17-AAG and Trastuzumab treatment induced synergistic growth arrest and cell death specifically in ErbB2-overexpressing but not in ErbB2-low breast cancer cells. Our results suggest the 17-AAG and Trastuzumab combination as a mechanism-based combinatorial targeted therapy for ErbB2-overexpressing breast cancer patients.

  10. Bidrag til automatisering af ortofotomosaikfremstilling

    DEFF Research Database (Denmark)

    Vestergaard, Jacob Schack; Andersen, Simon G.; Nielsen, Allan Aasbjerg

    Mosaikker af nabo-ortofotos, der udgør et vigtigt element i dagens automatiske kortfremstilling og -opdatering, laves i dag ved håndkraft. Her vil vi vise en vigtig byggeklods til automatisering af denne proces. Der findes metoder, der baserer sig på den såkaldte “bidirectional reflectance...... bestemt ortofoto typisk vil skulle kalibreres til flere nabo-ortofotos. Disse flere kalibreringer vil iblandt være i modstrid med hinanden. For eksempel kan en kalibrering til et ortofoto mod nord udsige, at pixels i ortofotoet skal have en højere værdi samtidigt med, at ortofotoet mod vest kræver en...

  11. Domesticeringen af Ford i Danmark

    DEFF Research Database (Denmark)

    Wagner, Michael

    2011-01-01

    Det amerikanske automobilfirma Ford Motor Company (1903) med hovedkvarter i Detroit begyndte at drive forretning i Danmark omkring 1906. Dermed havde Ford tidligt fået et stærkt fodfæste i Nordeuropa, som udviklingen i salget af Ford automobiler de næste årtier til fulde skulle demonstrere....... Artiklen har fokus på Ford Motor Companys aktiviteter som agent for fordismen i en dansk kulturel kontekst. Hvordan reagerede de danske forretningsforbindelser, politikere, arbejdere og deres fagforeninger, samt forbrugerne på fordismen og de amerikanske forretningsmetoder. På hvilken måde blev forbrugeren...... defineret og inklineret af Ford Motor Company og de danske forhandlere gennem annoncer og andre marketingstiltag, og hvordan blev Ford automobilet kulturelt iscenesat som en ’dansk’ bil....

  12. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  13. Vaccination af slagtekalve mod BRSV

    DEFF Research Database (Denmark)

    Graumann, Anne Mette; Larsen, Lars Erik

    2009-01-01

    Rspiratory Suncytial Virus) blev fundet til at være den typisk fundne virus, der forårsager lungebetændelse. Vacciner imod BRSV er tilgængelige på markedet, men de er aldrig blevt afprøvet systematisk under danske forhold. Formålet med dette forsøg er at undersøge effekten af to forskellige...

  14. Domesticeringen af Ford i Danmark

    DEFF Research Database (Denmark)

    Wagner, Michael

    forstand voksede sig stor og stærk i den selv samme periode som Ford Motor Company gennem udbredelse af bilismen. Det var især FDM's medlemsblad MOTOR, som løbende bragte en stor mængde artikler om Ford Motor Company og reklamer for firmaets produkter i hele perioden 1906-1940. De to store aktører...

  15. Fermentering af korn øger fordøjeligheden af næringsstoffer

    DEFF Research Database (Denmark)

    Pedersen, Anni Øyan; Jørgensen, Henry Johs. Høgh; Knudsen, Knud Erik Bach

    2010-01-01

    Et fordøjelighedsforsøg har vist, at energiværdien af byg og hvede steg ved fermentering. Effekten var størst ved fermentering af byg, hvor fordøjeligheden af organisk stof for enden af tyndtarmen steg statistisk sikkert med 9 %. Ved fermentering af hvede steg fordøjeligheden af organisk stof...... af vand og dels CO2-produktion og dermed tørstoftab. Anbefaling om beregning af energiværdi i fermenteret korn vil blive foretaget ud fra resultaterne af et produktionsforsøg med slagtesvin, som er under publicering. Fosforudnyttelse i fermenteret korn undersøges yderligere i et produktionsforsøg med...

  16. Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG.

    Science.gov (United States)

    Faingold, Dana; Filho, Vasco Bravo; Fernandes, Bruno; Jagan, Lisa; de Barros, Alexandre M; Orellana, Maria Eugenia; Antecka, Emilia; Burnier, Miguel N

    2014-11-01

    Focal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells. FAK expression was assessed in 39 UM specimens, FAK[pY397] expression was assessed in 51 UM specimens, and both FAK and FAK[pY397] expression were assessed in 20 normal eyes. The expression of FAK and FAK[pY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG. FAK was positive in 87.2% and FAK[pY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAK[pY397], and the levels of FAK and FAK[pY397] were decreased in the presence of 17-AAG starting with 24 h of exposure. FAK and FAK[pY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAK[pY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition.

    Directory of Open Access Journals (Sweden)

    Guanxiong Ding

    Full Text Available Though prostate cancer (PCa has slow progression, the hormone refractory (HRCP and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.

  18. Effekter af koordineret hjerneskaderehabilitering. Et systematisk litteraturreview

    DEFF Research Database (Denmark)

    Glintborg, Chalotte; Hansen, Tia G. B.

    beskrevet. Der er ingen klar dansk definition af koordination. Begrebet bliver ofte brugt inkonsistent, og koordination er meget forskelligt tilrettelagt. Derfor kan man ikke generelt dokumentere, om koordinatorfunktioner er en sikker vej til forbedring af komplekse rehabiliteringsforløb. Sundhedsstyrelsen......Forskningsprojekt udvikler ny definition af begrebet koordination Som et led i forskningsprojektet ”Bio-psyko-sociale effekter af koordineret hjerneskaderehabilitering” er der udviklet en ny definition af koordinationsbegrebet. Forskningsprojektet ”Bio-psyko-sociale effekter af koordineret...... senhjerneskadeområdet – initiativer, der skal fremme en sammenhængende og helhedsorienteret rehabiliteringsindsats. Men hvad dækker begrebet koordination egentlig over? Det har et nyt forskningsprojekt set på og kommer med et bud på en ny definition. Dansk definition mangler Indholdet i koordination har været upræcist...

  19. Depressive patienters oplevelse af at modtage ECT

    DEFF Research Database (Denmark)

    Jensen, Christine Damsbo

    Dette studie handler om, hvordan det opleves for den voksne depressive patient at gennemgå et ECT-behandlingsforløb (electroconvulsive therapy). Formålet med projektet er dels at undersøge, hvordan processen omkring ECT-behandlingen udspiller sig og dels at undersøge patienternes oplevelse......, reaktioner og tanker omkring ECT-behandlingen. Studiet bygger på den eksisterende viden om patienters oplevelse af ECT. Metoden er feltforskning med deltagende observation og etnografisk interview. Dette suppleres af to spørgeskemaer. Der blev inkluderet 8 patienter i undersøgelsen. Analysen udspringer af...... konstruktivistisk epistemiologisk vinkel. Ved en teoristyret analyse fremkom 2 overordnede temaer: Anspændthed og tryghed. Disse temaer blev behandlet i en procesorienteret forståelse af ECT-forløbet. Denne proces bestod af: Betingelser, interaktion og konsekvenser. Diskussionen er en kritisk diskussion af fund og...

  20. Gennemgang af den danske samfundsregulering

    DEFF Research Database (Denmark)

    Falch, Morten

    investeringer hos en bred række af markedsaktører’1. Midlet til at opnå dette mål har været at skabe et regelsæt der gør det lettere for nye virksomheder at komme ind på det nye telemarked, og konkurrere på lige fod med TDC. Herudover, har man hjulpet de nye operatører på vej gennem en såkaldt asymmetrisk...

  1. Rekruttering og fastholdelse af seniorer

    DEFF Research Database (Denmark)

    Luccat, Dorte

    Denne undersøgelse har til formål at afdække holdninger, praksis, barrierer og muligheder i forhold til rekruttering og fastholdelse af seniorer. Undersøgelsen er baseret på 19 kvalitative interviews med henholdsvis tillidsrepræsentanter og personaleledere på 13 forskellige arbejdspladser. De...... udvalgte arbejdspladser repræsenterer såvel den offentlige som den private sektor samt større (mindst 50 ansatte) og mindre (under 50 ansatte) arbejdspladser. Vi har endvidere besøgt virksomheder, der henholdsvis har og ikke har seniorer ansat, for at indsamle information om holdninger og praksis fra flere...

  2. Bekæmpelse af elmesyge

    DEFF Research Database (Denmark)

    Thomsen, Iben Margrete; Kristoffersen, Palle; Ravn, Hans Peter

    2004-01-01

    Elmesygen kom til Danmark i 1970’erne. Efter 1985 er udbredelsen gået stærkt, og elmesygen har været katastrofal for bestanden af bytræer og træer i landskabet. Bekæmpelse består fortrinsvis af sanering, dvs. fjernelse af syge og billeangrebne træer inden 1. maj....

  3. Offentliggørelse af kursrelevante oplysninger

    DEFF Research Database (Denmark)

    Werlauff, Erik; Schaumburg-Müller, Peer

    2013-01-01

    Artiklen analyserer, særligt på baggrund af EU-Domstolens dom af 28. juni 2012 i C-19/11, Daimler AG, hvilken betydning en række mellemliggende trin, der fører frem til en kursrelevant og offentliggørelsespligtig begivenhed, har for tidspunktet for indtrædelsen af pligten til offentliggørelse. De...

  4. Konceptuelt design og udvikling af Intergomus

    DEFF Research Database (Denmark)

    Ellebæk, P.; Pedersen, T.; Stendal, Karsten

    1999-01-01

    Denne rapport gennemgår udviklingsforløbet af et træningsapparat til genoptræning af læderede fingre. Rapporten omhandler kun den mekaniske del af udstyret. Opgaven er blevet løst i samarbejde med Ergoterapien på Køge Amtssygehus, Procare, Centret forAvanceret Teknologi og flere afdelinger på RIS...

  5. Forsegling af okklusal dentincaries i permanente molarer

    DEFF Research Database (Denmark)

    Qvist, Vibeke; Borum, Mette Kit; Dynes Møller, Kirsten

    2017-01-01

    Der findes ingen eksakte tal for forekomsten af fødevareallergi i den danske befolkning. Den kumulerede forekomst af fødevareallergi hos børn i de første tre leveår skønnes at være på 7-8 %, hvoraf hovedparten vokser sig fra det. Punktprævalensen af diagnosticeret fødevareallergi hos voksne er 3 ...

  6. NIR: optimerer produktionen af gammeldags modnede sild

    DEFF Research Database (Denmark)

    Svensson, T.; Bro, Rasmus; Nielsen, Henrik Hauch

    2005-01-01

    Måling med nærinfrarødt (NIR) lys er et godt supplement til de nuværende metoder til at følge modningen af sild saltede i tønder. Det viser resultaterne af et forskningsprojekt udført i samarbejde mellem Lykkeberg A/S, Danmarks Fiskeriundersøgelser og Den Kgl Veterinær- og Landbohøjskole. Ved hjælp...... af avanceret matematik er det nemt og hurtigt at bestemme modningsgraden af sild direkte fra en NIR måling....

  7. Evaluering af FIU`s akademiuddannelser

    DEFF Research Database (Denmark)

    Hansen, Agnete Meldgaard; Nielsen, Kurt Aagaard

    I rapporten præsenteres en empirisk evaluerinf af to nye uddannelser i FIUs regi. I forlængelse af evalueringen præsenteres en forskningsmæssig analyse a uddannelsernes rolle i fagbevægelsens modernisering......I rapporten præsenteres en empirisk evaluerinf af to nye uddannelser i FIUs regi. I forlængelse af evalueringen præsenteres en forskningsmæssig analyse a uddannelsernes rolle i fagbevægelsens modernisering...

  8. Didaktisk design af et pervasive learning game

    DEFF Research Database (Denmark)

    Oldenskov, Joakim; Westergren, Jens; Frank, Anders Bredahl

    2010-01-01

    Projektet er et studie i det teoretiske grundlag for, og en empirisk undersøgelse, af en prototype for et didaktisk design af et pervasive learning game. Der arbejdes overordnet med udviklingen af et didaktisk design af et læringsspil som kombinerer mobile teknologier, det fysiske rum og eleverne...... game med en analyse af legen og motivationen iboende spillet. I det læringsteoretiske felt inddrages og diskuteres forskellige tilgange til læring og pervasive games, som alle repræsenterer et socialkonstruktivistisk syn på læring. Det didaktiske design danner grundlag for et prototypedesign af et...... funktionalitet som en del af undervisningen. Det er afgørende at teknologien er pålidelig og er let at gå til, da det er kernefunktionen i denne type af spil. Legens rolle er vigtig for motivationen, men må ikke overtage de formelle krav til den undervisning, som spillet er del af. Det var entydigt omkring...

  9. Omsætning af fast ejendom

    DEFF Research Database (Denmark)

    Edlund, Hans Henrik

    Bogen er en systematisk gennemgang af lov om omsætning af fast ejendom, der regulerer ejendomsmægleres virke. Følgende emner er bl.a. behandlet: Hvem kan drive ejendomsmæglervirksomhed og ejendomsmæglernes pligter og ansvar.......Bogen er en systematisk gennemgang af lov om omsætning af fast ejendom, der regulerer ejendomsmægleres virke. Følgende emner er bl.a. behandlet: Hvem kan drive ejendomsmæglervirksomhed og ejendomsmæglernes pligter og ansvar....

  10. Snit af målinger: VK afhængig af DF og NA

    DEFF Research Database (Denmark)

    Thomsen, Søren Risbjerg

    2007-01-01

    ANALYSE: Ekstra Risbjerg-snit af meningsmålinger grundet fortsat valgrummel - VK-regeringen vil blive afhængig af både DF og NA. Udgivelsesdato: 21. august 2007......ANALYSE: Ekstra Risbjerg-snit af meningsmålinger grundet fortsat valgrummel - VK-regeringen vil blive afhængig af både DF og NA. Udgivelsesdato: 21. august 2007...

  11. Forskningsoversigt - Effekterne af Cooperative Learning

    DEFF Research Database (Denmark)

    Larsen, Lea Lund

    Kan Cooperative Learning - en undervisningsform hvor lærerens tid ved tavlen mindskes og hvor de lærende samarbejder om stoffet - maksimere de lærendes indlæring og medvirke til en forbedring af deres interpersonelle og kommunikative kompetencer, samt øge deres motivation for læring? Den megen...... forskning fra USA viser, at Cooperative Learning øger lærerens bevidsthed om, hvilken adfærd, han er medvirkende til at skabe blandt de lærende. Og den øger lærerens bevidsthed omkring interaktioner i klasserummet, og giver god plads og taletid til hver enkelt lærende. Set i lyset heraf kan Cooperative......, at Cooperative Learning har lige så høj grad af positiv effekt, som den viser sig at have på grundskoleområdet. Det er sigtet med denne oversigt over den empiriske forskning. Til start præsenteres Cooperative Learning som metode, dens rødder og udvikling, dernæst skitseres den omfattende forskning omkring...

  12. Hvad er ledelse af brugerinddragelse?

    DEFF Research Database (Denmark)

    Holm-Petersen, Christina; Navne, Laura Emdal

    2015-01-01

    Brugerinddragelse i det danske sundhedsvæsen står højt på den politiske dagsorden, men det er stadig en udfordring at implementere visionen i klinisk praksis. Ledelse af brugerinddragelse bliver aktuelt udpeget som en central nøgle til at føre visionen ud i livet. Samtidig er der kun relativt lidt......, at brugerinddragelse skal implementeres i en verden, hvor der allerede er en række andre mål tilstede. En central ledelsesudfordring er derfor, at nogle af målene med brugerinddragelse forudsætter nye måder at organisere ikke bare arbejdet og kompetencer på, men også relationer til patienter og pårørende. En væsentlig...... that organize relations Patient involvement in the health services in Denmark is high on the political agenda, though continues to be a challenge to implement. It is increasingly said that leadership is crucial to the implementation process. However, research into the role of leaders in patient involvement...

  13. Pilotprojekt - In situ test af stimuleret aerob nedbrydning til oprensning af pesticidpunktkilder

    DEFF Research Database (Denmark)

    Tsitonaki, Katerina; Roost, Sandra; Larsen, Lars

    Denne rapport omhandler et pilotforsøg i felten, hvor det er undersøgt, hvorvidt aerob nedbrydning af phenoxysyre-pesticider kan stimuleres ved tilsætning af ilt suppleret med tilsætning af specifikke pesticidnedbrydende bakterier. Forsøget er udført på en forurenet lokalitet, Skelstofte, hvor der...

  14. Midler til lindring af mundtørhed og stimulation af spytsekretion

    DEFF Research Database (Denmark)

    Dynesen, Anja Weirsøe; Pedersen, Anne Marie Lynge; Jensen, Allan Bardow

    2013-01-01

    effekt. I relation til risikoen for at udvikle caries, der er forhøjet hos den mundtørre patient, er det dog væsentligt at anbefale produkter uden sukker. Ligesom produktets indhold af syre og dermed det erosive potentiale er af betydning i forhold til udviklingen af dentale erosioner. Systemisk...

  15. Fluorerede stoffer i mademballage af pap og papir

    DEFF Research Database (Denmark)

    Trier, Xenia; Cederberg, Tommy Licht; Jensen, Lisbeth Krüger

    andre typer af madbokse. Prøverne er blevet analyseret for flere forskellige typer af fluorerede stoffer, der anvendes til at imprægnere disse typer af emballager, så de ikke suger fedt eller vand. I ingen af prøverne er der fundet indhold af fluorerede stoffer, der overstiger analysemetodens...

  16. 17-AAG mediated targeting of Hsp90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry.

    Science.gov (United States)

    Chaklader, M; Das, P; Pereira, J A; Law, A; Chattopadhyay, S; Chatterjee, R; Mondal, A; Law, S

    2012-07-01

    Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery - heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.

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

    Science.gov (United States)

    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.

  18. Opfattelser af integration blandt unge med migrantbaggrund

    DEFF Research Database (Denmark)

    Skytte, Marianne; Bryderup, Inge

    2014-01-01

    I artiklen formidles analyser af otte interview med unge med migrantbaggrund. Der er fokus på de unges oplevelser og opfattelser af integration. Der er tale om komplekse processer og vekselvirkninger i forholdet mellem de samfundsmæssige kategoriseringer og individernes selvopfattelser. De unge o...

  19. Optimalt design af fødevarer

    DEFF Research Database (Denmark)

    Bech, Anne C.; Engelund, Erling; Juhl, Hans Jørn

    1993-01-01

    Udformningen af fødevarer opfattes som et designproblem, det består i at omsætte markedskrav, belyst gennem markedsanalyser, til egenskaber ved de fremstillede produkter under hensyntagen til de dermed forbundne omkostninger. Denne oversættelse af forbrugerønsker antages at kunne ske effektivt ge...

  20. Prioriteringer af efterretninger i kampen mod terror

    DEFF Research Database (Denmark)

    Nielsen, Thomas Galasz

    2015-01-01

    Efterretningstjenesterne indsamler stadig flere informationer i forsøget på at opdage og imødegå terrorister. Men mængden af informationer gør det ikke nødvendigvis lettere at forudsige terrorhandlinger. Efterretningstjenesterne bør derfor prioritere bearbejdning af oplysningerne højere, end de g...

  1. En bid af ældres hverdagsliv

    DEFF Research Database (Denmark)

    Bundgaard, Karen Marie; Top Christensen, Boye

    2000-01-01

    Undersøgelsen har udforsket hjemmeboende ældres egen forståelse og oplevelse af måltiddsaktiviteters betydning, og hvilke behov aktiviteterne dækker hos de ældre. Aktiviteterne har betydninger der knytter sig til maden men aktiviteterne har også betydninger i sig selv. Undersøgelsen er en af fler...

  2. Lokal integration af førtidspensionister

    DEFF Research Database (Denmark)

    Jacobsen, Joannes; Lindstrøm, Maia

    Denne rapport kortlægger livsvilkårene for en bred gruppe af førtidspensionister med fokus på deres hverdag og de vilkår, som omgiver dem. Derudover identificerer rapporten en gruppe af førtidspensionister, der selv ønsker mere social interaktion og indhold i hverdagen. Undersøgelsen viser, at de...

  3. Udforskning af dialoger om et regnehul

    DEFF Research Database (Denmark)

    Lindenskov, Lena

    2007-01-01

    Med introduktionen af det danske begreb 'regnehuller' om matematikvanskeligheder bliver det muligt at udforske dialoger i klasserummet med brug af værktøjer fra Augusto Boals Forumteater. Principperne i Boals tre faser præsenteres som værktøjer for læreres refleksive praksis. Ud fra datamateriale...

  4. Udvikling af pille-doserings teknologi

    DEFF Research Database (Denmark)

    Brændgaard, Rikke; Churchill, Inge-Lise; Bolvig Poulsen, Søren

    2015-01-01

    Lab. X har i samarbejde med Brønderslev Kommune og Firmaet LT Automation i et idegenereringsforløb omhandlende viden om "pillens vej", indhentet viden om udfordringer og barrierer i forbindelse med udlevering af medicin fra apoteket til den afslutningsvis indtages af borgeren. Formålet med unders...

  5. Revisionsklienters anvendelse af serviceleverandører

    DEFF Research Database (Denmark)

    Kjersgaard, Lisbeth; Kiertzner, Lars

    2011-01-01

    Artiklen præsenterer det overordnede indhold af den ajourførte ISA 402 om revisionsmæssige overvejelser ved revision af regnskaber for virk somheder, der anvender service-leverandører. Artiklen er opbygget efter de tre grundlæggende elementer i revisionsprocessen - planlægning, udførelse og rappo...

  6. Fastholdelse af erhvervsskoleelever i det danske erhvervsuddannelsessystem

    DEFF Research Database (Denmark)

    Nielsen, Klaus; Jørgensen, Christian Helms; Koudahl, Peter

    2013-01-01

    Forskningsprojektet ”Retention of Vocational Students in the Danish VET System” undersøger de påvirkelige faktorer, der kan bidrage til at mindske frafaldet på de erhvervsfaglige uddannelser (EUD). For etablering af en sådan viden er dannet et konsortium bestående af såvel forskere med stor...

  7. Forført af hjernen?

    DEFF Research Database (Denmark)

    Lieberoth, Andreas

    2013-01-01

    Blandingen af offentlig interesse, gode mediehistorier og smarte sælgere har ført til sejlivede neuromyter, der ikke bare distraherer almindelige mennesker, men også fører til udbredte misforståelser blandt professionelle som lærere og plejepersonale. I bedste fald leder neuromyter til spild af t...

  8. Økonomisk vurdering af energibesparende foranstaltninger

    DEFF Research Database (Denmark)

    Johnsen, Kjeld; Andersen, Hans Skifter

    Anvisningen gennemgår detaljeret hvordan man gennemfører analyser af lønsomhed og likviditetsvirkninger som led i udarbejdelsen af det teknisk-økonomiske grundlag for beslutninger om energibesparende investeringer. Anvisningen indeholder blandt andet en række enkle skemaer, der kan lette og syste...

  9. Tema 1: Programmering af robotenheder i grundskolen

    Directory of Open Access Journals (Sweden)

    Stine Ejsing-Duun

    2016-01-01

    Full Text Available I denne artikel undersøger vi potentialerne for at lære matematik gennem programmering af robotter. Vi foreslår en model med tre indbyrdes afhængige læringspotentialer, som programmering fordrer. Det omfatter elevens evne til at; (1 tænke i algoritmer, (2 producere viden og artefakter gennem brug af matematik og (3 foretage abstraktion og indkapsling. Programmering er blevet en del af grundskolens læringsmål i flere lande. I Danmark er programmering et læringsmål i forenklede fælles mål for Fysik/Kemi og desuden en del af den nationale undervisningsvejledning for matematik. En analyse af potentialerne i at anvende programmering i forbindelse med disse fag er derfor væsentlig. I denne artikel fokuserer vi på samspillet mellem matematik og programmering gennem litteraturstudier og analyse af empiriske situationer fra undervisning i programmering af LEGO Mindstorms. Teoretisk anvendes den instrumentelle tilgang til teknologi i matematikundervisning. Analysen viser en række måder, hvorpå didaktisk opmærksomhed på epistemisk forhandling kan understøtte læring af matematik gennem programmering.

  10. Professionel udvikling af naturfagslærere

    DEFF Research Database (Denmark)

    Krogh, Lars Brian

    2016-01-01

    & Hollingsworth, 2002) som model for tænkning omkring TPD, samt anvende en mange-lags evalueringsoptik i overensstemmelse med Guskey (2002). Den eksisterende viden om, hvad der skal til for at professionelle udviklingsaktiviteter får virkning opsummeres som afsæt for en drøftelse af TPD-design. Endelig...

  11. Sproget afhænger af stedet

    DEFF Research Database (Denmark)

    Monka, Malene

    2014-01-01

    I artiklen præsenteres resultaterne af et ph.d.-projekt ved Nordisk Forskningsinstitut ved Københavns Universitetet, der undersøger sammenhænge mellem sted og sprogforandring. Projektet er en undersøgelse af sprogforandring i virkelig tid, hvor gamle og nye optagelser med 23 informanter fra tre j...

  12. Måling af virksomheders administrative byrder

    DEFF Research Database (Denmark)

    Langsted, Lars Bo

    2004-01-01

    Selskabsstyrelsen har offentliggjort rapporten: "Rapport om måling af virksomhedernes administrative byrder ved årsregnskabsloven og rapport om revisionshonorar for B-virksomheder."......Selskabsstyrelsen har offentliggjort rapporten: "Rapport om måling af virksomhedernes administrative byrder ved årsregnskabsloven og rapport om revisionshonorar for B-virksomheder."...

  13. Måling af stress hos mink

    DEFF Research Database (Denmark)

    Malmkvist, Jens

    2010-01-01

    Sammendrag Stress indgår som et element ved vurdering af dyrevelfærd. Endvidere kan stress mål anvendes i undersøgelser, hvor forskellige typer af avl, burmiljø og pasning af mink sammenlignes. Men hvad er stress egentlig og hvordan måles det? Er unormal adfærd koblet til stress hos mink? På...... temadagen præsenteres nye resultater og metoder til at vurdere stress hos mink. I en metode måles koncentrationen af nedbrydningsprodukter af hormonet cortisol i gødning fra mink. Der er en række fordele ved denne metode, frem for blodprøvetagning. Forsøg viste, at hovedparten af cortisol udskilles i fæces...... (83 %) frem for i urin (17 %), samt at omsætningen af radioaktivt mærket cortisol ikke er forskellig mellem mink med hhv. lav og høj forekomst af stereotypi. Denne viden kan bruges til bedre at forstå koblingen f.eks. unormal adfærd og stress hos mink....

  14. Beskrivelse og modellering af produktionssystemer, Tulip

    DEFF Research Database (Denmark)

    Jacobsen, Peter

    1997-01-01

    produktionssystemer til brug ved optimering af drift og planlægning/udvikling af nye produktionssystemer. For at opnå et nødvendigt informationsgrundlag udføres projektet i samarbejde med udvalgte virksomheder.Rapporten er udført i samarbejde med Tulip International A/S i Vejle, hvor den del, der omfatter...

  15. Digital visualisering i udbygning af Roskilde Universitetscenter

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke

    Rapporten beskriver tre forsøg med 3D-visualisering i forbindelse med konkurrencer vedrørende udbygning af Roskilde Universitetscenter. Første forsøg var en metode til hurtigt at skabe en række digitale modeller i højt abstraktionsniveau. Forsøget resulterede i 15 små animationer, der blev benyttet...... af dommerkomiteen til volumenstudier af bygningskonkurrencens indsendte forslag. Andet forsøg var afprøvning af et modelleringsarbejde i lavere abstraktionsniveau, som resulterede i en animation af vinderprojektet. I sidste forsøg blev de praktiske erfaringer fra de to første forsøg implementeret hos...

  16. Evaluering af en sygeplejestyret hjertesvigtsklinik

    DEFF Research Database (Denmark)

    Streym, Súsanna við

    2008-01-01

    den helbredsrelaterede livskvalitet målt ved hjælp af Minnesota Living with Heart Failure Questionnaire (MLHF) ved baseline og efter der minimum var gået 10 uger. Genindlæggelseshyppigheden og gennemsnitsindlæggelsestiden, blev målt ved at sammenligne alle førstegangsindlæggelser fra 1. marts 2006 til...... tilbuddet om fysisk træning, ville have taget imod det (n=18). Konklusion: Den helbredsrelaterede livskvalitet var signifikant forbedret efter opfølgende undersøgelse. Dog kan dette studie ikke påvise, eksakt hvilke interventioner der har haft indflydelse på forbedringen. Der er ingen forskel på...

  17. Om Hegels opfattelse af Gorgias, set på baggrund af tidligere filosofihistorikeres fremstilling

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2010-01-01

    En undersøgelse af Hegels tolkning af sofisten Gorgias giver anledning til at se på receptionen af sofisterne hos notable filosofihistorikere i det 18. århundrede. En sådan undersøgelse viser, at Hegel har en original og velvillig tolkning af sofisterne koncentreret omkring begrebet Bildung og det...... at give grunde for noget. Hegels udlægning af Gorgias bygger på hans tolkning af eleaterne, især af Zenon. Når Hegel har en særlig tolkning af eleaterne, skyldes det hans egne mangeårige filosofiske bestræbelser, og en identificering af en særlig, immanent objektiv dialektik hos Zenon, som han finder......, at Gorgias fører videre. Hegels filosofiske forståelse er tilstrækkelig udviklet til at kunne knytte positive kommentarer til alle dele af diskussionen i Gorgias' ræsonnement Om det ikkeværende, eller Om naturen. Det lykkes dog bedst i forhold til de to første af Gorgias' tre underteser. I hegelsk perspektiv...

  18. Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEU-NT mice monitored by Magnetic Resonance Spectroscopy.

    Science.gov (United States)

    Rodrigues, Loreta M; Chung, Yuen-Li; Al Saffar, Nada M S; Sharp, Swee Y; Jackson, Laura E; Banerji, Udai; Stubbs, Marion; Leach, Martin O; Griffiths, John R; Workman, Paul

    2012-05-23

    The importance of ERBB2/NEU/HER2 in the response of breast tumours to the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; tanespimycin) has been demonstrated in the clinic. ERBB2 is an oncoprotein client that is highly dependent on HSP90. This and other oncogenic client proteins (e.g. B-RAF, C-RAF, ALK and CDK4) are depleted by 17-AAG in both animal tumours and patients. Here we investigate by Magnetic Resonance Spectroscopy (MRS) the metabolic response of 17-AAG in spontaneous, NEU/HER2 driven mammary tumours in transgenic MMTV-NEU-NT mice and in cells isolated and cultured from these tumours. Mammary tumours were monitored by 31P MRS in vivo and in tumour extracts, comparing control and 17-AAG treated mice. A cell line derived from NEU/HER2 mammary tumours was also cultured and the effect of 17-AAG was measured by 31P MRS in cell extracts. Molecular biomarkers were assessed by immunoblotting in extracts from cells and tumours. For comparison of tumour volume, metabolite concentrations and Western blot band intensities, two-tailed unpaired t-tests were used. The NEU/HER2 mammary tumours were very sensitive to 17-AAG and responded in a dose-dependent manner to 3 daily doses of 20, 40 and 80mg/kg of 17-AAG, all of which caused significant regression. At the higher doses, 31P MRS of tumour extracts showed significant decreases in phosphocholine (PC) and phosphoethanolamine (PE) whereas no significant changes were seen at the 20mg/kg dose. Extracts of isolated cells cultured from the mammary carcinomas showed a significant decrease in viable cell number and total PME after 17-AAG treatment. Western blots confirmed the expected action of 17-AAG in inducing HSP72 and significantly depleting HSP90 client proteins, including NEU/HER2 both in tumours and in isolated cells. The data demonstrate the high degree of sensitivity of this clinically relevant NEU/HER2-driven tumour model to HSP90 inhibition by 17-AAG, consistent with the

  19. Anvendelse af koldpresset rapsolie på varebiler

    DEFF Research Database (Denmark)

    Nielsen, Claus Suldrup; Ivarsson, Anders; Schramm, Jesper

    Denne rapport sammenfatter resultaterne af undersøgelserne omkring anvendelse af koldpresset rapsolie på varebiler. Undersøgelsen, som er udført af Danmarks Tekniske Universitet, Institut for Mekanisk Teknologi, er en del af et større projekt, som er finansieret af Trafikstyrelsens (tidligere Fær...... Færdselsstyrelsen) tilskudsordning til forsøg med biodiesel. Projektet har været administreret af Odense Kommune....

  20. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

    Directory of Open Access Journals (Sweden)

    Tapas K. Nayak

    2017-01-01

    Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

  1. Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.

    Science.gov (United States)

    Nayak, Tapas K; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K; Sahoo, Subhransu S; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2017-01-06

    Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

  2. Typebestemmelse af de danske M. bovis stammer

    DEFF Research Database (Denmark)

    Kokotovic, Branko

    Mycoplasma bovis er en af de mest betydningsfulde mykoplasma i kvægbruget på verdensplan. Bakterien findes oftest i forbindelse med mastitis, lunge- og ledbetændelse, men andre kliniske manifestationer kan også forekomme. Der findes ikke præcise, nyere beregninger over konsekvenser af M. bovis...... relateret sygdomme, men det anses, at infektionen hvert år globalt set pålægger en økonomisk byrde til kvægbruget i en multimillion skala. M. bovis blev for første gang påvist i Danmark i 1981 og gennem 1980’erne har bakterien forårsaget store udbrud af mastitis. I de følgende årtier blev bakterien isoleret...... sporadisk fra mange forskellige kvægbesætninger, men på trods af en tilsyneladende stigende forekomst i 1990’erne, blev der ikke registret omfattende sundhedsmæssige problemer som følge af M. bovis smitte. Siden 2011 er M. bovis dog kommet i fokus igen på grund af alvorlige udbrud af især ledbetændelse, men...

  3. Distribution af video – lige meget hvordan?

    Directory of Open Access Journals (Sweden)

    Diba Markus

    2009-04-01

    Full Text Available Artiklen omhandler løsninger til distribution af video og de faktorer, der kan være udslagsgivende, når man som underviser eller universitet skal vælge, hvilken man vil gøre brug af. De kommercielle løsninger såsom YouTube m.fl. er kendt af de fleste. Hvad færre måske ved er, at der eksisterer alternativer. På europæisk plan har en række institutioner og forskningsnet, herunder det danske, således valgt at lave deres egne løsninger. Der er afgørende forskelle i disse hhv. kommercielle og ikke-kommercielle videodistributionstjenesters tilgange til problemstillinger vedrørende adgangsbegrænsning, ophavsret, metadatering og bevaring samt kvalitetssikring af indhold - forskelle, der for en stor del udspringer af deres respektive opdrag og muligheder for brugerautentificering. Kun de færreste af alternativerne kan bruges af danske studerende og universitetsansatte. Som der argumenteres for i artiklen, er disse problemstillinger imidlertid vigtig baggrundsinformation, når der skal tages stilling til, hvordan man bedst distribuerer videoressourcer. I artiklen beskrives overordnede fællestræk ved hhv. de kommercielle og de ikke-kommercielle distributionsløsninger, og de helt grundliggende forskelle mellem dem diskuteres.

  4. The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA glycosylase-deficient Aag null mice.

    Science.gov (United States)

    Branda, Richard F; O'Neill, J Patrick; Brooks, Elice M; Powden, Cheryl; Naud, Shelly J; Nicklas, Janice A

    2007-02-03

    Folic acid deficiency (FA-) augments DNA damage caused by alkylating agents. The role of DNA repair in modulating this damage was investigated in mice. Weanling wild-type or 3-methyladenine glycosylase (Aag) null mice were maintained on a FA- diet or the same diet supplemented with folic acid (FA+) for 4 weeks. They were then treated with methyl methanesulfonate (MMS), 100mg/kg i.p. Six weeks later, spleen cells were collected for assays of non-selected and 6-thioguanine (TG) selected cloning efficiency to measure the mutant frequency at the Hprt locus. In wild-type mice, there was no significant effect of either MMS treatment or folate dietary content on splenocyte non-selected cloning efficiency. In contrast, non-selected cloning efficiency was significantly higher in MMS-treated Aag null mice than in saline treated controls (diet-gene interaction variable, p=0.04). The non-selected cloning efficiency was significantly higher in the FA+ diet than in the FA- diet group after MMS treatment of Aag null mice. Mutant frequency after MMS treatment was significantly higher in FA- wild-type and Aag null mice and in FA+ Aag null mice, but not in FA+ wild-type mice. For the Aag null mice, mutant frequency was higher in the FA+ mice than in the FA- mice after either saline or MMS treatment. These studies indicate that in wild-type mice treated with MMS, dietary folate content (FA+ or FA-) had no effect on cytotoxicity, but FA- diet increased DNA mutation frequency compared to FA+ diet. In Aag null mice, FA- diet increased the cytotoxic effects of alkylating agents but decreased the risk of DNA mutation.

  5. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

    Science.gov (United States)

    Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

    2015-06-28

    ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

  6. Vurdering af omfang og konsekvenser af sprøjtning og gødskning af § 3-beskyttede naturarealer

    DEFF Research Database (Denmark)

    Strandberg, Morten Tune; Bak, Jesper Leth; Bladt, Jesper Stentoft

    2012-01-01

    Det er overvejende de ferske enge, der gødskes og sprøjtes, hvorimod dette kun undtagelsesvist er konstateret på andre naturtyper som overdrev og heder m.m. De ferske enge er samtidig den mest udbredte § 3-naturtype. Behandling i form af gødskning og sprøjtning foregår anslået på op til 20 % af a...

  7. Optimering af byggeprocessen via bedre/forøget brug af digitale modeller

    DEFF Research Database (Denmark)

    Carlsen, Mads; Grøn, Dorte Marie Frilund; Alon, Nevo

    2013-01-01

    Projektet klarlægger nødvendigheden for, og muligheder i, en struktureret og konsekvent planlægning ved anvendelsen af BIM i relation til projektering, udførelse og drift af byggeri. Der er udarbejdet et planlægningsværktøj, der muliggør en sådan planlægning. Samtidig kortlægges de nødvendige data......, der kan udtrækkes af en BIM model ved gennemførelsen af en LCA simulering. Projektet afsluttes med en præsentation af en udviklet demonstratorapplikation til gennemførelse af LCA simuleringer koblet med BIM modellen....

  8. Air Emissions/IGD: EF_AFS

    Data.gov (United States)

    U.S. Environmental Protection Agency — EF_AFS is a subset of facilities from FRS_INTEREST and FRS_FACILITY_SITE which are updated on a monthly basis as part of the Locational Reference Tables (LRT)...

  9. Crowdings betydning for antallet af tvangsfikseringer

    DEFF Research Database (Denmark)

    Bak, Jesper; Nielsen, Lea Marie; Hæssum, Birte

    2017-01-01

    I denne artikel vil vi beskrive et par af resultaterne fra forskningsprojektet ”Mechanical restraint. Preventive Factors in Theory and Practice” samt et eksempel fra praksis om crowdings betydning for hvor meget der bliver tvangsfikseret....

  10. Kortlægning af Hadforbrydelser

    DEFF Research Database (Denmark)

    Drud Jensen, Mads Ted; Kromand, Rolf; Birgit, Lindsnæs

    Kortlægning af hadforbrydelser baserer sig på selvrapporteret udsathed for kriminalitet samt e-survey gennemført blandt minoritetsgrupper, der antages at være særlig udsat for hadforbrydelser....

  11. Danskernes brug af business case og gevinstrealisering

    DEFF Research Database (Denmark)

    Ernst, Martin

    2013-01-01

    Business case og gevinstrealisering har længe været faste begreber, når man taler effektivisering, implementering af strategi etc. Mange bruger det, flere brugere det delvist, og nogle bruger det slet ikke.......Business case og gevinstrealisering har længe været faste begreber, når man taler effektivisering, implementering af strategi etc. Mange bruger det, flere brugere det delvist, og nogle bruger det slet ikke....

  12. Selskaberne er en del af staten

    DEFF Research Database (Denmark)

    Hein Jessen, Mathias

    2016-01-01

    Lækket af Panama Papers fremhæver endnu engang den paradoksale rolle, ikke mindst multinationale selskaber spiller i politik og økonomi: De er både skabt af staten, og fremstår stadig som uden for og i opposition til staten. Hvis vi vil gøre noget ved problemet, må vi forstå, hvordan stat og...

  13. Arbejdsmiljø ved udbud af busdrift

    DEFF Research Database (Denmark)

    Wiegmann, Inger-Marie; Mathiesen, Karin; Hasle, Peter

    En undersøgelse af sammenhængen mellem arbejdsmiljø og udbud af busdrift i tre trafikselskabet. Resultaterne peger på at arbejdsmiljøet går fra udelukkende til at være et anliggende mellem arbejdsgiver og arbejdstager til et trepartsforhold hvor også udbyder (trafikselskabet) får et ansvar og har...

  14. Omrids af en trækultur

    DEFF Research Database (Denmark)

    Rauff Greisen, Johannes

    2007-01-01

    høje prioritering af de fysiske rammer kan aflæses i de store linjer såvel som i de redelige detaljer. Artiklens spørgsmål er, hvorledes håndværkstraditionens kvaliteter og kerne kan overleveres til det moderne byggeri, der også i Vorarlberg i stigende grad præges af industrialiseringen, samt i hvilke...

  15. Forekomst af parodontitis og FORL hos perserkatte

    DEFF Research Database (Denmark)

    Flørnæs, Maria L. Topholm; Lund, Mette; Kortegaard, Hanne Ellen

    2007-01-01

    I dette studie er omfanget af tandrelaterede sygdomme heriblandt parodontitis og feline odontoklastiske resorptions læsioner (FORL) blandt 19 perserkatte (heraf 2 exotics) på 3 til 9 år undersøgt både klinisk og radiografisk. Ingen af kattene havde tidligere fået renset tænder i anæstesi. Alle ka...

  16. Blended Learning Analytics Model for Evaluation (BLAME). Et case-studie af universitetsunderviseres brug af Blackboard

    DEFF Research Database (Denmark)

    Musaeus, Peter; Bennedsen, Andreas Brændstrup; Hansen, Janne Saltoft

    2015-01-01

    I denne artikel vil vi præsentere en strategi til inddragelse af læringsanalytik (learning analytics) ved evaluering af universitetsunderviseres brug af et nyt LMS på Aarhus Universitet: Blackboard. Vi diskuterer en model (BLAME: Blended Learning Analytics Model of Evaluation) for, hvordan...... kategorisering af kurser og data om læringsanalytik indsamlet på Blackboard kan integreres. Endvidere belyser vi, hvilke implikationer en sådan læringsanalytik kan have for blended learning ved at analysere to forskellige uddannelses-cases/illustrationer. Dernæst diskuterer vi pædagogisk udvikling i forbindelse...

  17. Kontrol af konventionelle våben i Europa

    DEFF Research Database (Denmark)

    Hoffmann, Rune; Kierulf, John; Pradhan-Blach, Flemming

    Rapporten indledes med en historisk gennemgang af tilblivelsen og udviklingen af Traktat om Konventionelle Væbnede Styrker i Europa (CFE), som blev iværksat af NATO og det tidligere Warszawapagten i 1973. Traktaten fastsætter et loft for antallet af kampvogne, pansrede kampkøretøjer, artilleripje...

  18. Tællinger af vandfugle i Danmark 1998-99

    DEFF Research Database (Denmark)

    Pihl, S.; Laubek, B.

    1999-01-01

    Denne rapport præsenterer Miljø- og Energiministeriets seks feltstationer med beskrivelse af deres historie, naturforhold og overvågningsprogram. Resultaterne af fugleobservationer i 1997 beskrives i sammenhæng med tidligere års udvikling. Desuden præsenteres resultater af tre undersøgelser af he...

  19. Erfaringer fra nedrivning af boligblok i Rødbyhavn

    DEFF Research Database (Denmark)

    Eriksen, Søren Skibstrup; Hansen, Klaus; Krogh, Hanne

    Denne meddelelse indeholder en beskrivelse af nedrivningen af et betonelementbyggeri. Der er foretaget en registrering af energiforbrug i forbindelse med nedrivningen og bortskaffelsen samt en registrering af de miljøbelastende stoffer i bygningsaffaldet. Inden bebyggelsen blev revet ned, blev de...

  20. Kommentarer til love og ændringer af love

    DEFF Research Database (Denmark)

    Møgelvang-Hansen, Peter

    2002-01-01

    folkeoplysende foreningsarbejde og Folkeuniversitetet (folkeoplysningsloven) og ophævelse af lov om daghøjskoler m.v. og lov om den fri ungdomduddannelse samt ændring af lov om refusion af udgifter til uddannelse i forbindelse med aktivering m.m. samt ændring af forskellige love (Reform for daghøjskolerne...

  1. DVD anmeldelse - En Verden af Lyd og Musik

    DEFF Research Database (Denmark)

    Holck, Ulla

    2006-01-01

    Anmeldelse af DVD-udgivelse af Claus Bang (2005): En Verden af Lyd og Musik. Musikterapi for døve, hørehæmmede og multihandicappede børn og unge. Al tale med undertekst eller tegnsprogstolkning. DVD-boks med 3 stk. dobbeltlag DVD beregnet til afspilning på PC. Udgivet af Musikterapi-foreningen En...

  2. Læring som improviseret udvikling af praksis

    DEFF Research Database (Denmark)

    Brinck, Lars

    2010-01-01

    Med afsæt i forfatterens fænomenografiske studie af amerikanske musikeres oplevelse af det at jamme diskuterer artiklen, hvorvidt jam-bandets spontant improviserende praksis kan give ny forståelse af rytmiske musikeres læring som et overordnet socialt fænomen. Ved at betragte jam-bandets praksis i...

  3. Om den sociale og symbolske funktion af uddannelsesevalueringer

    DEFF Research Database (Denmark)

    Nørholm, Morten

    Ph.d.-afhandlingen handler om evalueringer, om evalueringer af uddannelse med et fokus og perspektiv som er begrænset til en afdækning af forhold om evalueringer, til en formulering af en teori om evalueringer. I afhandlingens analyser og diskussioner anvendes teorier af Émile Durkheim, Pierre...

  4. Miljørigtig ombygning af Mallinggård

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2002-01-01

    Resume af rapport om den byggetekniske anvendelse af alternativ isolering ved en ombygning af Mallinggårds lade til undervisningslokaler, udarbejdet af Bent Møller fra Rudolf Steiner Skolen i Skanderborg under Energistyrelsens udviklingsprogram "Miljø- og arbejdsmiljøvenlig isolering"...

  5. En kvantitativ metode til analyse af radio

    Directory of Open Access Journals (Sweden)

    Christine Lejre

    2014-06-01

    Full Text Available I den danske såvel som den internationale radiolitteratur er bud på metoder til analyse af radiomediet sparsomme. Det skyldes formentlig, at radiomediet er svært at analysere, fordi det er et medie, der ikke er visualiseret i form af billeder eller understøttet af printet tekst. Denne artikel har til formål at beskrive en ny kvantitativ metode til analyse af radio, der tager særligt hensyn til radiomediets modalitet – lyd struktureret som et lineært forløb i tid. Metoden understøtter dermed både radiomediet som et medie i tid og som et blindt medie. Metoden er udviklet i forbindelse med en komparativ analyse af kulturprogrammer på P1 og Radio24syv lavet for Danmarks Radio. Artiklen peger på, at metoden er velegnet til analyse af ikke kun radio, men også andre medieplatforme samt forskellige journalistiske stofområder.

  6. Selektiv avl af racehunde og -katte

    DEFF Research Database (Denmark)

    Sandøe, Peter; Meyer, Iben Helene Coakley; Fredholm, Merete

    2014-01-01

    Dette kapitel ser nærmere på de velfærdsmæssige problemstillinger, der opstår som følge af måden, hvorpå racehunde og -katte påvirkes gennem selektiv avl. Først beskrives, hvordan avlen af racehunde og -katte er organiseret. Dernæst gøres der rede for de dyrevelfærdsmæssige konsekvenser heraf....... Selektiv avl af hunde og katte tjener til at vedligeholde en stor racemæssig diversitet. De racemæssige forskelle gør det muligt for mennesker at vælge især hunde, der har nogle egenskaber, som passer til individuelle behov og ønsker. Desværre er der også en række bivirkninger for de pågældende dyrs...... problemer, som knytter sig til selektiv avl af racehunde og -katte, gennemgås og diskuteres mulige praktiske tiltag, som kan trække udviklingen i retning af at reducere forekomsten af disse problemer....

  7. Pædagogisk brug af test

    DEFF Research Database (Denmark)

    Nordenbo, Sven Erik; Allerup, Peter; Andersen, Hanne Leth

    Publikationen er resultatet af et systematisk review foretaget i regi af Dansk Clearinghouse for Uddannelsesforskning. Reviewets grundspørgsmål er: Hvordan kan grundskolelæreres individ- og klassecentrerede brug af data fra test forbedre læreres didaktiske og/eller fagdidaktiske tiltag i klasser...... med almindelige elever? Spørgsmålet vedrører alene testtyper, som indgår i nationale test i de nordiske lande. Og hvordan indvirker indførelsen af testning på læreres didaktiske beslutninger og elevers læringsadfærd? Vi fandt frem til at grundskolelæreres individ- og klassecentrerede brug af testdata...... i klasser med almindelige elever forbedres, når de didaktiske og/eller fagdidaktiske tiltag bygger på test, som lærerne oplever et medejerskab for. Vi fandt fremtil, at introduktion af test fra instanser over klasseniveau med det formål at indvirke på undervisning og elevers læringsadfærd har...

  8. Enzymatisk omestring til produktion af biodiesel

    DEFF Research Database (Denmark)

    Fjerbæk, Lene

    2007-01-01

      Biodiesel er i dag sammen med bioethanol et bud på, hvordan transportsektoren kan nedbringe sin netto CO2-emission til atmosfæren og lagrene af fossilt brændstof kan strækkes. På verdensplan forventes der en produktion af biodiesel på 7,9 mio. tons i 2007. Ved den industrielle fremstilling af...... biodiesel benyttes i dag kemiske katalysatorer såsom H2SO4, NaOH, MeONa eller KOH, der efterfølgende fjernes fra den producerede biodiesel med store mængder vand og derved produceres store mængder spildevand. Ved at benytte enzymer i processen kan man reducere mængden af spildevand, der skal renses. Enzymer...... benyttes ikke i de eksisterende processer, men det forventes, at udviklingen af processerne vil øge deres anvendelse i biodieselproduktion. I artiklen præsenteres fordele og ulemper ved anvendelse af enzymer til biodiesel produktion....

  9. Biotransformering af pyren i havbørsteormen Nereis virens

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Giessing, Anders; Juul Rasmussen, Lene

    føden og ved overførsel over epithelet. Graden af systemisk akkumulering af PAHer afhænger af optaget men ligeledes af effektiviteten af biotransformering i den pågældende organisme. N. virens er kendt for effektivt at biotransformere PAHer. I nærværende undersøgelse blev biotransformering undersøgt med......-glucuronid er den fase II metabolit der primært produceres ved biotransformering af pyren. Dette indikerer at de vigtigste enzymer i biotransformering af pyren i N. virens er CYP enzymer og glucuronosyl transferase enzymer....

  10. Digital innovation af folkeskolernes åbenhed og sammenlignelighed

    DEFF Research Database (Denmark)

    Andersen, Kim Normann; Henriksen, Helle Zinner; Agger Nielsen, Jeppe

    2013-01-01

    Denne artikel præsenterer en normativ model (Public Sector Process Rebuilding, PPR), som kan indfange, hvor innovativt offentlige organisationer anvender digitale løsninger. Optag af digital innovation anskues ofte i litteraturen binært – enten er innovationen anskaffet eller ikke anskaffet. Vores...... argument er imidlertid, at optag af digitale innovationer kan gradbøjes. Vores sigte er derfor at få fokus væk fra anskaffelse og mere i retning af udnyttelse af digitaliseringen med henblik på at skabe forbedring af kerneydelserne og gavne slutbrugerne. Med empirisk afsæt i danske folkeskolers tolkning af...

  11. Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

    Science.gov (United States)

    Saif, M W; Erlichman, C; Dragovich, T; Mendelson, D; Toft, D; Burrows, F; Storgard, C; Von Hoff, D

    2013-05-01

    17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

  12. International fragmentation af produktionen og vertikal disintegration af styringsformer i produktionskæderne

    DEFF Research Database (Denmark)

    Refslund, Bjarke

    Stigende international økonomisk integration har betydet en stigende fragmentering af produktionen, hvor store dele udføres i forskellige lande. Dertil kommer en stigende disintegration af vertikale styringsformer i produktions-værdikæder (Global Value Chains). Dette konferencepaper diskutere...

  13. For bestemmelse af drivhusgasudledning ved udtagning/Ekstensivering af landbrugsjorder på kulstofrige lavbundsjorder

    DEFF Research Database (Denmark)

    Gyldenkærne, Steen; Greve, Mogens Humlekrog

    Sammenfatning: Rapporten beskriver hvordan man kan beregne ændringen i drivhusgasemissionen ved omlægning af landbrugsjord til naturarealer. Rapporten er primært rettet mod tilskudsordningen vedr. udtagning af organiske lavbundsjorde, men kan også anvendes i andre sammenhænge. Rapporten anvender de...

  14. Identifikation af forkullet lig ved hjælp af ganeaftryk og koralnyresten

    DEFF Research Database (Denmark)

    Leth, Peter Mygind; Bindslev, Dorthe Arenholt; Kristensen, Ingrid Bayer

    1997-01-01

    En retstodontologisk undersøgelse af en dødfunden, uidentificeret person, bygger almindeligvis på en undersøgelse af tandsættet. Hvis personen er tandløs må andre identifikationsmetoder tages i anvendelse. Fingeraftryk er et almindelig kendt eksempel på en alternativ metode, som bygger på, at cri...

  15. Evaluering af ordning med psykologbehandling af personer med let til moderat depression

    DEFF Research Database (Denmark)

    Fjeldsted, Rita; Christensen, Kaj Sparle

    Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter, psykolo......Herværende rapport evaluerer den pr. 1.4.2008 indførte ordning med mulighed for henvisning til psykologbehandling med 60 % tilskud for patienter med let til moderat depression. Evalueringen har betjent sig af flere gensidigt supplerende metoder: spørgeskemaundersøgelser overfor patienter...... tidligere evaluering af forsøgsordning af psykologbehandling af depression i perioden 2005-06. 18.419 personer i alderen 18-37 år blev henvist til psykolog i den undersøgte ordning i perioden 1.2.2009 – 31.1.2010, svarende til en henvisningshyppighed på 1,6 % af baggrundsbefolkningen i samme aldersgruppe....... Ordningen giver mulighed for én rehenvisning, og 9 % blev rehenvist i perioden. Spørgeskemaresultater viser, at kun 33 % af de henviste falder ind under henvisningskriteriet ” let til moderat depression” på tidspunktet for opstart af psykologbehandling, 39 % har ingen tegn på depression, og 28 % har svær...

  16. Fermentering af korn øger fordøjeligheden af næringsstoffer

    DEFF Research Database (Denmark)

    Pedersen, Anni Øyan; Jørgensen, Henry; Bach Knudsen, Knud Erik

    2010-01-01

    foderblandingerne med ikke-fermentet korn var dog lavere end normalt, hvilket kan have påvirket resultaterne, så effekten af fermentering er større i dette forsøg, end hvad der normalt kan forventes. Kornet var groft formalet (ca. 30 % under 1 mm), hvilket kan have påvirket resultaterne. Ved finere formaling af...

  17. The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous cell carcinoma cell lines via the Akt/XIAP pathway.

    Science.gov (United States)

    Ui, Takashi; Morishima, Kazue; Saito, Shin; Sakuma, Yuji; Fujii, Hirofumi; Hosoya, Yoshinori; Ishikawa, Shumpei; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro; Yasuda, Yoshikazu

    2014-02-01

    Although cisplatin (CDDP) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC), acquired chemoresistance remains a major problem. Combination therapy may represent one strategy to overcome this resistance. Heat shock protein 90 (HSP90) is known to be overexpressed in several types of cancer cells, and its inhibition by small molecules, either alone or in combination, has shown promise in the treatment of solid malignancies. In the present study, we evaluated the synergistic effects of combining CDDP with the HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) on two CDDP-resistant human esophageal squamous cancer cell lines, KYSE30 and KYSE150. The results obtained demonstrated the synergistic inhibitory effects of CDDP and 17-AAG on the growth of KYSE30 and KYSE150 cells. Cell growth and cell number were more effectively reduced by the combined treatment with CDDP and 17-AAG than by the treatment with either CDDP or 17-AAG alone. Western blotting revealed that the combined action of CDDP and 17-AAG cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, which demonstrated that the reduction in both cell growth and cell number was mediated by apoptosis. Time-course experiments showed that reduction in X-linked inhibitor of apoptosis protein (XIAP) and phosphorylated Akt were concomitant with apoptosis. The results of the present study demonstrate that 17-AAG synergizes with CDDP and induces apoptosis in CDDP-resistant ESCC cell lines, and also that modulation of the Akt/XIAP pathway may underlie this synergistic effect. Combination therapy with CDDP and an HSP90 inhibitor may represent a promising strategy to overcome CDDP resistance in ESCC.

  18. Does an interdisciplinary outpatient atrial fibrillation (AF) clinic affect the number of acute AF admissions?

    DEFF Research Database (Denmark)

    Frydensberg, Vivi Skibdal; Brandes, Axel

    2018-01-01

    AIMS AND OBJECTIVES: To investigate the impact of a multidisciplinary outpatient clinic for patients with atrial fibrillation (AF-clinic) on the number of acute hospitalizations for atrial fibrillation compared with usual outpatient care for this condition before the establishment of the AF-clinic....... BACKGROUND: Guidelines recommend a structured outpatient clinic follow-up in multidisciplinary teams for patients with atrial fibrillation due to fewer hospitalizations and death. However the evidence base is weak. DESIGN: The study is a retrospective cohort study including a total of 129 patients from...... the cardiac outpatient clinic at a large Danish University Hospital. The study population consisted of two groups: a usual care group before a dedicated AF-clinic was established (n=73) and the AF-clinic group (n=56). The primary endpoint was acute hospitalization for AF. METHODS: Cox regression was used...

  19. Optisk scanning af spørgeskemaer

    DEFF Research Database (Denmark)

    Paulsen, Aksel

    / 1000 felter= 0.370 (95% CI: 0.160-0.729), (p= 0.020)). Der var ingen statistisk forskel mellem optisk scanning (fejl/ 1000 felter= 0.046 (95% CI: 0.001-0.258)) og manuel dobbelt indtastning (p=1.000). Konklusioner: Optisk scanning er et godt alternativ til manuel dobbelt indtastning for spørgeskema med......Formål og baggrund: Patient rapporterede outcomes i form af spørgeskemaer bruges i øgende grad i sundhedssektoren både i klinisk praksis og forskning. Ofte bruges spørgeskemaer i papirformat. Manuel dobbelt indtastning er defineret som guld standard for overføring af data til et elektronisk format......, men processen er tidkrævende. Optisk scanning af spørgeskemaer med automatisk registrering af svar kan være et alternativ, men videre validering af metoden er nødvendig. Design: 200 patienter blev tilfældigt udvalgt fra en kohorte på 5777 patienter der tidligere havde svaret på to forskellige...

  20. Evaluering af metoder til risikovurdering af kombinationseffekter og etablering af PBTK/TD modeller for pesticider - et ph.d.-projekt

    DEFF Research Database (Denmark)

    Reffstrup, Trine Klein

    2012-01-01

    I dette ph.d.-projekt ved DTU Fødevareinstituttet er den nuværende viden om metoder til risikovurdering af kombinationseffekter af kemiske stoffer med fokus på pesticider gennemgået. Endvidere undersøgtes, hvordan man kan implementere matematiske computermodeller som et værktøj i vurderingen af...

  1. E1AF degradation by a ubiquitin-proteasome pathway

    International Nuclear Information System (INIS)

    Takahashi, Akiko; Higashino, Fumihiro; Aoyagi, Mariko; Yoshida, Koichi; Itoh, Miyuki; Kobayashi, Masanobu; Totsuka, Yasunori; Kohgo, Takao; Shindoh, Masanobu

    2005-01-01

    E1AF is a member of the ETS family of transcription factors. In mammary tumors, overexpression of E1AF is associated with tumorigenesis, but E1AF protein has hardly been detected and its degradation mechanism is not yet clear. Here we show that E1AF protein is stabilized by treatment with the 26S protease inhibitor MG132. We found that E1AF was modified by ubiquitin through the C-terminal region and ubiquitinated E1AF aggregated in nuclear dots, and that the inhibition of proteasome-activated transcription from E1AF target promoters. These results suggest that E1AF is degraded via the ubiquitin-proteasome pathway, which has some effect on E1AF function

  2. Lejere der bliver sat ud af deres bolig

    DEFF Research Database (Denmark)

    Christensen, Gunvor; Nielsen, Torben Heien

    Antallet af lejere, der bliver sat ud af deres bolig, er steget i perioden 2002-06. I 2006 blev 2600 husstande, svarende til 0,1 pct. af samtlige husstande i Danmark, sat ud af deres bolig. Stigningen er især sket i de fem største byer: København, Århus, Odense, Ålborg og Esbjerg. I dette...... skal give viden om, hvilke årsager der er til, at nogle lejere bliver sat ud af deres bolig, og hvorfor der er sket en stigning i antallet af udsættelser. Den endelige afrapportering af undersøgelsen af udsættelser i Danmark vil ske i foråret 2008. Undersøgelsen er finansieret af Socialministeriet....

  3. Produktudvikling af fødevarer med Quality Function Deployment

    DEFF Research Database (Denmark)

    Bech, Anne C.

    1998-01-01

    Produktudvikling af fødevarer stiller stadig større krav til virksomhedernes kompetencer. QFD filosofien kan bidrage til at skabe en fælles forståelse af grundlaget for udvikling af nye produkter. Udgangspunktet er en forståelse af forbrugernes behov i relation til virksomhedens muligheder...... konkurrentprodukter. Efterfølgende faser handler om at generere forskellige mulige løsninger, inden der træffes valg af løsningsalternativ. Anvendelse af QFD modellen for produktudvikling betyder, at forbrugernes behov er centrale i hele produktudviklingsforløbet, samt at det udviklede produkt sigter mod at opfylde...... væsentlige identificerede behov set fra forbrugernes synspunkt. At virksomheden ser implementering af QFD som en investering, medarbejdernes commitment og målrettet projekt, er væsentlig for en succesfuld implementering af QFD til produktudvikling. QFD tankegangen illustreres med et eksempel på udvikling af...

  4. Undersøgelsen af brugernes evaluering af kontorpakker på Århus Sygehus og i Psykiatrien i Århus

    DEFF Research Database (Denmark)

    Hørlück, Jens

    En analyse af brugernes opfattelse af kvaliteten af tre office pakker: MS Office 2003 / 2007 og OpenOffice.  ......En analyse af brugernes opfattelse af kvaliteten af tre office pakker: MS Office 2003 / 2007 og OpenOffice.  ...

  5. Svingningsundersøgelse af betonskorsten

    DEFF Research Database (Denmark)

    Dalgaard, Lars-Bo; Kristensen, Peter

    Dette projekt omhandler en teoretisk og en eksperimentel undersøgelse af svingningsforholdene for en 110 meter høj betonskorsten. Skorstenen tilhører I/S Nordjyllands elektricitetsforsyning(NEFO) og er opført i forbindelse med en udbygning af Vendsysselværket med en sektion II med en turbine effe...... på 300 MW. Vendsysselværkets sektion I og II er afbilledet i figur 1.1.1, hvor værket er set fra nordøst med den undersøgte skorsten til højre i billedet. Skorstenen er projekteret af firmaet Rambøll og Hannemann og taget i brug i foråret 1977....

  6. Bestemmelse af spormetaller i organisk materiale

    DEFF Research Database (Denmark)

    Tjell, Jens Christian; Palfeldt, Kirsten

    Behovet for pålidelige analysemetoder til bestemmelse af spormetalindhold i organiske materialer, f.eks. planter, slam og dyrevæv er stigende på grund af den stigende erkendelse af disse stoffers betydning for organismers fysiologi, både hvor disse stoffer optræder i uønskede koncentrationer som...... der over de sidste år udviklet en analyseprocedure hvorefter det er muligt at analysere for metallerne Mn, Cu, Ni, Co, Cr, Zn, Cd og Pb i planter, dyrevæv, jord, slam og andre materialer med standardafvigelser på mellem 5 og 10%. Der gøres rede for denne metode....

  7. Ternary CaCu4P2-type pnictides AAg4Pn2 (A=Sr, Eu; Pn=As, Sb)

    Science.gov (United States)

    Stoyko, Stanislav S.; Khatun, Mansura; Scott Mullen, C.; Mar, Arthur

    2012-08-01

    Four ternary pnictides AAg4Pn2 (A=Sr, Eu; Pn=As, Sb) were prepared by reactions of the elements at 850 °C and their crystal structures were determined from single-crystal X-ray diffraction studies. These silver-containing pnictides AAg4Pn2 adopt the trigonal CaCu4P2-type structure (Pearson symbol hR21, space group R3¯m, Z=3; a=4.5555(6) Å, c=24.041(3) Å for SrAg4As2; a=4.5352(2) Å, c=23.7221(11) Å for EuAg4As2; a=4.7404(4) Å, c=25.029(2) Å for SrAg4Sb2; a=4.7239(3) Å, c=24.689(2) Å for EuAg4Sb2), which can be derived from the trigonal CaAl2Si2-type structure of the isoelectronic zinc-containing pnictides AZn2Pn2 by insertion of additional Ag atoms into trigonal planar sites within [M2Pn2]2- slabs built up of edge-sharing tetrahedra. Band structure calculations on SrAg4As2 and SrAg4Sb2 revealed that these charge-balanced Zintl phases actually exhibit no gap at the Fermi level and are predicted to be semimetals.

  8. Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

    Science.gov (United States)

    Hughes, Juliana Bentes; Rødland, Marianne Skeie; Hasmann, Max; Madshus, Inger Helene; Stang, Espen

    2012-01-01

    ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90) are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only. PMID:24281706

  9. Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] in a Pregnant Thai Woman.

    Science.gov (United States)

    Panyasai, Sitthichai; Thongsuk, Pollawat; Pornprasert, Sakorn

    2016-01-01

    Hb Agenogi [β90(F6)Glu→Lys (GAG>AAG) HBB: c.271G>A)] is a very rare β-globin chain variant. We report for the first time this hemoglobinopathy in a pregnant 20-year-old Thai woman. She was seen by an obstetrician at her 14th week of gestation. She was pale and had an inflammatory lesion of her lower left leg. The hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) and low pressure liquid chromatography (LPLC) showed a peak of abnormal Hb at the C window. On capillary electrophoresis (CE), the abnormal Hb peak was observed at electrophoretic zone 4 that corresponded to the Hb E (HBB: c.79G>A) peak. Direct DNA sequencing revealed a GAG>AAG mutation at codon 90 of the β-globin gene. Thus, even though Hb Agenogi is very rare, it can be found in Thai people. The knowledge and understanding of this hemoglobinopathy will be used to assist in diagnosis, management and counseling for patients.

  10. Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab

    Directory of Open Access Journals (Sweden)

    Juliana Bentes Hughes

    2012-06-01

    Full Text Available ErbB2 is an important oncogenic protein involved in carcinogenesis of, among others, breast, gastric, and ovarian carcinoma. Over-expression of ErbB2 is found in almost 20% of breast cancers, and this results in proliferative and anti-apoptotic signalling. ErbB2 is therefore an important treatment target. Antibodies recognizing full-length ErbB2 are clinically established, and drugs targeting the ErbB2 stabilizing heat shock protein 90 (Hsp90 are under clinical evaluation. We have investigated effects of the ErbB2-binding antibodies trastuzumab and pertuzumab alone and in combination, as well as the effect of the antibodies in combination with the Hsp90 inhibitor 17-AAG. Our results confirm the notion that combination of different ErbB2-binding antibodies more efficiently down-regulates ErbB2 than does one antibody in isolation. Additionally, our data demonstrate that ErbB2 is most efficiently down-regulated upon incubation with anti-ErbB2 antibodies in combination with Hsp90 inhibitors. The combination of anti-ErbB2 antibodies, and especially the combination of antibodies with 17-AAG, did also increase the inhibition of Akt activation of either agent, which could suggest an anti-proliferative effect. In such case, combining these agents could be beneficial in treatment of tumors not responding to trastuzumab only.

  11. MR-AFS: a global hierarchical file-system

    International Nuclear Information System (INIS)

    Reuter, H.

    2000-01-01

    The next generation of fusion experiments will use object-oriented technology creating the need for world wide sharing of an underlying hierarchical file-system. The Andrew file system (AFS) is a well known and widely spread global distributed file-system. Multiple-resident-AFS (MR-AFS) combines the features of AFS with hierarchical storage management systems. Files in MR-AFS therefore may be migrated on secondary storage, such as roboted tape libraries. MR-AFS is in use at IPP for the current experiments and data originating from super-computer applications. Experiences and scalability issues are discussed

  12. Leagile Manufacturing - implementering af modulariserede produktplatforme

    DEFF Research Database (Denmark)

    Bjarnø, Ole-Christian

    2003-01-01

    Lean og Agile (Leagile) Manufacturing indebærer ikke blot den rette balance (dekobling) mellem lean producerede komponenter og agile konfigurerede færdigvarer, og dermed til levering af individualiserede produkter til konkurrencedygtige priser og høj kvalitet, men også til effektivitet og...... fleksibilitet i produktudvikling og produktion. For at opnå integrationen mellem agile og lean kan der arbejdes med en vifte af integrationsmekanismer inden for organisatoriske og teknologiske virkemidler. Projektet har til formål at identificere, strukturere og modellere de centrale analyse- og...

  13. Medicinsk teknologivurdering af akupunktur til gravide

    DEFF Research Database (Denmark)

    Feenstra, Maria Monberg; Johansen, Marianne; Sørensen, Lisbeth Falborg

    -, organisatorisk- og økonomisk perspektiv. Metode: Der blev udarbejdet en medicinsk teknologivurdering (MTV). En alsidig og systematisk litteraturgennemgang af akupunkturbehandling til gravide med emesis/hyperemesis gravidarum, bækkenrelaterede smerter eller depression/angst blev udført. Den udvalgte litteratur...... behandlingen udføres korrekt af TCM-uddannet sundhedspersonale. Undersøgelser har vist høj patienttilfredshed blandt gravide ved akupunkturbehandling. Økonomiske beregninger dokumenterer, at akupunktur er et billigt behandlingstilbud. Konsekvenser for praksis: Det anbefales, at tilbyde gravide med emesis...

  14. Supervision af psykologkandidater i privat praksis

    DEFF Research Database (Denmark)

    Petersen, Birgitte

    et litteratur review over relevante temaer i supervisionslitteraturen samt overvejelser om læring i supervision. Afhandlingens empiriske resultater vil blive belyst og diskuteret med udgangspunkt i tilsvarende fænomener i supervisionslitteraturen. Resultaterne af undersøgelsen viser, at der er en...... række vigtige elementer ved supervision, der skal være opfyldt, hvis den skal opleves som udviklende og lærerig af praksiskandidaterne. Det er elementer som kontraktetablering, rådgivning og teoretisk refleksion, en tydelig teoretisk referenceramme samt støtte og anerkendelse fra supervisor. Det...

  15. Design og analyse af eksperimenter i R

    DEFF Research Database (Denmark)

    Dahl, Malte Rokkjær

    2017-01-01

    eksperimentelle studier med afsæt i statistikprogrammet R. Det er håbet, at notatet vil være en hjælp til at reflektere over, designe, og analysere eksperimenter i forbindelse med bachelorprojekter eller specialer - og forhåbentligt også i arbejde med eksperimenter uden for instituttets mure. Notatet berører......, herunder balancetest, hypotesetest med og uden kovariatjustering, interaktioner samt udledning af konfidensintervaller. Det antages, at læseren har et grundlæggende kendskab til R samt til *potentiel outcomes*-frameworket. De indledende kapitler i Gerber & Green (2012) eller Imbens & Athey (2017) er gode...

  16. Epichlorhydrin og bisphenol A i mat-kontaktmaterialer af epoxylakeret metal og/eller af plast

    DEFF Research Database (Denmark)

    Petersen, Jens Højslev; Pedersen, Gitte Alsing; Foverskov, Annie

    Det er ikke længere tilladt af bruge bisphenol A baseret polycarbonatplast til fremstilling af tåteflasker. Mattilsynet udtog i vinteren 2012/2013 7 typer af sutteflasker som blev kontrolleret for om de indeholdt polycarbonatbaserede plastdele. I alt 28 enkeltdele blev kontrolleret ved infrarød...... spektrometri. Herudover blev 6 tutekopper, bestående af 38 enkeltdele, analyseret med samme teknik. Der blev ikke påvist bisphenol A baseret plast ved analyserne. Dåser, bægre, tuber og skruelåg kan være lakeret på matkontaktsiden med epoxylakker fremstillet af monomererne epichlorhydrin og bisphenol A. Alle...... 50 enkeltdele fra disse prøver blev undersøgt ved infrarød spektrometri og 9 af prøverne viste tegn på at indeholde epoxylak. Disse prøver blev undersøgt ved en ”worst case” ekstraktionstest hvor der kunne påvises små indhold af bisphenol A i ekstrakterne mens der ikke kunne påvises epichlorhydrin...

  17. Test af to versioner af Modflow-LGR til simulering af grundvandsstrømninger i områder med begravede dale – syntetisk studie

    DEFF Research Database (Denmark)

    Vilhelmsen, Troels Norvin; Christensen, Steen

    .eks. findes i begravede dale. Manglende opløsning af geologiske aflejringer på lokal skala kan potentielt resultere i fejlagtige prædiktioner af konsekvensen af grundvandsindvinding på kildeplads niveau. For i højere grad at kunne forvalte disse grundvandsressourcerne skal nye metoder undersøges. Dette er...... specielt gældende for komplekse begravede dalsystemer, som interagerer med omkringliggende regionale grundvandsystemer. I dette syntetiske studie er to versioner af MODFLOW - Local Grid Refinment (LGR) testet til simulering af grundvandsstrømninger i områder med begravede dale. Forsøgene er gennemført som...

  18. Global opvarmning neutraliserer effekten af parasitisme på strandsnegles konsumption af makroalger

    DEFF Research Database (Denmark)

    Larsen, Martin H.; Mouritsen, Kim Nørgaard

    Det er veldokumenteret, at parasitter kan påvirke værternes adfærd, overlevelse, reproduktion, fysiologi og evolution. Disse parasit-vært interaktioner kan føre til radikale ændringer af naturlige samfunds struktur og diversitet. Eksperimenter har eksempelvis vist, at trematoder indirekte kan ændre...... strukturen af makroalgesamfund ved at reducere konsumptionsraten hos den herbivore strandsnegl Littorina littorea. Det er endvidere vist, at produktionen af trematode-larver (cercarier) i sneglens fordøjelseskanal og gonade kompleks øges kraftigt når vandtemperaturen stiger. Man kan derfor forvente...

  19. Domesticeringen af Ford i Danmark:Den kulturelle tilegnelse af Ford og fordismen, 1920-1940

    OpenAIRE

    Wagner, Michael

    2009-01-01

    Det amerikanske automobilfirma Ford Motor Company med hovedkvarter i Detroit begyndte at drive forretning i Danmark omkring 1906. De første aktiviteter blev konsolideret samme år ved udnævnelsen af motorforhandleren F. Bülow & Co. til salgsagent i Danmark og importør af Ford automobiler til det skandinaviske marked. Dermed havde Ford tidligt fået et stærkt fodfæste i Nordeuropa, som udviklingen i salget af Ford autobiler de næste årtier til fulde skulle demonstrere. Ford Motor Company er ...

  20. Degradation of AF1Q by chaperone-mediated autophagy

    International Nuclear Information System (INIS)

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-01-01

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components

  1. Degradation of AF1Q by chaperone-mediated autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Huanjie; Cui, Taixing; Li Wang, Xing [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: tangdq@sdu.edu.cn [Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China); Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan 250033 (China); Ji, Chunyan, E-mail: jichunyan@sdu.edu.cn [Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012 (China)

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  2. Gymnasie ikke absolut fravalg af EUD

    DEFF Research Database (Denmark)

    Juul, Tilde Mette; Pless, Mette

    2015-01-01

    Den faldende søgning til erhvervsuddannelserne har i medierne og den politiske debat ofte været begrundet med, at de unge ikke ser erhvervsuddannelserne som prestigefyldte. Nyt forskningsprojekt fra Center for Ungdomsforskning viser, at de unges opfattelser af erhvervsuddannelserne er mere nuance...

  3. Coaching af ph.d.-studerende

    DEFF Research Database (Denmark)

    Godskesen, Mirjam Irene

    Rapporten danner grundlag for at etablere et koncept for ph.d.-coaching. Erfaringerne fra et 2-årigt projekt om ph.d.-coaching i SCKK regi beskrives. De centrale temaer er tilrettelæggelse af den individuelle coaching, typiske temaer i coachingen og arbejdsdeling mellem coach og vejleder. Der er...

  4. Indeklimamærkning af byggevarer

    DEFF Research Database (Denmark)

    Nielsen, P.A.; Wolkoff, P.

    I denne rapport beskrives på prototypeniveau en frivillig indeklimamærkningsordning for byggevarer. Ordningen er baseret på bestemmelse af byggevarernes afgasningsprofil, fastlagt ud fra laboratoriemålinger. Ved modelberegning bestemmes dernæst koncentrationsprofilen i et standardrum, og der udfø...

  5. Retsplejelovens regulering af politiets adgang til teledata

    DEFF Research Database (Denmark)

    Lentz, Lene Wacher

    2017-01-01

    Politiet kan som led i en strafferetlig efterforskning få adgang til en række data om telekommunikation efter retsplejeloven, hvis regulering nu må revideres i lyset af ”Tele2-sagen”, hvor EU-domstolen fandt, at en generel logningspligt for teleudbyderne til at sikre teledata til brug for eventue...

  6. Brands som brikker i konstruktionen af identitet

    DEFF Research Database (Denmark)

    Hermansen, Judy

    2008-01-01

    Forbrug spiller en vigtig rolle i produktionen af mening og værdier, som kan skabe og vedligeholde både forbrugerens personlige og sociale verden - og derfor er reklame også en vigtig kilde til disse symbolske betydninger. Udgivelsesdato: juni...

  7. Topological ferrimagnetic behaviours of coordination polymers containing manganese(II) chains with mixed azide and carboxylate bridges and alternating F/AF/AF'/AF'/AF interactions.

    Science.gov (United States)

    Wang, Yan-Qin; Liu, Hou-Ting; Qi, Yan; Gao, En-Qing

    2014-08-21

    Two Mn(ii) complexes with azide and a new zwitterionic tetracarboxylate ligand 1,2,4,5-tetrakis(4-carboxylatopyridinium-1-methylene)benzene (L(1)), {[Mn5(L(1))2(N3)8(OH)2]·12H2O}n () and {[Mn5(L(1))2(N3)8(H2O)2](ClO4)2·6H2O}n (), have been synthesized and characterized crystallographically and magnetically. and contain similar alternating chains constructed by azide and carboxylate bridges. The independent sets of bridges alternate in an ABCCB sequence between adjacent Mn(ii) ions: (EO-N3)2 double bridges (EO = end-on) (denoted as A), [(EO-N3)(OCO)2] triple bridges (denoted as B) and [(EO-N3)(OCO)] double bridges (denoted as C). The alternating chains are interlinked into 2D coordination networks by the tetrapyridinium spacers. Magnetic studies demonstrate that the magnetic coupling through the double EO azide bridges is ferromagnetic and that through mixed azide/carboxylate bridges is antiferromagnetic. The unprecedented F/AF/AF'/AF'/AF coupling sequence along the chain dictates an uncompensated ground spin state (S = 5/2 per Mn5 unit) and leads to one-dimensional topological ferrimagnetism, which features a minimum in the χT versus T plot.

  8. Digitalisering af ældre menneskers hverdag

    DEFF Research Database (Denmark)

    Borchorst, Ditte Stilling; Sillesen, Agnete; Sommer, Finn M.

    2016-01-01

    Mange kommuner har inddraget frivillige som led i implementeringen af den offentlige digitaliseringsstrategi, der forpligter alle borgere til at kommunikere digitalt med offentlige myndigheder. Artiklen diskuterer erfaringer med at inddrage frivillige til at vejlede ældre mennesker i at anvende d...

  9. Karakterisering af Materialer fra atom til makro

    DEFF Research Database (Denmark)

    Brøndsted, Povl; Somers, Marcel A.J.

    2002-01-01

    Denne årbog er udgivet i forbindelse med Dansk Metallurgisk Selskabs Vintermøde, der fandt sted på Hotel Koldingfjord, Kolding i dagene 2. til 4. januar 2002. Bogen indeholder de foredrag, der blev præsenteret på Vintermødet. Emnet for mødet var " Karakterisering af Materialer - fra atom til makro...

  10. Den teoretiske udvikling af Supply Chain Strategimodeller

    DEFF Research Database (Denmark)

    Arvad Johansen, Jens

    2011-01-01

    segmentering via postponement-princippet, har givet mærkbare forbedringer. Det beskrives endvidere, hvordan produkternes livscyklus påvirker valget af supply chain design. Begrebet Demand Chain Management( DCM), hvormed strategimodeller bruger klassiske marketingelementer sammen med Supply Chain Management...... (SCM), bliver behandlet og der udvikles en DCM-strategimodel....

  11. Så lyt dog til kritikken af Sundhedsplatformen

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Søgaard, Jes

    2017-01-01

    Det er på tide, at Region Hovedstaden tager klinikernes bekymringer og kritik af Sundhedsplatformen alvorligt. Tiden er ikke inde til 'gevinstrealisering', men til at løse de alvorlige problemer, man kæmper med ude på hospitalerne...

  12. Konsolidering af læring

    DEFF Research Database (Denmark)

    Kirkegaard, Preben Olund; Geisnæs, Dorthe

    2016-01-01

    . Opbyggelse af konsolideringsstrategier er en langvarig proces. Processen er lang, fordi vidensabstraktion tager tid. Vidensopbyggelsen skal være så velkendt for eleven, at det er muligt for eleverne at genkende og hermed anvende viden til at kunne analysere fremtidige opgaver. https://www.youtube...

  13. Social praksisteoretiske analyser af unge i partnerskaber

    DEFF Research Database (Denmark)

    Mørck, Line Lerche; Munkholm, Merete

    Denne bog analyserer lokale partnerskaber mellem produktionsskoler og virksomheder, institutioner og civilsamfund. Bogen illustrerer, hvordan vi med social praksis teori kan forstå partnerskaber som grænsefællesskaber, hvor partnerskaber arrangeres i og på tværs af forskellige fællesskaber og han...

  14. Livsvalg konceptualiseret som dynamisk realisering af livsbaner

    DEFF Research Database (Denmark)

    Schnieber, Anette

    2009-01-01

    De valgsituationer, man i daglig tale kender som ”tilværelsens store valg”, mangler definition i den psykologiske litteratur, og det er således ikke klart, hvorvidt og evt. hvorledes disse valg adskiller sig fra andre typer. I artiklen gives en definition af ”de store valg”, og de adskilles fra...

  15. Måling af radon i bygninger

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    endvidere til at vurdere radon­eksponeringen i forhold til det nationale referenceniveau. Anvisningen dækker radonmåling i boliger og andre bygninger, fx kontorer, skoler og institutioner. Den henvender sig til bygningsejere, bygherrer, projekterende og brugere af bygninger. Desuden henvender anvisningen...

  16. Udvikling af universitetsundervisning - rammer, barrierer og muligheder

    DEFF Research Database (Denmark)

    Horst, Sebastian; Jensen, Ane; Johannsen, Bjørn Friis

    2011-01-01

    Dansk Universitetspædagogisk Netværk (DUN) afholdt sin årlige konference i 2011 den 30.-31. maj med temaet “Udvikling af universitetsundervisning - rammer, barrierer og muligheder”. På konferencen arbejdede ca. 100 personer fra alle niveauer i universitetsverdenen på at beskrive hvordan vi kan...

  17. På sporet af magtspillet om dansk naturfagsundervisning

    DEFF Research Database (Denmark)

    Schmidt, Jette Reuss

    Den neoliberale diskurs med tilhørende konkurrencemoment har længe været under beskydning i internationale forskningssammenhænge. Men der savnes konkrete eksempler på, hvordan neoliberal styring kommer til udtryk i nationale uddannelser. I denne afhandling følges derfor nogle af neoliberalismens...

  18. En tegning af æstetik 2013

    DEFF Research Database (Denmark)

    Buhl, Mie; Ejsing-Duun, Stine

    2013-01-01

    Denne artikel fremstiller skredet fra det individuelle fokus til den sociale forhandling omkring en situation, som er det nye perspektiv indenfor æstetik. Derigennem identificeres tendenser som er med til at udgøre platformen for børn og unges kulturer, hvor det handler om, at et æstetisk system er...... selvproducerende og stiller sig til rådighed for erkendelse. Disse kulturer udfolder sig i formater, som skolen ikke er gearet til at imødekomme. Som eksempel ville DrawSomething vanskeligt kunne begrundes i forhold til billedkunstfagets af ministeriet fastsatte ”fælles mål” – eller kan det? En central udfordring...... er, hvordan der skal arbejdes med æstetiske praksisformer i en nutidig læringskontekst, når børn og unges kulturer udfolder og udvikler sig i formater, der er præget af foranderlighed og flygtighed; af en uendelig skaben for nogen og med nogen og af situationer, der bebos med attituder? Vi diskuterer...

  19. Hvorfor lejere bliver sat ud af deres bolig

    DEFF Research Database (Denmark)

    Nielsen, Torben Heien; Christensen, Gunvor

    Antallet af lejere, der bliver sat ud af deres bolig, er steget fra 1499 i 2002 til 2589 i 2006. Lejere kan blive sat ud af deres bolig, hvis de ikke betaler deres husleje til tiden, eller hvis de ikke overholder husordenen det sted de bor. Denne rapport beskriver årsager til, at lejere bliver sat...... ud af deres boliger og baggrunden for stigningen i antallet af udsættelser. desuden beskriver rapporten konsekvenser af en udsættelse og kommer med en række anbefalinger til indsatsområder. Af afgørende betydning for, at lejere bliver sat ud af deres bolig, er lav indkomst, lavt rådighedsbeløb, stor...

  20. Subregional innovation – indikatorer til optimering af den erhvervsrettede innovationspolitik

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl; Graversen, Ebbe Krogh; Haase, Sanne Schioldann

    områder tilgodeses bedst muligt. Desuden kan en differentieret, subregional innovations-politik give erhvervslivet bedre udbytte end en samlet regional eller national innovationspolitik. Selvom Danmark er et lille land, er der store geografiske forskelle internt i landets erhvervsstruktur og i...... virksomhedernes innovationsaktiviteter. Som resultat af en udvidelse af den danske del af CIS 2006-undersøgelsen2 med ekstra virksomheder kan der gives en betydeligt mere nuanceret karak-teristik af virksomheder helt ned på subregionalt niveau. Analysen underbygger, at de innovations-politiske tiltag, der sættes......, lokal brug af resultaterne er nødvendig. Først gennemgås de valgte målepunkter. Det primære er en opdeling i praksis- og forsknings-orientering af virksomheders innovationstilgang, hvorved der identificeres fire grupper af innovationsaktive virksomheder. Det andet er korrektion af de anvendte...

  1. Vidensledelse og den sociale dimension i deling af viden

    DEFF Research Database (Denmark)

    Lauring, Jakob

    2004-01-01

    imidlertid et alternativt syn på viden som i højere grad inddrager den sociale dimension ved vidensdeling - den socialkonstruktivistiske opfattelse. I denne artikel vil jeg beskæftige mig med den socialkonstruktivistiske opfattelse af viden og beskrive, hvorledes denne synsvinkel kan rette fokus mod nogle...... meget væsentlige problemstillinger ved organisatorisk adfærd, som man ofte kommer til at ignorere, hvis man i for høj grad baserer ledelsen på en funktionalistisk opfattelse af viden. Delingen af viden er en aktuel udfordring for anvendelse af viden i forretningssammenhæng. Det er hovedsageligt det, som...... gør vidensbegrebet interessant i forhold til ledelse af virksomheder. - Fokus på de sociale barrierer for deling af viden Jeg vil i det kommende illustrere, hvilke betydninger den sociale dimension i deling af viden kan have for videnledelse. Det vil jeg gøre gennem beskrivelser af to forskellige...

  2. Uddrag af Ph.d.-afhandlingen Den groteske modernisme

    DEFF Research Database (Denmark)

    Lübker, Henrik

    2011-01-01

    Om forholdet mellem "det groteske" og "den groteske modernisme" eksemplificeret i en læsning af E.A. Poes "The Fall of the House of Usher" og flere af Francis Bacons malerier.......Om forholdet mellem "det groteske" og "den groteske modernisme" eksemplificeret i en læsning af E.A. Poes "The Fall of the House of Usher" og flere af Francis Bacons malerier....

  3. Portræt af litteraturkritikeren som ungt menneske

    DEFF Research Database (Denmark)

    Schatz-Jakobsen, Claus

    2004-01-01

    Artiklen præsenterer den amerikanske litteraturkritiker Geoffrey Hartmans tidlige forfatterskab og fremdrager dets selvbiografiske undertekst som nødvendig effekt af den unge Hartmans fascination af den engelske romantiker William Wordsworths forfatterskab.......Artiklen præsenterer den amerikanske litteraturkritiker Geoffrey Hartmans tidlige forfatterskab og fremdrager dets selvbiografiske undertekst som nødvendig effekt af den unge Hartmans fascination af den engelske romantiker William Wordsworths forfatterskab....

  4. Anmeldelse af Eigil Lego Andersen: Dirigent og generalforsamling

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2011-01-01

    Artiklen er en anmeldelse af advokat, adj. professor, dr. jur. Eigil Lego Andersens juridiske monografi om dirigenten og generalforsamlingen, herunder med lancering af en række nye afstemningsmetoder til brug for generalforsamlingen i (større) aktieselskaber.......Artiklen er en anmeldelse af advokat, adj. professor, dr. jur. Eigil Lego Andersens juridiske monografi om dirigenten og generalforsamlingen, herunder med lancering af en række nye afstemningsmetoder til brug for generalforsamlingen i (større) aktieselskaber....

  5. Udvikling af en internetsøgestrategi til identifikation af ny medicinsk teknologi inden for prostatacancer

    DEFF Research Database (Denmark)

    Thygesen, Marianne; Vondeling, Hindrik; Douw, Karla

    2007-01-01

    internetsider efter efficiens. Her er efficiens forstået som mindst antal minutter brugt pr. fund af information om en ny væsentlig medicinsk teknologi. Resultater: Strategien består af ti sider, som bør benyttes i følgende rækkefølge: YahooHealth, DoctorsGuide, The National Electronic Library for Medicines...

  6. Ternary CaCu4P2-type pnictides AAg4Pn2 (A=Sr, Eu; Pn=As, Sb)

    International Nuclear Information System (INIS)

    Stoyko, Stanislav S.; Khatun, Mansura; Scott Mullen, C.; Mar, Arthur

    2012-01-01

    Four ternary pnictides AAg 4 Pn 2 (A=Sr, Eu; Pn=As, Sb) were prepared by reactions of the elements at 850 °C and their crystal structures were determined from single-crystal X-ray diffraction studies. These silver-containing pnictides AAg 4 Pn 2 adopt the trigonal CaCu 4 P 2 -type structure (Pearson symbol hR21, space group R3-bar m, Z=3; a=4.5555(6) Å, c=24.041(3) Å for SrAg 4 As 2 ; a=4.5352(2) Å, c=23.7221(11) Å for EuAg 4 As 2 ; a=4.7404(4) Å, c=25.029(2) Å for SrAg 4 Sb 2 ; a=4.7239(3) Å, c=24.689(2) Å for EuAg 4 Sb 2 ), which can be derived from the trigonal CaAl 2 Si 2 -type structure of the isoelectronic zinc-containing pnictides AZn 2 Pn 2 by insertion of additional Ag atoms into trigonal planar sites within [M 2 Pn 2 ] 2− slabs built up of edge-sharing tetrahedra. Band structure calculations on SrAg 4 As 2 and SrAg 4 Sb 2 revealed that these charge-balanced Zintl phases actually exhibit no gap at the Fermi level and are predicted to be semimetals. - Graphical abstract: SrAg 4 As 2 and related pnictides adopt a CaCu 4 P 2 -type structure in which additional Ag atoms enter trigonal planar sites within slabs built from edge-sharing tetrahedra. Highlights: ► AAg 4 Pn 2 are the first Ag-containing members of the CaCu 4 P 2 -type structure. ► Ag atoms are stuffed in trigonal planar sites within CaAl 2 Si 2 -type slabs. ► Ag–Ag bonding develops through attractive d 10 –d 10 interactions.

  7. Ternary CaCu{sub 4}P{sub 2}-type pnictides AAg{sub 4}Pn{sub 2} (A=Sr, Eu; Pn=As, Sb)

    Energy Technology Data Exchange (ETDEWEB)

    Stoyko, Stanislav S.; Khatun, Mansura; Scott Mullen, C. [Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada); Mar, Arthur, E-mail: arthur.mar@ualberta.ca [Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2 (Canada)

    2012-08-15

    Four ternary pnictides AAg{sub 4}Pn{sub 2} (A=Sr, Eu; Pn=As, Sb) were prepared by reactions of the elements at 850 Degree-Sign C and their crystal structures were determined from single-crystal X-ray diffraction studies. These silver-containing pnictides AAg{sub 4}Pn{sub 2} adopt the trigonal CaCu{sub 4}P{sub 2}-type structure (Pearson symbol hR21, space group R3-bar m, Z=3; a=4.5555(6) A, c=24.041(3) A for SrAg{sub 4}As{sub 2}; a=4.5352(2) A, c=23.7221(11) A for EuAg{sub 4}As{sub 2}; a=4.7404(4) A, c=25.029(2) A for SrAg{sub 4}Sb{sub 2}; a=4.7239(3) A, c=24.689(2) A for EuAg{sub 4}Sb{sub 2}), which can be derived from the trigonal CaAl{sub 2}Si{sub 2}-type structure of the isoelectronic zinc-containing pnictides AZn{sub 2}Pn{sub 2} by insertion of additional Ag atoms into trigonal planar sites within [M{sub 2}Pn{sub 2}]{sup 2-} slabs built up of edge-sharing tetrahedra. Band structure calculations on SrAg{sub 4}As{sub 2} and SrAg{sub 4}Sb{sub 2} revealed that these charge-balanced Zintl phases actually exhibit no gap at the Fermi level and are predicted to be semimetals. - Graphical abstract: SrAg{sub 4}As{sub 2} and related pnictides adopt a CaCu{sub 4}P{sub 2}-type structure in which additional Ag atoms enter trigonal planar sites within slabs built from edge-sharing tetrahedra. Highlights: Black-Right-Pointing-Pointer AAg{sub 4}Pn{sub 2} are the first Ag-containing members of the CaCu{sub 4}P{sub 2}-type structure. Black-Right-Pointing-Pointer Ag atoms are stuffed in trigonal planar sites within CaAl{sub 2}Si{sub 2}-type slabs. Black-Right-Pointing-Pointer Ag-Ag bonding develops through attractive d{sup 10}-d{sup 10} interactions.

  8. Ekstraktion af æteriske olier fra oregano

    DEFF Research Database (Denmark)

    Ellitsgaard Jakobsen, Jens; Ankerfeldt, Dorte; Jensen, Morten Busch

    2010-01-01

    med keratin - Ammoniakforurening reduceres med ny teknologi - Genvinding og genanvendelse af ammoniak fra spildevand og husdyrgødning - Ginseng - en virkningsfuld medicinplante - Ekstraktion af æteriske olier fra oregano "Biotek" er udviklet med udgangspunkt i originalartikler udarbejdet af forskere...

  9. Eksperimentel bakteriofagterapi til behandling af kronisk Pseudomonas aeruginosaotitis hos hund

    DEFF Research Database (Denmark)

    Moodley, Arshnee; Mølgaard, Jesper

    2016-01-01

    Vi beskriver en case med anvendelsen af bakteriofager til behandling af kronisk otitis forårsaget af multiresistente Pseudomonas aeruginosa som en sidste behandlingsmulighed før aflivning. Trods gentagne behandlinger, både topikalt og systemisk, med op til seks forskellige antibiotika over en...

  10. Når ledelse af ledelse rettes mod selvet

    DEFF Research Database (Denmark)

    Krause-Jensen, Niels Henrik

    2012-01-01

    Der fokuseres på det nye selvledelsesforhold som ledelse af ledelse er med til at fremkalde. Ud fra et signalement af det nye arbejdsliv beskrives det hvordan ledelse af ledelse skal forvalte en indgriben i medarbejderens selvforhold, hvor både magt og afmagt vil gøre sig gældende....

  11. Arbejdsmiljøet ved udbud af renovationsarbejde

    DEFF Research Database (Denmark)

    Busck, Ole Gunni

    Forfatteren gennemførte 2003-2005 en undersøgelse for Branchearbejdsmiljådet for transport af danske kommuners praksis i forbindelse med udbud og udlicitering af renovationsopgaver. Formålet var at kortlægge og analysere erfaringerne med varetagelse af arbejdsmiljøhensyn i kommunernes udbud og dr...

  12. Måling af lydisolation og efterklangstid i praksis

    DEFF Research Database (Denmark)

    Kristensen, J.

    Meddelelsen omhandler undersøgelser af mulighederne for at forbedre reproducerbarheden ved måling af luftlydisolation, trinlydniveau og efterklangstid under betingelser, der svarer til måling i den indflytningsfærdige bygning. Der omtales resultater fra måling med to forskellige udformninger af h...

  13. Benchmarking af udsættelser i kommunerne

    DEFF Research Database (Denmark)

    Christensen, Gunvor; Jeppesen, Anders Gade; Markwardt, Kristoffer

    2015-01-01

    nuværende tidspunkt stadig mangler relevante forhold i benchmarking-modellen. Eksempelvis antallet af stofmisbrugere, antallet af borgere med psykiatriske indlæggelser samt forekomsten af projekter med henblik på at forebygge udsættelser (fx gældsrådgivning). Disse data er først tilgængelige i 2015....

  14. Anmeldelse af: Afghantsy. The Russians in Afghanistan 1979-89

    DEFF Research Database (Denmark)

    Vestenskov, David

    2012-01-01

    Baseret på nyligt afklassificeret materiale fra arkiverne i Moskva samt fremstillinger af russiske historikere, tegnes et anderledes og mere nuanceret billede af de sovjetiske erfaringer fra Afghanistan. De første spadestik til opgøret med den amerikanske stempling af den sovjetiske ageren i...

  15. Antitrombotisk behanding af patienter med valvulær atrieflimren

    DEFF Research Database (Denmark)

    Bovin, Ann; Christensen, Thomas Decker; Grove, Erik Lerkevang

    2017-01-01

    with valvular AF. Although the definition of valvular AF is disputed, the lack of evidence regarding the use of NOACs for these patients is not. We discuss the definition of valvular AF, the risk of thromboembolism, and the antithrombotic treatment for stroke prevention in these patients....

  16. Effektivitet af naturligt drevne radontiltag året rundt

    DEFF Research Database (Denmark)

    Haker Høegh, Britt; Rasmussen, Torben Valdbjørn

    Denne rapport omhandler projektet Effektivitet af naturligt drevne radontiltag året rundt. Projektet er et spireprojekt finansieret af Innovationsnetværket InnoBYG og Forsknings- og Innovationsstyrelsen. Projektet er gennemført af Teknologisk Institut i samarbejde med Statens Byggeforskningsinsti...

  17. Barriere for Studerendes Læring af Holistisk Systemudvikling

    DEFF Research Database (Denmark)

    Levinsen, Karin; Madsen, Sabine

    Ud fra aktionsforskning af faget Informationsbehandling på bachelorprogrammet HA/DØK ved Copenhagen Business School undersøger vi i denne artikel hvilke barriere de studerende oplever i forbindelse med læring af holistisk systemudvikling og hvorfor. Siden 1980'erne har man i (dele af) litteraturen...

  18. Afståelsesbeskatning ved flytning af DEMPE-funktioner

    DEFF Research Database (Denmark)

    Kjærsgaard, Louise Fjord; Bundgaard, Jakob

    2017-01-01

    OECD har i den senest opdaterede version af Transfer Pricing Guidelines fastsat en definition af immaterielle aktiver og har samtidig indført konceptet DEMPE-funktioner, der omfatter visse vigtige funktioner relateret til immaterielle aktiver. SKAT synes at være af den opfattelse, at DEMPE...

  19. Studerende og underviseres brug af digitale medier - En kvantitativ undersøgelse af Aarhus Universitets studerende og underviseres brug af digitale medier og internettet anno 2008

    Directory of Open Access Journals (Sweden)

    Maria Hvid Stenalt

    2009-06-01

    • Hvilke medier anvender universitetsstuderende generelt? • Ligner undervisernes medievalg/forbrug de studerendes? • Hvilke medier inddrager underviserne i undervisningen? Nærværende artikel vil forsøge at besvare disse spørgsmål på baggrund af en kvantitativ spørgeskemaundersøgelse af Aarhus Universitets studerende og underviseres brug af digitale medier og internettet. Undersøgelsen blev gennemført i efteråret 2008 af E-læringsenheden ved Aarhus Universitet som led i en almen kvalitetssikring på media- og e-læringsområdet, samt som led i en behovsafklaring vedrørende etablering af et medie- og podcastarkiv. E-læringsenheden er en administrativ enhed, der teknisk og pædagogisk understøtter underviseres inddragelse af digitale medier i undervisningen.

  20. Spin structures of S = 5/2 antiferromagnetic triangular lattices: AAg{sub 2}M[VO{sub 4}]{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, Angela; Amuneke, Ngozi E.; Tapp, Joshua [Department of Chemistry and TcSUH, University of Houston (United States); Cruz, Clarina R. de la [Quantum Condensed Matter Division, ORNL, Oak Ridge (United States)

    2015-07-01

    The AAg{sub 2}M[VO{sub 4}]{sub 2} compounds present a unique series for studying structure-property relationships. The size of the A cation (Ba{sup 2+}, K{sup +}, Rb{sup +}, or Ag{sup +}) controls (i) the inter-layer distances between the magnetic triangular lattices (M, here Mn{sup 2+} or Fe{sup 3+}) and (ii) the distortion of the non-magnetic vanadate units. The crystal and magnetic structures were refined from neutron diffraction data under applied fields (ORNL, HB2A) and reveal the complex magnetic phase diagrams of frustrated S=5/2 triangular lattices with axial and XY-anisotropy, respectively.

  1. Delevalueringer af teknologi og velfærd i 4skit

    DEFF Research Database (Denmark)

    Miller, Tanja; Haslam, Trine Lolk; Abildgaard, Katrine Copmann

    Som et led i evaluering af satspuljeprojekt i regi af AMU - Aalborg har CEPRA udført en række delevaluering af udvalgte projekter......Som et led i evaluering af satspuljeprojekt i regi af AMU - Aalborg har CEPRA udført en række delevaluering af udvalgte projekter...

  2. An Interface Transformation Strategy for AF-IPPS

    Science.gov (United States)

    2012-12-01

    Oracle, or SAP . Like other AF and Department of Defense (DoD) ERP programs, AF-IPPS is expected to have 100+ interfaces with 90+ external trading partners...platform such as PeopleSoft, Oracle, or SAP . Like other AF and Department of Defense (DoD) ERP programs, AF-IPPS is expected to have 100...currently perform these functions. The core of AF-IPPS will be implemented using an Enterprise Resource Planning ( ERP ) platform such as PeopleSoft

  3. The small-molecule kinase inhibitor D11 counteracts 17-AAG-mediated up-regulation of HSP70 in brain cancer cells.

    Science.gov (United States)

    Schaefer, Susanne; Svenstrup, Tina H; Guerra, Barbara

    2017-01-01

    Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years. Exposure of cancer cells to HSP90 inhibitors, including 17-AAG, has been shown to cause resistance to chemotherapeutic treatment mostly attributable to induction of the heat shock response and increased cellular levels of pro-survival chaperones. In this study, we show that treatment of glioblastoma cells with 17-AAG leads to HSP90 inhibition indicated by loss of stability of the EGFR client protein, and significant increase in HSP70 expression. Conversely, co-treatment with the small-molecule kinase inhibitor D11 leads to suppression of the heat shock response and inhibition of HSF1 transcriptional activity. Beside HSP70, Western blot and differential mRNA expression analysis reveal that combination treatment causes strong down-regulation of the small chaperone protein HSP27. Finally, we demonstrate that incubation of cells with both agents leads to enhanced cytotoxicity and significantly high levels of LC3-II suggesting autophagy induction. Taken together, results reported here support the notion that including D11 in future treatment regimens based on HSP90 inhibition can potentially overcome acquired resistance induced by the heat shock response in brain cancer cells.

  4. Udvikling af medicinsk behandling mod bipolar lidelse

    DEFF Research Database (Denmark)

    Ellegaard, Pernille Kempel

    2015-01-01

    Selvom Esbjerg ligger i vandkants Danmark, er det den Psykiatriske Forskningsenhed i denne by, der er primus motor for et stort forsøg blandt mennesker, der lider af bipolar lidelse. Forsøget hedder ”NACOS”, og er et medicinsk forsøg til mennesker, der befinder sig i den depressive fase.......Selvom Esbjerg ligger i vandkants Danmark, er det den Psykiatriske Forskningsenhed i denne by, der er primus motor for et stort forsøg blandt mennesker, der lider af bipolar lidelse. Forsøget hedder ”NACOS”, og er et medicinsk forsøg til mennesker, der befinder sig i den depressive fase....

  5. Obama skal ikke nyde noget af Syrien

    DEFF Research Database (Denmark)

    Ulrich, Philip Christian

    2013-01-01

    Mange har i lang tid undret sig over at konflikten i Syrien har kunnet få lov at stå på i så lang tid, uden at USA har vist lederskab og grebet ind. Det er jo den rolle vi er vant til at se USA i. Men Obama skal ikke nyde noget af at engagere sig i Syrien. Det har USA ikke råd til......Mange har i lang tid undret sig over at konflikten i Syrien har kunnet få lov at stå på i så lang tid, uden at USA har vist lederskab og grebet ind. Det er jo den rolle vi er vant til at se USA i. Men Obama skal ikke nyde noget af at engagere sig i Syrien. Det har USA ikke råd til...

  6. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    Science.gov (United States)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  7. At afsøge mulige selv

    DEFF Research Database (Denmark)

    Kruse, Tove Elisabeth

    2015-01-01

    Artiklen undersøger, hvad der karakteriserer den fortid, der gøres levende ifm. en pilgrimsvandring i Frans af Assisis fodspor, og hvilken brugsværdi denne fortid har i nutiden. Undersøgelsen viser, at den fortid, der har brugsværdi i nutiden er en autentisk fortid. Frans er en historisk person, og...... nærværende og bringes i spil ift. deltagernes nutid og fremtid. Fortiden bliver levendegjort på mangfoldige måder: gennem den konkrete både åndelige og kropslige imitation af fortidig praksis, gennem de flerstemmige narrativer om Frans, gennem deltagernes fransinspirerede narrativer om sig selv. Den...

  8. CERN’s AFS replacement project

    Science.gov (United States)

    Iven, J.; Lamanna, M.; Pace, A.

    2017-10-01

    OpenAFS is the legacy solution for a variety of use cases at CERN, most notably home-directory services. OpenAFS has been used as the primary shared file-system for Linux (and other) clients for more than 20 years, but despite an excellent track record, the project’s age and architectural limitations are becoming more evident. We are now working to offer an alternative solution based on existing CERN storage services. The new solution will offer evolved functionality, and is expected to eventually benefit from operational synergies. In this paper we will present CERN’s usage and an analysis of our technical choices: we will focus on the alternatives chosen for the various use cases (among them EOS, CERNBox and CASTOR); on implementing the migration process over the coming years; and the challenges and opportunities of the migration.

  9. Den kulturelle dimension af virksomhedens internationalisering

    DEFF Research Database (Denmark)

    Langhoff, Tine

    1994-01-01

    Artiklen omhandler den kulturelle dimensions indvirkning på virksomhedens internationalisering og diskuterer mulige internationalisieringsstrategier for virksomheder, der konfronteres med kulturforskelle. Med udgangspunkt i en kritik af den hidtidige forskning på området, hvor det såkaldte psykiske...... distancebegreb har haft en central placering, foreslås det, at man som alternativ til dette begreb skal fokusere på virksomhedens markedsbaserede innovationsevne. Denne betegnes som dens interkultu kompetence og vedrører dens evne til at identificere og udnytte muligheder i fremmede kulturelle sammenhænge. Det...... er herved, at den kulturelle dimension påvirker virksomheden og dens fortsatte udvikling. En empirisk analyse i den danske fødevarebranche afdækker virksomheders interkulturelle kompetence ved hjælp af to spørgsmål: (1) Hvorledes formår virksomheder med begrænsede ressourcer til deres disposition...

  10. Nye ledelsesudfordringer i forebyggelse af stress i videnarbejdet

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Ipsen, Christine; Mogensen, Mette

    arbejdssituation og muligheder for forebyggelse af arbejdsrelateret stress i vidensarbejdet. – Et kvalitaivt studie af arbejdsrelateret stress i vidensarbejdet. Lyngby, The Technical University of Denmark. Kärreman, Dan, Stefan Svenningson and Mats Alvesson (2003): The Return of the Machine Bureaucracy? Management......Afsættet for projektet ”Forebyggelse af stress i videnarbejdet – mellem begejstring og belastning” er, at der er behov for en ny forståelse af stress i det moderne arbejdsliv, for at kunne arbejde med stressforebyggelse blandt videnarbejdere. I dette paper tager vi udgangspunkt i begrebet...... mangetydighed/ambiguity som en karakteristik af videnarbejdet, da det stiller nogle helt nye udfordringer til hvordan ledelse af videnarbejdet skal foregå, når målet er at forebygge arbejdsrelateret stress. Vi karakteriserer videnarbejdet som mangetydigt og som Alvesson (2004) påpeger, udgør dilemmaerne i...

  11. Organisering af basal uddannelse i laparoskopisk kirurgi

    DEFF Research Database (Denmark)

    Lund, Lars; Høj, Lars; Poulsen, Johan

    2010-01-01

    evalueringsmetode er anvendt objective structured clinical examination (OSCE-test) og objective structured assessment of technical skills (OSATS-test). Resultater: Af de 106 læger er der færdigtrænet 80 læger på modul 1 og 2. Deltagernes fordeling på specialer var ved modul 1: kirurgi 47 læger, urologi 14 læger og...

  12. Vindafstivende vægge af letbetonelementer

    DEFF Research Database (Denmark)

    Buhelt, M.

    Rapporten beskriver en forsøgsserie med 18 afstivende vægge opbygget af etagehøje, sammenlimede letbetonelementer. Der redegøres for de nødvendige kraftoverførende samlinger og der angives bæreevner for samlingerne og for væggen som helhed. Det konkluderes at sådanne vægge er velegnede som afstiv...

  13. En kvantitativ analyse af danskernes huskesedler

    DEFF Research Database (Denmark)

    Schmidt, Marcus

    2005-01-01

    .Samlet rummede de 871 sedler 8047 vareemner. Skønsvist drejer det sig om mellem 600 og 800 forskellige produkter. Det præcise tal lader sig ikke helt fastlægge, idet visse vareemner ("grønt", "pålæg" og "tøj" osv. i modsætning til agurker, hamburgerryg og Adidas T-shirt XL) ikke tillader identifikation af et...

  14. Evaluering af Familiehuset i Rebild Kommune

    DEFF Research Database (Denmark)

    Hansen, Helle; Arendt, Kasper Skou; Mehlsen, Line

    Evalueringen af Familiehuset i Rebild Kommuner viser, at børnenes trivsel forbedres, og de får færre følelsesmæssige problemer og adfærdsvanskeligheder. Samtidig falder forældrenes stressniveau i rollen som forældre. Baggrund: Rebild kommune har henvendt sig til VIVE for at få evalueret deres fam...

  15. Pressetørring af parketstave - Simulationsmodel

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad; Sørensen, Mads Peter; Pinholt, Peter

    2004-01-01

    Nærværende rapport indgår som en del af det arbejde der er udført under BIPS centeret. Rapporten vedrører modelleringsarbejdet med Junckers pressetørringsproces. Det er målet at opstille en termodynamisk og mekanisk model for parketstavene under pressetørring med henblik på at forklare og om muligt...

  16. Forankring af kvarterløft

    DEFF Research Database (Denmark)

    Mazanti, B.

    Kvarterløft er et offentligt initiativ, der har til formål at forbedre sociale, bygningsmæssige og andre forhold i en afgrænset bydel. Kvarterløft er per definition tidsbegrænset til fem eller syv år. Mens et kvarterløft står på, er der ofte en mængde og mangfoldighed af aktiviteter og projekter....

  17. Evaluering af Relationskompetenceprojektet 2012-16

    DEFF Research Database (Denmark)

    Nielsen, Birgitte Lund

    kollegafællesskab, at have fået øget bevidsthed om relationers betydning og om at være fuldt til stede i en undervisningssituation, og ikke mindst at have mødt og afprøvet konkrete værktøjer i arbejdet med elever i skolen for lærerne eller for de lærerstuderende i praktik. Nogle udfordringer der fremhæves har...... handlet om de såkaldte indre øvelser. Det ser således ud til, at det systematiske arbejde med disse øvelser, der fremstår som særdeles udbytterigt for nogle aktører, er op-levet mindre positivt af andre. Det har også været en udfordring når udefrakommende har været kritiske over for projektet. Projektets...... karakter med samarbejde på tværs af aktørgrupper ser ud til at have været et afgørende perspektiv for det store oplevede udbytte. For de lærerstuderende ser indsatsen over tid ud til at have været vigtig. Den fortsatte deltagelse på 4. år af studiet var frivillig, og de lærerstuderende der valgte dette til...

  18. En fascinerende fortælling om det 20. århundredes musik

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2011-01-01

    Anmeldelse af Karl Aage Rasmussen: Musik i det tyvende århundrede: En fortælling. Gyldendal 2011.......Anmeldelse af Karl Aage Rasmussen: Musik i det tyvende århundrede: En fortælling. Gyldendal 2011....

  19. NCBI nr-aa BLAST: CBRC-DSIM-02-0026 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DSIM-02-0026 gb|AAG22709.1|AF280553_1 methuselah [Drosophila melanogaster] gb|...AAG22710.1|AF280554_1 methuselah [Drosophila melanogaster] gb|AAG22711.1|AF280555_1 methuselah [Drosophila mela...nogaster] gb|AAG22713.1|AF280557_1 methuselah [Drosophila melanogaster] gb|AAG22714.1|AF280558_1 methuselah [Drosophila mela...nogaster] gb|AAG22716.1|AF280560_1 methuselah [Drosophila mela...nogaster] gb|AAG22718.1|AF280562_1 methuselah [Drosophila melanogaster] gb|AAG22720.1|AF280564_1 methuselah [Drosophila mela

  20. Overvågning af orkidéer 2000

    DEFF Research Database (Denmark)

    Wind, P.

    resultaterne af orkidéovervågningen (Wind 2001). Hertil kommer præsentationen af projektet og dets resultater efter forløbet af de første tre år (Løjtnant 1991a) og en bearbejdning af projektets resultater for årene 1987-1995 (Wind 1997). I nærværende rapport undersøges skov-hullæbe for en eventuel sammenhæng...... mellem skudanlæggelsen udtrykt ved antallet af blomstrende og vegetative skud i et givet år og nedbørsmængder i august og september året før. Det er en udbredt antagelse at der er en sammenhæng mellem skudanlæggelse og mængden af nedbør det foregående år. Undersøgelser af skov-hullæbe populationer i...... truet og sårbar samt de to arter der er omfattet af Habitatdirektivets bilag 2. I 2000 kan det i forhold til 1999 konstateres at der i 15 bestande er optalt et øget antal skud. I 11 bestande er der noteret en nedgang i antallet af skud sammenlignet med optællingerne i 1999. Af disse er der 2 be...

  1. Evaluering af den ernæringsmæssige kvalitet af madordninger i daginstitutioner

    DEFF Research Database (Denmark)

    Nielsen, Marie Heyn; Lassen, Anne Dahl; Christensen, Lene Møller

    Fokus på madordninger i daginstitutioner og kvaliteten heraf har været stigende de seneste år. Mange nye madordninger er etableret i løbet af 2009 og 2010 især i børnehaver og i børnehavegrupper i de integrerede daginstitutioner. I 2009 opstillede Fødevarestyrelsen anbefalinger for den ernæringsm...... fedt samt at servere fisk, grøntsager, kartofler, samt fuldkornsvarianter af ris, pasta og brød mere hyppigt....

  2. En litteraturbaseret gennemgang af mulige velfærdsmæssig betydning af brugen af længerevarende smertelindring til kalve efter afhorning

    DEFF Research Database (Denmark)

    Herskin, Mette S.; Nielsen, Bodil Højlund

    2018-01-01

    Dette er et udvidet sammendrag af vidensyntesen. Store dele af vidensyntesen er under review til et videnskabeligt tidsskrift, og kan derfor ikke offentliggøres elektronisk før denne proces er afsluttet. Den fulde rapport kan fremsendes pr. mail. Hvis du gerne vil have den tilsendt, så send en mail...

  3. Vurdering af effekten af en vindmøllepark ved Overgaard på forekomsten af fugle i EF-fuglebeskyttelsesområde nr. 15

    DEFF Research Database (Denmark)

    Clausen, P.; Larsen, J. K.

    forekomsten af en række arter der enten yngler eller raster inden for EF-fuglebeskyttelsesområdet, og er omfattet af EF-fuglebeskyttelsesdirektivets bilag I. Det drejer sig om arterne skarv Phalacrocorax carbo sinensis, blå kærhøg Circus cyaneus, hjejle Pluvialis apricaria, brushane Philomachus pugnax, klyde...

  4. Sorter af afgræsningslucerne

    DEFF Research Database (Denmark)

    Søegaard, Karen

    2011-01-01

    – to nye sorter Verbena og Camboregio og en ældre sort Luzelle. Sorterne blev dyrket i renbestand og to forskellige blandinger med alm. rajgræs. Parcellerne blev afgræsset af kvier, med en forholdsvis hård afgræsning, i to forskellige slæt/afgræsnings systemer. Generelt klarede Verbena sig bedst og...... afgørende forskelle mellem denne ældre og de to nye sorter. Resultaterne for Luzelle lå generelt mellem Verbena og Camporegio....

  5. Innovation af “social kapital”

    DEFF Research Database (Denmark)

    Jønsson, Thomas

    2008-01-01

    I de fleste organisationer anerkendes det positive potentiale ved sociale relationer og organisering i grupper, hvilket fx søges opnået gennem teamorganisering. I nogle sammenhænge omtales det socialpsykologiske potentiale i en organisation som “social kapital”. Forskning fra socialpsykologien...... interesser. Det vil også stille krav til medarbejderne i retningen af øget engagement og involvering. Omvendt vil der være udsigt til at medarbejdernes deltagelse i beslutninger forbedrer muligheder for succes i kombination med kompetenceudvikling og (andre) såkaldte Human Resource Management praktikker....

  6. Energirenovering af større bygninger

    DEFF Research Database (Denmark)

    Mortensen, Lone Hedegaard; Birck Laustsen, Jacob; Vorre, Mette Havgaard

    involverede parter i et renoveringsprojekt om, hvordan energirenoveringsprojekter gennemføres i alle faser. SBi-anvisning 269 kan bruges som styringsredskab for bygherrer og kravgrundlag for rådgivere, entreprenører og andre parter, der leverer ydelser til bygherren. For institutioner, der stiller kapital til......​SBi-anvisning 269 omhandler metode og proces for gennemførelse af energirenoveringsprojekter for større bygninger fra idefase til driftsfase. Større bygninger omfatter etageboliger, bygninger til privat handel- og service samt offentlige institutioner. Anvisningen giver vejledning for de...

  7. Bohr vs. Einstein: Fortolkning af kvantemekanikken

    DEFF Research Database (Denmark)

    Andersen, Christian Kraglund; Wade, Andrew Christopher James

    2013-01-01

    Siden 1913, da Bohr fremlagde sin kvantemekaniske model for atomet, har fysikere diskuteret, hvordan kvan- temekanikken skal fortolkes. Specielt aktive i denne diskussion var Bohr og Einstein, som havde modstridende opfattelser af, hvordan kvantemekanikken skulle forstås. Kan katte være både...... levende og døde på samme tid? Kan vi teleportere partikler mellem Månen og Jorden? Disse spørgsmål, og mange flere, forsøgte Bohr og Einstein at besvare, og det vil vi ligeledes i denne artikel....

  8. Er genomisk selektion en revolution af avlsarbejdet med mink?

    DEFF Research Database (Denmark)

    Berg, Peer

    2011-01-01

    Genomisk selektion udnytter, at den enkelte mink kan genotypes for tusindvis af genetiske markører. Et dyrs avlsværdi kan skønnes med ret stor sikkerhed på basis af en blod- eller hårprøve, hvor dyrets sæt af genetiske markører bestemmes. Det er altså ikke nødvendigt at registrere minkens egne eg...

  9. Udvikling af informationskompetence i problemorienteret arbejde med brug af digitale værktøjer

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Lerche; Birch Andreasen, Lars; Jørgensen, Lars

    2006-01-01

    vejledningsformer. Visionen for projektet er, at arbejdet med at støtte de studerendes udvikling af informationskompetence ikke alene ses som en opgave for biblioteker biblioteker, men som en opgave der skal løses i et tættere integreret samarbejde mellem biblioteker og faglige uddannelsesmiljøer. Pilotprojektet...

  10. Udvikling af vejledningspraksis i kurser for undervisere i brugen af blended learning-aktiviteter

    DEFF Research Database (Denmark)

    Stenalt, Maria Hvid; Wichmann-Hansen, Gitte; Rossen, Dorte Sidelmann

    Hvert semester tilbyder Center for Undervisning og Læring (CUL) ved School of Business and Social Sciences ved Aarhus Universitet et 1-årig langt kompetenceudviklingsforløb i brugen af blended learning for lektorer og professorer. I løbet af denne periode skal deltagerne gennemføre et indledende...... blended learning-kursusforløb på 5 uger efterfulgt af en udviklings- og afprøvningsfase. Som afslutning skal deltagerne skrive en refleksionsrapport. Forløbet indebærer to vejledningsmøder med en eller flere af de undervisningsudviklere fra CUL, der er ansvarlige for forløbet: 1) Et individuelt...... vejledningsmøde, hvor deltagerne skal finde frem til, hvordan de vil eller kan omlægge deres undervisning til blended learning og 2) et kollektivt vejledningsmøde efter første udviklingsfase, hvor deltagerne modtager feedback på deres igangværende udviklingstiltag fra gruppemedlemmer og undervisningsudviklere. Et...

  11. Rensning af et skulpturportræt af maleren C.W. Eckersberg

    DEFF Research Database (Denmark)

    Cone, Louise

    2016-01-01

    Rensning af gips er et kompliceret emne. Gips er et hygroskopisk (vand elskende) materiale som let optager vand. Rensning med almindelig vand er derfor helt umuligt, da snavs på overfladen vil blive transporteret ind i porestrukturen sammen med vandet. Når man støber i gips, frigiver den en masse...

  12. Om zeppelinere, forsvaret af København, blokaden af Tyskland og spionanklagen mod ritmester Frederik Moltke

    DEFF Research Database (Denmark)

    Clemmesen, Michael Hesselholt

    2015-01-01

    Artiklen følger Hærens indkøbschef, ritmester Frederik Moltkes, virksomhed i England fra eftersommeren 1915. Han endte på grund af sin energiske indsats også som fungerende militærattaché samt gennem halvbrorens profil som dansk gesandt i Berlin med at blive spionmistænkt og fanget i den britiske...

  13. En kvalitativ undersøgelse af gravides valg af nakkefoldscanning

    DEFF Research Database (Denmark)

    Sørensen, Stina Lou; Dahl, Katja; Beck risør, Mette

    2007-01-01

    valg. Vi ønskede at undersøge informationens rolle i den gravides forståelse og valg af nakkefoldskanning. Materiale og metoder: Seksogtyve gravide blev interviewet efter første svangrekonsultation og igen efter misdannelseskanningen. Undersøgelsesresultaterne i denne artikel stammer primært fra første...

  14. Forekomst af alkohol, narkotika og medicin hos bilister

    DEFF Research Database (Denmark)

    Bernhoft, Inger Marie

    2011-01-01

    Inden for rammerne af det fælles-europæiske forskningsprojekt DRUID (DRiving Under the Influence of Drugs, alcohol and medicines) er forekomsten af alkohol og/eller andre stoffer blevet undersøgt i et stort antal europæiske lande, bl.a. i Danmark.......Inden for rammerne af det fælles-europæiske forskningsprojekt DRUID (DRiving Under the Influence of Drugs, alcohol and medicines) er forekomsten af alkohol og/eller andre stoffer blevet undersøgt i et stort antal europæiske lande, bl.a. i Danmark....

  15. Overvågning af karplanter i Suserup Skov

    DEFF Research Database (Denmark)

    Wind, P.

    1999-01-01

    Vejler, i alt ca. 5.500 ha. Feltstationen blev oprettet i 1978, og siden har observatørerne registreret fuglelivet i Vejlerne og de omgivende arealer foruden vandstand, saltholdighed og drift af området. Tipperne ligger i den sydlige del af Ringkøbing Fjord. Fuglelivet blev fredet i 1898. Reservatet blev...... en samlet fredning af Vadehavet, omfatter øen Langli på 80 ha og vandarealer på i alt ca. 8.000 ha. Øen består af klitter og salte strandenge. Vandområdet er præget af tidevand, hvor vidtstrakte sand- og mudderflader og spredte muslingebanker er synlige ved lavvande. Vorsø ligger i Horsens Fjord...... saltholdighed i Ringkøbing Fjord bevirker, at vandplanter vokser dårligt eller forsvinder. Vandplanter udgør en væsentlig del af føden for visse andefugle og kan derfor have stor betydning for antallet af rastende fugle. Der blev registreret lave antal af knortegå, gråand, pibeand og krikand. Af blishøne blev...

  16. Frisættelse af fødderne

    DEFF Research Database (Denmark)

    Kirkeby, Ole Fogh

    2013-01-01

    Kropskultur. Amerikansk journalist og forfatter hævder, at løb - og fødder - giver adgang til livets mening. Anmeldelse af: Christoffer McDougall: Født til løb. Oversat af Jacob Giese efter Born to Run. Forlaget Turbulenz, 400 sider.......Kropskultur. Amerikansk journalist og forfatter hævder, at løb - og fødder - giver adgang til livets mening. Anmeldelse af: Christoffer McDougall: Født til løb. Oversat af Jacob Giese efter Born to Run. Forlaget Turbulenz, 400 sider....

  17. Dilemmaer i musikterapeutisk behandling af en traumatiseret flygtning med musikerbaggrund

    Directory of Open Access Journals (Sweden)

    Bolette Daniels Beck

    2016-12-01

    Full Text Available Denne artikel præsenterer et single case-studie af et receptivt musikterapiforløb med en 55-årig syrisk flygtning, som har været udsat for fængsling og tortur på grund af sine aktiviteter som protestsanger og musiker. Der beskrives problemstillinger og dilemmaer relateret til at anvende musik, der både kan trigge traumer, men også vække indre ressourcer. Kortlægning af patientens forskellige personlighedsdele og musikkens evne til integration af dem vil blive belyst gennem teorien om strukturel dissociation.

  18. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab.

    Science.gov (United States)

    Modi, Shanu; Stopeck, Alison; Linden, Hannah; Solit, David; Chandarlapaty, Sarat; Rosen, Neal; D'Andrea, Gabriella; Dickler, Maura; Moynahan, Mary E; Sugarman, Steven; Ma, Weining; Patil, Sujata; Norton, Larry; Hannah, Alison L; Hudis, Clifford

    2011-08-01

    HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28). This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted. ©2011 AACR.

  19. In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines.

    Science.gov (United States)

    Ghadban, Tarik; Jessen, André; Reeh, Matthias; Dibbern, Judith L; Mahner, Sven; Mueller, Volkmar; Wellner, Ulrich F; Güngör, Cenap; Izbicki, Jakob R; Vashist, Yogesh K

    2016-10-01

    Heat shock protein (HSP)90 has emerged as an important target in cancer therapeutics. Diverse HSP90 inhibitors are under evaluation. The aim of the present study was to investigate the growth inhibitory effects of the newly developed water-soluble HSP90 inhibitors, 17-[2-(Pyrrolidin-1-yl)ethyl]amino-17-demethoxygeldanamycin (17-AEPGA) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), compared to that of the non-water-soluble HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG). The anti-proliferative effects of the 3 drugs on the human breast cancer cell lines, MCF-7, SKBR-3 and MDA-MB-231, were examined in vitro. In addition, tumor progression factors, including human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor 1 (EGFR1) and insulin-like growth factor type 1 receptor (IGF1R), as well as apoptotic markers were analysed. We found a time- and dose-dependent effect in all the tested cell lines. The effects of 17-AEPGA and 17-DMAG were equal or superior to those of 17-AAG. The 50% growth inhibition concentration was AAG.

  20. Gruppebaseret behandling af BED - et faseopdelt behandlingstilbud

    DEFF Research Database (Denmark)

    Laust, Jakob; Lau, Marianne Engelbrecht; Waaddegaard, Mette

    2015-01-01

    konsekvenser. BED blev i 2013 optaget i DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) som en selvstændig diagnose og BED forventes medtaget i den forestående revision af det internationale diagnose system, ICD-11. Sundhedsstyrelsen gav på denne baggrund satspuljemidler til erfaringsopsamling...... EDE-Q: 1,7 og ved EDI: 1,5), ligesom de generelle psykiske symptomer blev mindsket i høj grad (effectsize ved WHO-5: 1,0 og ved GSI meanscore: 0,8). I alt 82 % opfyldte før behandlingens start DSM-4’s diagnostiske kriterier for BED mod 11,5 % efter behandling. 52 % fik fuld remission (ingen...... accept af og tilfredshed med behandlingen. Der var stor effekt på antal overspisninger. Før behandling havde patienterne gennemsnitligt 23,7 overspisninger pr. mdr. mod 2,3 efter behandling (effect size: 5,4). Udbyttet i forhold til den samlede spiseforstyrrelsessymptomatologi var høj (effect size ved...

  1. Tilsætning af uorganisk og organisk kobber til smågrisefoder

    DEFF Research Database (Denmark)

    Maribo, Hanne; Poulsen, Hanne Damgaard

    2011-01-01

    Et højt indhold af kobber i foderet udgør en risiko for belastning af miljøet, og en begrænsning i udledningen af kobber er derfor ønskelig. Brug af organisk bundet kobber (kobberlysin) som alternativ til uorganisk kobber (kobbersulfat) i foderblandinger kan muligvis begrænse det totale forbrug af...

  2. Bakteriesensor til on-line identifikation/bestemmelse af mikrobiel drikkevandskvalitet

    DEFF Research Database (Denmark)

    Bentien, Anders; Tilsted Mogensen, Claus; Østergaard, Else-Marie

    Over det meste af verden defineres den mikrobielle drikkevandskvalitet primært på baggrund af grænseværdier for E. coli, coliforme bakterier og kimtal. Anvendelsen af den totale bakteriekoncentration til bestemmelse af mikrobiel drikkevandskvalitet er (af historiske årsager) ikke udbredt og primært...

  3. Miljøoptimering af afvaskning ved tryk med vandfortyndbar flexotrykfarve

    DEFF Research Database (Denmark)

    Larsen, Henrik Fred; Helweg, Christian; Pedersen, Anne Rathmann

    Rapporten beskriver praksis ved afvaskning af vandfortyndbare flexotrykfarver i emballageindustrien og anviser muligheder for indførelse af renere teknologi til reduktion af spildevandsbelastningen. Anbefalingerne omfatter a) udformning af farveværker med henblik på effektiv tømning af farve og e...

  4. Dansk oversættelse af MiDAS, et redskab til assessment af musikterapi for personer med demens

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Lykkegaard, Chris; McDermott, Orii

    2018-01-01

    Music in Dementia Assessment Scales, MiDAS, er udviklet til at vurdere ændringer i trivsel hos borgere med demens som har deltaget i musikterapi. Målingen udføres af 1) personale før og efter musikterapien for at vurdere om der er en indflydelse i hverdagssituationer efterfølgende, eller af 2......) musikterapeuten umiddelbart efter sessionen for at vurdere forandringer i selve sessionen. Der har været stor interesse for at anvende MiDAS i flere Europæiske lande, herunder Danmark. Derfor undersøgte udviklerne af MiDAS hvilke procedurer der anvendes til oversættelse og kulturel tilpasning af...... assessmentredskaber, og anbefalede på den baggrund en ti-trins procedure. Vi anvendte denne procedure til oversættelsen af MiDAS og således udviklingen af den danske MiDAS-DK. Den danske version af MiDAS er afprøvet af mere end 20 fagpersoner på baggrund af 296 udfyldte MiDAS-skemaer. Målet med artiklen er...

  5. AAg2M[VO4]2 (A=Ba,Sr; M=Co,Ni): A series of ferromagnetic insulators

    Science.gov (United States)

    Möller, Angela; Amuneke, Ngozi E.; Daniel, Phillip; Lorenz, Bernd; de la Cruz, Clarina R.; Gooch, Melissa; Chu, Paul C. W.

    2012-06-01

    AAg2M[VO4]2 with A=Sr2+ or Ba2+ present a series of layered compounds featuring a triangular lattice of transition metal cations, M = Co2+ or Ni2+, connected via nonmagnetic ortho-vanadates, which provide the magnetic superexchange within the layers. For this series of insulating compounds, ferromagnetic long-range order below 10 K is suggested by magnetization and specific heat measurements and confirmed by neutron diffraction experiments. We have investigated the impact of the spacer size of A2+ separating the layers leading to a tilting of the vanadates and consequently inducing a change in the effective magnetic correlations. Magnetization and specific heat measurements corroborate the important dependence of the magnetic superexchange on the orientation of the vanadates and the respective spin system. Furthermore, the ground state properties of the spin systems, S=1 (Ni2+) and S=3/2 (Co2+) in their respective octahedral coordination of oxygen, are evaluated. Calculated magnetic moments of the single ion complexes agree well with the magnetic structure. We, furthermore, report the dependence of Tc on applied isotropic pressure suggestive of a pressure effect on the effective ferromagnetic exchange coupling constants. In addition spectroscopic investigations probing the electronic structure of the [MO6] complexes and the vibrational structure of the [VO4] units are given.

  6. Sammenligning af laboratorieforsøg med kemiske, biologiske og termiske metoder til oprensning af residual fri fase under grundvandsspejlet i Kærgård Plantage

    DEFF Research Database (Denmark)

    Christophersen, Mette; Christensen, Jørgen Fjeldsø; Jørgensen, Torben H.

    , sulfonamider, barbiturater, anilin, cyanid og kviksølv, og det har resulteret i en meget kompleks forurening. Efter afgravning af 4000 tons meget forurenet jord ned til grundvandsspejlet i to af de seks gruber er næste skridt afprøvning af forskellige metoder til fjernelse af den kraftige grundvandsforurening...

  7. Røveri af bil - forbrydelsen der ikke findes

    DEFF Research Database (Denmark)

    Lentz, Lene Wacher

    2018-01-01

    Artiklen behandler den særegne strafferetlige problematik, at røveri af bil ikke straffes som sådan, men alene som ulovlig tvang og brugstyveri. Dette skyldes en formodning om, at tyven kun vil bruge bilen, ikke tilegne sig bilen. Konsekvensen bliver en langt lavere straf for "røveri af bil", end...

  8. Retsbeskyttelsen af fostre og befrugtede æg

    DEFF Research Database (Denmark)

    Herrmann, Janne Rothmar

    tydeliggøres og analyseres forskellige problemstillinger: -Abort og fosterreduktion - Fosterdiagnostik - Fosteret som patient og forsøgsperson - Anvendelse af føtale celler og væv - Fosterets status som afdød - Fertilitetsbehandling og sortering af befrugtede æg - Fertilitetsturisme - Stamcelleforskning...

  9. Lyv og Død af H Andersen levnet

    DEFF Research Database (Denmark)

    Askgaard, Ejnar Stig

    2016-01-01

    I anledning af 200-året for H.C. Andersens fars død redegøres for friskomager Hans Andersens levned.......I anledning af 200-året for H.C. Andersens fars død redegøres for friskomager Hans Andersens levned....

  10. Erfaringer med dokumentation af musikterapeutisk praksis i kommunal demensomsorg

    DEFF Research Database (Denmark)

    Krøier, Julie Kolbe; Jefsen, Anders

    2016-01-01

    Denne artikel afdækker centrale erfaringer fra etableringen af faste musikterapitilbud i kommunerne Hillerød og Sønderborg. I begge kommuner er musikterapien blevet et fast tilbud på baggrund af en prøvepe- riode, og der er blevet skabt en systematisk dokumentationspraksis. Denne er blevet etable...

  11. Krigens splittelse af det kropslige fællesskab

    DEFF Research Database (Denmark)

    Krejberg, Kasper Green

    2015-01-01

    Judith Butlers kritik af krigen mod terror opfordrer os til at bryde med de rammer, der styrer vores tænkning og sansning......Judith Butlers kritik af krigen mod terror opfordrer os til at bryde med de rammer, der styrer vores tænkning og sansning...

  12. Udstilling af børn og fostre med misdannelser

    DEFF Research Database (Denmark)

    Meyer, Ion

    2008-01-01

    Artiklen beskriver baggrunden for etableringen af de første anatomiske samlinger og de første samlinger med teratologiske præparater i Sct. Petersborg og Berlin. Den Saxtorphske Samling på Medicinsk Museion indeholder den største samling af teratologiske præparater i Danmark, og bagrunden for sam...

  13. Sparring på evaluering af Destination Trivsel

    DEFF Research Database (Denmark)

    Schulz, Anette

    , konklusion – hvor udsagn fra elever i henholdsvis indskolingen, mellemtrinnet og udskolingen indledningsvist behandles separat og deskriptivt. Efterfølgende er data analyseret med afsæt i en kryds-case-analyse, hvor der på baggrund af den deskriptive analyse koblet til de respektive målgrupper er udledt en...

  14. Lukning og indskrænkninger af virksomheder

    DEFF Research Database (Denmark)

    Pico Geerdsen, Peter; Høgelund, Jan; Larsen, Mona

    Der tales meget om de negative konsekvenser af globalisering. I denne rapport søger forfatterne at vurdere risikoen for svagere tilknytning til arbejdsmarkedet og forringet indkomstudvikling blandt fratrådte lønmodtagere i de dele af industrien, der er særligt udsat for konkurrence fra...

  15. Kontrol af konserveringsmidler og farvestoffer i legetøjskosmetik

    DEFF Research Database (Denmark)

    Rastogi, S. C.; Jensen, G. H.

    deklarationerne på de udtagne produkter er indholdet af formaldehyd analyseret i 4 produkter, dehydroacetic acid i 2 produkter og Kathon CG i 9 produkter. Parabener, 2-phenoxy-ethanol samt organiske farvestoffer er analyseret i samtlige udtagne produkter. Det er blevet påvist, at 42% af de udtagne produkter (n=19...

  16. Spilteorien og (et par af) dens fædre

    DEFF Research Database (Denmark)

    Hansen, Sune Welling

    2011-01-01

    Boganmeldelse af Robert Leonard's "Von Neumann, Morgenstern, and the Creation of Game Theory: From Chess to Social Science, 1900-1960". Cambridge University Press.......Boganmeldelse af Robert Leonard's "Von Neumann, Morgenstern, and the Creation of Game Theory: From Chess to Social Science, 1900-1960". Cambridge University Press....

  17. Strukturreformens succes afhænger af de offentlige ledere

    DEFF Research Database (Denmark)

    Pedersen, John Storm

    2005-01-01

    Bliver strukturreformen en succes eller fiasko? Det afhænger af ledernes evner og muligheder for at omstille driften i den offentlige sektors mange institutiner.......Bliver strukturreformen en succes eller fiasko? Det afhænger af ledernes evner og muligheder for at omstille driften i den offentlige sektors mange institutiner....

  18. Evaluering af Senter for flerkulturelt og internasjonalt arbeid (SEFIA)

    DEFF Research Database (Denmark)

    Stensaker, Bjørn; Benedicte, Brøgger; Nielsen, Kjeld

    2006-01-01

    Rapporten indeholder en beskrivelse af resultaterne fra en intern og ekstern evaluering af SEFIA - et center der driver undervisning og forsknings- og udviklingsarbejde samt formidling inden for temaerne flerkulturel forståelse og internationalt udviklingsarbejde. Evalueringen er foretaget på gru...

  19. Evaluering af ny kokkeuddannelse for hørehandicappede

    DEFF Research Database (Denmark)

    Hansen, Niels-Henrik Møller

    2010-01-01

    Center for Ungdomsforskning har netop afsluttet en evaluering af en ny uddannelse indenfor madproduktion, rettet imod personer med et hørehandicap. Hensigten med uddannelsen er, at kunne tilbyde døve, døvblinde og hørehæmmede personer et uddannelsestilbud indenfor fremstilling af mad. Konkret han...

  20. Testning af alment ordforråd hos danske universitetsstuderende

    DEFF Research Database (Denmark)

    Sørensen, Louise Langhoff; Ravn, Ida Elise; Weed, Ethan

    2017-01-01

    Artiklen indeholder udviklingen og afprøvningen af en ordforrådstest designet specielt til universi- tetsstuderende. Testen er en elektronisk, revideret version af ’Hvilket billede passer til ordet’ udviklet med udgangspunkt i de billeder og ord, der bruges i Vejledende Læsetest for Voksne (VLV)....

  1. “All That Jazz” - bagsiden af showbizz

    DEFF Research Database (Denmark)

    Eigtved, Michael

    2017-01-01

    Artiklen, der er skrevet til programmet ifbm premieren på musicalen Chicago på Det Ny Teater beskriver den tendens i broadwaymusicals, som begynder i slutningen af 1960’erne med bla forestillingen Cabaret, hvor det er skyggesiden af underholdningens industrien, der selvrefleksivt er emnet for for...

  2. Skattemæssig behandling af virtuelle valutaer

    DEFF Research Database (Denmark)

    Kjærsgaard, Louise Fjord; Weber, Katja Dyppel

    2018-01-01

    Udbredelsen og anvendelsen af virtuelle valutaer er stigende, og der synes derfor behov for en analyse af den skattemæssige kvalifikation og behandling heraf. Skatterådet har ved to lejligheder haft mulighed for at foretage denne analyse; i henholdsvis SKM2014.226.SR om Bitcoins og SKM2017.520.SR...

  3. Fremstilling af CO2-neutral benzin og diesel

    DEFF Research Database (Denmark)

    Stummann, Magnus Zingler; Høj, Martin; Jensen, Peter Arendt

    2018-01-01

    Siden 1965 er verdens energiforbrug mere end femdoblet og forbruget forventes at fortsætte med at stige i fremtiden. Imens mindskes reserverne af fossilt brændstof hastigt og CO2-udledningen fra forbrændingen af fossile brændstoffer medfører global opvarmning. Vi har derfor brug for hurtigt at fi...

  4. Anvendelse af webkonference på Syddansk Universitet

    DEFF Research Database (Denmark)

    Kjær, Christopher; Christensen, Inger-Marie F.; Blok, Rasmus

    2009-01-01

    Artiklen videregiver en række praktiske erfaringer med anvendelse af webkonferencesystemet Adobe Connect Pro i forbindelse med undervisning på Syddansk Universitet (SDU). Via tre pilotprojekter fra forskellige fagområder præsenteres de første konkrete og indledende erfaringer med anvendelsen af det...

  5. Test af et satellitbaseret kørselsafgiftssystem

    DEFF Research Database (Denmark)

    Sørensen, Simon Bojer; Lahrmann, Harry

    2007-01-01

    I dette paper beskrives opbygningen af en model af et takstsystem, som skal fungere i et satellitbaseret kørselsafgiftssystem. Modellen er forholdsvis simpel og bygger på et buffersystem, og der anvendes således ikke nogen avanceret map matching. Det beskrives, hvordan modellen afprøves med tilfæ...

  6. En retorisk analyse af en Hodayot-salme fra Qumran

    DEFF Research Database (Denmark)

    Hasselbalch, Trine Bjørnung

    2007-01-01

    I salmesamlingen Hodayot (1QHa), fundet blandt Dødehavsrullerne, skelner man mellem to grupper af salmer på baggrund af måden hvorpå salmisten fremtræder. Når forskere diskuterer salmesamlingens organisationsprincip, bygger de ofte deres synspunkter på den antagelse at der har været mindst to for...

  7. Overvågning af influenza i svin 2011

    DEFF Research Database (Denmark)

    Hjulsager, Charlotte Kristiane; Breum, Solvej Østergaard; Larsen, Lars Erik

    2012-01-01

    Influenza i dyr udgør en trussel mod dyresundheden, dyrevelfærden, produktionsøkonomien, fødeva-resikkerheden og har givet anledning til flere pandemier i mennesker. For at kunne agere hurtigt på nye trusler (early warning) og derved holde konsekvensen af fundet af et nyt virus på et minimum, er...

  8. Danske mediers dækning af Rusland

    DEFF Research Database (Denmark)

    Kabel, Lars

    eller forstået 2016 – Brexit i Storbritannien og Donald Trumps valg kom som en stor overraskelse – medierne havde igen ikke fat i det magtfulde, der vokser frem i samfundet på trods af eliten. Udenrigsdækningen er delvist ude af sync med den verden, den beskriver. Den er for elitær. Den er for indlejret...

  9. Forhandlinger af mangfoldighed i danske kommunernes kostpolitikker for dagtilbud

    DEFF Research Database (Denmark)

    Damgaard Warrer, Sarah; Leer, Jonatan

    2018-01-01

    Artiklen præsenterer en diskurs analytisk undersøgelse af danske kommuners kostpolitikker. Formålet med studiet er at kortlægge kommunernes forhandling af mangfoldighed og den måltidspædagogiske opgave, hvilket udgør et arbejdsredskab for pædagogerne i kommunale dagtilbud. Studiet er baseret på e...

  10. Målstyring af og frihedsgrader til de menneskelige ressourcer

    DEFF Research Database (Denmark)

    Nielsen, Kjeld

    2010-01-01

    bevaring af arbejdspladser. I den voluntaristiske tilgang til ledelse af personale bevæger virksomhederne sig i en ”sociologisk dualisme” mellem hårde og bløde tilgange. Strukturerne på arbejdsmarkedet og kulturelle forhold i samspillet mellem samfund og virksomhed i det danske samfund betyder, at begge...

  11. Overvågning af influenza i svin 2012

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Larsen, Lars Erik

    % af de positive indsendelser. Dette fald kan indikere at dette virus har toppet i udbredelse, men det kan også være en tilfældig variation. I overvågningen 2011 fandt vi udover de forventede subtyper også nye svineinfluenzavirus subtyper. En af de nye subtyper - H1avN2hu - blev fundet i...

  12. Om den sociale og symbolske funktion af uddannelsesevalueringer

    DEFF Research Database (Denmark)

    Nørholm, Morten

    Afhandlingens teoretiske udgangspunkt er hos Émile Durkheim, Pierre Bourdieu, Ulf P. Lund­gren, Staf Callewaert, det konkrete er en række evalueringer af uddannelser til (semi)professioner inden for sundhedssektoren.                I afhandlingen konstrueres den sociale og symbolske funktion af...

  13. Aftaler om arbejdsmiljø - en analyse af udvalgte overenskomster

    DEFF Research Database (Denmark)

    Petersen, Jens Voxtrup; Wiegmann, Inger-Marie; Vogt-Nielsen, Karl

    En analyse af overenskomsters betydning for arbejdsmiljøet indenfor industri, slagterier, rengøring, det grønne område, hotel og restauration og busdrift.......En analyse af overenskomsters betydning for arbejdsmiljøet indenfor industri, slagterier, rengøring, det grønne område, hotel og restauration og busdrift....

  14. African Network Operators Group (AfNOG) Training Workshops and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The African Network Operators Group (AfNOG) is a forum for technical cooperation and coordination between African network operators and engineers from the region's universities, research institutions and industry. This year, AfNOG's training workshops and meetings will be held in Rabat, Morocco, between 24 May and 6 ...

  15. Udførelse af bygningsakustiske målinger

    DEFF Research Database (Denmark)

    Rasmussen, Birgit; Hoffmeyer, Dan; Olesen, Henrik S.

    Denne anvisning definerer og beskriver udførelse af bygningsakustiske målinger m.m. i relation til Bygningsreglement 2015 (BR15), kapitel 6.4, Akustisk Indeklima (Trafik- og Byggestyrelen, 2016). Anvisningen er en opdatering af den første udgave fra 2008. Den nye udgave er ajourført med vejledning...... knyttet til blandt andet de nye standarder med feltmålemetoder for lydisolation. Anvisningen henvender sig primært til personer og firmaer, der udfører bygningsakustiske målinger, men vil også være et vigtigt redskab for rådgivere, udførende og leverandører i forbindelse med projektering af bygninger....... Anvisningen er også relevant for kommunerne i forbindelse med kontrol af opfyldelsen af lydbestemmelserne i bygningsreglementet....

  16. Udkantsdanmark: Avisernes (med)produktion af Nordjyllands territorielle stigma

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene; Christensen, Sascha

    2013-01-01

    Artiklen undersøger hvordan Region Nordjylland (NJ) beskrives i medierne og hvordan diskursen om Udkanten dominerer avisernes fremstilling af regionen . Baggrunden herfor er en interesse for social ulighed, og i denne sammenhæng Wacquants begreb om territorielt stigma (1996, 2007). Wacquant føjer...... stigma. I Gunnar Lind Haase Svendsens studie af italesættelsen af ’udkanten’ fra 1996-2011 ses fx en gennem de seneste år stigende anvendelse af termer som ’den rådne banan’ og ’Udkantsdanmark’ i medierne (Svendsen 2013: 12). Dette stigma forbindes med flere dele af Danmark (se bl.a. Arbejderbevægelsens...

  17. Skattemæsssig kvalifikation af trusts i praksis

    DEFF Research Database (Denmark)

    Feldthusen, Rasmus Kristian

    2013-01-01

    Artiklen har til formål at systematisere og redegøre for skattemyndighedernes fremgangsmåde og kvalifikation af trusts i dansk ret. Baggrunden herfor er, at antallet af trust-sager for såvel de administrative myndigheder som domstolene relativt set er vokset betydeligt siden årtusindeskiftet. Ud...... fra en gennemgang af doms- og administrativ praksis kan det konstateres, at kvalifikationen af trusts kan opdeles i fire hovedkategorier, som er væsentlige at have kendskab til, såfremt en skattesag indeholdende trust-elementer måtte være under opsejling. Endvidere inddrages skattestrafferetlig...... praksis på baggrund af en nyligt afsagt landsretsdom vedrørende en offshore trust....

  18. Forbedring af GIS data til trafikmodeller

    DEFF Research Database (Denmark)

    Hansen, Stephen; Landex, Alex; Nielsen, Otto Anker

    2005-01-01

    indbyggere og arbejdspladser er meget inhomogen. Dette er især tilfældet for zonerne i Frederiksborg og Roskilde Amter. For at opnå mere detaljerede resultater er det nødvendigt at opdele disse zoner. I artiklen præsenteres forskellige GIS-baserede metoder, der er blevet benyttet til at forbedre og kombinere...... eksisterende GIS-baserede datakilder, så der er opnået en hidtil uset nøjagtighed i trafikmodellernes geografiske data. Herefter beskrives, hvordan der med udgangspunkt i disse forbedrede data er foretaget analyser af zonerne i modellen, og hvordan zoner som ikke lever op til den ønske detaljegrad, er splittet...

  19. Implementering af tre misbrugsbehandlinger for udsatte unge

    DEFF Research Database (Denmark)

    Weatherall, Cecilie Dohlmann; Termansen, Tina

    2015-01-01

    SFI- Det Nationale Forskningscenter for Velfærd skal evaluere ”Projekt misbrugsbehandling for udsatte unge”, som løber fra 2011 til 2014. De tre behandlingsmodeller, som indgår i Socialstyrelsens (SOS) ”Projekt misbrugsbehandling for udsatte unge”, er MST-SA (Multi Systemic Therapy Substance Abuse...... både i Danmark og internationalt. Dog er der et stigende fokus på, at det er et centralt element for at opnå gode evalueringer (Fixen m.fl., 2005; Fixen m.fl., 2009; Durlak & DuPre, 2008), idet implementeringen af en indsats kan have stor betydning for den effekt, der observeres. Ifølge Durlak og Du...

  20. Supervision af nyudnævnte officerer

    DEFF Research Database (Denmark)

    Jeppesen, Lennart Schou; Okholm, René

    for instituttet, skoler, lærere og elever, der giver opdateret viden om premierløjtnantens praksis. Projektets effekt kan ikke beskrives fuldstændigt, men dette brief kan ses som et generelt ønske om i højere grad at danne bro mellem Forsvarets skoler og den praksis, vi uddanner til. Projektet har allerede...... ledelseseksamen for hold Pløger i 2016. - Ændret fokus i ledelses- og lederudviklingsundervisningen i retning af: 1) at øge refleksionsevnen hos kadetterne, 2) at styrke deres personaleledelseskompetencer og 3) at indføre Leadership Pipeline-tankegangen. - Input til VUK, særligt i forhold til chefens rolle og...

  1. Arbejdsformer under anvendelse af 4. generationsværktøjer

    DEFF Research Database (Denmark)

    Christensen, Søren; Grønbæk, Kaj; Rolskov, Tove

    En belysning af sammenhængen mellem arbejdsformer og anvendelse af 4. generationsværktøjer i systemudvikling -- baseret på en undersøgelse af 9 systemudviklingsprojekter og et litteraturstudium...

  2. Succesfulde virksomheder ledes af mænd - Ikke succesfulde af kvinder?

    DEFF Research Database (Denmark)

    Madsen, Mona Toft; Madsen, Henning; Neergaard, Helle

    fra amerikanske og britiske undersøgelser (Schein, 1973, 75, 96; Ryan et al., 2005a) ved at teste dem i et kulturelt miljø karakteriseret af mere feminine ledertræk (Hofstede, 1991). Undersøgelsen tager udgangspunkt i et sæt af person-karakteristika, der er blevet anvendt til at undersøge sammenfald...... mellem mandlige karakteristika og succesfuld ledelse (Schein, 1973, 75, 96). På lige fod med nyere britiske undersøgelser (Ryan et al. 2005a), er den aktuelle undersøgelse imidlertid udvidet til også at omhandle lederes perceptioner i forhold til ledelse i virksomheder uden succes. Resultaterne viser...

  3. Cape Newenham AFS, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

    Science.gov (United States)

    1983-04-01

    TEMPERATURE DEPRESION F, ’O.AL 3 - 4 5- 6 8 9- 1 11 12 13 14 𔃿 t 11 1 9 :," 2. 4 :.! 2 2 5 . . I TAL .4’ 373 - .. .. 776 7 7 8 * ... .. H- j4 93 4 5 7...H ;AVETA: PSYCHROMETRIC SUMMARY; A:Z, %EAT ER SER VCLPI ’ 7 CARUP li i.L -AF -- AM---.- 7-. - _ PAGE 1 2 WET BLLB TEmPEPATURE DEPRESION F, " AL .’ 3

  4. Energi i økologisk jordbrug. Reduktion af fossilt energiforbrug og produktion af vedvarende energi

    DEFF Research Database (Denmark)

    2004-01-01

    Målsætningen om at reducere forbruget af fossil energi er klart formuleret i de økologiske principper. Desuden er der både forsyningsmæssige og geopolitiske grunde til, at det kan være klogt at fremtidssikre økologisk jordbrug ved at øge selvforsyningsgraden. På den baggrund iværksatte FØJO i eft...

  5. Læremiddeltjek af Fandange - dansk for 5. klasse af Trine May og Susanne Arne-Hansen

    DEFF Research Database (Denmark)

    Christensen, Mette Vedsgaard

    2013-01-01

    Fandango 5 er skrevet af Trine May og Susanne Arne-Hansen og er første gang udgivet i 2009. Systemet er siden kommet i flere oplag. Fandango – dansk for 5. klasse består af en grundbog (264 sider) Arbejdsbog A (64 sider) Arbejdsbog B (64 sider), en lærervejledning (ca. 220 sider) og en hjemmeside...

  6. Undersøgelse af mulighederne for anvendelse af open source Integrated Library Systems (ILS) i universitetsbiblioteket

    DEFF Research Database (Denmark)

    Greve, Eli; Bøgh Pedersen, Kasper

    Dette projekt har til formål, at to biblioteker med meget forskellige profiler gennemfører test af konkrete open source baserede ILS systemer, formidler resultaterne til FFU-bibliotekerne og deres interessenter, og herved bidrager til en nuancering af beslutningsprocesserne i de kommende år omkring...

  7. Udvikling og afprøvning af it-støttet vejledning af lærerstuderende i praktik

    DEFF Research Database (Denmark)

    Clemens, Heidie

    2011-01-01

    samarbejdet mellem læreruddannelsen og praktikinstitutionerne omkring vejledning af de studerende i praktikken via Skype eller VIAs platform og at afprøve en vejledningsform, der har karakter af procesvejledning. Erfaringer med at afprøve den virtuelle mødeform i denne sammenhæng muliggør mødet mellem...

  8. Et nationalt studie af bankrøveri

    DEFF Research Database (Denmark)

    Hansen, Maj; Elklit, Ask

    11,1 % (n = 41) af ASD og seks måneder efter røveriet led 6,2 % (n = 23) af PTSD. Begge prævalenser var begrænset af kravet om undgåelsessymptomer (ASD uden undgåelse: 14 %, PTSD uden undgåelse: 17,8 %), men ASD diagnosen var især begrænset af kravet om dissociationssymptomer (ASD uden dissociation......: 26,7 %). Hierarkisk regressionsanalyse viste, at 51 % af variansen i PTSD sværhedsgrad blev forklaret af peritraumatisk dissociation, ASD sværhedsgrad, emotionel coping og negative tanker om egen person og evner. ASD sværhedsgrad var den stærkeste prædiktorer for PTSD sværhedsgrad og forudsagde alene...... diagnoser. Særligt ASD sværhedsgrad og negative tanker om egen person og evner synes at kunne forudsige PTSD sværhedsgrad efter bankrøveri. Det anbefales derfor, at ”Acute Stress Disorder Scale” anvendes til at screene for PTSD efter bankrøveri. Fremtidig forskning anbefales at fokusere på udvikling af...

  9. Brugen af personas hos danske virksomheder - 2012/13

    DEFF Research Database (Denmark)

    Nielsen, Lene; Nielsen, Kira Storgaard

    2013-01-01

    Denne rapport er skrevet på baggrund af et projekt initieret og finansieret af InfinIT – Innovationsnetværket for IT. Formålet med projektet er at undersøge hvorledes personas i dag etableres, kommunikeres, anvendes og vedligeholdes i forskellige typer af virksomheder samt etablere et opdateret sæt...... af anbefalinger for deres anvendelse. Virksomheders erfaringer med personas vil blive adresseret fra to forskellige vinkler:. Fokus vil bl.a. være på hvordan personas udvikles og vedligeholdes, om og hvordan de bruges, og hvad de bruges til. Personas er beskrivelser af fiktive brugere og bruges i...... designprocesser. Beskrivelserne er skabt på baggrund af data indsamlet om slutbrugerne. En samling af personas, som regel mellem 2 og 6 beskrivelser, vil i denne rapport benævnes et personasæt. Når personabeskrivelserne indgår i designprocessen bruges de til at få ideer til og beskrive, hvordan brugerne vil...

  10. Telefonitis: unge danskeres brug af telefonen i IT-tidsalderen

    Directory of Open Access Journals (Sweden)

    Gitte B. Stald

    2000-09-01

    Full Text Available Den udbredte brug af mobiltelefoner har sat fornyet fokus på telefonens betydning i vores tid. Som følge af den informationsteknologiske udvikling ændrer telefonen karakter fra at være en kanal for kommunikation til at være et medie for flere funktioner, samtidig med at dens konkrete og sym- bolske betydning forstærkes. Dette kan i særlig grad aflæses i større børns og unges brug af telefonen, der dels er karakteriseret ved stor selvfølgelig- hed, dels ved at have en betydning, der rækker ud over funktioner: den er markør af ungdomskultur, den er garant for tryghed, og den muliggør fast- holdelse af sociale og personlige relationer. Telefonen befordrer etablering- en af et virtuelt rum, hvor intimitet og fortrolighed er mulig. Set i lyset af den informationsteknologiske udvikling, der har bragt e-mail, chat og andre for- mer for on- og offline kommunikation ind i de fleste unge danskeres tilvæ- relse, er det interessant, at telefonen har fastholdt og endog forstærket sin betydning.

  11. Metodik til studiet af strategiske ledelsesprocesser i organisationer

    Directory of Open Access Journals (Sweden)

    Jørgen Gulddahl Rasmussen

    2010-10-01

    Full Text Available Denne artikel handler om at skabe viden om en hverdagspraksis, der sjældent er sat ord på. Den behandler de ledelsesprocesser, der i virksomheder producerer strategi og omsætter sådanne strategier i produktive handlinger. Det er processer, der i små og mellemstore virksomheder er præget af intuition og af meget uformelle samspil mellem virksomhedsledere og medarbejdere. Metodikken er en videreudvikling af de metoder til produktion af kvalitative data, som FIRM-gruppen har eksperimenteret med gennem nogle år. Artiklen kan ses som en afrapportering af et flerårigt metodeudviklingsarbejde. Da erfaringer fra sådanne virksomheder viser, at strategiske processer i høj grad udvikler sig gennem uformel kommunikation, og at lederes intuition spiller en meget stor rolle, arbejder metodikken med en struktureret udviklingsdialog mellem et mindre antal virksomhedsledere med strategiske opgaver og forskere. Denne udviklingsdialog har til formål at følge og forstå de processer, der skaber ledernes egne praksisrelaterede ”teorier” for strategisk handling. Efter en præsentation af temaet gennemgås metodikkens praktiske fremgangsmåde med undersøgelser i en række virksomheder, opbygning af cases i samarbejde med ledere fra disse virksomheder, diskussion af disse og foreløbige konklusioner hen mod de næste trin i metodikken. Artiklen er skrevet samtidigt med arbejdet på et igangværende forskningsprojekt og vil derfor både være en præsentation og en udvikling af muligheder og vanskeligheder i metodikken.

  12. Telefonitis: unge danskeres brug af telefonen i IT-tidsalderen

    OpenAIRE

    Gitte B. Stald

    2000-01-01

    Den udbredte brug af mobiltelefoner har sat fornyet fokus på telefonens betydning i vores tid. Som følge af den informationsteknologiske udvikling ændrer telefonen karakter fra at være en kanal for kommunikation til at være et medie for flere funktioner, samtidig med at dens konkrete og sym- bolske betydning forstærkes. Dette kan i særlig grad aflæses i større børns og unges brug af telefonen, der dels er karakteriseret ved stor selvfølgelig- hed, dels ved at have en bet...

  13. De dankse domstoles håndtering af CISG

    DEFF Research Database (Denmark)

    Lookofsky, Joseph

    2012-01-01

    Købelovskonventionen (CISG) forpligter de danske domstole til at tage hensyn til traktatens internationale karakter og til behovet for at fremme ensartet anvendelse af den. Artiklen peger på, at danske domspræmisser efterlader indtryk af sjældent at tage hensyn til disse pligter. Problemet - som...... parternes advokater er med til at skabe - understreges af fodnoten til en højesteretsdom, der synes at bekræfte, at de danske CISG-sager endnu ikke kører på det internationale spor....

  14. På sporet af fremtidens forsyningskæde: Agile Logistics?

    DEFF Research Database (Denmark)

    Møller, Charles

    2001-01-01

    PRODUKTION OG LOGISTIK. På en lang række områder er vilkårene for industriel produktion dramatisk forandret. Nye teknologier står på spring til at ændre kendte forudsætninger på afgørende områder. Det vi ser er fremkomsten af nye forretningskoncepter, hvor behovet for hurtig udvikling og leveranc...... af kundetilpassede og individualiserede produkter og services sætter hidtil uhørte høje krav til effektiviteten og fleksibiliteten af både produktions- og logistiksystemerne....

  15. Didaktisk design af IKT og medier til fysioterapeutuddannelsen

    DEFF Research Database (Denmark)

    Nielsen, Kim

    2012-01-01

    eksisterer i den reale verden som love og regler for materielle/fysiske forhold ved fænomener, objekter, kultur, natur og vores krop, eller brug af objekter og fænomener som kan repræsentere teorier, modeller, love og regler fysisk frem for artikulation af den reale verden. Et valg som antager at viden er...... regler. Især æstetisk design, men også kirurgi, spilplatforme og nogle få IKT- og medieeksempler til uddannelsesområdet, bidrager med forskellige forslag til udvikling af didaktiske design som kunne matche undervisningens centrale menneskesyn, viden- og læringsopfattelse. Samtidigt peger ny neurologisk...

  16. Novel cross-strand three-purine stack of the highly conserved 5'-GA/AAG-5' internal loop at the 3'-end termini of Parvovirus Genomes

    International Nuclear Information System (INIS)

    Chou, S.-H.; Chin, K.-H.

    2001-01-01

    We have used two-dimensional nuclear magnetic resonance (2D-NMR), distance geometry (DG) and molecular dynamics / energy minimization (MD/EM) methods to study a 2x3 asymmetric internal loop structure of the highly conserved '5'-(GA)/(AAG)-5' bubble' present at the 3'-end hairpin of the single-stranded DNA genome of parvoviruses. This motif contains an unpaired adenosine stacked between two bracketed sheared G·A pairs. However, the phenomenal cross-strand G-G and A-A stacking in the tandem sheared G·A pairs has undergone considerable change. A novel three-purine stacking pattern is observed instead; the inserted A18 base is completely un-stacked from its neighboring G17 and A19 bases, but well stacked with the cross-strand A4 and G3 bases to form a novel A4/A18/G3 stack that is different from the double G/G, A/A or quadruple G/G/G/G stack present in the 5'-(GA)/(AG)-5' or 5'-(GGA)/(AGG)-5' motifs. Unlike the bulged purine residue that usually causes about 20 degree kink in the helical axis of the parent helix when bracketed by canonical G·C or A·T base pairs, no significant kink is observed in the present helix containing a bulged-adenine that is bracketed by sheared G ·A pairs. The phosphodiesters connecting G3-A4 and G17-A18 residues adopt unusual ζ torsional angles close to the trans domain, yet that connecting A18-A19 residues resumes the normal ζ(g - ) value. The well structured '5'-(GAA)/(AG)-5'' internal loop in the parvovirus genomes explains its resistance to single-strand specific endonuclease susceptibility

  17. Monitering, modellering og miljøvurdering af fuldskala afværge af TCE fourening ved stimuleret reduktiv deklorering

    DEFF Research Database (Denmark)

    Westergaard, Claus; Lemming, Gitte; Janniche, Gry Sander

    På Sortebrovej 26 i Tommerup blev der i 2006 gennemført afværgeforanstaltninger ved stimuleret reduktiv deklorering (SRD) ved injektion af donor og bakterier i kildeområdet med henblik på at oprense en forurening med TCE. Kildeområdet befinder sig 10-20 m u. t. i sandet og opsprækket moræneler...... gunstige forhold for nedbrydning af de klorerede ethener ved reduktiv deklorering. Der ses da også en klar dominans af nedbrydningsprodukterne DCE og VC samt ethen og ethan i grundvandet. I nogle boringer, ses dog en stagnerende omsætning af TCE og DCE i grundvandet. Årsagen her til kan være, at donoren...... da også fordoblet fra 2008 til 2010. Der er observeret zoner med betydelig omsætning af TCE, hvor cis-DCE dominerer, og der ses generelt VC og ethen centralt i disse zoner. Koncentrationsniveauet af fermenteringsprodukter er aftaget og består ved en sandslire (B370 K1) alene af acetat og methan...

  18. Dansk oversættelse af MiDAS, et redskab til assessment af musikterapi for personer med demens

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner; Lykkegaard, Chris; McDermott, Orii

    2018-01-01

    DAS explored which procedures is used for outcome measure translation and cultural adaptation, and based on this recommended a ten-step procedure. We applied this procedure in order to translate MiDAS and hereby develop the Danish MiDAS-DK. The Danish MiDAS version has been tested by more than 20 professionals......) musikterapeuten umiddelbart efter sessionen for at vurdere forandringer i selve sessionen. Der har været stor interesse for at anvende MiDAS i flere Europæiske lande, herunder Danmark. Derfor undersøgte udviklerne af MiDAS hvilke procedurer der anvendes til oversættelse og kulturel tilpasning af...... assessmentredskaber, og anbefalede på den baggrund en ti-trins procedure. Vi anvendte denne procedure til oversættelsen af MiDAS og således udviklingen af den danske MiDAS-DK. Den danske version af MiDAS er afprøvet af mere end 20 fagpersoner på baggrund af 296 udfyldte MiDAS-skemaer. Målet med artiklen er...

  19. Implementering af ITIL® IT-governance

    DEFF Research Database (Denmark)

    Salling, Allan

    The IT Infrastructure Library (ITIL) fremhæves ofte som et IT-governance best practice framework, men det er tilsyneladende vanskeligt at implementere. ”Many organizations that decide to implement ITIL fail completely [...]” (Pereira og da Silva 2010). Dette vurderes som et væsentligt IS-forsknin......The IT Infrastructure Library (ITIL) fremhæves ofte som et IT-governance best practice framework, men det er tilsyneladende vanskeligt at implementere. ”Many organizations that decide to implement ITIL fail completely [...]” (Pereira og da Silva 2010). Dette vurderes som et væsentligt IS......-forskningsproblem. ITIL-litteraturen anviser bl.a. Critical Success Factors (CSF) som en løsning. Baseret på et identificeret litteraturgap blev det besluttet at undersøge, om kendte CSF kunne løse problemet. På den baggrund er der gennemført et aktionsforskningsprojekt, hvor ITILimplementeringsproblemet søges løs ved......, at kulturen delvist kunne forklare problemerne, og på den baggrund blev der opstillet handleanvisninger for diagnosticering og ændring af kulturen. ITIL-implementeringen var kun delvist en succes, men under aktionsforskningen blev der alligevel etableret en række holdbare rutiner, der stadig bruges flere år...

  20. Buksevand for øjnene af hele verden

    DEFF Research Database (Denmark)

    Fugl, Marie

    2009-01-01

    På internettet udvides randen af mobbetilskuere til potentielt hele verden. Det kan mangedoble de følelser, der er forbundet med en offentliggjort ydmygelse, fortæller mobbeforsker Jette Kofoed. Udgivelsesdato: Maj...